STEPTRACKERREPRODUCTIVE + ONCOLOGY | PATHOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Prostate Carcinoma

The most common cancer in men — where it starts, how it's graded, why it goes to the spine, and how androgen blockade treats it.

FOCUS ON
Adenocarcinoma of the peripheral zone → hard nodule on DRE, often silent until advanced. Small glands with no basal cell layer, prominent nucleoli; Gleason score from architecture. Spreads to lumbar spine via Batson plexus → osteoblastic lesions, ↑ ALP. Treat with surgery, radiation, and androgen deprivation (GnRH agonists/antagonists, AR blockers, abiraterone).
TOPIC
MECHANISM · DETAILS
FEATURES
CLUE
Risk factors
Androgen-dependent growth; age, Black men, family history, BRCA2, HOXB13, Lynch
Rare before 50; most common cancer in men, 2nd leading cancer death
Castrated men don't get it
Location & presentation
Peripheral zone (posterior, palpable)
Usually asymptomatic; hard irregular nodule on DRE; urinary symptoms only when large; bone pain when metastatic
BPH is central (transition zone)
Precursor
High-grade prostatic intraepithelial neoplasia (PIN)
Atypical cells within ducts, basal layer still present
Basal cells lost → invasion
Histology
Small crowded infiltrating glands with a single cell layer (no basal cells), prominent nucleoli; perineural invasion
AMACR ⁺; p63 and high-molecular-weight keratin ⁻ (no basal cells)
TMPRSS2-ERG fusion, PTEN loss
Gleason grade
Grade by gland architecture, not nuclei; primary + secondary pattern (each 1–5)
Score 6–10, translated into Grade Groups 1–5
Higher score → worse prognosis
PSA
Serine protease that liquefies semen; prostate-specific, not cancer-specific
↑ in cancer, BPH, prostatitis, after ejaculation/instrumentation; ↓ free PSA fraction in cancer
Shared-decision screening 55–69 · monitors recurrence
Local & nodal spread
Seminal vesicles, bladder base (obstruction), rectum (Denonvilliers fascia limits)
Obturator and iliac lymph nodes
Seminal vesicle invasion = worse stage
Bone metastases
Through the valveless vertebral venous (Batson) plexus
Osteoblastic lesions in lumbar spine, pelvis; bone pain, ↑ ALP; risk of cord compression
Dense sclerotic lesions on X-ray
Local treatment
Radical prostatectomy or radiation; active surveillance for low grade
Prostatectomy risks: erectile dysfunction (cavernous nerves), incontinence
Low risk → watchful surveillance
Androgen deprivation
GnRH agonist (leuprolide, continuous) → downregulation; antagonist (degarelix); AR blockers (flutamide, bicalutamide, enzalutamide); CYP17 inhibitor (abiraterone)
Hot flashes, ↓ libido, gynecomastia, osteoporosis, metabolic syndrome
Agonist "flare" in first weeks → add AR blocker
Castration-resistant disease
AR amplification/mutation, intratumoral androgen synthesis
Rising PSA despite castrate testosterone
Enzalutamide, abiraterone, docetaxel, PARP inhibitors (BRCA)

Mechanism — androgen axis and its blockers

HypothalamusGnRH (pulsatile)
→
Pituitary LH
→
Leydig testosterone+ adrenal androgens (CYP17)
→
DHT → androgen receptor
→
Tumor growth, PSA

Continuous GnRH agonist → LH falls after an initial surge · degarelix blocks GnRH receptor (no flare) · abiraterone blocks CYP17 · flutamide/enzalutamide block the receptor.

Drugs at a glance

DRUG
TARGET
NOTE
Leuprolide (continuous)
GnRH receptor agonist
Initial testosterone flare
Degarelix
GnRH receptor antagonist
No flare
Flutamide, bicalutamide
Androgen receptor
Gynecomastia, hepatotoxicity
Enzalutamide
AR (also blocks nuclear entry)
Castration-resistant disease
Abiraterone
CYP17 (17α-hydroxylase)
Give with prednisone (↑ mineralocorticoid)
Finasteride
5α-reductase
Not a cancer treatment; ↓ PSA

How it's tested

COMMON CONFUSIONGleason is graded on gland architecture (patterns), not on nuclear atypia. Most cancers also differ from BPH by zone: peripheral vs transition.
THE TRAPProstate cancer bone metastases are osteoblastic — dense on X-ray with high ALP — not lytic. Lytic lesions point to myeloma, lung, kidney or thyroid.
YOUR APPROACHAge + race + family → DRE + PSA → biopsy (no basal cells, AMACR) → Gleason → spread (Batson plexus, osteoblastic) → treatment and its side effects.

If you see… think…

Older man with a hard posterior prostate nodule → prostate adenocarcinoma
Zone where prostate cancer arises → peripheral zone
Glands lacking basal cells, AMACR⁺ → prostate adenocarcinoma
Low back pain, ↑ ALP, sclerotic vertebrae in an older man → osteoblastic prostate metastases
Route of spread to lumbar spine → Batson vertebral venous plexus
Bone pain worsening in the first week of leuprolide → testosterone flare
GnRH antagonist with no flare → degarelix
CYP17 inhibitor for castration-resistant cancer → abiraterone
Gynecomastia on flutamide → androgen receptor blockade
Erectile dysfunction after radical prostatectomy → cavernous nerve injury