Prostate Cancer

Prostate Cancer: Epi & Risks - Prostate Primer

• Epidemiology:
  • Incidence ↑ with age (peak 65-74 yrs).
  • India: Rising incidence, often late presentation.
  • Higher in African Americans; lower in Asians.
• Risk Factors:
  • Age: Strongest risk.
  • Family History: 2-3x ↑ risk (1st-degree relative).
  • Genetics: BRCA1/2, HOXB13.
  • Race: African American > Caucasian > Asian.
  • Diet: High animal fat, low vegetables.
• Pathology Primer:
  • Adenocarcinoma: >95%.
  • Site: Peripheral zone (~70-80%), often DRE palpable.

⭐ High-Yield: The peripheral zone is the most common site for prostate adenocarcinoma, making Digital Rectal Examination (DRE) a key diagnostic aid.

Prostate Cancer: Signs & Screening - Detective Work

• Clinical Presentation:
  • Early: Often asymptomatic.
  • Locally Advanced: LUTS (obstructive: hesitancy, weak stream; irritative: frequency, urgency), hematuria/hematospermia.
  • Metastatic: Bone pain (esp. axial), constitutional symptoms.
• Initial Investigation:
  • Digital Rectal Exam (DRE): Palpable nodules, induration, asymmetry.
  • Prostate-Specific Antigen (PSA):
    • < 4 ng/mL: Low risk.
    • 4-10 ng/mL (Grey Zone): Evaluate %free PSA (<25% ↑risk), PSA density (PSAD >0.15 ng/mL/cc ↑risk), PSA velocity.

    • 10 ng/mL: High risk.

• Biopsy Triggers: Abnormal DRE, PSA >10 ng/mL, suspicious parameters in grey zone, or concerning mpMRI (PI-RADS ≥3).

  ⭐ Most prostate cancers (adenocarcinomas) arise in the peripheral zone, making them often palpable on DRE.

Prostate Cancer: Grading & Staging - Score & Scope

• Gleason Score (Pathological Grading): Sum of two most prevalent patterns (primary + secondary).
  • Each pattern graded 1-5 (well-differentiated to poorly-differentiated).
  • Total score 2-10.
  • ISUP Grade Groups (Prognostic):
    • Grade Group 1: Gleason Score $\leq$ 6
    • Grade Group 2: Gleason Score 3+4=7
    • Grade Group 3: Gleason Score 4+3=7
    • Grade Group 4: Gleason Score 8
    • Grade Group 5: Gleason Score 9-10

• TNM Staging (AJCC 8th Ed.): Clinical (cTNM) & Pathological (pTNM).

  • T (Primary Tumor):
    • cT1: Non-palpable/invisible on imaging.
    • cT2: Palpable/visible, confined to prostate (T2a, T2b, T2c based on extent).
    • T3: Extracapsular extension (T3a: ECE; T3b: Seminal vesicle invasion).
    • T4: Invades adjacent structures (rectum, bladder neck, external sphincter, pelvic wall).
  • N (Regional Lymph Nodes): N0 (no regional mets), N1 (regional mets).
  • M (Distant Metastasis): M0 (no distant mets), M1 (distant mets; M1a: non-regional LN, M1b: bone, M1c: other sites).

• Risk Stratification (e.g., NCCN Guidelines): Combines PSA, Gleason Score/Grade Group, Clinical T stage.

  • Categories: Very Low, Low, Favorable Intermediate, Unfavorable Intermediate, High, Very High, Regional, Metastatic.

⭐ Gleason Score 7 is a critical prognostic point: 3+4=7 (Grade Group 2) has a better prognosis than 4+3=7 (Grade Group 3).

Prostate Cancer: Management - Battle Plan

• Treatment guided by risk stratification (e.g., D'Amico: PSA, Gleason, T-stage), overall stage & patient factors.

⭐ In metastatic hormone-sensitive prostate cancer (mHSPC), adding a novel hormonal agent (NHA like Abiraterone) or Docetaxel to ADT significantly improves overall survival compared to ADT alone.

High‑Yield Points - ⚡ Biggest Takeaways

• Predominantly adenocarcinoma; arises mostly in the peripheral zone.
• PSA > 4 ng/mL and abnormal DRE are key initial indicators.
• Gleason score is critical for prognosis and treatment guidance.
• TRUS-guided biopsy confirms diagnosis; 10-12 core biopsy is standard.
• Bone (osteoblastic) is the most common site of metastasis.
• Androgen Deprivation Therapy (ADT) is a cornerstone for metastatic disease.
• Radical prostatectomy or radiotherapy for localized disease.