Prostate Cancer
BASICS
- Prostate: Walnut-sized male reproductive gland, produces seminal fluid, enlarges after age 50.
- Anatomy: Peripheral zone (most common CaP site, palpable DRE), central zone (ejaculatory ducts), transition zone (adjacent to urethra).
- PSA: Prostate-specific antigen produced by prostatic epithelium, used for screening/tumor marker.
EPIDEMIOLOGY
- Incidence: ~288,300 new cases (US, 2023); 15% of all new cancer diagnoses.
- Mortality: ~34,700 deaths (US, 2023); 5.7% of cancer deaths.
- Median age: 67 years; lifetime risk by age 70 β 11%.
- Autopsy: Latent CaP in 50% of men >80 years.
ETIOLOGY & PATHOPHYSIOLOGY
- Type: >95% adenocarcinoma.
- Location: 70% peripheral zone, 20% transitional, 5-10% central.
- Risk Factors: Age >50, African American, family history.
- Prevention: Finasteride reduces risk but may increase high-grade CaP.
SCREENING (Controversial)
- USPSTF: Shared decision-making for men 55β69. Not recommended <40 or >70, or life expectancy <10 years.
- AUA: Similar, individualized approach.
- Harms: Of 1,000 men screened, 240 positive, 100 cancer, 80 treatedβ1 fewer death, 50 develop ED, 15 permanent incontinence.
DIAGNOSIS
History
- Symptoms: Bladder outlet obstruction, voiding difficulty (late finding).
Physical Exam
- DRE: Palpate for firmness, asymmetry, or nodules.
Differential Diagnosis
- BPH, prostatitis, prostatic intraepithelial neoplasia (PIN), ASAP, prostate stones.
Initial Tests
- PSA: β₯4 ng/mL concerning (sensitivity 21%, specificity 91%).
- 5-Ξ±-reductase inhibitors decrease PSA by ~50%.
- PSA velocity, %free PSA, PSA density, and age/race adjustments can help risk stratify.
- MRI: Can guide biopsy.
- Prostate Biopsy: Indicated for elevated PSA, abnormal DRE, or suspicious MRI.
- Systematic random core biopsy (8β12 cores).
- Prebiopsy MRI increases detection of clinically significant disease.
- Gleason Grade/Score: Most CaP is Gleason 6β10.
- Grade group 1 (Gleason 6), 2 (3+4), 3 (4+3), 4 (8), 5 (9β10).
- Staging: TNM system; PSMA-PET is preferred for advanced imaging.
TREATMENT
Risk Stratification
- Low/Very Low Risk: T1βT2a, PSA <10, grade group 1.
- Intermediate: T2bβT2c, PSA 10β20, grade group 2β3.
- High/Very High Risk: T3a+, PSA >20, grade group 4β5, other high-risk features.
Localized Disease
- Low Risk: Active surveillance is preferred. Radical prostatectomy or radiation as alternatives.
- Intermediate Risk: Radical prostatectomy or radiation. Active surveillance for favorable subset.
- High Risk: Radical prostatectomy and/or radiation; consider adjuvant therapy.
Locally Advanced Disease
- Mainstay: ADT (androgen deprivation) + radiation; surgery and adjuvant radiation as needed.
- **Add abiraterone + prednisone for high-risk, locally advanced disease starting long-term ADT.
- Mainstay: ADT Β± RT.
- High-volume: Early docetaxel chemo with ADT.
- Low-volume: ADT + abiraterone + prednisone.
- ADT options: GnRH agonists (leuprolide, goserelin), GnRH antagonists (degarelix).
- Side effects: Osteoporosis, gynecomastia, ED, decreased libido, obesity, diabetes, CVD, hot flashes (flare phenomenon).
- Flare prevention: Antiandrogen before GnRH agonist if spinal mets.
Castrate-Resistant Prostate Cancer (CRPC)
- Options: 177Lu-PSMA-617, docetaxel, cabazitaxel, abiraterone, enzalutamide, olaparib, pembrolizumab, radium-223, rucaparib, sipuleucel-T.
- **Continue ADT in non-metastatic; add apalutamide, darolutamide, or enzalutamide.
Bone Health
- Prevention: Denosumab, zoledronic acid (esp. with ADT).
Other
- Cryotherapy, brachytherapy, HIFU, immunotherapy in selected cases.
FOLLOW-UP
- Post-prostatectomy: PSA, DRE, imaging as indicated; salvage radiation/ADT for recurrence.
- Post-radiation: PSA, DRE, imaging; salvage therapies if recurrence.
PROGNOSIS
- Localized: Frequently curable; 5-year survival local/regional 100%, distant 30%.
- Recurrence: Higher risk if extraprostatic extension, positive margins, seminal vesicle invasion.
COMPLICATIONS
- Prostatectomy: Urinary incontinence, ED.
- Radiation: Incontinence, ED, cystitis, proctitis.
- ED Treatment: PDE5 inhibitors, intracavernosal injections, prosthesis, vacuum pump.
- Incontinence: Medications, sling, artificial sphincter.
ICD-10 CODES
- C61 Malignant neoplasm of prostate
- Z80.42 Family history of malignant neoplasm of prostate
- D07.5 Carcinoma in situ of prostate
CLINICAL PEARLS
- PSA screening is controversial; discuss benefits and harms with patients.
- Interpreting PSA is complicated in those on 5-Ξ±-reductase inhibitors.
- Decision to treat is based on risk, life expectancy, patient factors.
- Survival for localized CaP is excellent, but treatment morbidity can be significant.