Prostate Cancer

The answer first

Prostate cancer is the second most commonly diagnosed cancer in men worldwide and a leading cause of cancer death. Most cases are localised at presentation and are either low-risk (managed by active surveillance) or localised/locally advanced (managed by radical prostatectomy, radiotherapy with or without androgen deprivation therapy, or in select older/frail men, watchful waiting). Metastatic disease is treated by combinations of androgen deprivation therapy and androgen-receptor pathway inhibitors or docetaxel (hormone-sensitive) and by sequential androgen-receptor pathway inhibitors, chemotherapy, radium-223, olaparib (BRCA-mutated) and Lu-PSMA (castration-resistant). ^[1]

A physician-level answer rests on four pillars. ^[1]

1. Apply a shared-decision PSA screening strategy — the 2018 USPSTF recommendation is individualised decision-making in men aged 55 to 69 (C recommendation) and against screening in men 70 and older (D recommendation); discuss benefits (1 in 1000 prostate-cancer-specific mortality benefit over 10 to 15 years) versus harms (overdiagnosis, biopsy complications, treatment-related sexual, urinary and bowel dysfunction). ^[1]
2. Risk-stratify every newly diagnosed case using prostate MRI, PI-RADS scoring, targeted biopsy and the ISUP grade group — low-risk disease (grade group 1, PSA below 10, clinical T1–T2a) is best managed by active surveillance; intermediate- and high-risk disease warrants definitive local therapy with or without androgen deprivation. ^[2]
3. Recognise and prevent the complications of androgen deprivation therapy — hot flushes, sexual dysfunction, gynaecomastia, metabolic syndrome, type 2 diabetes, cardiovascular events, osteoporotic fracture, sarcopenia, depression and cognitive change; baseline bone density, cardiovascular risk assessment, exercise prescription, smoking cessation, bone-protection (calcium, vitamin D, bisphosphonate or denosumab), and metabolic monitoring are part of every ADT prescription. ^{[6] [7]}
4. Sequence systemic therapy by disease state in metastatic disease — for hormone-sensitive disease add docetaxel (CHAARTED/STAMPEDE) or an androgen-receptor pathway inhibitor (abiraterone, enzalutamide, apalutamide) to androgen deprivation therapy; for castration-resistant disease use androgen-receptor pathway inhibitors, docetaxel, cabazitaxel, radium-223 for symptomatic bone-only disease, olaparib for BRCA1/2-mutated disease, and Lu-PSMA-617 for PSMA-avid taxane-pretreated disease. ^{[8] [9] [10]}

DWE high-yield: The single most-tested rule in newly diagnosed low-risk prostate cancer is active surveillance, not immediate treatment. Grade group 1 (Gleason 3+3) prostate cancer has a 10-year cancer-specific survival above 99 percent on active surveillance, and the harms of immediate surgery or radiotherapy (incontinence, erectile dysfunction, bowel toxicity) outweigh any benefit. ^{[3] [4]}

References12ShowHide

1. [1]Grossman DC, Curry SJ, Owens DK, et al. Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. JAMA, 2018.PMID 29801017
2. [2]Burk KS, Naik S, Lacson R, et al. MRI-Targeted, Systematic, or Combined Biopsy for Detecting Clinically Significant Prostate Cancer. J Am Coll Radiol, 2023.PMID 37315913
3. [3]Tosoian JJ, Mamawala M, Epstein JI, et al. Active Surveillance of Grade Group 1 Prostate Cancer: Long-term Outcomes from a Large Prospective Cohort. Eur Urol, 2020.PMID 31918957
4. [4]Newcomb LF, Schenk JM, Zheng Y, et al. Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer. JAMA, 2024.PMID 38814624
5. [5]Hamdy FC, Donovan JL, Lane JA, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med, 2016.PMID 27626136
6. [6]Allan CA, Collins VR, Frydenberg M, et al. Androgen deprivation therapy complications. Endocr Relat Cancer, 2014.PMID 24872511
7. [7]Magee DE, Singal RK Androgen deprivation therapy: indications, methods of utilization, side effects and their management. Can J Urol, 2020.PMID 32101695
8. [8]Vale CL, Fisher DJ, Godolphin PJ, et al. Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials. Lancet Oncol, 2023.PMID 37414011
9. [9]Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med, 2013.PMID 23863050
10. [10]de Bono J, Mateo J, Fizazi K, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med, 2020.PMID 32343890
11. [11]de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med, 2019.PMID 31566937
12. [12]Tombal B, Choudhury A, Saad F, et al. Enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer: results of the EORTC 1333/PEACE-3 trial. Ann Oncol, 2025.PMID 40450503