Benign and Malignant Diseases of the Prostate¶

Oncology and Hematology | Part 4 – Oncology: Solid Tumors · Part 4 – Oncology: Solid Tumors · Chapter 92

Key Clinical Points¶

PSA is kallikrein-related peptidase 3 (KLK3); levels rise in BPH, prostatitis, or cancer.
USPSTF recommends individualized screening for ages 55–69; no screening for ≥70.
AUA suggests starting at age 40–45 for high-risk groups (Black ancestry, germline mutations, strong family history).
Gleason grading sums two patterns (1–5) to a total score of 6–10; Grade Groups (1–5) clarify risk levels.
TNM Staging: T1 (inapparent), T2 (confined), T3 (extracapsular/seminal vesicle), T4 (adjacent structures).
Active surveillance is for low-risk tumors (Grade Group 1) with >10-year life expectancy.
PSADT <3 months indicates high risk for future clinically relevant events.
PSMA PET scans are superior to conventional imaging for detecting metastases in intermediate/high-risk cases.
Neoadjuvant hormonal therapy alone does not improve outcomes for surgically treated patients.
Local/Regional disease (T1–T4 without metastasis) has a 100% 5-year survival rate; Distant disease (T4 with metastasis) has a 30% 5-year survival rate.

DEFINITION & CLASSIFICATION¶

• Scope: Includes conditions from benign prostatic hyperplasia (BPH) to localized and metastatic prostate cancer. • Anatomy: Prostate is a pelvic gland adjacent to rectum, bladder, and urinary sphincter; contains tubuloalveolar glands in lobules with fibromuscular stroma. • PSA Definition: > Definition (Harrison's 22e): PSA (kallikrein-related peptidase 3; KLK3) is a kallikrein-related serine protease that causes liquefaction of seminal coagulum. • PSA Dynamics: Produced in epithelial cells; circulates as inactive complexes with α-antichymotrypsin or free PSA. • Free PSA: Lower levels correlate with higher cancer likelihood at biopsy.

Anatomy and Physiology¶

• Transition Zone: Periurethral zone expands during puberty and after age 55 due to nonmalignant growth. • Peripheral Zone: Site of most cancers; may or may not be palpable on DRE.

EPIDEMIOLOGY¶

• Mortality Ratio: High incidence/mortality ratio; most diagnosed men do not die from the disease. • Genetic Risk: ◦ Family History: Risk increases 2.5× with first-degree family history. ◦ Mutations: BRCA2, HOXB13, ATM, and PALB2 mutations increase risk. ◦ GWAS: >100 susceptibility loci identified (up to 25% of risk). • Ethnicity: African-American patients have higher incidence and more aggressive cancers. • Environmental Factors: ◦ Risk factors: High dietary fat (α-linoleic acid, polycyclic aromatic hydrocarbons). ◦ Protective factors: Lycopene and statins.

ETIOLOGY & PATHOPHYSIOLOGY¶

• Androgen Dependence: Prostate cancer is androgen-dependent; cells express androgen receptors (ARs). • Mechanism: Testosterone converted to dihydrotestosterone (DHT) by 5α-reductase. • Histology: >95% are adenocarcinomas; rare types include squamous or transitional cell tumors.

Gleason Grading System¶

• Grading Logic: Based on dominant and secondary patterns scored 1–5 (well to undifferentiated), summed for total score 6–10. • Grade Group Classification: ◦ Grade Group 1: Gleason ≤6 ◦ Grade Group 2: 3+4=7 ◦ Grade Group 3: 4+3=7 ◦ Grade Group 4: Gleason 8 ◦ Grade Group 5: Gleason 9–10 • Clinical Utility: Prevents misinterpretation of Gleason 6 as intermediate risk.

CLINICAL FEATURES¶

• Benign Diseases: Characterized by bladder outlet obstruction symptoms vs. intervention risks. • Malignancies: Balance between cancer significance and treatment risks. • DRE Findings: 20–25% of abnormal DRE cases are prostate cancer; tumors appear hard, nodular, and asymmetric. • Prostatitis: Requires antibiotics before biopsy if symptomatic.

Screening Controversies¶

• USPSTF Guidelines: ◦ Age 55–69: Individualized decision-making. ◦ Age ≥70: No screening recommended. • AUA Guidelines: ◦ Age 40–45: Offer for high-risk (Black ancestry, germline mutations, strong family history). ◦ Age 50–69: Offer every 2–4 years. • Exclusion: No rationale for PSA screening in asymptomatic patients with short life expectancy.

DIFFERENTIAL DIAGNOSIS¶

• BPH: Induration may be due to BPH or calculi. • Prostatitis: Requires antibiotics before biopsy in symptomatic cases. • Metastatic Disease: Bladder/colon cancers may invade via direct extension. • Other Tumors: Rare histologies include squamous, transitional cell, carcinosarcoma, and small-cell.

DIAGNOSTIC APPROACH¶

Initial Assessment: Evaluate symptoms, DRE, or elevated PSA.
Risk Stratification: Consider genetic risk and family history.
Imaging (mpMRI): ◦ PI-RADS 1–2 → avoid biopsy ◦ PI-RADS 3–5 → targeted biopsy
Biopsy: Perform extended-pattern 12-core biopsy if indicated.
Pathology Review: Evaluate Gleason score and Grade Group.
Staging: Utilize TNM system to determine extent of disease.
Risk Categorization: Determine risk category for treatment planning.

• PSA Criteria: ◦ >90% of cancers identified at PSA ≥4 ng/mL. ◦ No absolute cutoff exists where cancer risk is zero.

• Advanced Imaging: ◦ PSMA PET: FDA-approved for intermediate- and high-risk; superior to conventional imaging for metastases.

TNM Staging System¶

• T1 (Localized): Clinically inapparent. ◦ T1a: <5% of resected tissue. ◦ T1b: >5% of resected tissue. ◦ T1c: Identified by needle biopsy (e.g., elevated PSA). • T2 (Localized): Confined within prostate. ◦ T2a: ≤ half of one lobe. ◦ T2b: >half of one lobe, not both. ◦ T2c: Both lobes. • T3 (Local Extension): ◦ T3a: Extracapsular extension. ◦ T3b: Seminal vesicle invasion. • T4 (Local Extension): Fixed or invades adjacent structures (e.g., bladder, rectum). • N1: Positive regional lymph nodes. • M1: Distant metastases.

Reference Table 92-1 for full TNM Classification.

MANAGEMENT & TREATMENT¶

Determine Clinical Status: Assess if disease is localized or advanced.
Localized Disease Management: ◦ Active Surveillance: For Grade Group 1 with >10-year life expectancy. ◦ Radical Prostatectomy: For Gleason 7+ with >10-year life expectancy; goal is clear margins and preservation of continence/potency. ◦ Radiation Therapy: IMRT or proton beam. → Dose 78 Gy: Associated with higher local control. → Dose 81 Gy: Better PSA control but increased toxicity risk.
Advanced Disease Management: ◦ Hormonal Therapy: Standard for metastatic disease; neoadjuvant use alone not shown to improve outcomes for surgical patients. ◦ Imaging Guidance: PSMA PET used to guide detection of metastases (superior to bone scintigraphy for lymph nodes).

Brachytherapy¶

• Procedure: Implantation of radioactive sources for localized irradiation.

PROGNOSIS & COMPLICATIONS¶

• Risk Indicators: ◦ Gleason score. ◦ PSADT: <3 months → high risk of mortality. • Survival Rates (Figure 92-2): ◦ Local/Regional Disease (T1–T4 without metastasis) → 100% 5-year survival. ◦ Distant Disease (T4 with metastasis) → 30% 5-year survival. • Complications: Urinary incontinence, erectile dysfunction, bowel issues from surgery or radiation.

Survival and Outcomes¶

• Localized Disease: >90% 5-year survival rate. • Metastatic Disease: ~30% 5-year survival rate.

SPECIAL POPULATIONS¶

• Genetic Counseling: Recommended for mutations in BRCA2, HOXB13, ATM, or PALB2. • Risk Scoring: Consideration of polygenic risk scores in high-risk populations. • Cultural Factors: Address disparities in screening uptake (e.g., African-American population).

KEY PEARLS & HIGH-YIELD POINTS¶

• PSA Utility: Not a definitive cancer marker; 90% of men with PSA >2 ng/mL do not die from prostate cancer. • mpMRI Role: Reduces unnecessary biopsies while identifying clinically significant cancers. • Grade Group Advantage: Prevents mislabeling Gleason 6 as intermediate risk. • PSADT Threshold: <3 months is a critical threshold for high-risk clinical events.

Reference Tables¶

TABLE 92-1 TNM Classification TNM (tumor, node, metastasis) Staging System for Prostate Cancer a Tx T0 Localized…¶

Harrison's 22e, p.698

TNM (tumor, node, metastasis) Staging System for Prostate Cancera
Tx	Primary tumor cannot be assessed
T0	No evidence of primary tumor
Localized Disease
Local Extension
T3	Tumor extends through the prostate capsulec
T3a	Extracapsular extension (unilateral or bilateral)
T3b	Tumor invades seminal vesicles
T4	Tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall
Metastatic Disease

TABLE 92-2 AUA Symptom Index¶

Harrison's 22e, p.703

QUESTIONS TO BE ANSWERED	AUA SYMPTOM SCORE (CIRCLE 1 NUMBER ON EACH LINE)
	NOT AT ALL	LESS THAN 1 TIME IN 5	LESS THAN HALF THE TIME	ABOUT HALF THE TIME	MORE THAN HALF THE TIME	ALMOST ALWAYS
	0+	1	2	3	4
Over the past month, how often have you had to urinate again less than 2 h after you finished urinating?	0	1	2	3	4	5
	0	1	2	3	4
Over the past month, how often have you found it difficult to postpone urination?	0	1	2	3	4	5
	0	1	2	3	4
Over the past month, how often have you had to push or strain to begin urination?	0	1	2	3	4	5
	(None)	(1 time)	(2 times)	(3 times)	(4 times)
Sum of 7 circled numbers (AUA Symptom Score): ____