Prostate Cancer Clinical Trials: Landmark Studies & Key Findings

Why are clinical trials important?

Clinical trials are the foundation of evidence-based medicine. Landmark trials have transformed prostate cancer treatment by:

• Establishing new standards of care
• Identifying ineffective or harmful treatments (e.g., SELECT trial)
• Improving survival and quality of life
• Personalising therapy (biomarker-driven trials)

STAMPEDE trial – multi-arm, multi-stage

The STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trial is a landmark multi-arm, multi-stage platform trial that has changed practice multiple times.

Key findings:

• Arm C (Abiraterone + ADT): Improved overall survival in mHSPC (HR 0.63, 5-year OS 60% vs. 41%) – standard of care
• Arm G (Abiraterone + ADT + enzalutamide): No benefit, increased toxicity – not recommended
• Arm J (Docetaxel + ADT): Improved survival in mHSPC (consistent with CHAARTED)
• Arm K (Metformin + ADT): No benefit

Impact:

• Established abiraterone + ADT as standard for mHSPC
• Demonstrated that triple therapy (ADT + abiraterone + enzalutamide) is harmful

CHAARTED trial – docetaxel for mHSPC

The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease) trial established docetaxel + ADT as standard for high-volume mHSPC.

Design:

• 790 men with mHSPC randomised to ADT vs. ADT + docetaxel (6 cycles)
• Stratified by disease volume (high vs. low)

Key findings:

• High-volume disease: Median OS 51.2 vs. 34.4 months (HR 0.63) – significant benefit
• Low-volume disease: No significant OS benefit (63.5 vs. 61.2 months)

Impact:

• Docetaxel + ADT became standard for high-volume mHSPC
• Low-volume mHSPC patients do not routinely receive docetaxel

LATITUDE and TITAN trials – abiraterone and apalutamide for mHSPC

LATITUDE trial (abiraterone):

• 1,199 men with high-risk mHSPC randomised to ADT vs. ADT + abiraterone + prednisone
• Median OS: 53.3 vs. 36.5 months (HR 0.66)
• Established abiraterone + ADT as standard for high-risk mHSPC

TITAN trial (apalutamide):

• 1,052 men with mHSPC (any risk) randomised to ADT vs. ADT + apalutamide
• Median OS: NR vs. 52.2 months (HR 0.67)
• Established apalutamide + ADT as standard for all mHSPC

PROfound trial – PARP inhibitors for HRR-mutated mCRPC

The PROfound trial was the first biomarker-driven trial to show benefit of a targeted therapy (PARP inhibitor) in prostate cancer.

Design:

• 387 men with HRR-mutated mCRPC (BRCA1/2, ATM, PALB2, etc.) progressed on abiraterone/enzalutamide
• Randomised to olaparib vs. physician's choice (abiraterone or enzalutamide)

Key findings:

• BRCA-mutated subgroup: Median rPFS 9.8 vs. 3.0 months (HR 0.22)
• Overall HRR-mutated: Median OS 19.1 vs. 14.7 months (HR 0.69)

Impact:

• Olaparib approved for HRR-mutated mCRPC after ARPI failure
• Rucaparib also approved
• Genetic testing became standard for metastatic prostate cancer

VISION trial – Lu-177-PSMA for mCRPC

The VISION trial established Lu-177-PSMA-617 (Pluvicto) as a new standard for PSMA-positive mCRPC.

Design:

• 831 men with PSMA-positive mCRPC after ARPI and taxane chemotherapy
• Randomised to Lu-177-PSMA + best standard of care vs. best standard of care alone

Key findings:

• Median OS: 15.3 vs. 11.3 months (HR 0.62)
• Median rPFS: 8.7 vs. 3.4 months (HR 0.40)

Impact:

• Lu-177-PSMA approved for PSMA-positive mCRPC after ARPI and taxane
• Theranostics (diagnostic PSMA PET + therapeutic Lu-177-PSMA) is now standard

SELECT trial – vitamin E and selenium (negative)

The SELECT (Selenium and Vitamin E Cancer Prevention Trial) is a landmark negative trial that disproved the benefits of these supplements.

Design:

• 35,533 men randomised to vitamin E, selenium, both, or placebo
• Stopped early due to futility and potential harm

Key findings:

• No reduction in prostate cancer risk (selenium or vitamin E)
• Vitamin E alone: 17% increased risk of prostate cancer (statistically significant)
• Selenium: Increased risk of diabetes

Impact:

• Vitamin E and selenium are NOT recommended for prostate cancer prevention
• Highlights importance of large, randomised trials before recommending supplements

ProtecT trial – active surveillance vs. surgery vs. radiation

The ProtecT (Prostate Testing for Cancer and Treatment) trial compared active monitoring, surgery, and radiation for localized prostate cancer.

Design:

• 1,643 men with localized prostate cancer (mostly low-risk) randomised to active monitoring, radical prostatectomy, or radiation
• Median follow-up: 10 years

Key findings:

• Prostate cancer mortality: No difference between groups (1% overall)
• Metastasis: Higher in active monitoring (6% vs. 3% for surgery/radiation)
• Side effects: Surgery (ED, incontinence); radiation (bowel, urinary)

Impact:

• Confirmed active surveillance is safe for low-risk prostate cancer
• Treatment decisions should consider patient preferences and side effect profiles

EMBARK trial – enzalutamide for high-risk BCR

The EMBARK trial established enzalutamide as a new option for high-risk biochemical recurrence (BCR).

Design:

• 1,068 men with high-risk BCR after radical prostatectomy (PSADT <9 months)
• Randomised to enzalutamide, enzalutamide + ADT, or placebo + ADT

Key findings:

• Enzalutamide + ADT improved metastasis-free survival vs. ADT alone (HR 0.42)
• Enzalutamide alone also improved MFS vs. ADT alone (HR 0.63)

Impact:

• Enzalutamide (with or without ADT) is an option for high-risk BCR
• First positive trial for systemic therapy in BCR

Interactive FAQ – Prostate cancer clinical trials

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Disclaimer: This information is for educational purposes and intended for clinicians and researchers. Clinical trial results should be interpreted in context.