Prostate Cancer

Prostate cancer is the most common non-skin cancer in American men and the second leading cause of cancer death. It arises from glandular cells of the prostate and ranges from slow-growing, low-grade disease (often managed without immediate treatment) to aggressive, high-grade tumors that metastasize to bone and lymph nodes. The American Cancer Society estimates approximately 300,000 new diagnoses and 35,000 deaths annually in the U.S. The Gleason grading system (now expressed as Grade Groups 1–5) and genomic risk tools guide treatment decisions. PSA (prostate-specific antigen) testing remains the cornerstone of early detection, despite ongoing debate about overdiagnosis of indolent tumors.

• Difficulty starting or stopping urination
• Weak or interrupted urine stream
• Frequent urination, especially at night (nocturia)
• Pain or burning during urination
• Blood in urine or semen (hematuria or hematospermia)
• Painful ejaculation
• Deep bone pain — hip, back, pelvis — which may indicate metastatic disease
• Note: early-stage prostate cancer is frequently asymptomatic

Prostate-specific antigen (PSA) blood testing is the primary screening tool. The USPSTF recommends shared-decision PSA screening for men aged 55–69. For Black men, ACS, AUA, and NCCN recommend initiating the screening conversation at age 40. Baseline PSA at 40 helps identify men with elevated risk trajectories. Digital rectal exam (DRE) adds modest additional detection when combined with PSA. Genomic biomarkers (4Kscore, SelectMDx, PHI) can refine biopsy decisions when PSA is in the borderline range (4–10 ng/mL). Family history of prostate cancer or BRCA2 mutation in any first-degree relative is an indication for earlier, more frequent screening.

Treatment is stage- and grade-dependent. Active surveillance (with regular PSA testing, MRI, and repeat biopsy) is appropriate for Grade Group 1 and selected Grade Group 2 low-volume disease. Radical prostatectomy and external beam radiation therapy (EBRT) or brachytherapy are equivalent curative options for localized disease; choice depends on patient anatomy, continence, and preference. For high-risk localized disease, radiation plus androgen deprivation therapy (ADT) is standard. Metastatic hormone-sensitive prostate cancer is treated with ADT plus docetaxel plus an androgen receptor pathway inhibitor (darolutamide, enzalutamide, or abiraterone) per ARASENS and PEACE-1 trial data. Olaparib and rucaparib (PARP inhibitors) are approved for BRCA-mutated metastatic castration-resistant prostate cancer. Lutetium-177-PSMA-617 (Pluvicto) is FDA-approved for PSMA-positive metastatic castration-resistant disease.