Prostate Cancer
Prostate cancer is a malignant neoplasm arising from the glandular epithelial cells of the prostate, most commonly adenocarcinoma, typically affecting older men and often characterized by slow growth and elevated prostate-specific antigen levels.
Prostate Cancer
Prostate cancer (PCa) is a malignant neoplasm arising from the epithelial cells of the prostate gland. > 95% of prostate cancers are adenocarcinoma [1][2]. The name itself is straightforward: "prostate" = the walnut-shaped gland below the bladder; "carcinoma" = cancer of epithelial origin; "adeno-" = glandular. So adenocarcinoma of the prostate = a cancer arising from the glandular epithelial cells of the prostate.
It is a disease of enormous clinical importance because it is extremely common, often indolent (slow-growing), yet can be lethal when advanced. The central clinical challenge is distinguishing clinically significant cancers that need treatment from indolent ones that can be safely observed — this is the core tension in prostate cancer management.
Key Concept
Prostate cancer overwhelmingly arises in the peripheral zone of the prostate. This has two critical clinical implications: (1) it is palpable on DRE (the peripheral zone is posteriorly located, abutting the rectum), and (2) it does not cause early obstructive urinary symptoms (unlike BPH, which arises in the transitional zone surrounding the urethra). Therefore, prostate cancer often presents late or is found incidentally.
2. Epidemiology
- Prostate cancer is the second most common cancer in men worldwide and the fifth leading cause of cancer death in men globally [3].
- There is enormous geographic variation: highest incidence in North America, Northern/Western Europe, Australia, and Caribbean (particularly Afro-Caribbean populations); lowest in Asia.
- This variation is partly genetic (ethnicity) and partly environmental/dietary (westernised diet, screening practices).
This is what matters for your exams:
- Prostate cancer is the 3rd most common cancer among males in Hong Kong [2][3].
- Lifetime risk: approximately 1 in 26–30 [2][4].
- Annual incidence: ~2,300 new cases per year [2].
- Incidence rate: 56.6 per 100,000 males; mortality rate: 12.1 per 100,000 males (4.9% of male cancer deaths, ranking 5th) [4].
- Used to be rare in HK but now has increasing incidence, probably due to ageing population, westernised lifestyle, and increased health awareness with increased screening PSA tests [4].
- 40–50% are diagnosed at stage I–II in HK (this proportion is higher in the West due to more widespread screening) [4].
- 1/3 of patients present with locally advanced or metastatic disease [2].
- More common in advanced age; one of the strongest relationships between age and any human malignancy [4].
- Rare before age 40 [4].
- Incidence rises steeply after age 50 and peaks in men aged 70–80.
- Autopsy studies show occult (clinically insignificant) prostate cancer in ~30% of men aged 50 and ~70% of men aged 80 — this underlines the concept that many men die with prostate cancer, not of it.
High Yield: In HK, prostate cancer is the 3rd most common male cancer with rising incidence. The key drivers are ageing, westernisation, and increased PSA testing.
3. Anatomy and Function of the Prostate
Understanding prostate anatomy is essential for understanding why BPH and prostate cancer behave differently, why DRE can detect prostate cancer, and how cancer spreads.
The prostate is a walnut-sized exocrine gland (~20g in young adults) located:
- Inferior to the urinary bladder
- Anterior to the rectum (hence palpable on DRE)
- Surrounding the prostatic urethra (the first segment of the urethra after the bladder neck)
- Superior to the external urethral sphincter and pelvic floor
The ejaculatory ducts (formed by the union of the vas deferens and seminal vesicle duct) pass through the prostate to open at the verumontanum (seminal colliculus) on the posterior wall of the prostatic urethra.
This is the modern anatomical classification and is critical for exams:
| Zone | % of Glandular Tissue | Clinical Significance |
|---|---|---|
| Peripheral zone | 65% | Common site of prostate cancer (70–80% arise here) and prostatitis [1][4][5] |
| Transitional zone | 10% | Common site of BPH (median lobe enlargement) [1][5] |
| Central zone | 25% | Surrounds ejaculatory ducts; ~8% of cancers arise here [4] |
| Anterior fibromuscular stroma | Non-glandular | No glandular tissue → cancers here are often missed by TRUS-guided biopsy [4]; 20–30% of cancers may arise in the anterior zone |
| Periurethral zone | Small | Surrounds prostatic urethra; site of periurethral BPH nodules |
Why does prostate cancer present late?
Because 70–80% of cancers arise in the peripheral zone, which is located posteriorly and away from the urethra. The cancer can grow substantially before it compresses the urethra enough to cause obstructive symptoms. In contrast, BPH arises in the transitional zone which directly surrounds the urethra, so even small amounts of hyperplasia can cause significant obstruction. This is why BPH causes early LUTS but prostate cancer often does not.
The prostate gland produces prostatic fluid, which constitutes about 20–30% of seminal fluid. Key components include:
- Prostate-Specific Antigen (PSA): a serine protease whose function is to liquefy the semen coagulum after ejaculation, facilitating sperm motility [2]. PSA is organ-specific but NOT cancer-specific — this is crucial for understanding PSA's limitations as a tumour marker.
- Citric acid, zinc, fibrinolysin, acid phosphatase
- Prostatic secretions are slightly acidic (pH ~6.5)
- The prostate is an androgen-dependent organ.
- Testosterone (from the testes, and a small amount from the adrenals) is converted to dihydrotestosterone (DHT) within the prostate by the enzyme 5α-reductase [1].
- DHT is the primary intraprostatic androgen and is ~5× more potent than testosterone at binding the androgen receptor (AR).
- Both prostatic epithelial cells and stromal cells express androgen receptors and depend on DHT for growth and survival [1].
- This androgen dependence is the basis for androgen deprivation therapy (ADT) in prostate cancer — remove the androgen signal, and prostate cancer cells undergo apoptosis (at least initially).
High Yield: The prostate depends on DHT (converted from testosterone by 5α-reductase). This is the basis for ADT in prostate cancer AND 5α-reductase inhibitors (finasteride/dutasteride) in BPH.
- Arterial supply: Branches of the internal iliac artery (inferior vesical artery)
- Venous drainage: The prostatic venous plexus (of Santorini) drains into the internal iliac veins and, critically, communicates with the vertebral venous plexus (Batson's plexus) [1][2].
- Batson's plexus is a valveless venous system that runs along the vertebral column. Because it lacks valves, blood can flow in either direction depending on intra-abdominal pressure. This provides a direct route for haematogenous spread of prostate cancer to the vertebral bodies and axial skeleton — explaining the classic pattern of osteoblastic bone metastases in the spine, pelvis, and ribs.
- Lymphatic drainage: Obturator and internal iliac nodes → external iliac → common iliac → para-aortic nodes
Batson's Plexus — Why Prostate Cancer Loves Bone
The prostatic venous plexus communicates with the valveless vertebral venous plexus (Batson's plexus). When intra-abdominal pressure increases (e.g., straining, coughing), venous blood is shunted retrograde into the vertebral venous system, carrying tumour cells with it. This is why prostate cancer preferentially metastasises to the axial skeleton (vertebrae, pelvis, ribs, skull) rather than the appendicular skeleton.
4. Etiology and Risk Factors
4.1 Non-Modifiable Risk Factors
- One of the strongest relationships between age and any human malignancy [4].
- Aging is the MOST important risk factor [1].
- Rare before age 40 [4].
- The mechanism: with ageing, there is cumulative exposure to androgens, accumulation of somatic mutations, epigenetic changes, chronic inflammation, and telomere shortening in prostatic epithelial cells.
- Blacks > Caucasians > Asians [4].
- African-American men have the highest incidence and mortality worldwide — they develop cancer earlier, present with higher-grade disease, and have worse outcomes even after adjusting for socioeconomic factors. This is thought to reflect both genetic susceptibility and differences in androgen metabolism.
- Asian men (including Hong Kong Chinese) historically have lower rates, but this gap is narrowing with westernisation [4].
- BRCA1 and BRCA2 mutations [1][4]:
- BRCA2 is a stronger risk factor for prostate cancer than BRCA1 [1].
- BRCA2 carriers have ~3–8× increased risk and tend to develop more aggressive, higher-grade disease.
- These are tumour suppressor genes involved in homologous recombination DNA repair. When both alleles are lost (germline mutation + somatic "second hit"), DNA damage accumulates → malignant transformation.
- BRCA mutations also confer sensitivity to PARP inhibitors (e.g., olaparib) — a therapeutic target in metastatic castration-resistant prostate cancer (mCRPC).
- Other heritable mutations: ATM, CHEK2, Lynch syndrome (HNPCC = hereditary non-polyposis colorectal cancer) [4].
- TMPRSS2-ETS fusion gene: present in ~50% of prostate cancers [2]. TMPRSS2 is an androgen-regulated gene; when fused with ETS family transcription factors (e.g., ERG), it drives androgen-dependent overexpression of oncogenic transcription factors.
4.2 Modifiable/Potentially Modifiable Risk Factors
- Growth of prostate cancer is stimulated by androgens [4].
- The role of 5α-reductase inhibitors (finasteride, dutasteride) is debated — they reduce overall prostate cancer incidence but there was concern about increasing high-grade cancer detection (likely a detection bias rather than a true increase) [4].
- Evidence is generally weak [4].
- Potentially protective: selenium, lycopene (tomatoes), vitamin E, green tea, possibly coffee [4].
- Potentially harmful: dietary fat (linked to obesity), isoflavonoids (soybean products — note: this is debated) [4].
- High animal fat intake may increase risk; high vegetable intake may be protective [1].
- Chronic prostatitis/inflammation: may contribute to carcinogenesis through oxidative stress and proliferative inflammatory atrophy (PIA) → prostatic intraepithelial neoplasia (PIN) → carcinoma sequence.
Risk Factors Summary Mnemonic: 'AGE BRCA FAT'
- Age (most important)
- Genetics (BRCA2 > BRCA1, TMPRSS2-ETS, ATM, CHEK2, Lynch)
- Ethnicity (Black > White > Asian)
- BRCA2 (aggressive disease, PARP inhibitor target)
- Relatives (FHx — number and age of affected first-degree relatives)
- Cancer history (Lynch syndrome association)
- Androgens (hormonal stimulation)
- Fat (dietary fat, obesity)
- Activity (lack of exercise)
- Tobacco (smoking — worse prognosis)
5. Pathophysiology
The current model of prostate carcinogenesis involves a stepwise progression:
- Normal epithelium → chronic inflammation and oxidative stress
- Proliferative Inflammatory Atrophy (PIA) → a regenerative lesion in response to chronic injury; increased cell proliferation with incomplete differentiation
- Prostatic Intraepithelial Neoplasia (PIN) → the recognised pre-malignant lesion
- Invasive adenocarcinoma → localised → locally advanced → metastatic
Other pre-malignant/atypical findings:
- Prostate cancer cells initially depend on androgen receptor (AR) signalling for survival and proliferation → this is androgen-sensitive (castration-sensitive) disease.
- Testosterone → DHT (by 5α-reductase) → DHT binds AR → AR translocates to nucleus → activates transcription of genes promoting proliferation (e.g., PSA gene, TMPRSS2).
- Androgen deprivation therapy (ADT) works by removing this signal → cancer cells undergo apoptosis.
- However, over time (months to years), cancer cells develop mechanisms to bypass androgen dependence:
- AR gene amplification or mutation (can be activated by low androgen levels or even anti-androgens)
- Intracrine androgen synthesis (tumour cells produce their own androgens)
- AR splice variants (e.g., AR-V7) that are constitutively active without ligand binding
- Activation of alternative signalling pathways (PI3K/AKT, Wnt, glucocorticoid receptor)
- This leads to castration-resistant prostate cancer (CRPC), which is the lethal form of the disease.
| Alteration | Frequency | Significance |
|---|---|---|
| TMPRSS2-ERG fusion | ~50% | Androgen-driven oncogene expression [2] |
| PTEN loss | ~40% | Loss of tumour suppressor → PI3K/AKT activation |
| TP53 mutation | ~20% (higher in CRPC) | Loss of cell cycle checkpoint |
| RB1 loss | ~10–20% in CRPC | Neuroendocrine differentiation |
| BRCA2/ATM/DNA repair defects | ~20–25% of mCRPC | Sensitivity to PARP inhibitors and platinum chemotherapy |
| AR amplification/mutation | Common in CRPC | Drives castration resistance |
| SPOP mutation | ~10% | Mutually exclusive with TMPRSS2-ERG; distinct molecular subtype |
This is critical for understanding staging and clinical presentation:
| Mode | Route | Common Sites |
|---|---|---|
| Direct extension | Local invasion | Bladder, seminal vesicles [1]; rectum (rare due to Denonvilliers' fascia) |
| Lymphatic spread | Regional lymphatics | Obturator nodes → internal iliac → external iliac → common iliac → pelvic and para-aortic lymph nodes [1] |
| Haematogenous spread | Prostatic venous plexus → vertebral venous plexus (Batson's plexus) | Bone (most common: vertebrae, pelvis, ribs, long bones), liver, lung, adrenal [1][2] |
Why are prostate cancer bone metastases osteoBLASTIC?
Most bone metastases from solid tumours are osteolytic (e.g., breast, lung, kidney). Prostate cancer is a classic exception — it typically produces osteoblastic (sclerotic) metastases. The mechanism: prostate cancer cells secrete factors such as endothelin-1, BMPs (bone morphogenetic proteins), and Wnt ligands that stimulate osteoblast activity and new (but disorganised) bone formation. This results in dense, sclerotic lesions on imaging. PSA itself may also play a role by cleaving parathyroid hormone-related protein (PTHrP), reducing osteoclast activation. Note that in practice, there is often a mixed osteoblastic-osteolytic pattern, but the osteoblastic component predominates.
6. Classification
- Adenocarcinoma (95%) [1][4] — the overwhelmingly dominant type
- Other histological variants [4]:
- Ductal adenocarcinoma
- Mucinous adenocarcinoma
- Signet ring cell carcinoma
- Small cell carcinoma (neuroendocrine) — highly aggressive, may not produce PSA, treated with platinum-based chemotherapy
- Sarcomatoid carcinoma
- Squamous cell carcinoma (very rare)
- Transitional cell carcinoma (extension from bladder)
6.2 Gleason Grading System
This is one of the most important concepts in prostate cancer and is extremely high yield.
- Commonly used system for classifying histologic characteristics of prostate cancer [1].
- Developed by Donald Gleason in the 1960s–70s, based entirely on architectural pattern (how glands are arranged), NOT nuclear features.
- The pathologist identifies the primary (most prevalent) pattern and the secondary (second most prevalent) pattern, each graded 1–5.
- Gleason score = primary pattern + secondary pattern (range: 2–10) [1].
- Gleason 8–10 is considered high-grade [1].
| Pattern | Description | Differentiation |
|---|---|---|
| 1 | Small, uniform glands, closely packed | Well differentiated |
| 2 | More stroma between glands; still fairly uniform | Moderately differentiated |
| 3 | Distinctly infiltrative margins; variable gland size | Moderate |
| 4 | Irregular masses of neoplastic glands; fused/cribriform glands | Poorly differentiated |
| 5 | Only occasional gland formation; sheets/cords of cells, comedonecrosis | Poorly differentiated / Anaplastic |
In modern practice (2014 ISUP modified Gleason), patterns 1 and 2 are essentially never assigned on needle biopsy — the minimum Gleason score on biopsy is 3+3 = 6.
The ISUP (International Society of Urological Pathology) introduced Grade Groups to simplify Gleason scoring and better stratify prognosis:
| Grade Group | Gleason Score | Gleason Pattern | Prognosis |
|---|---|---|---|
| 1 | ≤ 6 | ≤ 3+3 | Excellent (most indolent) |
| 2 | 7 | 3+4 | Good (predominantly well-formed glands with some fused) |
| 3 | 7 | 4+3 | Intermediate (predominantly poorly formed/fused glands) |
| 4 | 8 | 4+4, 3+5, 5+3 | Poor |
| 5 | 9–10 | 4+5, 5+4, 5+5 | Very poor (most aggressive) |
Why does Gleason 3+4 ≠ 4+3?
Students often assume Gleason 7 is Gleason 7. This is wrong. A Gleason 3+4 = 7 (Grade Group 2) has a significantly better prognosis than Gleason 4+3 = 7 (Grade Group 3). The primary (dominant) pattern matters more — if the majority of the tumour is pattern 4 (poorly formed/fused glands), the biology is more aggressive. This distinction changes management: 3+4 may be suitable for active surveillance in select cases, while 4+3 generally warrants definitive treatment.
6.3 TNM Staging (AJCC 8th Edition, 2017)
| Stage | Description |
|---|---|
| T1 | Clinically inapparent (not palpable, not visible on imaging) |
| T1a | Incidental finding in ≤ 5% of resected tissue (e.g., TURP specimen) |
| T1b | Incidental finding in > 5% of resected tissue |
| T1c | Identified by needle biopsy (e.g., due to elevated PSA) |
| T2 | Organ-confined, palpable |
| T2a | Involves ≤ half of one lobe |
| T2b | Involves > half of one lobe |
| T2c | Involves both lobes |
| T3 | Extracapsular extension |
| T3a | Extracapsular extension (unilateral or bilateral) or microscopic bladder neck invasion |
| T3b | Invasion of seminal vesicle(s) |
| T4 | Fixed or invades adjacent structures other than seminal vesicles (e.g., external sphincter, rectum, levator muscles, pelvic wall) |
| Stage | Description |
|---|---|
| N0 | No regional lymph node metastasis |
| N1 | Regional lymph node metastasis (obturator, internal/external iliac, presacral) |
| Stage | Description |
|---|---|
| M0 | No distant metastasis |
| M1a | Non-regional lymph node metastasis (e.g., para-aortic, inguinal) |
| M1b | Bone metastasis |
| M1c | Other sites (lung, liver, adrenal, brain) with or without bone disease |
Localised prostate cancer is stratified into risk groups to guide management:
| Risk Group | Criteria (any of the following) |
|---|---|
| Low | T1–T2a AND Gleason ≤ 6 (Grade Group 1) AND PSA < 10 |
| Intermediate | T2b–T2c OR Gleason 7 (Grade Group 2–3) OR PSA 10–20 |
| High | T3a OR Gleason 8–10 (Grade Group 4–5) OR PSA > 20 |
| Very High | T3b–T4, primary Gleason pattern 5, > 4 cores with Gleason 8–10, or ≥ 2 high-risk features |
7. Clinical Features
As discussed above, 70–80% of cancers arise in the peripheral zone, away from the urethra. The cancer can grow silently for years without compressing the urethra. Many prostate cancers are discovered incidentally through PSA testing or DRE screening before any symptoms develop. When symptoms do occur, they often indicate locally advanced or metastatic disease.
7.2 Symptoms
- Incidental findings: abnormal DRE, elevated PSA [2]
- Increasingly, prostate cancer is detected before symptoms develop because of routine or opportunistic PSA testing.
Obstructive LUTS are late findings because cancer arises in the peripheral zone [2].
LUTS occur when the cancer grows large enough to compress the urethra or invade the bladder neck/trigone:
Voiding (Obstructive) Symptoms:
- Hesitancy (difficulty initiating micturition) — the enlarged prostate compresses the prostatic urethra, increasing urethral resistance
- Weak stream / decreased force — same mechanism
- Intermittency (stop-start stream) — detrusor struggles against obstruction
- Straining to void
- Terminal dribbling
- Incomplete emptying
- Urinary retention (acute or chronic) — complete obstruction
Storage (Irritative) Symptoms:
- Frequency and urgency — secondary detrusor overactivity from chronic obstruction, or direct tumour invasion of the bladder wall/trigone irritating detrusor muscle
- Nocturia — same mechanism
- Urge incontinence
Note: These symptoms are indistinguishable from BPH on history alone. You cannot differentiate BPH from prostate cancer based on LUTS pattern — that's why DRE and PSA are essential.
- Haematuria / haemospermia [2] — cancer eroding into the prostatic urethra or ejaculatory ducts, disrupting blood vessels.
- Haemospermia (blood in the semen) is usually benign, but new-onset haemospermia in an older man should raise suspicion for prostate cancer.
- New-onset erectile dysfunction [2] — may indicate local invasion of the neurovascular bundles (of Walsh) that run posterolateral to the prostate and are responsible for cavernous nerve-mediated erection.
- Perineal/pelvic pain — perineural invasion (prostate cancer has a particular tropism for perineural invasion) or direct extension into pelvic floor muscles
- Rectal symptoms (tenesmus, rectal bleeding — rare because Denonvilliers' fascia acts as a barrier between the prostate and rectum)
- Ureteric obstruction → hydronephrosis → flank pain, renal impairment — from local extension into the trigone/ureteric orifices or bulky pelvic lymphadenopathy compressing ureters
- Lower limb oedema — bulky pelvic lymphadenopathy compressing iliac veins or lymphatics
Metastatic sites: bone (vertebra via Batson's venous plexus), liver, adrenal [2]
- Bone pain (most common symptom of metastatic prostate cancer):
- Persistent, dull, deep ache, often in the lower back, pelvis, hips
- Worse at night (unlike mechanical back pain)
- Pathophysiology: osteoblastic metastases stimulate periosteal nerve stretching and local inflammation
- Pathological fractures — weakened bone (despite being osteoblastic, the new bone is structurally disorganised and weak)
- Spinal cord compression (oncological emergency):
- Back pain → progressive lower limb weakness → sensory level → urinary retention/incontinence
- From vertebral body collapse or epidural tumour extension compressing the spinal cord
- Bone marrow failure (pancytopenia) — extensive marrow infiltration by metastatic disease (leukoerythroblastic blood film)
- Constitutional symptoms: weight loss, fatigue, anorexia — cytokine-mediated cancer cachexia
- Hypercalcaemia — less common in prostate cancer than in other bone-metastasising cancers because osteoblastic lesions tend to sequester calcium rather than release it (in fact, prostate cancer patients may even be hypocalcaemic from avid bone uptake)
7.3 Signs
DRE is the single most important physical examination for prostate cancer.
DRE findings in prostate cancer (only 25% of cancers are palpable) [2]:
- Asymmetrically enlarged prostate
- Hard, irregular nodule (in contrast to BPH, which is smooth, firm, and rubbery with a symmetrically enlarged gland)
- Loss of the midline sulcus (the normal median groove between the two lobes is obliterated by tumour)
- Fixed (cannot be moved — suggests extracapsular extension)
- Surface may be nodular or craggy
Why only 25% palpable? Because:
- Many cancers are small (T1c — detected by PSA, not palpable)
- Anterior tumours (20–30%) are beyond the reach of the examining finger
- DRE can only assess the posterior and lateral aspects of the prostate
DRE Pearl
A normal DRE does NOT exclude prostate cancer. Up to 75% of prostate cancers are impalpable at diagnosis. Conversely, an abnormal DRE warrants further investigation regardless of the PSA level — approximately 25% of men with prostate cancer have a PSA in the "normal" range ( < 4 ng/mL).
- Palpable bladder — if urinary retention has developed from obstruction
- Lower limb lymphoedema — bulky pelvic lymphadenopathy
- Bony tenderness — metastatic bone disease (percussion tenderness over spine)
- Neurological signs — if spinal cord compression (upper motor neuron signs below the level of compression: hyperreflexia, upgoing plantars, sensory level, urinary retention)
- Cachexia — advanced/metastatic disease
- Pallor — anaemia from bone marrow infiltration or chronic disease
8. PSA — Prostate-Specific Antigen (Detailed Discussion)
PSA is so central to prostate cancer that it deserves its own section.
- Arbitrary cutoff: PSA < 4 ng/mL [2] is traditionally considered "normal."
- Higher PSA levels = greater chance of prostate cancer AND higher risk of advanced disease [2].
- The upper normal limit should be age-related [2]:
| Age | Suggested Upper Limit of PSA |
|---|---|
| 40–49 | 2.5 ng/mL |
| 50–59 | 3.5 ng/mL |
| 60–69 | 4.5 ng/mL |
| 70–79 | 6.5 ng/mL |
Factors that INCREASE PSA [2]:
- Prostate cancer
- BPH
- Acute urinary retention (AROU)
- UTI / prostatitis
- Vigorous cycling
- Recent ejaculation ( < 48 hours)
- DRE (modest transient rise — debated whether clinically significant)
- Prostate biopsy, TURP (significant rise)
Factors that DECREASE PSA [2]:
- Castration (surgical or medical)
- 5α-reductase inhibitors (finasteride, dutasteride) — approximately halve PSA levels; must double the measured PSA for true estimate
- Prostate radiotherapy
Because PSA alone has limited specificity (especially in the "grey zone" of 4–10 ng/mL, where only ~25% of men actually have cancer), several PSA derivatives have been developed:
| Derivative | Concept |
|---|---|
| Free-to-Total PSA ratio | Cancer cells produce more complexed (bound) PSA; low free/total ratio ( < 25%) suggests cancer |
| PSA density | PSA ÷ prostate volume (on TRUS/MRI); > 0.15 suggests cancer (BPH produces PSA proportional to gland size, cancer produces disproportionately more) |
| PSA velocity | Rate of PSA rise over time; > 0.75 ng/mL/year is suspicious |
| Prostate Health Index (PHI) | Combines total PSA, free PSA, and [-2]proPSA (p2PSA, a cancer-specific PSA isoform); PHI > 35 → proceed to prostate biopsy [2] |
Benefits of PSA screening [3]:
- May reduce prostate cancer mortality (ERSPC trial showed 20% relative reduction in prostate cancer mortality at 16 years in the screened group)
Harms of PSA screening [3]:
- False positives leading to anxiety and unnecessary biopsies
- Overdiagnosis and overtreatment of indolent cancers (many low-grade cancers detected by screening would never have caused symptoms or death)
- Complications from biopsy and treatment (incontinence, erectile dysfunction)
EAU Guideline 2025: Screening targets men aged 55–69 primarily, with risk stratification including family history, ethnicity, and genetic predispositions (e.g., BRCA mutations). Men at higher risk are screened earlier and more intensively. [3]
PSA screening recommendations [2][4]:
- Not recommended for age < 40 or > 77 (with life expectancy < 10 years)
- May be considered for age 55–77
- May be considered for age 40–55 with family history
- Deferred follow-up of 8 years for those with normal PSA ( < 1 ng/mL at age 40 and < 2 ng/mL at age 60) [4]
- Further workup (risk calculator, additional serum/urine tests, imaging) before biopsy if equivocal PSA (2–10 ng/mL) [4]
- Proceed to prostate biopsy if elevated PSA ( > 10 ng/mL) or palpable DRE nodule [4]
High Yield: PSA is organ-specific but NOT tumour-specific. The "grey zone" is PSA 4–10 ng/mL. Use PHI, free/total PSA ratio, MRI, and clinical context to decide on biopsy. Screening is controversial — shared decision-making is key.
Indications for prostate biopsy [2]:
- Elevated PSA > 10 ng/mL
- Abnormal DRE
- PHI > 35
- Early prostate cancer on active surveillance (for re-staging)
- Abnormal MRI prostate (PI-RADS 4–5)
Approach [2]:
- Transrectal (with TRUS or MRI guidance)
- Transperineal (with TPUS or MRI guidance) — increasingly preferred due to lower infection risk
- "Fusion biopsy": combines pre-biopsy MRI images with real-time ultrasound for targeted biopsies of suspicious lesions [2]
Preparation: Check MSU 1 week prior; treat UTI if positive [2]
Technique: Take 12–18 random systematic biopsies (sampling all zones) plus targeted biopsies of MRI-suspicious lesions [2]
Complications [2]:
- Bleeding: haematuria, PR bleeding, haemospermia
- Infection: < 0.5% for transperineal; ~5% for transrectal (antibiotic prophylaxis with fluoroquinolone required for transrectal approach)
- Acute urinary retention (1–2%): from pain and swelling of the prostate
High Yield Summary
Definition: Adenocarcinoma (95%) arising predominantly from the peripheral zone of the prostate.
Epidemiology (HK): 3rd most common male cancer; rising incidence; lifetime risk ~1/26–30; 1/3 present with locally advanced/metastatic disease.
Risk Factors: Age (most important) > ethnicity (Black > White > Asian) > family history (2× if 1 FDR, 4.5× if 2 FDR) > genetics (BRCA2, TMPRSS2-ERG, ATM, Lynch) > androgens > obesity/diet > smoking.
Anatomy: Peripheral zone (65%, cancer), Transitional zone (10%, BPH), Central zone (25%), Anterior fibromuscular stroma. Cancer in peripheral zone → late symptoms, palpable on DRE.
Spread: Direct (bladder, seminal vesicles) → Lymphatic (pelvic → para-aortic LN) → Haematogenous (Batson's plexus → axial skeleton: osteoblastic bone mets).
Gleason/Grade Groups: Gleason score = primary + secondary pattern (1–5). Grade Groups 1–5 (ISUP 2014). Gleason 3+4 ≠ 4+3 (different grade groups, different prognosis!).
Clinical Features: Often asymptomatic early. LUTS are late (peripheral zone origin). DRE: hard, irregular, nodule, loss of midline sulcus (only 25% palpable). Metastatic: bone pain (axial skeleton), cord compression, pathological fractures.
PSA: Organ-specific, NOT tumour-specific. Cutoff 4 ng/mL (age-adjusted). Grey zone 4–10 → PHI, free/total ratio, MRI. Factors ↑PSA: cancer, BPH, UTI, AROU, ejaculation, cycling. Factors ↓PSA: castration, 5ARI, RT.
Screening (EAU 2025): Risk-stratified, primarily age 55–69; earlier for high-risk (FHx, BRCA). Shared decision-making. Not for < 40 or > 77 with life expectancy < 10 years.
Active Recall - Prostate Cancer (Definition, Epidemiology, Risk Factors, Anatomy, Pathophysiology, Classification, Clinical Features)
[1] Senior notes: felixlai.md (Prostate cancer section) [2] Senior notes: maxim.md (Section 2.5 Urological neoplasm — Prostate cancer) [3] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p35 — Benefits and Harms of PSA Screening, EAU 2025 guidelines) [4] Senior notes: Ryan Ho Urogenital.pdf (p180 — Section 8.4.2 Carcinoma of the Prostate) [5] Lecture slides: Benign Prostatic Hyperplasia.pdf (p3 — McNeal's zonal anatomy; p5 — Etiology and risk factors; p6 — Pathophysiology)
Differential Diagnosis of Prostate Cancer
Before diving into the list, let's think about this from first principles. A patient doesn't walk into clinic saying "I have prostate cancer." They present with one (or more) of the following clinical scenarios, and our job is to figure out whether prostate cancer is the cause:
- An elevated PSA (incidental or screening)
- An abnormal DRE finding (hard nodule, asymmetry, loss of midline sulcus)
- Lower urinary tract symptoms (LUTS) — voiding and/or storage symptoms
- Haematuria or haemospermia
- Bone pain or pathological fractures (metastatic presentation)
- Obstructive uropathy / renal failure
Each scenario has a different differential diagnosis. The art is knowing which diagnoses to consider for each presentation and how to distinguish them. Let's work through this systematically.
Differential Diagnosis by Clinical Scenario
PSA is organ-specific but NOT tumour-specific [1][2]. This means anything that affects the prostate — benign or malignant — can raise PSA. The differential for an elevated PSA is essentially: "What is happening to the prostate?"
| Condition | Why PSA is Elevated | Distinguishing Features |
|---|---|---|
| Prostate cancer | Malignant epithelial cells produce PSA; disrupted glandular architecture allows more PSA to leak into the bloodstream | Often asymptomatic; abnormal DRE (hard, irregular nodule); PSA typically > 10 ng/mL carries ~50% cancer risk [1]; low free/total PSA ratio; PHI > 35 [2] |
| BPH | Increased prostatic tissue mass → more PSA production proportional to gland volume | Smooth, symmetrically enlarged, firm prostate on DRE with intact median groove [6]; predominantly voiding LUTS; PSA density < 0.15 (PSA appropriate for gland size) |
| UTI / Acute prostatitis | Inflammation and infection cause release of intracellular PSA into the bloodstream through disrupted epithelial barriers | Fever, dysuria, frequency, perineal pain; irritative symptoms with dysuria, associated with pyuria and significant bacteriuria on urine culture [6]; tender, boggy prostate on DRE (do NOT massage vigorously — risk of bacteraemia) |
| Acute urinary retention (AROU) | Bladder overdistension causes back-pressure on the prostate; prostatic congestion releases PSA | History of sudden inability to void; palpable distended bladder; Do NOT take PSA during AROU → can cause false elevation (defer PSA 4–6 weeks) [7] |
| Recent ejaculation ( < 48h) | Ejaculation causes prostatic secretion release and transient PSA leak | Ask about recent sexual activity before interpreting PSA [2] |
| Vigorous cycling | Perineal pressure on the prostate causes microtrauma and PSA release | History of cycling before blood draw [2] |
| DRE / Prostate biopsy / TURP | Physical manipulation disrupts prostatic tissue, releasing PSA | Iatrogenic — history of recent procedure [2] |
| 5α-reductase inhibitors | These decrease PSA (roughly halve it) — must double the measured value for accurate interpretation | Drug history (finasteride, dutasteride) [2] |
Critical Clinical Point
A common exam mistake is to see a PSA of 6 ng/mL and immediately jump to "prostate cancer." Remember: PSA 4–10 ng/mL is the "grey zone" — only about 20–25% of men in this range actually have cancer [1]. You must consider BPH, prostatitis, AROU, and other causes. Use PHI, free/total PSA ratio, MRI, and clinical context to decide whether to biopsy. Conversely, ~15% of men with PSA < 4 ng/mL DO have prostate cancer — PSA alone cannot rule it out.
DRE is performed to assess prostate size, symmetry, consistency, surface, tenderness, and median groove [4][6]. An abnormality on DRE narrows the differential:
| Finding | Condition | Explanation |
|---|---|---|
| Hard, irregular nodule; asymmetric induration; loss of midline sulcus; fixed to pelvic wall | Prostate cancer | Cancer creates a hard, irregular mass due to desmoplastic reaction and dense cellular proliferation in the peripheral zone [2][4] |
| Smooth, symmetrically enlarged ( > 3 finger breadths), firm, intact median groove, no nodules | BPH | Benign hyperplasia of the transitional zone produces diffuse, symmetric enlargement with preserved architecture [6] |
| Tender, boggy, warm prostate | Acute prostatitis | Inflammation and oedema make the gland soft/boggy and exquisitely tender; be gentle — vigorous examination risks bacteraemia |
| Firm, irregular, non-tender | Granulomatous prostatitis | Can mimic cancer on DRE; caused by BCG therapy (intravesical), TB, sarcoidosis, or post-TURP granulomas; PSA may be elevated |
| Hard, gritty feel | Prostatic calculi | Calcified corpora amylacea within the gland; usually incidental and asymptomatic; detected on imaging |
| Asymmetrically enlarged irregular prostate with loss of median sulcus → consistent with CA prostate; symmetrical enlargement and firmness → consistent with BPH | Comparison | This distinction is the classic DRE teaching point [1] |
High Yield: An abnormal DRE is an indication for prostate biopsy regardless of PSA level [2]. Approximately 25% of men with prostate cancer detected by abnormal DRE have PSA < 4 ng/mL.
Bladder outlet obstruction typically presents with predominantly voiding symptoms; overactive bladder typically presents with predominantly storage symptoms [1].
This is the most common clinical scenario — an older man presenting with LUTS. The differential is broad:
| Condition | Type of LUTS | Key Distinguishing Features | Pathophysiology |
|---|---|---|---|
| BPH | Predominantly voiding (hesitancy, weak stream, intermittency, incomplete emptying) | Most common cause; smooth enlarged prostate on DRE; IPSS symptom score; uroflowmetry Qmax < 15 mL/s [6] | Transitional zone hyperplasia → mechanical compression of prostatic urethra + dynamic smooth muscle tone (α1-mediated) |
| Prostate cancer | Obstructive LUTS are late findings [2] | Often asymptomatic; hard irregular nodule on DRE; elevated PSA; cancer arises in peripheral zone so LUTS occur only when tumour is large | Large peripheral zone cancer compresses the urethra; or cancer invades bladder neck/trigone |
| Urethral stricture | Voiding symptoms; very weak/spraying stream | History of prior instrumentation, trauma, or STDs [6]; younger men more common; retrograde urethrogram for diagnosis | Fibrotic narrowing of the urethra reduces luminal diameter |
| Bladder neck contracture | Voiding symptoms | Usually from prior urological surgery or RT for CA prostate [6]; history of TURP, radical prostatectomy, or pelvic radiation | Post-surgical/post-radiation scarring at the bladder neck |
| UTI / Acute prostatitis | Usually irritative symptoms with dysuria [6] | Fever; pyuria; positive urine culture; tender prostate on DRE in prostatitis | Infection causes mucosal inflammation → detrusor irritation → storage symptoms |
| Overactive bladder (OAB) | Predominantly storage (frequency, urgency, urge incontinence) | Exclude infection/stone/tumour first [2]; frequency-volume chart shows frequent voiding of small volumes; normal prostate on DRE; good flow rate on uroflowmetry [2]; diagnosis of exclusion | Detrusor overactivity — involuntary detrusor contractions during bladder filling |
| Bladder cancer | Irritative symptoms (in situ) → obstructive symptoms (tumour obstructing ureteric orifice/bladder neck) [8] | Painless gross haematuria is the hallmark [8]; risk factors: smoking, occupational chemical exposure; diagnosed by cystoscopy ± biopsy | Tumour mass within the bladder irritates detrusor (CIS) or mechanically obstructs outflow |
| Neurogenic bladder | Variable (detrusor overactivity → storage; detrusor underactivity → voiding) | Underlying neurological conditions, e.g., multiple sclerosis, spinal cord injury [6]; abnormal neurological examination; urodynamics diagnostic | Disruption of neural pathways controlling the detrusor-sphincter coordination |
| Chronic constipation | Voiding symptoms (extrinsic compression) | History of constipation; faecal loading on abdominal examination/X-ray | Loaded rectum physically compresses the prostatic urethra |
| Drugs | Variable | Drug history: codeine, beta-blockers, anticholinergics, TCAs [6] causing urinary retention; or diuretics causing frequency | Pharmacological effects on detrusor or sphincter function |
The LUTS DDx Approach
When an older man presents with LUTS, think systematically: (1) Is this obstructive/voiding? → BPH, stricture, cancer, bladder neck contracture, drugs, constipation. (2) Is this storage/irritative? → OAB, UTI, bladder cancer, neurogenic. (3) Is there an overlap? → Many conditions cause mixed symptoms; secondary detrusor changes from chronic obstruction can cause storage symptoms on top of voiding symptoms. Always check DRE + PSA + urinalysis as a minimum in any man with LUTS.
Painless gross haematuria in age > 35 = malignancy until proven otherwise [9].
The differential depends on whether the haematuria is glomerular or non-glomerular, and where in the urinary tract it originates:
| Condition | Features | Distinguishing Clues |
|---|---|---|
| Bladder cancer | Painless gross haematuria throughout the stream [8]; irritative LUTS; constitutional symptoms | Most important diagnosis to exclude; risk factors: smoking, chemical exposure; flexible cystoscopy is gold standard [8] |
| Prostate cancer | Haematuria / haemospermia ( < 1%) — uncommon, can also be due to BPH [4] | Usually with elevated PSA and abnormal DRE; terminal haematuria (from prostatic urethra) |
| BPH | Haematuria can occur from BPH [4] — diagnosis by exclusion after malignancy excluded | Smooth enlarged prostate; diagnosis of exclusion [9] |
| UTI / Prostatitis | Dysuria, frequency, fever; positive urine culture | Pyuria, bacteriuria on urinalysis |
| Urolithiasis | Unilateral flank colic radiating to groin [9]; often with microscopic haematuria | CT KUB diagnostic; irritative symptoms if bladder stone |
| Renal cell carcinoma | Classic triad: flank pain, painless haematuria, palpable flank mass (rare) [9] | Constitutional symptoms; paraneoplastic syndromes (polycythaemia, hypercalcaemia) |
| Upper tract urothelial carcinoma | Similar to bladder cancer but originating in renal pelvis/ureter | CT urogram with delayed phase shows filling defect |
For haemospermia specifically: most cases are benign and self-limiting (idiopathic, post-ejaculatory trauma, seminal vesiculitis). However, new-onset haemospermia in a man > 40 warrants investigation for prostate cancer, seminal vesicle pathology, or infection.
When a patient presents with back pain, bone pain, or a pathological fracture, the differential for the underlying malignancy includes:
| Condition | Type of Bone Lesion | Key Features |
|---|---|---|
| Prostate cancer | Osteoblastic (sclerotic) | Elderly male; elevated PSA; axial skeleton predominance (Batson's plexus); often multifocal |
| Breast cancer | Mixed (osteoblastic + osteolytic) | Female; known breast cancer history; can also be osteoblastic |
| Lung cancer | Osteolytic | Smoking history; CXR/CT chest abnormality; weight loss |
| Renal cell carcinoma | Osteolytic (highly vascular) | Haematuria; flank mass; hypervascular mets on imaging |
| Multiple myeloma | Osteolytic (punched-out lesions); NO blastic response | Bone pain, anaemia, renal failure, hypercalcaemia (CRAB) [10]; protein electrophoresis shows M-spike |
| Lymphoma | Variable | Lymphadenopathy; B symptoms; variable imaging appearance |
| Thyroid cancer (follicular) | Osteolytic | Thyroid mass; thyroglobulin elevated |
Osteoblastic vs Osteolytic — A Quick Rule
The classic osteoblastic bone metastases: Prostate and Breast (can be either). Remember "Prostate = Productive (blastic)" and "Lung, Kidney, Thyroid, Myeloma = Lytic (destructive)." Prostate cancer bone metastases are osteoblastic because cancer cells secrete endothelin-1 and BMPs that stimulate osteoblasts.
Prostate cancer can cause obstructive uropathy and renal failure due to ureteric/trigone invasion [4]. The differential for post-renal AKI in a male includes [11]:
| Condition | Mechanism |
|---|---|
| BPH | Bladder outlet obstruction → chronic retention → bilateral hydronephrosis |
| CA prostate | Local invasion of trigone/ureteric orifices, or bulky pelvic lymphadenopathy compressing ureters [11] |
| Bladder neck tumour / CA bladder | Tumour obstructing ureteric orifices or bladder outlet [11] |
| Urinary stones | Bilateral ureteric obstruction (or unilateral in a single kidney) |
| Retroperitoneal fibrosis | Rare; idiopathic or drug-related (methysergide, ergotamine); encases ureters |
| Neurogenic bladder | Detrusor failure → chronic retention → bilateral hydronephrosis |
This is one of the most commonly tested comparisons:
| Feature | BPH | Prostate Cancer | Acute Prostatitis |
|---|---|---|---|
| Age | > 50 (50% have LUTS at 50) | > 50 (rare < 40) | Any age (often younger) |
| Zone | Transitional (periurethral) | Peripheral | Peripheral / diffuse |
| Symptoms | Early voiding LUTS | Late LUTS / asymptomatic / metastatic | Irritative LUTS + dysuria + systemic symptoms |
| DRE | Smooth, symmetric, firm, intact median groove [6] | Hard, irregular, asymmetric, nodule, loss of median sulcus, fixed [2] | Tender, boggy, warm, swollen |
| PSA | Mildly elevated (proportional to gland size); PSA density < 0.15 | Disproportionately elevated; low free/total ratio | Elevated (inflammation-driven); do NOT biopsy acutely |
| Relationship | Does NOT predispose to prostate cancer [1] | Independent disease | Can coexist; must exclude cancer after infection treated |
| Biopsy | Not needed (clinical + uroflowmetry diagnosis) | Needed for definitive diagnosis | Contraindicated acutely (risk of sepsis); consider after treatment |
BPH Does NOT Cause Prostate Cancer
A very common student misconception. BPH does NOT predispose to prostate cancer [1]. They arise in different zones (transitional vs peripheral) and have different pathogeneses (stromal-epithelial growth factor-mediated hyperplasia vs malignant transformation from somatic mutations). They can and often do coexist in the same patient (both are common in elderly men), but one does not lead to the other. An elevated PSA in BPH is due to the increased mass of benign tissue, not malignant transformation.
Imagine: 72-year-old man, PSA = 7.5 ng/mL, normal DRE, no LUTS.
How do you think through the differential?
- PSA is in the grey zone (4–10 ng/mL) → only ~20–25% chance of cancer [1]
- Normal DRE → rules out palpable peripheral zone cancer (but does NOT exclude cancer)
- The elevated PSA could be from: BPH (most likely given age), subclinical prostatitis, recent activity (ejaculation, cycling), or early prostate cancer
- Next steps: repeat PSA in a few weeks [4]; check PHI (if PSA 4–10 + normal DRE → PHI; if PHI > 35 → prostate biopsy [2]); consider mpMRI prostate (PI-RADS scoring); ask about confounders (ejaculation, cycling, UTI)
- The challenge of CA prostate is not to diagnose a case but to correctly risk-stratify them [4] — distinguishing those needing treatment from those who can be safely observed
High Yield Summary — Differential Diagnosis of Prostate Cancer
By presentation:
- Elevated PSA: BPH (most common cause), prostatitis/UTI, AROU, recent ejaculation/cycling, prostate cancer. PSA is organ-specific but NOT tumour-specific.
- Abnormal DRE: BPH (smooth, symmetric, firm) vs prostate cancer (hard, irregular, nodule, loss of sulcus) vs prostatitis (tender, boggy) vs granulomatous prostatitis (mimics cancer).
- LUTS: BPH (#1 cause in elderly men), OAB, UTI/prostatitis, urethral stricture, bladder neck contracture, neurogenic bladder, bladder cancer, drugs, constipation. Prostate cancer causes LUTS late.
- Haematuria: Bladder cancer (#1 to exclude), RCC, BPH, UTI, stones. Painless gross haematuria > 35yo = malignancy until proven otherwise.
- Bone pain: Prostate cancer (osteoblastic), lung/breast/renal cancer (usually osteolytic), myeloma (punched-out lytic), lymphoma.
- Obstructive uropathy: BPH, prostate cancer (trigone/ureteric invasion), bladder cancer, stones, retroperitoneal fibrosis.
Key distinction: BPH vs Prostate Cancer — different zones (transitional vs peripheral), different DRE findings, different PSA profiles. BPH does NOT predispose to cancer. They commonly coexist.
Active Recall - Differential Diagnosis of Prostate Cancer
References
[1] Senior notes: felixlai.md (Prostate cancer section; BPH section) [2] Senior notes: maxim.md (Section 2.5 Urological neoplasm — Prostate cancer; Overactive bladder; Bladder cancer) [4] Senior notes: Ryan Ho Urogenital.pdf (p180–182 — Section 8.4.2 Carcinoma of the Prostate: clinical features, evaluation, biopsy) [6] Senior notes: Ryan Ho Urogenital.pdf (p173 — BPH diagnosis and differential diagnosis) [7] Senior notes: Ryan Ho Fundamentals.pdf (p352 — Urinary retention workup: do NOT take PSA in AROU) [8] Senior notes: maxim.md (Bladder cancer — clinical features, investigations) [9] Senior notes: Ryan Ho Fundamentals.pdf (p340, p342 — Haematuria differential diagnosis and clinical approach) [10] Senior notes: Ryan Ho Chemical Path.pdf (p23 — Hypercalcaemia in malignancy, multiple myeloma CRAB) [11] Senior notes: Ryan Ho Critical Care.pdf (p25 — Post-renal AKI causes including BPH, CA prostate, bladder neck tumour)
Diagnosis of Prostate Cancer: Criteria, Algorithm & Investigations
Before we get into the nuts and bolts, understand the fundamental principle that governs prostate cancer diagnosis. Unlike most cancers where you find it and treat it, prostate cancer has a unique diagnostic challenge:
The challenge of CA prostate is not to diagnose a case but to correctly risk-stratify them such that those requiring treatment can be offered timely treatment and those who do not can have their treatment deferred to decrease complications [4].
This is because prostate cancer spans a vast biological spectrum — from indolent, clinically insignificant tumours (which many men will die with, not of) to highly aggressive, lethal disease. The entire diagnostic pathway is designed to answer two questions: (1) Is there cancer? and (2) If so, how dangerous is it?
Diagnostic Criteria
There is no single "diagnostic criterion" for prostate cancer the way there is for, say, diabetes (fasting glucose ≥ 7.0). Instead, diagnosis follows a stepwise pathway from clinical suspicion to tissue confirmation:
Clinical suspicion arises from:
- Elevated PSA (the most common trigger in the modern era)
- Abnormal DRE (hard, irregular nodule; loss of midline sulcus; asymmetric induration) [2][4]
- Symptoms suggestive of locally advanced or metastatic disease (bone pain, haematuria, obstructive uropathy)
- Incidental finding on TURP specimen or imaging
Not every elevated PSA leads to a biopsy. The workup depends on the PSA level and DRE findings:
- PSA < 1 ng/mL at age 40 or < 2 ng/mL at age 60 → deferred follow-up at 8 years [4]
- PSA 2–10 ng/mL (equivocal/"grey zone") → further workup before biopsy [4]: risk calculators, additional serum/urine tests (PHI, 4K score, PCA3), mpMRI prostate
- PSA > 10 ng/mL or palpable DRE nodule → proceed to prostate biopsy [4]
Definitive diagnosis is established by an image-guided needle biopsy [1]. There is no substitute — you cannot diagnose prostate cancer on imaging or blood tests alone. The biopsy provides:
- Histological confirmation of adenocarcinoma
- Gleason grading (architectural pattern → Grade Group 1–5)
- Extent of disease (number of positive cores, percentage of core involvement, presence of perineural invasion)
Once cancer is confirmed, staging investigations are performed based on risk stratification to determine T, N, M status and guide management.
The Diagnostic 'Triad' of Prostate Cancer
The three pillars that determine diagnosis AND risk stratification are:
- PSA level (biochemical)
- DRE findings (clinical T stage)
- Gleason score / ISUP Grade Group (histological — from biopsy)
All three are needed together. No single element is sufficient alone.
The following algorithm represents the current standard of care, integrating EAU 2024/2025 guidelines with the practical approach used in Hong Kong:
Investigation Modalities — Detailed Breakdown
We will organise investigations into three phases: (A) Initial workup (suspicion and confirmation), (B) Tissue diagnosis (biopsy), and (C) Staging investigations (extent of disease).
A. Initial Workup Investigations
| Test | Purpose | Key Findings & Interpretation |
|---|---|---|
| PSA (total) | Trigger for further investigation; correlates with cancer risk and stage | PSA < 4 ng/mL = traditionally "normal" [1]; PSA 4–10 = grey zone, ~20–25% chance of cancer [1]; PSA ≥ 10 = ~50% chance of cancer [1]. Higher PSA = greater chance of cancer AND higher risk of advanced disease [2] |
| CBC with differentials | Assess for anaemia (bone marrow infiltration, chronic disease) and infection | Anaemia → metastatic bone marrow infiltration; leukocytosis → UTI/prostatitis (confounder for elevated PSA) [1] |
| RFT | Assess renal function | Elevated creatinine → obstructive uropathy from bladder outlet obstruction or ureteric invasion [1][6] |
| LFT (including ALP) | Serum ALP level to evaluate for bone metastasis [1] | Elevated ALP (bone isoenzyme) → osteoblastic bone metastases; also elevated in Paget's disease, osteomalacia |
| Serum Ca²⁺ | Evaluate for bone metastasis [1] | Hypercalcaemia less common in prostate cancer than other bone-metastasising cancers (osteoblastic lesions sequester calcium); if present, consider concurrent PTHrP or other cause [10] |
| Urinalysis | Evaluate for haematuria; exclude UTI | Haematuria → further urological workup; pyuria/bacteriuria → UTI causing elevated PSA [1] |
These are strategies to improve PSA accuracy when the total PSA is in the equivocal range, where the pre-test probability of cancer is only ~20–25%:
| Test | Principle | Threshold | Interpretation |
|---|---|---|---|
| PSA density | PSA ÷ estimated prostate volume (on TRUS/MRI) [4] | > 0.15 ng/mL/cc suggestive of CA prostate [4] | A large BPH prostate will produce PSA proportional to its volume; cancer produces disproportionately more PSA for the same volume |
| PSA velocity | Rise in PSA level per year (requires 3 serial readings over ≥ 12–24 months) [1][4] | > 0.75 ng/mL/year suggestive of CA prostate [1][4] | Cancer causes PSA to rise more rapidly than benign conditions. However, velocity has limited standalone value |
| % Free PSA (free/total ratio) | CA prostate gives increased bound PSA relative to free PSA [4] | ↓ free/total ratio suggests cancer [4]; fPSA < 10% → 56% cancer probability; fPSA > 25% → 8% cancer probability [1] | Cancer cells release more complexed (α1-antichymotrypsin-bound) PSA; free PSA is higher in BPH |
| Prostate Health Index (PHI) | Index derived from [-2]proPSA + % free PSA + total PSA [4] | PHI > 35 → proceed to prostate biopsy [2] | [-2]proPSA is a cancer-specific isoform; ↑ [-2]proPSA + ↓ % fPSA in CA prostate [4]. Used at QMH [4] |
| PSA doubling time (PSADT) | Rate at which PSA doubles | ≤ 3 years considered pathological [4] | Important in monitoring after treatment (post-prostatectomy or post-RT biochemical recurrence) |
| PCA3 test | Gene-based urine test for PCA3/PSA mRNA ratio [4] | No universal cutoff | PCA3 is highly overexpressed (66×) in almost ALL CA prostate but not in benign disease [4]; role in screening/diagnosis still being explored |
Free/Total PSA Ratio — Understanding from First Principles
PSA exists in the blood in two forms: free PSA (unbound) and complexed PSA (bound to protease inhibitors like α1-antichymotrypsin). In BPH, the glandular architecture is preserved, so PSA is released normally → higher proportion of free PSA. In cancer, the disrupted architecture and altered cellular processing lead to more complexed PSA being released → lower free/total ratio. So a low free/total ratio ( < 25%) favours cancer, while a high ratio ( > 25%) favours benign disease.
DRE: insensitive (cannot detect small cancers and cancers in other areas) and non-specific (30% PPV only) [4]
| Finding | Interpretation |
|---|---|
| Asymmetric induration | Suggestive of cancer [4] |
| Frank hard irregular nodule fixed to pelvic wall | Highly suggestive of cancer, possibly locally advanced (T3–T4) [4] |
| Obliteration of median groove | Cancer has grown across both lobes [4] |
| Normal: smooth, firm, symmetric, intact median groove | Consistent with BPH or normal prostate [6] |
DRE can theoretically obtain T staging [4]: T1 (impalpable), T2 (palpable, confined), T3 (extracapsular — firm extension beyond gland), T4 (fixed to pelvic wall/invading adjacent structures).
Limitations [1]:
- Stage T1 cancers are by definition non-palpable
- Only detects tumours in the posterior and lateral aspects of the prostate
- Cannot detect anterior zone tumours (20–30% of cancers)
- Traditional cutoff for PSA ≥ 4 with DRE: Sensitivity = 59%, Specificity = 94%, PPV = 5–30% [1]
B. Tissue Diagnosis — Prostate Biopsy
Prostate biopsy indications: only when it changes the plan of management or oncological outcome [4]:
| Indication | Rationale |
|---|---|
| DRE abnormality suggestive of CA prostate | Hard nodule, asymmetric induration → high suspicion [4][3] |
| Elevated PSA if it would affect treatment decision (life expectancy > 10 years) | Only biopsy if the result will change management [4][1] |
| Clinically metastatic disease if diagnosis is doubtful | To confirm histology for treatment planning [4] |
| Abnormal MRI prostate (PI-RADS 4–5) [2] | Elevated PSA with suspicious lesion on MRI [3] |
| PHI > 35 [2] | In grey zone PSA with normal DRE |
Non-indications for biopsy [4]:
- No clinically obvious disease (e.g., asymptomatic + marginal PSA increase)
- Does not prolong survival (e.g., short life expectancy < 10 years)
- Clinically metastatic disease + diagnosis obvious — e.g., hard nodule on DRE + sky-high PSA + bone lesions on imaging → can skip biopsy and proceed directly with staging/treatment [4]
| Approach | Description | Advantages | Disadvantages |
|---|---|---|---|
| Transrectal (TRUS-guided) | Needle passes through rectal wall into prostate | Traditional; widely available | Increased infection risk (~5%); cannot access anterior prostate [2][4]; requires fluoroquinolone prophylaxis |
| Transperineal (TPUS/MRI-guided) | Needle passes through perineal skin into prostate | Allows access to ALL areas of the prostate; better cancer detection rate; lower infection rate ( < 0.5%) [2][4]; no need for antibiotic prophylaxis in some centres | Slightly more painful; may need GA/sedation |
| MRI-TRUS fusion biopsy | Combines pre-biopsy MRI images with real-time ultrasound [2] | Targeted biopsies of MRI-suspicious lesions + systematic biopsies; better detection of clinically significant cancer | Requires pre-biopsy MRI; operator-dependent; available in specialised centres [4] |
- Check MSU 1 week prior to procedure; treat UTI if positive [2]
- 12-core systematic biopsy with labelling from different areas of the prostate [2][4] — this samples all zones systematically
- Plus targeted biopsies of any MRI-suspicious lesion (PI-RADS 3–5)
- Labelling cores by location is important because it guides resection margin planning in subsequent prostatectomy [4]
| Finding | Significance | Action |
|---|---|---|
| Benign prostatic tissue | No cancer | Reassure; continue PSA monitoring |
| Low-grade PIN (PIN 1) | NO clinical significance [4] | Does NOT require repeat biopsy [4] |
| High-grade PIN (PIN 2/3) | 13–27% risk of CA prostate on repeat biopsy [4] | Should re-biopsy [4] |
| Atypical small acinar proliferation (ASAP) | ~40% risk of cancer on repeat biopsy | Re-biopsy recommended |
| Adenocarcinoma | Cancer confirmed | Gleason grading → ISUP Grade Group → risk stratification → staging |
Complications (~3% overall) [4]:
| Complication | Frequency | Mechanism |
|---|---|---|
| Fever | 1 in 4 (common despite prophylactic antibiotics) [4] | Transient bacteraemia from rectal flora (transrectal approach) |
| Bleeding: PR bleed, haematochezia, haemospermia, haematuria | ~1% [4] | Needle traverses vascular prostatic tissue |
| Urosepsis | ~1% (uncommon but can be severe) [4] | Rectal bacteria seeded into prostate/bloodstream; give prophylactic gentamicin beforehand [4] |
| AROU | 1–2% | Pain and swelling of the prostate causes obstruction [2][4] |
Transperineal vs Transrectal — The Shift in Practice
Modern practice is increasingly shifting toward transperineal biopsy as the standard approach. The key reason is the dramatically lower infection rate ( < 0.5% vs ~5% for transrectal), because the needle does not traverse the rectal mucosa and its resident flora. The transperineal approach also allows sampling of the anterior prostate (which TRUS cannot reach), where 20–30% of cancers reside. The EAU 2024 guidelines recommend transperineal as the preferred approach when available.
C. Staging Investigations
Once prostate cancer is histologically confirmed, staging investigations are selected based on risk stratification. Not every patient needs every test — this is a tiered approach:
| Modality | Findings | Role |
|---|---|---|
| Multiparametric MRI (mpMRI) prostate | Typically T2W-hypointense lesion [4]; shows tumour location, size, extracapsular extension (T3a), seminal vesicle invasion (T3b) | Good sensitivity for detection/localisation of high-grade (GS ≥ 7) tumour [4]; can be used for detection or guidance for biopsy [4]; best modality for local T staging |
| DRE | Clinical T staging (T1–T4) | Initial clinical staging; low sensitivity but contributes to staging |
| TRUS | No TRUS finding consistently indicates cancer with certainty; NOT used for staging [1]; cancer can be hyperechoic, isoechoic, or hypoechoic | Primarily used for biopsy guidance, NOT for staging; low sensitivity and specificity [1] |
Multiparametric (mp) MRI uses multiple imaging sequences to characterise prostate tissue [1]:
| Sequence | What It Shows | Cancer Appearance |
|---|---|---|
| T2-weighted (T2W) | Anatomical detail; zonal anatomy | Hypointense lesion in the normally hyperintense peripheral zone [4] |
| Diffusion-weighted imaging (DWI) | Water molecule diffusion; restricted in dense cellular tissue | High signal on DWI / low ADC values → restricted diffusion in cancer (dense cellularity) |
| Dynamic contrast-enhanced (DCE) | Vascular permeability and perfusion | Early, rapid enhancement → tumour neoangiogenesis |
PI-RADS (Prostate Imaging — Reporting and Data System) v2.1 Scoring:
| PI-RADS Score | Interpretation | Action |
|---|---|---|
| 1 | Very low suspicion (clinically significant cancer very unlikely) | No biopsy needed |
| 2 | Low suspicion | No biopsy needed |
| 3 | Equivocal | Consider biopsy based on clinical context (PSA, density, DRE) |
| 4 | High suspicion (clinically significant cancer likely) | Proceed to biopsy [2] |
| 5 | Very high suspicion (clinically significant cancer highly likely) | Proceed to biopsy [2] |
mpMRI Before Biopsy — The Modern Paradigm
The current EAU 2024/2025 guidelines recommend mpMRI before biopsy in most cases. This is a major shift from the old practice of "elevated PSA → straight to TRUS biopsy." The rationale: mpMRI can (1) identify men who do NOT need a biopsy (PI-RADS 1–2, avoiding unnecessary biopsies and their complications), (2) identify suspicious lesions for targeted biopsy (improving detection of clinically significant cancer), and (3) reduce detection of clinically insignificant cancer (reducing overdiagnosis). Indications for mpMRI include: guide targeted prostate biopsy in patients with elevated PSA but negative TRUS biopsy, which has been shown to result in reduction in number of unnecessary biopsies, higher yield of significant cancer, and fewer biopsy cores [1].
| Modality | Findings | Role |
|---|---|---|
| CT abdomen + pelvis | Evaluation of regional lymph node enlargement [1]; CT-directed biopsy of pathologically enlarged nodes | Standard for nodal staging in intermediate/high-risk; limited sensitivity (relies on size criteria: > 8–10mm short axis) |
| 68Ga-PSMA PET-CT | Prostate-specific tracer; newer modality to visualise small metastasis [4] | Far superior sensitivity for detecting small nodal and distant metastases compared to conventional CT; increasingly the gold standard for staging intermediate-to-high-risk disease |
| mpMRI | Can detect pelvic lymphadenopathy | Primarily for local staging but contributes to nodal assessment |
| Modality | Findings | Role |
|---|---|---|
| Bone scan (99mTc-MDP) | Confirms bony metastasis [12]; increased uptake at sites of osteoblastic activity (vertebrae, pelvis, ribs, femur); superscan = intense symmetric bone activity with diminished renal/soft tissue activity [12] | Traditional standard for bone staging; high sensitivity but low specificity (also picks up fractures, arthritis, Paget's) |
| 68Ga-PSMA PET-CT | PSMA (prostate-specific membrane antigen) overexpressed on prostate cancer cells → prostate-specific tracer [4] | Newer modality; visualises small metastases [4] missed by bone scan and CT; detects both skeletal and soft-tissue metastases in one scan; becoming first-line staging for high-risk disease (EAU 2024) |
| CT chest/abdomen/pelvis | Visceral metastases (lung, liver, adrenal), lymphadenopathy | Standard cross-sectional imaging for staging |
| X-ray pelvis and lumbar spine | Osteosclerotic metastasis [1]; bone metastasis in CA prostate is predominantly OSTEOBLASTIC [1] | Simple initial investigation for bone pain; largely superseded by bone scan/PSMA PET |
| 11C-acetate or 11C-choline PET | Alternative PET tracers for CA prostate [12] | Used in some centres; choline PET has been largely supplanted by PSMA PET |
| MRI spine | Vertebral metastases, cord compression | Used when spinal cord compression suspected; better soft tissue detail than CT |
Principle: bone-seeking radiopharmaceuticals (99mTc-MDP) are analogues of calcium/phosphate that are adsorbed onto bone surface. Adsorption rate is affected by osteoblastic activity and vascularity [12].
This is why bone scan is excellent for detecting prostate cancer metastases (which are osteoblastic) but may miss purely osteolytic lesions (e.g., multiple myeloma). The superscan pattern — intense symmetric bone uptake with absent renal activity — indicates widespread metastatic disease and should not be confused with a "normal" scan [12].
PSMA PET-CT — The Game Changer
68Ga-PSMA PET-CT is transforming prostate cancer staging and recurrence detection. PSMA (prostate-specific membrane antigen) is a transmembrane protein massively overexpressed on prostate cancer cells (not to be confused with PSA, which is a secreted protease). Gallium-68 labelled PSMA ligand binds to cancer cells with high specificity, allowing detection of tiny metastases (even at PSA levels as low as 0.2–0.5 ng/mL in biochemical recurrence). The EAU 2024/2025 guidelines increasingly recommend PSMA PET-CT over conventional bone scan + CT for staging of intermediate and high-risk localised, as well as metastatic, prostate cancer.
Staging investigation: risk stratification determines treatment and extent of staging workup [4]:
| Risk Group | Required Staging Investigations |
|---|---|
| Low risk (T1–T2a, GS ≤ 6, PSA < 10) | Usually NO further staging needed (risk of occult metastasis < 5%); mpMRI may be done for active surveillance planning |
| Intermediate risk (T2b–T2c, GS 7, PSA 10–20) | mpMRI prostate (local staging); consider bone scan/PSMA PET-CT if PSA > 10 or Grade Group ≥ 3 |
| High risk (T3a, GS 8–10, PSA > 20) | mpMRI prostate + CT abdomen/pelvis (or PSMA PET-CT) + bone scan (or PSMA PET-CT) |
| Very high risk / Metastatic | PSMA PET-CT (preferred) or CT + bone scan; MRI spine if cord compression suspected |
AJCC8 staging of CA prostate [4]:
Prognostic Staging Groups integrate TNM + PSA + Gleason/ISUP Grade Group:
| Stage | Criteria |
|---|---|
| I | cT1N0M0 + PSA < 10 + Grade Group 1; or pT2N0M0 + PSA < 10 + Grade Group 1 |
| IIA | PSA ≥ 10 but < 20 |
| IIB | Grade Group 2 |
| IIC | Grade Group 3 |
| IIIA | PSA ≥ 20 |
| IIIB | T3–T4 |
| IIIC | Grade Group 5 |
| IVA | N1 |
| IVB | M1 |
Clinical vs Pathological Staging
Clinical staging is assigned at diagnosis based on DRE, imaging, and biopsy findings — this guides initial treatment decisions. Pathological staging is assigned only after radical prostatectomy based on histological examination of the surgical specimen. Patients who do NOT undergo prostatectomy (e.g., treated with radiation or ADT) are NOT assigned a pathological stage, and treatment decisions remain based on clinical stage [1]. Note that there is no pathological T1 — because T1 is by definition "clinically inapparent," and once the prostate is removed, the tumour becomes apparent.
| Category | Investigation | Purpose |
|---|---|---|
| Bloods | PSA (total ± free/total ratio), CBC, RFT, LFT (ALP), Ca²⁺ | Screening, baseline, metastatic workup |
| PSA derivatives | PHI, PSA density, PSA velocity, PCA3 | Improve specificity in grey zone |
| Physical exam | DRE | Clinical T staging, trigger for biopsy |
| Imaging — Pre-biopsy | mpMRI prostate | Lesion detection, PI-RADS scoring, biopsy guidance |
| Tissue | Prostate biopsy (transperineal preferred) | Definitive diagnosis + Gleason grading |
| Staging — Local | mpMRI prostate | T staging (ECE, SVI) |
| Staging — Nodal | CT A+P or PSMA PET-CT | N staging |
| Staging — Metastatic | Bone scan or PSMA PET-CT, CT chest, XR pelvis/spine | M staging |
| Special | MRI spine (cord compression), PSMA PET-CT (biochemical recurrence) | As clinically indicated |
High Yield Summary — Diagnosis of Prostate Cancer
Diagnostic pathway: Clinical suspicion (PSA + DRE) → Confirmatory workup (PSA derivatives, mpMRI) → Tissue diagnosis (prostate biopsy) → Risk stratification (PSA + T-stage + Grade Group) → Staging investigations (tiered by risk).
PSA interpretation: < 4 normal; 4–10 grey zone (20–25% cancer risk) — use PHI, free/total ratio, mpMRI; > 10 → biopsy; ≥ 10 ng/mL = ~50% cancer risk.
mpMRI: T2W-hypointense lesion; PI-RADS 4–5 = biopsy; PI-RADS 1–2 = monitor. Now recommended BEFORE biopsy.
Biopsy: Transperineal preferred (lower infection, accesses all zones). 12-core systematic + targeted. Complications: fever, bleeding, urosepsis, AROU.
Histology: High-grade PIN → re-biopsy (13–27% cancer risk). Low-grade PIN → no action.
Staging: AJCC 8th edition TNM + PSA + Grade Group = Prognostic Stage I–IV. Staging workup extent depends on risk group. PSMA PET-CT is replacing conventional bone scan + CT.
Key principle: The challenge is not just finding cancer — it's correctly risk-stratifying it so you treat those who need it and observe those who don't.
Active Recall - Diagnosis of Prostate Cancer
References
[1] Senior notes: felixlai.md (Prostate cancer section — investigations, PSA, TRUS, mpMRI, staging) [2] Senior notes: maxim.md (Section 2.5 Urological neoplasm — Prostate cancer: investigations, biopsy, PHI) [3] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p36 — Investigation: mpMRI, biopsy indications) [4] Senior notes: Ryan Ho Urogenital.pdf (p179–183 — PSA derivatives, clinical features, evaluation, biopsy, AJCC8 staging) [6] Senior notes: Ryan Ho Urogenital.pdf (p173 — BPH diagnosis, relevant investigations) [10] Senior notes: Ryan Ho Chemical Path.pdf (p23 — Hypercalcaemia in malignancy) [12] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p68, p74, p77, p79 — Bone scan, PET/CT, PET/MR, interventional radiology biopsy)
Management of Prostate Cancer
Management of prostate cancer is arguably the most nuanced in all of oncology. Unlike most cancers where "find it and treat it aggressively" is the default, prostate cancer management is governed by a fundamental tension:
Many men die with prostate cancer, not of it. The challenge is to treat aggressively enough to cure those who will die of their cancer, while avoiding over-treatment (and its devastating side effects) in those whose cancer would never have caused harm.
This means management decisions hinge on three things:
- Disease risk (PSA + T-stage + Gleason/Grade Group)
- Patient fitness and life expectancy (age, comorbidities)
- Patient preference (quality of life vs quantity of life)
Summary Table (EAU 2024/2025 Recommendations)
| Risk / Stage | Treatment Options | Key Details |
|---|---|---|
| Old / frail patients | Watchful waiting [3] | Palliative intent; start hormonal treatment (ADT) when symptomatic or high PSA [3] |
| Low risk (cT1–T2a, GS ≤ 6, PSA < 10) | Active surveillance [3][4] | Curative intent; defer radical treatment and treatment-related morbidities; stringent protocol with regular DRE, PSA, MRI and biopsy [3] |
| Intermediate risk | Radical prostatectomy (robotic) OR radiotherapy with adjuvant LHRHa [3] | RP ± extended PLND; EBRT + neoadjuvant/concomitant ADT [4] |
| High risk | Radical prostatectomy (robotic) OR radiotherapy with adjuvant LHRHa [3] | RP + ePLND; EBRT + long-term adjuvant ADT (2–3 years) [4] |
| Locally advanced (T3–T4) | RP + ePLND + adjuvant EBRT/ADT; or EBRT + adjuvant ADT; or ADT monotherapy if unfit [4] | Prior RT renders subsequent surgery difficult → usually prefer initial radical prostatectomy [4] |
| Metastatic: Low volume | ADT + Novel hormonal agent + Radiotherapy [3] | Novel hormonal agents: Enzalutamide / Apalutamide / Abiraterone [3] |
| Metastatic: High volume | ADT + Novel hormonal agent + Chemotherapy (docetaxel) [3] | High volume metastasis: ≥ 4 bone mets including 1 outside axial skeleton or visceral mets [3] |
| Castration-resistant (CRPC) | Continue ADT + add 2nd-line agents [4] | Abiraterone, enzalutamide, docetaxel, cabazitaxel, 223Ra, 177Lu-PSMA, sipuleucel-T [4] |
Detailed Treatment Modalities
1. Deferred Treatment (Conservative)
The rationale for deferred treatment is that CA prostate is a slow-growing disease; there is little difference in survival between active treatment or watchful waiting within 5 years [4].
| Feature | Detail |
|---|---|
| Intent | Curative — to individualise and defer radical treatment until progression [4] |
| Patient selection | Surgically fit, life expectancy > 10 years [4] |
| Tumour criteria | Low risk: cT1–T2a, GS < 7 (Grade Group 1), PSA < 10 [4] |
| Monitoring protocol | DRE, PSA, re-biopsy, mpMRI [3][4]; stringent protocol with regular DRE, PSA, MRI and biopsy [3] |
| Triggers for treatment | Disease progression evident as short PSA doubling time, high-grade or more extensive cancer on biopsy [4] |
| Outcomes | 90% overall survival, 99.7% cancer-specific survival [4] |
Why does this work? Grade Group 1 (Gleason ≤ 6) prostate cancer has an extremely low risk of metastasis or cancer-specific death within 10–15 years. The "cost" of radical treatment (incontinence, erectile dysfunction) outweighs the marginal survival benefit in this group. AS allows intervention only when the biology declares itself as more aggressive.
Active Surveillance vs Watchful Waiting
Students frequently confuse these two. They are fundamentally different:
- Active surveillance = curative intent. You monitor closely and treat radically (surgery/RT) at the first sign of progression. The patient is fit for treatment. Think of it as "holding your sword ready."
- Watchful waiting = palliative intent. You do NOT monitor as stringently. You treat symptoms when they arise (usually with ADT). The patient is NOT fit for curative treatment or has limited life expectancy. Think of it as "putting your sword away."
| Feature | Active Surveillance | Watchful Waiting |
|---|---|---|
| Intent | Curative | Palliative |
| Patients | Surgically fit, > 10y life expectancy | Surgically unfit, < 10y life expectancy |
| Tumour | Low risk (cT1–2a, GS < 7, PSA < 10) | Any asymptomatic tumour |
| Monitoring | DRE, PSA, re-biopsy, mpMRI | NOT required |
| Treatment trigger | Disease progression | Symptomatic → offer palliative Tx |
- Palliative intent for old fragile patients [3]
- Start hormonal treatment (ADT) when symptomatic or high PSA [3]
- No survival benefit of treatment in 12–13 years in newer studies [4] — i.e., for older men with limited life expectancy, aggressive treatment does not prolong life compared to managing symptoms as they arise
- Risk of disease progression to require palliative intervention is approximately 40–50% over 10 years, but many will die of other causes first
2. Radical Prostatectomy (RP)
"Robotic-assisted resection of prostate gland + seminal vesicles + ampulla of vas deferens ± pelvic LN dissection" [2]
- Mainly for localised disease (≤ T3), only highly selected if locally advanced (T3 or N1) [4]
- Confirmed histological diagnosis [1]
- Life expectancy > 10 years [1]
- Patients fully counselled and aware of possible complications and alternative treatment options [1]
- PSA level < 20 ng/mL (> 20 is much more likely to have spread) [1]
- Gleason grade < 8 (≥ 8 is much more likely to have spread, often at a micrometastatic level) [1]
- Negative bone scan ± Negative MRI scan [1]
- Life expectancy < 10 years (no survival benefit from surgery)
- Unfit for general anaesthesia
- T4 disease (fixed tumour invading rectum, levators, pelvic wall — technically not resectable)
- Extensive nodal or distant metastatic disease (surgery alone will not be curative)
- Patient preference against surgery
Open (retropubic/perineal), laparoscopic, or robotic — none has clearly shown superiority over others [4], though robotic-assisted laparoscopic prostatectomy is now the most widely used approach worldwide due to improved ergonomics, 3D visualisation, and possibly lower blood loss.
Open approaches including retropubic or perineal have become largely extinct; laparoscopic and robotic-assisted approach is the preferred treatment [1].
Three surgical goals [1]:
- Excise cancer completely with a clear margin
- Maintain continence by preserving the external sphincter — the external urethral sphincter sits at the prostatic apex and must be carefully preserved during apical dissection
- Maintain potency by sparing autonomic nerves in the neurovascular bundles — cavernous nerves lie immediately posterolateral to the prostatic capsule [1]
Nerve-sparing technique may be used in most patients to ↓ risk of erectile dysfunction, but is contraindicated if there is high risk of extracapsular extension [4] — because the neurovascular bundles abut the prostatic capsule, and preserving them in the setting of T3a disease risks leaving cancer behind.
Adjuvant EBRT if pT3N0 margin-positive or pT3b; adjuvant ADT if N1 [4]
Why? Positive surgical margins or seminal vesicle invasion (pT3b) indicate that microscopic cancer may remain in the surgical bed → adjuvant radiotherapy reduces local recurrence. N1 disease means systemic micrometastases are likely → adjuvant ADT addresses occult systemic disease.
| Complication | Frequency | Mechanism |
|---|---|---|
| Erectile dysfunction | 30% even with good nerve sparing [4]; 50% overall [2] | Damage to cavernous nerves in neurovascular bundles; even "nerve-sparing" causes neuropraxia (stretching/bruising of nerves) that may take 6–24 months to recover |
| Urinary incontinence | 50% early (immediate post-op), 5–10% long-term [4]; stress urinary incontinence 10% [2] | Damage to the external urethral sphincter during apical dissection; managed with pelvic floor muscle exercises or artificial sphincter [1] |
| Anastomotic stricture | 5–10% [4] | Scarring at the vesicourethral anastomosis (bladder neck-to-urethral stump junction) — bladder neck contracture [1] |
| Bleeding | 5–10% [4] | The dorsal venous complex (plexus of Santorini) overlies the prostate apex; division during surgery risks haemorrhage |
| Rectal injury | < 5% [4] | Prostate is immediately anterior to the rectum; Denonvilliers' fascia is the plane of dissection |
| General perioperative | Mortality < 0.3% [4] | MI, DVT [1], infection |
| Urine leaks | Uncommon | Anastomotic leak in the early post-op period |
Post-op care: Foley catheter should be placed for ≥ 7 days post-op [4] to allow the vesicourethral anastomosis to heal.
Why Does RP Cause Incontinence and Erectile Dysfunction?
The prostate sits at the crossroads of continence and potency:
- Continence: The prostatic urethra is supported by the internal sphincter (bladder neck) above and the external sphincter (rhabdosphincter) below. RP removes the prostate AND bladder neck → the patient relies entirely on the external sphincter for continence. Any damage to this during apical dissection → stress urinary incontinence.
- Potency: The cavernous nerves (parasympathetic fibres from S2–S4 that mediate erection) run in the neurovascular bundles immediately posterolateral to the prostatic capsule. Even with nerve-sparing technique, traction and neuropraxia are inevitable → erectile dysfunction. Recovery depends on age, baseline function, and nerve preservation quality.
3. Radiotherapy (RT)
Avoids the risk of surgery and general anaesthesia, but provides equivalent oncological control [2].
| Type | Description | Indications |
|---|---|---|
| External beam radiotherapy (EBRT) / Intensity-modulated RT (IMRT) | High-energy photon beams delivered from outside the body; IMRT allows precise dose shaping to conform to the prostate while sparing surrounding tissues | Localised or locally advanced disease; primary treatment or adjuvant after RP |
| Interstitial brachytherapy | Radioactive seeds (e.g., I-125 or Pd-103) permanently implanted into the prostate, delivering radiation from within | Low-to-intermediate risk localised disease; rarely done in HK [4] |
- Neoadjuvant + concomitant ADT if intermediate risk [4] — typically 4–6 months of ADT before and during RT
- Adjuvant ADT × 2–3 years if high-risk localised or locally advanced [4]
Why combine ADT with RT? ADT causes tumour shrinkage (cytoreduction) → smaller radiation target; it also induces apoptosis in cancer cells, making them more radiosensitive; and it controls micrometastatic disease systemically. Randomised trials (e.g., EORTC 22863, RTOG 9202) have shown significant survival benefit from adding long-term ADT to RT in high-risk disease.
| Complication | Mechanism |
|---|---|
| Erectile dysfunction: up to 30% [4] | Radiation damage to the neurovascular bundles and penile vasculature; onset is gradual (6–36 months post-RT), unlike RP where ED is immediate |
| Radiation cystitis: up to 10% [4] | Radiation injury to the bladder mucosa → frequency, urgency, dysuria, haematuria |
| Radiation proctitis: up to 10% [4] | Radiation injury to the anterior rectal wall → diarrhoea, tenesmus, PR bleeding |
| GI symptoms [1] | Proctitis, enteritis, diarrhoea, frequency, urgency, tenesmus |
| UG symptoms [1] | Cystitis, urethritis, frequency, urgency, dysuria |
| ↓ Stress urinary incontinence compared to RP, but similar ED rates [2] | RT preserves the sphincter mechanism (no dissection near the sphincter) |
| ↑ Irritative symptoms (FUN: frequency, urgency, nocturia) [2] | Radiation-induced detrusor overactivity and mucosal inflammation |
RP vs RT — How to Counsel Patients
Oncological outcomes between radiotherapy and radical surgery are equally favourable and the choice of treatment is up to the patient [1]. But the side effect profiles differ:
- RP: Higher risk of incontinence and immediate ED, but these improve over time; no radiation exposure; provides pathological staging
- RT: Lower risk of incontinence; ED develops gradually; higher risk of long-term cystitis/proctitis; no pathological staging; prior RT renders subsequent operation difficult [4] (complicates salvage surgery if cancer recurs)
In general: younger, fitter patients tend to prefer RP (definitive removal, pathological staging, preserves RT as a salvage option); older patients or those prioritising continence may prefer RT.
4. Androgen Deprivation Therapy (ADT)
Prostate cancer cells depend on androgen receptor (AR) signalling for survival and proliferation. Testosterone (mainly from testes) is converted to DHT (by 5α-reductase) in the prostate → DHT binds AR → activates transcription of pro-survival genes. Remove the androgen signal → cancer cells undergo apoptosis. This is the basis of ADT, first demonstrated by Charles Huggins (Nobel Prize, 1966).
| Modality | Mechanism | Key Details |
|---|---|---|
| Bilateral orchiectomy (surgical castration) | Removes the testes → eliminates > 90% of testosterone production | GOLD STANDARD but rarely done nowadays due to effective medical therapy [1]; irreversible; psychological impact; immediate castrate testosterone levels |
| GnRH agonists (e.g., Goserelin, Leuprolide) | Initially ↑↑ LH and FSH (stimulates testes to produce testosterone) → "flare" → then downregulation of GnRH receptors in the pituitary → ↓ LH and FSH → ↓ testosterone [1] | Most widely used form of ADT; requires anti-androgen cover for first 2–4 weeks to prevent flare; depot injections (monthly or 3-monthly) |
| GnRH antagonists (e.g., Degarelix, Relugolix) | Directly blocks GnRH receptors → ↓ testosterone without initial rise [1] | No flare phenomenon → preferred when flare is dangerous (e.g., impending cord compression, severe bone pain); Relugolix is an oral GnRH antagonist (newer) |
> 90% of male hormones (testosterone) originate from the testes; < 10% (DHEA, DHEA-S, androstenedione) originate from the adrenals [1]
GnRH Agonist Flare — Why It Happens and Why It Matters
GnRH agonists (like goserelin) initially stimulate the pituitary because they are agonists — they cause a surge of LH/FSH release, which in turn causes a testosterone surge ("flare") lasting 1–2 weeks. In a patient with widespread bone metastases or impending cord compression, this flare can cause catastrophic worsening — increased bone pain, cord compression, or ureteric obstruction.
Solution: Either (1) use a GnRH antagonist (no flare) or (2) cover with an anti-androgen (e.g., bicalutamide) for the first 2–4 weeks to block the testosterone flare at the receptor level.
| Agent | Generation | Mechanism | Role |
|---|---|---|---|
| Flutamide / Nilutamide / Bicalutamide | 1st generation | Block ligand binding to androgen receptor [1] | Block disease flare that may occur with the rise of serum testosterone associated with GnRH agonist therapy [1]; also used in combined androgen blockade (CAB) |
| Enzalutamide / Apalutamide / Darolutamide | 2nd generation (next-generation anti-androgens) | Block AR signalling at multiple steps: inhibit AR nuclear translocation, DNA binding, and coactivator recruitment | Used in mCRPC and now upfront in mHSPC; much more potent than 1st-generation agents |
| Agent | Mechanism | Indication |
|---|---|---|
| Abiraterone + Prednisolone | CYP17 inhibitor [4] — blocks CYP17A1 enzyme in the adrenal glands, testes, and tumour cells, preventing synthesis of androgens (and cortisol, hence need for prednisolone to prevent adrenal insufficiency and mineralocorticoid excess) | mHSPC (upfront with ADT); mCRPC [4] |
| Enzalutamide | Inhibitor of androgen receptor signalling [4] — potent AR antagonist; blocks AR nuclear translocation and DNA binding | mHSPC (upfront with ADT); mCRPC [3][4] |
| Apalutamide | Similar to enzalutamide; potent AR antagonist | mHSPC; nmCRPC (non-metastatic CRPC) [3] |
Side effects of testosterone-lowering agents [1]:
| Side Effect | Mechanism |
|---|---|
| Hot flushes | Loss of testosterone disrupts hypothalamic thermoregulation (similar to menopausal hot flashes) |
| Fatigue | Multifactorial: anaemia, loss of muscle mass, metabolic changes |
| Erectile dysfunction | Loss of androgen-mediated libido and penile vascular function |
| Loss of libido | Testosterone is the primary driver of male sexual desire |
| Anaemia | Androgens stimulate erythropoiesis; their removal → ↓ RBC production |
| Gynecomastia | Altered androgen/oestrogen ratio → oestrogen-mediated breast tissue proliferation; also a side effect of anti-androgens [1] |
| ↓ Lean body mass, ↑ body fat, ↓ muscle strength [4] | Androgens are anabolic; their loss causes sarcopenia and fat redistribution |
| ↑ Risk of cardiovascular disease and ↑ insulin resistance [4] | Metabolic syndrome from androgen deprivation |
| Osteoporosis → pathological fractures | Androgens maintain bone density; their loss → accelerated bone resorption |
| Cognitive changes, depression | Androgens have neuroprotective and mood-regulating effects |
5. Systemic Therapy for Metastatic Prostate Cancer
This is newly diagnosed metastatic disease that has NOT yet been treated with ADT (or is still responding to ADT).
- Traditional approach: ADT monotherapy first → add others if CRPC [2] — this is outdated
- New approach: upfront combination therapy [2][3] — multiple landmark trials (CHAARTED, LATITUDE, STAMPEDE, ENZAMET, TITAN, ARASENS) have proven that upfront intensification dramatically improves survival
Treatment by metastatic volume [3]:
| Volume | Definition | Treatment |
|---|---|---|
| Low volume | < 4 bone metastases AND no visceral mets AND all within axial skeleton | ADT + Novel hormonal agent (Enzalutamide / Apalutamide / Abiraterone) + Radiotherapy to the primary tumour [3] |
| High volume | ≥ 4 bone metastases including ≥ 1 outside the axial skeleton, OR visceral metastases [3] | ADT + Novel hormonal agent + Chemotherapy (docetaxel) [3] |
Why treat the primary tumour with RT in low-volume disease? The STAMPEDE trial showed that in patients with low metastatic burden, adding radiotherapy to the prostate (while on systemic ADT) improved overall survival — likely because the primary tumour is a source of ongoing seeding of metastatic clones.
Definition of CRPC [4]:
- Castrate level of testosterone ( < 50 ng/dL) — i.e., the patient IS on ADT
- PLUS disease progression defined as:
- Biochemical progression: 3 consecutive rises in PSA 1 week apart with 2 × 50% increase over nadir and one PSA > 2 ng/mL
- Radiological progression: ≥ 2 new bone lesions on bone scan or enlarging soft tissue lesion
- Symptomatic progression alone is NOT sufficient to diagnose CRPC [4]
Mechanism: either tumour cells becoming testosterone-independent or autonomous androgen secretion [4] — through AR gene amplification, AR splice variants (AR-V7), intracrine androgen synthesis, or activation of alternative growth pathways.
Treatment of CRPC [4]: Usually continue ADT + add 2nd-line treatment:
| Agent | Mechanism | Key Points |
|---|---|---|
| Abiraterone + prednisone | CYP17 inhibitor [4] | Blocks adrenal and intratumoral androgen synthesis |
| Enzalutamide / Apalutamide | Inhibitor of androgen receptor signalling [4] | Blocks AR at multiple levels even in CRPC |
| Docetaxel | Taxane chemotherapy; stabilises microtubules → prevents mitotic spindle disassembly → cell cycle arrest and apoptosis | First-line chemotherapy for mCRPC [4]; also used upfront in high-volume mHSPC |
| Cabazitaxel | Semi-synthetic taxane | Second-line chemotherapy after docetaxel failure; active against docetaxel-resistant cells |
| 223-Radium (Alpharadin) | Localises to bone → emits α-particles to relieve skeletal symptoms [4] | Calcium mimetic taken up by bone → delivers high-energy, short-range alpha radiation to bone metastases; improves OS in symptomatic bone-predominant mCRPC |
| 177Lu-PSMA | Newer treatment that localises to CaP cells [4] | Lutetium-177 labelled PSMA ligand → binds PSMA on cancer cells → delivers beta radiation to tumour; VISION trial showed OS benefit in PSMA-positive mCRPC |
| Sipuleucel-T | Dendritic cell vaccine programmed to target prostatic acid phosphatase [4] | Immunotherapy; autologous dendritic cells activated ex vivo with PAP-GM-CSF fusion protein; modest survival benefit (~4 months); mainly used in US |
| PARP inhibitors (Olaparib, Rucaparib) | Synthetic lethality in tumours with homologous recombination repair defects (BRCA1/2, ATM) | Indicated in mCRPC with BRCA/HRD mutations; cancer cells with BRCA loss cannot repair double-strand DNA breaks → PARP inhibition blocks the backup repair pathway → cell death |
Prostate cancer has a particular tropism for bone, and skeletal complications (pain, fractures, cord compression) are a major source of morbidity. Bone-directed therapies are used alongside systemic treatment:
Bisphosphonates and RANK-Ligand Inhibitors
| Agent | Mechanism | Indication |
|---|---|---|
| Bisphosphonates (e.g., zoledronic acid) | Bind to hydroxyapatite on bone surfaces → inhibit osteoclast-mediated bone resorption | Prevent skeletal-related events (SREs) in mCRPC with bone metastases; also prevent ADT-related osteoporosis |
| Denosumab (RANK-ligand inhibitor) | Monoclonal antibody against RANKL → prevents RANKL from activating RANK on osteoclast precursors → inhibits osteoclast differentiation and function | Superior to zoledronic acid in preventing SREs in mCRPC; does not require renal dose adjustment |
Side effects: osteonecrosis of the jaw (ONJ — hence dental review before starting), hypocalcaemia (supplement calcium and vitamin D), atypical femoral fractures.
Palliative treatment options [4]:
| Symptom | Management |
|---|---|
| Bone symptoms | Osteoclast inhibition (bisphosphonate, denosumab), palliative RT, analgesics [4] |
| Spinal cord compression | High-dose steroids (dexamethasone), decompressive surgery, palliative RT [4] — oncological emergency |
| Urinary symptoms (obstruction) | May consider TURP to relieve obstruction [4]; catheterisation; ureteric stenting for ureteric obstruction |
| Pain | WHO analgesic ladder; palliative RT for focal bone pain; radionuclides (223Ra) for diffuse bone pain |
| Anaemia | Transfusion; erythropoiesis-stimulating agents if appropriate |
Depletion of androgens by surgical means [1]:
- > 90% of male hormones (testosterone) originate from the testes; < 10% (DHEA, DHEA-S, androstenedione) originate from the adrenals [1]
- GOLD STANDARD but rarely done nowadays due to effective medical therapy and more widespread use of hormones [1]
- Advantages: immediate castrate levels, 100% compliance, one-time procedure, low cost
- Disadvantages: irreversible, psychological impact, visible loss (though subcapsular orchiectomy preserves the testicular shell)
Prognosis [4]:
| Stage | 5-Year Survival |
|---|---|
| Localised | Almost 100% |
| Locally advanced | Almost 100% |
| Metastatic | ~29% |
This stark difference between localised/locally advanced (~100%) and metastatic (~29%) underlines why early detection and correct risk stratification matter — but also why over-treating indolent localised disease with its attendant morbidity must be avoided.
High Yield Summary — Management of Prostate Cancer
Conservative:
- Active surveillance: Curative intent; low-risk disease; fit patient > 10y life expectancy; monitor with DRE/PSA/MRI/re-biopsy; treat on progression. 90% OS, 99.7% CSS.
- Watchful waiting: Palliative intent; unfit/elderly patient < 10y life expectancy; treat symptoms with ADT when they arise.
Localised disease (curative):
- Low risk: Active surveillance (preferred); RP or RT as alternatives
- Intermediate risk: RP (robotic) ± ePLND; or EBRT + neoadjuvant/concomitant ADT
- High risk: RP + ePLND; or EBRT + long-term adjuvant ADT (2–3y)
Locally advanced: RP + ePLND + adjuvant RT/ADT; or EBRT + ADT; or ADT alone if unfit.
Metastatic (mHSPC):
- Low volume: ADT + novel hormonal agent + RT to primary
- High volume (≥ 4 bone mets incl. 1 outside axial skeleton, or visceral mets): ADT + novel hormonal agent + docetaxel
CRPC (castrate testosterone + progression): Continue ADT + add abiraterone/enzalutamide/docetaxel/cabazitaxel/223Ra/177Lu-PSMA/PARP inhibitors.
ADT: GnRH agonist (cover flare with anti-androgen) or GnRH antagonist (no flare). Side effects: hot flushes, ED, osteoporosis, metabolic syndrome, CVD risk, gynecomastia.
RP complications: ED (30–50%), incontinence (5–10% long-term), anastomotic stricture, bleeding, rectal injury.
RT complications: ED (30%), cystitis/proctitis (10%), less incontinence than RP.
Prognosis: Localised ~100% 5y survival; metastatic ~29%.
Active Recall - Management of Prostate Cancer
References
[1] Senior notes: felixlai.md (Prostate cancer — treatment section: conservative, medical, surgical, radiotherapy, orchiectomy) [2] Senior notes: maxim.md (Section 2.5 — Prostate cancer management: localised and advanced disease) [3] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p41–43 — Prostate cancer treatment: localised, watchful waiting, active surveillance, metastatic) [4] Senior notes: Ryan Ho Urogenital.pdf (p184–186 — Approach to treatment, deferred treatment, locoregional treatment, systemic therapy, CRPC, prognosis)
Complications of Prostate Cancer
Complications of prostate cancer can be organised into three broad categories that are conceptually distinct and must be understood separately:
- Complications of the disease itself (local progression and metastatic disease)
- Complications of treatment (surgery, radiotherapy, androgen deprivation therapy, chemotherapy)
- Complications of diagnostic procedures (biopsy) and screening (overdiagnosis)
Understanding why each complication occurs — from first principles — is far more useful than memorising a list. Each complication has a clear pathophysiological basis rooted in anatomy, tumour biology, or the mechanism of the treatment that caused it.
A. Complications of the Disease Itself
These complications arise because the cancer either grows locally (compressing or invading adjacent structures) or metastasises distantly.
A1. Local Complications
- Mechanism: Although prostate cancer arises in the peripheral zone (and therefore causes LUTS late), large tumours or those with central/transitional zone extension eventually compress or invade the prostatic urethra and bladder neck → increased urethral resistance → voiding difficulty → ultimately acute urinary retention (AROU).
- Clinical presentation: Progressive voiding LUTS (hesitancy, weak stream, incomplete emptying) → AROU (inability to void, suprapubic pain, palpable distended bladder)
- Management: Urethral catheterisation; if failed, suprapubic catheter; may consider TURP to relieve obstruction [4] (palliative TURP — note that this does NOT cure the cancer, it simply debulks the intraprostatic component to relieve the obstruction)
- Mechanism: Cancer invading the bladder trigone or ureteric orifices → unilateral or bilateral ureteric obstruction → hydronephrosis → obstructive nephropathy → post-renal AKI [11]. Alternatively, bulky pelvic lymphadenopathy can extrinsically compress the ureters.
- Clinical presentation: May be silent (bilateral chronic partial obstruction → gradual renal impairment detected on bloods); or acute with flank pain if sudden complete obstruction
- Key point: Post-renal disease is rapidly reversible if recognised early, but prolonged obstruction progresses to tubulointerstitial fibrosis (i.e., irreversible intrinsic renal disease) [11]
- Management: Ureteric stenting (retrograde via cystoscopy, or antegrade via percutaneous nephrostomy) to relieve obstruction; treat underlying cancer
- Mechanism: Tumour eroding into the prostatic urethra or ejaculatory ducts disrupts vascular integrity → blood in the urine or semen
- Haematuria or haemospermia ( < 1%): uncommon, can also be due to BPH [4]
- Management: Usually conservative (tumour-directed treatment will reduce bleeding); severe haematuria may require bladder irrigation, cystoscopy with fulguration, or palliative RT
- Direct extension: stromal invasion through prostatic capsule → urethra, bladder base, seminal vesicles [4]
- Rectal invasion is rare because Denonvilliers' fascia acts as a natural barrier between the prostate and rectum, but can occur in T4 disease → tenesmus, rectal bleeding, fistula formation
- Neurovascular bundle invasion → new-onset erectile dysfunction (cavernous nerves immediately posterolateral to prostate capsule)
- Lower limb lymphoedema → lymphoedema due to pelvic lymphadenopathy or lymph node metastases [4]; bulky inguinal/pelvic nodes obstruct lymphatic drainage
A2. Metastatic Complications
Vertebral metastasis is the commonest metastatic site [4]. Reason: Batson's plexus connects prostatic venous plexus to internal vertebral plexus [4].
| Complication | Mechanism | Management |
|---|---|---|
| Bone pain | Osteoblastic metastases cause periosteal stretching, microfractures, and local inflammatory mediator release; typically dull, deep, progressive, worse at night | Analgesics (WHO ladder), palliative RT (excellent for focal pain), osteoclast inhibition (bisphosphonate, denosumab) [4] |
| Pathological fractures | Despite being osteoblastic, new bone is structurally disorganised and weak → fractures through vertebral bodies, pelvis, proximal femur | Orthopaedic fixation if long bone; vertebroplasty/kyphoplasty if vertebral; treat underlying disease |
| Spinal cord compression (SCC) | Vertebral body collapse or epidural tumour extension compresses the spinal cord → oncological emergency | High-dose steroids (dexamethasone), decompressive surgery, palliative RT [4] |
| Hypercalcaemia | Less common in prostate cancer than other bone-metastasising cancers (osteoblastic lesions sequester calcium); when present, usually due to PTHrP secretion or massive disease burden [10][14] | IV normal saline rehydration, bisphosphonate (zoledronic acid), calcitonin, treat underlying disease [14] |
| Bone marrow failure | Extensive marrow infiltration by metastatic deposits → crowding out of normal haematopoietic cells → pancytopenia (anaemia, thrombocytopenia, leukopenia) | Transfusion support; treat underlying cancer; leukoerythroblastic blood film on peripheral smear |
This is an oncological emergency that demands immediate recognition and treatment. Delay of even hours can result in irreversible paraplegia.
- Epidemiology: prostate cancer accounts for ~20% of all malignant cord compression [15]; > 90% vertebral, especially thoracic [15]
- Routes of spread: haematogenous (most common), direct invasion, lymphatics [15]
- Presentation: bone pain and tenderness → motor/sensory symptoms → sphincter disturbance (late) [15]
- The classic sequence is: back pain (often the first symptom, present for weeks before neurological signs) → radiculopathy (band-like pain in a dermatomal distribution) → motor weakness (upper motor neuron pattern below the level: spasticity, hyperreflexia, upgoing plantars) → sensory level (loss of sensation below the compression) → sphincter dysfunction (urinary retention, faecal incontinence — this is a LATE sign and indicates severe cord damage)
- Investigations [15]:
- MRI of the entire spine: confirm extradural compressive lesion
- Important to image the entire spine because 33% have multilevel involvement [15]
- Plain X-ray: may show osteolytic/osteoblastic lesions, vertebral collapse, pedicle erosion (the "winking owl" sign — loss of one pedicle on AP view)
- Management [15]:
- Dexamethasone 4 mg IV Q6H if neurological symptoms present — reduces peritumoral oedema and buys time
- Surgical decompression + stabilisation followed by RT if unstable spine
- RT alone if stable spine OR unfavourable prognosis
Spinal Cord Compression — The Golden Rule
If a patient with known prostate cancer develops new back pain — especially if it is progressive, worse at night, and associated with ANY neurological symptom (even subtle leg weakness or altered sensation) — treat it as cord compression until proven otherwise. Get an urgent MRI of the entire spine and start dexamethasone immediately. Once the patient becomes paraplegic, recovery is unlikely even with treatment.
- Liver metastases: hepatomegaly, deranged LFTs, RUQ pain, jaundice (late) [4]
- Lung metastases: usually asymptomatic (incidental CXR/CT finding); late: cough, haemoptysis, breathlessness [16]
- Adrenal metastases: usually asymptomatic; rarely symptomatic adrenal insufficiency [16]
- Disseminated intravascular coagulation (DIC): uncommon but reported in advanced prostate cancer; the mechanism involves release of tissue factor and procoagulant substances from tumour cells
B. Complications of Treatment
Complications of radical prostatectomy [1][3][4]:
| Complication | Frequency | Mechanism | Management |
|---|---|---|---|
| Erectile dysfunction | 30% even with good nerve sparing [4]; 50% overall [2] | Damage to cavernous nerves lying immediately posterolateral to the prostatic capsule [1]; even nerve-sparing causes neuropraxia (stretch injury) with potential recovery over 6–24 months | PDE5 inhibitors (sildenafil, tadalafil) or penile prosthesis [1]; vacuum erection device; intracavernosal injections (alprostadil) |
| Stress urinary incontinence | 50% early (immediate post-op), 5–10% long-term [4]; 10% [2] | Damage to the external urethral sphincter during apical dissection; the patient loses the internal sphincter (bladder neck is removed with prostate) and relies entirely on the external sphincter | Pelvic floor muscle exercises (Kegels) first-line; artificial urinary sphincter (AMS 800) for refractory cases [1] |
| Anastomotic (bladder neck) stricture | 5–10% [4] | Scarring at the vesicourethral anastomosis (where the bladder neck is re-joined to the urethral stump) → fibrotic narrowing | Endoscopic incision/dilation; rarely requires repeat surgery |
| Bleeding | 5–10% [4] | Division of the dorsal venous complex (Santorini's plexus) overlying the prostatic apex; prostatic arterial branches | Intra-operative haemostasis; transfusion if significant |
| Rectal injury | < 5% [4] | Prostate sits immediately anterior to the rectum; the posterior dissection plane (Denonvilliers' fascia) is thin → inadvertent perforation | Intra-operative primary repair; temporary diverting colostomy if large injury |
| General perioperative | Mortality < 0.3% | MI, DVT [1], pulmonary embolism, wound infection, anaesthetic complications | Standard VTE prophylaxis, cardiac risk assessment |
| Urine leaks | Uncommon | Anastomotic leak early post-op; usually resolves with prolonged catheter drainage | Keep Foley for ≥ 7 days [4]; re-catheterise if detected late |
| Ureteral injury | Rare | During dissection of the bladder base, the ureteric orifices may be inadvertently injured | Intra-operative recognition and reimplantation |
Anejaculation is universal after RP because the seminal vesicles, vas deferens ampullae, and prostatic urethra are all removed — there is no ejaculatory apparatus remaining. Orgasm is typically NOT affected [17], as orgasmic sensation is mediated by somatic sensory nerves (pudendal nerve) that are usually preserved.
Retrograde Ejaculation vs Anejaculation — Know the Difference
- After TURP (for BPH): retrograde ejaculation (40–60%) — the bladder neck is resected, so semen flows backwards into the bladder instead of out through the urethra. The patient still produces semen but it goes the "wrong way."
- After radical prostatectomy: anejaculation (100%) — the entire prostate, seminal vesicles, and ejaculatory ducts are removed. There is NO semen produced at all. The patient is infertile. This is fundamentally different from retrograde ejaculation.
Complications of radiotherapy [1][4]:
| Complication | Frequency | Mechanism |
|---|---|---|
| Erectile dysfunction | Up to 30% [4] | Radiation damage to the neurovascular bundles and penile vasculature; onset is gradual (6–36 months), unlike RP where ED is immediate |
| Radiation cystitis | Up to 10% [4] | Radiation injury to the bladder urothelium → mucosal oedema, telangiectasia, ulceration → frequency, urgency, dysuria, haematuria [1] |
| Radiation proctitis | Up to 10% [4] | Radiation injury to the anterior rectal wall (rectum is immediately posterior to the prostate) → diarrhoea, tenesmus, PR bleeding [1] |
| Irritative LUTS | Common | Radiation-induced inflammation of the prostatic urethra and bladder → detrusor overactivity and mucosal irritation; GI: proctitis, enteritis, diarrhoea, frequency, urgency, tenesmus; UG: cystitis, urethritis, frequency, urgency, dysuria [1] |
| Urethral stricture | Late | Radiation-induced fibrosis of the urethra |
| Secondary malignancy | Very rare, late | Radiation-induced carcinogenesis (bladder cancer, rectal cancer) — typically > 10 years after treatment |
| Lower stress incontinence rate compared to RP [2] | — | RT preserves the external sphincter (no surgical dissection near the sphincter); however, increased irritative symptoms (FUN: frequency, urgency, nocturia) [2] |
ADT removes the androgen signal that is essential for multiple physiological functions beyond the prostate. This creates a constellation of side effects that is essentially a male hypogonadal syndrome:
| Side Effect | Mechanism | Management |
|---|---|---|
| Hot flushes [1] | Loss of testosterone disrupts hypothalamic thermoregulatory set-point (analogous to menopausal hot flashes from oestrogen withdrawal) | Medroxyprogesterone acetate, venlafaxine, gabapentin |
| Erectile dysfunction / loss of libido [1] | Testosterone is the primary driver of male sexual desire and contributes to erectile function; its removal → loss of sexual interest and ability | PDE5 inhibitors (limited effect without libido); psychosexual counselling |
| Gynecomastia [1] | Androgen deprivation shifts the androgen/oestrogen ratio in favour of oestrogen (aromatisation of residual adrenal androgens) → oestrogen-stimulated breast tissue proliferation | Prophylactic breast irradiation, tamoxifen |
| Osteoporosis → pathological fractures | Androgens maintain bone density; their removal → accelerated osteoclastic resorption → bone mineral density loss (~4% per year on ADT) | Bisphosphonates (alendronate, zoledronic acid) or RANK-ligand inhibitor (denosumab) for prevention of bone loss [1]; calcium and vitamin D supplementation; weight-bearing exercise; baseline and serial DEXA scans |
| ↓ Lean body mass, ↑ body fat, ↓ muscle strength [4] | Androgens are anabolic hormones that maintain muscle mass; their loss → sarcopenia and central adiposity | Resistance exercise; dietary counselling |
| ↑ Risk of cardiovascular disease and ↑ insulin resistance [4] | ADT causes a metabolic syndrome-like picture: dyslipidaemia, insulin resistance, central obesity, increased inflammatory markers | Monitor metabolic parameters (glucose, HbA1c, lipid profile); cardiovascular risk factor management; exercise; GnRH antagonists (relugolix) may have lower cardiovascular risk than GnRH agonists |
| Anaemia [1] | Androgens stimulate erythropoiesis (both directly on marrow and via EPO production); their removal → decreased RBC production | Monitor Hb; transfusion if symptomatic; ESAs rarely used |
| Fatigue [1] | Multifactorial: anaemia, loss of muscle mass, metabolic changes, psychological impact | Exercise (strongest evidence); address other contributing factors |
| Cognitive impairment / depression | Androgens have neuroprotective and mood-regulatory roles; their removal → mood disturbance, impaired concentration, depression | Screening and psychological support; consider intermittent ADT in appropriate patients |
Bone Health in ADT — Don't Forget!
Men on long-term ADT lose bone at a rate comparable to postmenopausal women. Without intervention, up to 20% will sustain an osteoporotic fracture within 5 years. Current guidelines recommend: baseline DEXA scan at initiation of ADT, calcium (1200 mg/day) and vitamin D (800–1000 IU/day) supplementation, weight-bearing exercise, and consideration of bisphosphonate or denosumab if the patient is at high fracture risk (T-score ≤ -2.5 or other risk factors).
- GnRH agonists cause an initial testosterone surge ("flare") for 1–2 weeks before receptor downregulation achieves castrate levels [1]
- In patients with extensive bone metastases or impending cord compression, this flare can cause catastrophic worsening: increased bone pain, cord compression, ureteric obstruction, DIC
- Prevention: Anti-androgen cover (e.g., bicalutamide) for the first 2–4 weeks; or use a GnRH antagonist (no flare)
| Complication | Mechanism |
|---|---|
| Myelosuppression (neutropenia, anaemia, thrombocytopenia) [1] | Taxanes disrupt microtubule dynamics in rapidly dividing cells → bone marrow suppression → infection risk (febrile neutropenia), bleeding, fatigue |
| Peripheral neuropathy | Microtubule stabilisation in sensory neurons → axonal transport disruption → painful paraesthesiae (dose-limiting) |
| Fatigue | Multifactorial: anaemia, cytokine release, metabolic effects |
| GI toxicity | Nausea, vomiting, diarrhoea, mucositis — rapidly dividing GI epithelial cells are affected |
| Fluid retention / oedema | Docetaxel-specific; mechanism not fully understood; premedication with dexamethasone reduces incidence |
| Allergic/hypersensitivity reactions | Polysorbate 80 (vehicle for docetaxel) can trigger reactions; premedication required |
| Complication | Mechanism | Prevention |
|---|---|---|
| Osteonecrosis of the jaw (ONJ) | Inhibition of osteoclasts impairs normal bone remodelling in the jaw (which has high turnover due to mastication and dental procedures) → exposed necrotic bone | Dental review and dental work BEFORE starting therapy; avoid invasive dental procedures while on treatment; good oral hygiene |
| Hypocalcaemia | Potent osteoclast inhibition → reduced calcium release from bone → serum calcium drops | Supplement calcium and vitamin D; monitor serum calcium |
| Atypical femoral fractures | Prolonged suppression of bone remodelling → accumulation of microdamage in cortical bone → stress fractures in the subtrochanteric region | Rare with short-term use; consider drug holiday after 3–5 years in osteoporosis (less relevant in cancer setting) |
| Renal toxicity (bisphosphonates) | IV bisphosphonates (especially zoledronic acid) are nephrotoxic; require adequate hydration and dose adjustment for renal impairment | Check creatinine before each dose; avoid if CrCl < 30 (zoledronic acid) |
C. Complications of Diagnostic Procedures
Complications of prostate biopsy (~3% overall) [4]:
| Complication | Frequency | Mechanism |
|---|---|---|
| Fever | 1 in 4 (common despite prophylactic antibiotics) [4] | Transient bacteraemia from rectal flora (especially transrectal approach) |
| Bleeding: PR bleed, haematochezia, haemospermia, haematuria | ~1% [4] | Needle traverses vascular prostatic tissue |
| Urosepsis | ~1% (uncommon but can be severe) [4] | Rectal bacteria seeded into prostate and bloodstream; give prophylactic gentamicin beforehand [4]; infection < 0.5% for transperineal, ~5% for transrectal (antibiotic prophylaxis with fluoroquinolone required) [2] |
| AROU | 1–2% [2] | Pain and swelling of the prostate from procedure-related inflammation → obstruction of prostatic urethra |
| Prostatitis and prostatic abscess [1] | Rare | Bacterial seeding during transrectal biopsy |
Harms of PSA screening [3][1]:
| Harm | Explanation |
|---|---|
| Overdiagnosis | Detection by screening of conditions that would not have become clinically significant [1] — many low-grade cancers detected by screening would never cause symptoms or death in the patient's lifetime |
| Overtreatment | Aggressive therapy including radical prostatectomy and radiation therapy are provided even with early-staged disease [1] → complications include urinary incontinence, bowel dysfunction and sexual dysfunction [1][3] |
| False positives leading to anxiety and unnecessary biopsies [3] | Elevated PSA from benign causes → patient undergoes biopsy (with its own risks) → no cancer found → but significant psychological distress throughout |
| Psychological harm | Being diagnosed with prostate cancer is psychologically distressing; negative biopsy result is also distressing since it cannot completely rule out cancer given the high false-negative biopsy rate [1] |
CRPC represents the final common pathway of prostate cancer and is the lethal phase of the disease. Complications at this stage are the culmination of treatment resistance and widespread disease:
- Progressive bone disease: increasing pain, pathological fractures, cord compression, hypercalcaemia
- Visceral metastases: liver failure (hepatic mets), respiratory failure (pulmonary mets)
- Bone marrow failure: pancytopenia from extensive marrow infiltration → infections, bleeding, transfusion dependence
- Cancer cachexia: progressive weight loss, sarcopenia, anorexia — mediated by tumour-derived cytokines (TNF-α, IL-6) disrupting metabolic homeostasis
- Thromboembolic disease: prostate cancer is a prothrombotic state → DVT, PE
- Treatment toxicity: cumulative side effects of multiple lines of systemic therapy (chemotherapy-induced neuropathy, myelosuppression, cardiotoxicity from ADT)
High Yield Summary — Complications of Prostate Cancer
Disease complications:
- Local: BOO/AROU (late, peripheral zone), obstructive uropathy/renal failure (trigone/ureteric invasion), haematuria, local invasion (bladder, seminal vesicles, neurovascular bundles)
- Metastatic: Bone pain, pathological fractures, spinal cord compression (emergency: dexamethasone + MRI whole spine + decompression/RT), bone marrow failure, hypercalcaemia (less common in prostate cancer), liver/lung/adrenal mets
Treatment complications:
- RP: ED (30–50%), stress incontinence (5–10% long-term), anastomotic stricture (5–10%), bleeding (5–10%), rectal injury ( < 5%), anejaculation (100%)
- RT: ED (30%, gradual onset), radiation cystitis/proctitis (up to 10%), lower incontinence than RP, secondary malignancy (rare, late)
- ADT: Hot flushes, ED, loss of libido, gynecomastia, osteoporosis, metabolic syndrome (obesity, CVD risk, insulin resistance), anaemia, fatigue, cognitive changes
- GnRH agonist flare: Testosterone surge → bone pain crisis, cord compression, ureteric obstruction. Prevent with anti-androgen cover or use GnRH antagonist.
- Chemotherapy: Myelosuppression, neuropathy, GI toxicity, fatigue
- Bone-directed therapy: ONJ, hypocalcaemia, atypical fractures, renal toxicity
Diagnostic complications:
- Biopsy: Fever (25%), bleeding (1%), urosepsis (1%), AROU (1–2%)
- Screening harms: Overdiagnosis, overtreatment (incontinence, ED, bowel dysfunction), false positives, anxiety
Active Recall - Complications of Prostate Cancer
References
[1] Senior notes: felixlai.md (Prostate cancer — complications of surgery, radiotherapy, ADT, bisphosphonates, screening harms, biopsy complications) [2] Senior notes: maxim.md (Section 2.5 — Prostate cancer: RP complications, RT complications, biopsy complications) [3] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p35 — Harms of PSA screening; p45 — Complication of surgery) [4] Senior notes: Ryan Ho Urogenital.pdf (p182 — Biopsy complications; p185 — RP complications, RT complications; p186 — ADT side effects, CRPC management, palliative treatment, prognosis; p177 — TURP complications) [10] Senior notes: Ryan Ho Chemical Path.pdf (p23 — Hypercalcaemia of malignancy mechanisms) [11] Senior notes: Ryan Ho Critical Care.pdf (p25 — Post-renal AKI: BPH, CA prostate as causes) [14] Senior notes: Ryan Ho Endocrine.pdf (p44 — Hypercalcaemia of malignancy management) [15] Senior notes: Ryan Ho Neurology.pdf (p170 — Spinal cord tumours: extradural metastatic tumours from prostate cancer, presentation, investigation, management) [16] Senior notes: Ryan Ho Respiratory.pdf (p143, p151 — Metastatic spread to lungs, bone, brain, adrenals; secondary tumours of the lungs) [17] Senior notes: Ryan Ho Psychiatry.pdf (p233 — Prostate surgery and ejaculatory function: radical prostatectomy causes anejaculation but orgasm typically NOT affected)
High Yield Summary
Definition: Adenocarcinoma (95%) arising predominantly from the peripheral zone of the prostate.
Epidemiology (HK): 3rd most common male cancer; rising incidence; lifetime risk ~1/26–30; 1/3 present with locally advanced/metastatic disease.
Risk Factors: Age (most important) > ethnicity (Black > White > Asian) > family history (2× if 1 FDR, 4.5× if 2 FDR) > genetics (BRCA2, TMPRSS2-ERG, ATM, Lynch) > androgens > obesity/diet > smoking.
Anatomy: Peripheral zone (65%, cancer), Transitional zone (10%, BPH), Central zone (25%), Anterior fibromuscular stroma. Cancer in peripheral zone → late symptoms, palpable on DRE.
Spread: Direct (bladder, seminal vesicles) → Lymphatic (pelvic → para-aortic LN) → Haematogenous (Batson's plexus → axial skeleton: osteoblastic bone mets).
Gleason/Grade Groups: Gleason score = primary + secondary pattern (1–5). Grade Groups 1–5 (ISUP 2014). Gleason 3+4 ≠ 4+3 (different grade groups, different prognosis!).
Clinical Features: Often asymptomatic early. LUTS are late (peripheral zone origin). DRE: hard, irregular, nodule, loss of midline sulcus (only 25% palpable). Metastatic: bone pain (axial skeleton), cord compression, pathological fractures.
PSA: Organ-specific, NOT tumour-specific. Cutoff 4 ng/mL (age-adjusted). Grey zone 4–10 → PHI, free/total ratio, MRI. Factors ↑PSA: cancer, BPH, UTI, AROU, ejaculation, cycling. Factors ↓PSA: castration, 5ARI, RT.
Screening (EAU 2025): Risk-stratified, primarily age 55–69; earlier for high-risk (FHx, BRCA). Shared decision-making. Not for < 40 or > 77 with life expectancy < 10 years.
High Yield Summary — Differential Diagnosis of Prostate Cancer
By presentation:
- Elevated PSA: BPH (most common cause), prostatitis/UTI, AROU, recent ejaculation/cycling, prostate cancer. PSA is organ-specific but NOT tumour-specific.
- Abnormal DRE: BPH (smooth, symmetric, firm) vs prostate cancer (hard, irregular, nodule, loss of sulcus) vs prostatitis (tender, boggy) vs granulomatous prostatitis (mimics cancer).
- LUTS: BPH (#1 cause in elderly men), OAB, UTI/prostatitis, urethral stricture, bladder neck contracture, neurogenic bladder, bladder cancer, drugs, constipation. Prostate cancer causes LUTS late.
- Haematuria: Bladder cancer (#1 to exclude), RCC, BPH, UTI, stones. Painless gross haematuria > 35yo = malignancy until proven otherwise.
- Bone pain: Prostate cancer (osteoblastic), lung/breast/renal cancer (usually osteolytic), myeloma (punched-out lytic), lymphoma.
- Obstructive uropathy: BPH, prostate cancer (trigone/ureteric invasion), bladder cancer, stones, retroperitoneal fibrosis.
Key distinction: BPH vs Prostate Cancer — different zones (transitional vs peripheral), different DRE findings, different PSA profiles. BPH does NOT predispose to cancer. They commonly coexist.
High Yield Summary — Diagnosis of Prostate Cancer
Diagnostic pathway: Clinical suspicion (PSA + DRE) → Confirmatory workup (PSA derivatives, mpMRI) → Tissue diagnosis (prostate biopsy) → Risk stratification (PSA + T-stage + Grade Group) → Staging investigations (tiered by risk).
PSA interpretation: < 4 normal; 4–10 grey zone (20–25% cancer risk) — use PHI, free/total ratio, mpMRI; > 10 → biopsy; ≥ 10 ng/mL = ~50% cancer risk.
mpMRI: T2W-hypointense lesion; PI-RADS 4–5 = biopsy; PI-RADS 1–2 = monitor. Now recommended BEFORE biopsy.
Biopsy: Transperineal preferred (lower infection, accesses all zones). 12-core systematic + targeted. Complications: fever, bleeding, urosepsis, AROU.
Histology: High-grade PIN → re-biopsy (13–27% cancer risk). Low-grade PIN → no action.
Staging: AJCC 8th edition TNM + PSA + Grade Group = Prognostic Stage I–IV. Staging workup extent depends on risk group. PSMA PET-CT is replacing conventional bone scan + CT.
Key principle: The challenge is not just finding cancer — it's correctly risk-stratifying it so you treat those who need it and observe those who don't.
High Yield Summary — Management of Prostate Cancer
Conservative:
- Active surveillance: Curative intent; low-risk disease; fit patient > 10y life expectancy; monitor with DRE/PSA/MRI/re-biopsy; treat on progression. 90% OS, 99.7% CSS.
- Watchful waiting: Palliative intent; unfit/elderly patient < 10y life expectancy; treat symptoms with ADT when they arise.
Localised disease (curative):
- Low risk: Active surveillance (preferred); RP or RT as alternatives
- Intermediate risk: RP (robotic) ± ePLND; or EBRT + neoadjuvant/concomitant ADT
- High risk: RP + ePLND; or EBRT + long-term adjuvant ADT (2–3y)
Locally advanced: RP + ePLND + adjuvant RT/ADT; or EBRT + ADT; or ADT alone if unfit.
Metastatic (mHSPC):
- Low volume: ADT + novel hormonal agent + RT to primary
- High volume (≥ 4 bone mets incl. 1 outside axial skeleton, or visceral mets): ADT + novel hormonal agent + docetaxel
CRPC (castrate testosterone + progression): Continue ADT + add abiraterone/enzalutamide/docetaxel/cabazitaxel/223Ra/177Lu-PSMA/PARP inhibitors.
ADT: GnRH agonist (cover flare with anti-androgen) or GnRH antagonist (no flare). Side effects: hot flushes, ED, osteoporosis, metabolic syndrome, CVD risk, gynecomastia.
RP complications: ED (30–50%), incontinence (5–10% long-term), anastomotic stricture, bleeding, rectal injury.
RT complications: ED (30%), cystitis/proctitis (10%), less incontinence than RP.
Prognosis: Localised ~100% 5y survival; metastatic ~29%.
High Yield Summary — Complications of Prostate Cancer
Disease complications:
- Local: BOO/AROU (late, peripheral zone), obstructive uropathy/renal failure (trigone/ureteric invasion), haematuria, local invasion (bladder, seminal vesicles, neurovascular bundles)
- Metastatic: Bone pain, pathological fractures, spinal cord compression (emergency: dexamethasone + MRI whole spine + decompression/RT), bone marrow failure, hypercalcaemia (less common in prostate cancer), liver/lung/adrenal mets
Treatment complications:
- RP: ED (30–50%), stress incontinence (5–10% long-term), anastomotic stricture (5–10%), bleeding (5–10%), rectal injury ( < 5%), anejaculation (100%)
- RT: ED (30%, gradual onset), radiation cystitis/proctitis (up to 10%), lower incontinence than RP, secondary malignancy (rare, late)
- ADT: Hot flushes, ED, loss of libido, gynecomastia, osteoporosis, metabolic syndrome (obesity, CVD risk, insulin resistance), anaemia, fatigue, cognitive changes
- GnRH agonist flare: Testosterone surge → bone pain crisis, cord compression, ureteric obstruction. Prevent with anti-androgen cover or use GnRH antagonist.
- Chemotherapy: Myelosuppression, neuropathy, GI toxicity, fatigue
- Bone-directed therapy: ONJ, hypocalcaemia, atypical fractures, renal toxicity
Diagnostic complications:
- Biopsy: Fever (25%), bleeding (1%), urosepsis (1%), AROU (1–2%)
- Screening harms: Overdiagnosis, overtreatment (incontinence, ED, bowel dysfunction), false positives, anxiety
Polycystic Kidney Disease
Polycystic kidney disease is a genetic disorder characterized by the progressive development of multiple fluid-filled cysts in the kidneys, leading to renal enlargement and eventual loss of kidney function.
Renal Cell Carcinoma
Renal cell carcinoma is a malignant neoplasm arising from the renal tubular epithelium, most commonly the clear cell subtype, typically presenting in adults with hematuria, flank pain, or a palpable mass.