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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‰ˆ 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 55–69. 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 treatedβ€”1 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 (8–12 cores).
  • Prebiopsy MRI increases detection of clinically significant disease.
  • Gleason Grade/Score: Most CaP is Gleason 6–10.
  • Grade group 1 (Gleason 6), 2 (3+4), 3 (4+3), 4 (8), 5 (9–10).
  • Staging: TNM system; PSMA-PET is preferred for advanced imaging.

TREATMENT

Risk Stratification

  • Low/Very Low Risk: T1–T2a, PSA <10, grade group 1.
  • Intermediate: T2b–T2c, PSA 10–20, grade group 2–3.
  • High/Very High Risk: T3a+, PSA >20, grade group 4–5, 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.

Metastatic Disease

  • 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.