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OncologyStudy NoteHigh YieldLast updated 30 May 2026

Prostate Cancer

High-yield revision notes — full detail, one scroll.

Pathology & Pre-Cancerous Lesions

PIN

  • Low-grade: no specific Rx → PSA + DRE follow-up
  • High-grade: unifocal vs multifocal
    • Unifocal → same as low-grade
    • Multifocal → PSA + DRE + repeat biopsy in 1–3 years | Cancer risk ≈ 30%

ASAP

  • HMWCK positive
  • Suspicious but non-diagnostic
  • ➡ Re-biopsy in 3–6 months
  • Cancer risk: 40–60%

Prostate Cancer Histology

  • HMWCK negative
  • Types:
    • Acinar (most common, 85% peripheral zone, multifocal in >85%)
    • Ductal (normal PSA) CI to AS
    • Intraductal (normal PSA) — high-grade marker, CI to AS

Risk Factors

  • Family Hx: 1st-degree → RR 3.3 | ≥2 affected → RR 5
  • African ancestry (incidence Black > White > Hispanic > Asian)
  • Age >40
  • Germline mutations: BRCA2 (most aggressive), BRCA1, CHEK2, Lynch (MLH1/MSH2/MSH6/PMS2)
  • Chromosome 8 abnormalities | TMPRSS2:ERG fusion in ~50% sporadic PCa
  • Mets pattern: LN → bone (osteoblastic) → lung → bladder → liver

PSA Biology & Interpretation

  • Half-life: 2–3 days
  • Bound to: α1-antichymotrypsin, α1-protease inhibitor
  • ↑ by: BPH, prostatitis, UTI, biopsy (↑6–8 ng/mL, normalizes 2–3 wk), TURP, cycling
  • Minimal effect: DRE, catheterization, TRUS without biopsy
  • 5-ARIs halve PSA at 12 mo → double observed value
  • 25–40% of newly elevated PSAs normalize → repeat before biopsy

Other Markers

  • Urine: PCA3 → predicts cancer on biopsy after prior negative biopsy
  • Tissue:
    • ConfirmMDx → predicts csPCa on rebiopsy after prior negative biopsy
    • Oncotype DX → post-biopsy: predicts T3 or Gleason 4
    • Polaris → post-biopsy: predicts CSM and recurrence

MRI & PI-RADS

PI-RADSCancer RiskcsPCa (GG≥2)
1–2~25%~7%
3~33%12–15%
4~62%39–48%
5~66% (GS ≥3+4; 37% GS 4+3)~72%
  • PI-RADS 5 with negative biopsy → repeat MRI then biopsy
  • Hypoechoic lesion on TRUS → ~57% cancer
  • Post-biopsy: wait 6–8 weeks before MRI

Factors Suggesting Need for Biopsy

  • Abnormal DRE
  • Abnormal PSA, PSAV, or PSAD (single abnormal PSA alone should not trigger biopsy → repeat first)
  • Abnormal MRI (PI-RADS ≥3)
  • PSA fails to decline on 5-ARI
  • After TRUS biopsy: ~75% negative | False-negative rate 20–30%
  • Most common complication post-biopsy: hematospermia

Seminal Vesicle Biopsy — Indications

  • Suspected SV invasion
  • Planning salvage cryotherapy after radiation

Prognostic Factors on TRUS Biopsy

  • Gleason score / Grade Group
  • Number & % of positive cores
  • SV involvement
  • Periprostatic invasion
  • Perineural invasion
  • Cribriform / intraductal patterns

TNM Staging (AJCC 8th)

T

  • T1 a/b/c → diagnosed by biopsy
  • T2 a/b/c → organ-confined, palpable
  • T3a → extracapsular extension (EPE)
  • T3b → SV invasion
  • T4 → invades adjacent organs

N

  • N1: regional LN

M

  • M1a: non-regional LN | M1b: bone | M1c: other (liver, lung, brain)

Gleason → ISUP Grade Group

GGGleason
1≤6
23+4=7
34+3=7
48
59–10

Risk Stratification

Very Low (Epstein)

  • PSA <10, GG1, ≤3 cores, ≤50% involvement, PSAD <0.15, T1c

Low

  • PSA <10 AND GG1 AND ≤T2a

➡ AS first choice | alternatives: RP, EBRT, brachy ➡ No imaging indicated

Intermediate — Favorable

  • GG1 + PSA <20 OR GG2 + PSA <10

➡ LE >10 yr: AS, RP ± PLND (if nomogram >2%), OR EBRT ± brachy ➡ LE <10 yr: Observation (preferred) OR EBRT ± brachy ➡ Imaging: A/P only; bone if symptomatic or ↑ALP

Intermediate — Unfavorable

  • GG2 + PSA 10–20 OR GG3 + PSA <20

➡ LE >10 yr: RP + PLND (first choice) OR EBRT + short-term ADT ➡ LE <10 yr: Observation OR EBRT + short-term ADT ➡ Imaging: A/P + bone

High Risk

  • PSA >20 OR GG4–5 OR ≥T3

➡ LE >5 yr: RP + PLND OR EBRT + long-term ADT (preferred) ➡ LE <5 yr: Observation OR ADT OR EBRT ➡ Imaging: A/P + bone

Imaging Indications

Bone Scan

  • Unfavorable or high risk
  • Bone pain
  • Elevated ALP

PSMA-PET

  • Biochemical recurrence after local therapy
  • High-risk disease (initial staging)
  • ~27% higher accuracy than conventional imaging (proPSMA)

Management Overview

  • Localized → risk-stratified (see above)
  • Locally advanced (T3 or N1):
    • Neoadjuvant ADT + EBRT + Adjuvant ADT (preferred)
    • RP + PLND ± XRT ± ADT
  • Metastatic → systemic therapy (see below)

Active Surveillance Protocol

  • PSA + DRE every 6 months
  • Confirmatory biopsy at 1 year
  • Then biopsy every 3–5 years
  • mpMRI to augment (does NOT replace biopsy)

Triggers for Intervention

  • Grade reclassification (GG≥2)
  • Volume reclassification
  • Rapidly rising PSA
  • Patient preference

Post-Prostatectomy Management

Indications for Adjuvant / Salvage RT

  • Positive surgical margin (most common site = apex)
  • Extracapsular extension
  • SV invasion (T3)
  • Detectable PSA

Indication for ADT after RP

  • Positive lymph nodes (pN1)

Salvage RT

  • Start at PSA ≤0.5 for best outcomes
  • Minimum dose: 64 Gy to prostatic bed
  • Add ADT if PSA >0.6 (RTOG 96-01)

Recurrence

After RP

  • PSA ≥0.2 with confirmatory rise
  • Imaging if mets suspected: CT, bone scan, or PSMA-PET
  • Risk assessment ➡ Salvage RT ± ADT

After RT

  • PSA ≥nadir + 2
  • Imaging if mets suspected: CT, bone scan, or PSMA-PET
  • Biopsy:
    • If localized → Salvage RP, cryotherapy, brachy ± ADT
    • If negative biopsy → ADT alone

Contraindications OF Radiotherapy (ST-LIAR)

LetterContraindication
SizeProstate >60 cc (brachy — ↑ urinary toxicity)
TURPPrior TURP if defect prevents seed placement (absolute for brachy)
LUTSSignificant baseline voiding symptoms
IBDActive inflammatory bowel disease
Ataxia telangiectasia(absolute — severe radiation response)
RadiationPrior pelvic radiotherapy

Biochemical Recurrence

Workup

  • PSMA-PET
  • Conventional CT/bone scan: low yield

Management

  • Local failure ➡ Salvage (see above)
  • Distant failure ➡ Treat as mHSPC (see below)

Androgen Deprivation Therapy (ADT)

Goal

  • Testosterone <50 ng/dL (or <1.7 nmol/L)

Mechanisms

Androgen biosynthesis inhibition

  • Abiraterone (CYP17 inhibitor) → must give steroids (mineralocorticoid excess)

1st-gen anti-androgens

  • Bicalutamide 50 mg OD — given to prevent flare with LHRH agonist induction

2nd-gen anti-androgens

  • Apalutamide
  • Enzalutamide (seizure risk)
  • Darolutamide (less CNS penetration → fewer falls/seizures)

LHRH Agonists

  • Goserelin 10.8 mg q3-monthly
  • Causes testosterone flare → cover with 1st-gen anti-androgen(Bicalutamide)

GnRH Antagonists

  • Degarelix: 280 mg induction → 80 mg q28 days
  • No flare | castration in ~3 days

Metastatic Prostate Cancer [all should be covered with ADT then …]

mCSPC

High volume (visceral mets OR ≥4 bone mets with ≥1 outside vertebrae/pelvis)

  • ADT + docetaxel OR 2nd-gen AR agent (Apalutamide,Enzalutamide,Darolutamide)

*CHAARTED: ADT + docetaxel benefit only in high-volume disease (OS +14 mo)

Low volume

  • ADT + 2nd-gen AR agent (Apalutamide,Enzalutamide,Darolutamide)
  • ± prostate radiation (STAMPEDE 2018 — OS benefit only in low-volume)

mCRPC

Definition: progression (PSA rise OR new mets OR progression of existing) despite castrate testosterone (<50 ng/dL or <1.7 nmol/L)

# No prior docetaxel

Prior 2nd-gen AROptions
NoADT + Docetaxel or Enzalutamide or Apalutamide, Radium-223 (asymp, no visceral, LN ≤3 cm)
YesADT + Docetaxel, Sipuleucel-T, Pembrolizumab (MMR/MSI-H), Olaparib/Rucaparib (BRCA2/HRR)

# Prior docetaxel

Prior 2nd-gen AROptions
NoADT + Cabazitaxel, Enzalutamide, Apalutamide, Radium-223, Sipuleucel-T
YesCabazitaxel, Radium-223, Sipuleucel-T, Pembrolizumab (MMR/MSI-H), Olaparib/Rucaparib (BRCA2/HRR)

nmCRPC

  • PSADT >10 months → observe
  • PSADT <10 months + LE >5 yr → ADT + AR-targeted therapy (Apalutamide / Enzalutamide / Darolutamide)

Bone Health in CRPC with Mets

  • Denosumab 120 mg SC q4wk OR Zoledronate 4 mg IV q4wk + Ca + vitamin D
  • Denosumab vs zoledronate: superior time-to-first SRE; no OS difference
  • Zoledronate contraindicated if CrCl <30; denosumab no renal adjustment
  • NOT approved for SRE prevention in mHSPC

Spinal Cord Compression

  • Emergency — MRI is diagnostic
  • ➡ Dexamethasone (10 mg load, 4 mg q6h) + RT ± surgical decompression
  • Surgery first if: unknown tissue dx, prior RT to area, pathological fracture with instability

Palliative RT for Bone Pain

  • Single fraction 800 cGy = preferred for uncomplicated non-spinal bone mets