- Prostate cancer is the most common visceral malignancy in US men; ≈1 in 8 men are diagnosed during their lifetime.
- Mortality in African-American men is approximately 2.4× higher than in Caucasian men.
- BRCA2 confers a stronger risk of aggressive prostate cancer than BRCA1; the BRCA-associated cancers are breast, ovarian, prostate, pancreatic, and melanoma.
- The most common gene fusion in localized prostate cancer is TMPRSS2:ERG.
- Most (≈85%) prostate cancers arise from the peripheral zone; extra-prostatic extension (EPE) is the preferred term over capsular invasion.
- Gleason Grade Group 1 = score ≤6; GG2 = 3+4=7; GG3 = 4+3=7; GG4 = 8; GG5 = 9–10.
- The three most informative randomized trials on PSA screening are PLCO (no net benefit), ERSPC (net benefit), and Göteborg (net benefit); all used cancer-specific mortality as the primary outcome.
- 2018 USPSTF: PSA screening is grade C for men aged 55–69 (individualized) and grade D for men ≥70.
- On mpMRI, the primary sequences for prostate cancer are T2WI (best for transition-zone lesions and anatomy) and DWI/ADC (best for peripheral-zone lesions); DCE is most useful when T2WI/DWI are equivocal.
- PI-RADS ≥4 should prompt biopsy; PI-RADS 5 has a positive predictive value of ≈72% for GG ≥2.
- A PSA density ≥0.15 ng/mL/cc raises concern for clinically significant cancer even with a negative MRI.
- PROMIS and PRECISION established the role of pre-biopsy MRI with targeted biopsy.
- Active surveillance is the preferred management for low-risk localized prostate cancer (2022 AUA).
- D'Amico/AUA risk groups stratify by PSA, clinical T-stage, and Gleason/Grade Group; intermediate-risk is further split into favorable vs. unfavorable based on percent positive cores.
- Radical retropubic prostatectomy allows for pelvic lymphadenectomy; perineal prostatectomy reduces blood loss but precludes lymphadenectomy.
- Radiotherapy contraindications follow the "ST-LIAR" mnemonic: prostate Size >60 cc for brachytherapy, prior TURP, severe LUTS, IBD, Ataxia telangiectasia, prior pelvic Radiotherapy.
- ASTRO definition of biochemical failure after radiotherapy = 3 consecutive PSA rises; Phoenix definition = PSA nadir + 2 ng/mL (not backdated).
- Post-radiation PSA bounce: rise of 0.1–0.5 ng/mL above nadir within ~12 months of EBRT or up to 30 months after brachytherapy; more common with brachytherapy.
- Biochemical recurrence after radical prostatectomy (AUA/ASTRO): PSA ≥0.2 ng/mL with a confirmatory value.
- Pound et al.: median time from biochemical recurrence to metastasis ≈8 years; from metastasis to death ≈5 years.
- The minimum recommended salvage radiation dose is 64 Gy; salvage radiation is most effective when delivered at PSA ≤0.5 ng/mL.
- LHRH antagonists (degarelix, relugolix) achieve castrate testosterone within days without a flare; LHRH agonists require concurrent anti-androgen for ~21–28 days to block testosterone flare.
- CHAARTED high-volume metastatic disease = visceral mets OR ≥4 bone lesions with ≥1 beyond the vertebral bodies/pelvis.
- LATITUDE high-risk criteria for adding abiraterone in mHSPC = ≥2 of: visceral metastasis, ≥3 bone lesions, Gleason ≥8.
- STAMPEDE: adding prostate radiation to ADT improves overall survival in low-burden but not high-burden metastatic disease.
- Castrate-resistant prostate cancer is defined by progression (PSA, radiographic, or new metastases) despite castrate testosterone <50 ng/dL; ADT should be continued indefinitely.
- For nmCRPC with PSA doubling time <10 months: apalutamide (SPARTAN), enzalutamide (PROSPER), or darolutamide (ARAMIS) improve metastasis-free and overall survival.
- For mCRPC with bone metastases: denosumab or zoledronic acid every 4 weeks plus calcium/vitamin D supplementation reduces skeletal-related events.
- Radium-223 is indicated for symptomatic bone metastases in the absence of visceral metastases and bulky (>3 cm) lymph nodes; should not be combined with abiraterone (ERA 223).
- Olaparib (PARP inhibitor) is approved for mCRPC with homologous recombination repair mutations (especially BRCA1/2) progressing after a novel hormonal agent.
- Urothelial CIS of the prostatic urethra is treated with TURP then BCG; prostatic stromal invasion (pT4a bladder) is treated with radical cystectomy ± urethrectomy.