prostate cancer
Prostate cancer trials now span the full disease spectrum from localized low-risk disease (active surveillance vs. focal therapy) to metastatic castration-resistant prostate cancer (mCRPC), where novel AR pathway inhibitors, PARP inhibitors for BRCA-mutated tumors, and radioligand therapies (PSMA-lutetium) have changed the treatment landscape.
Current trials evaluate darolutamide combinations, PSMA-directed radioligand therapy (177Lu-PSMA-617) in earlier disease settings, bispecific antibodies targeting PSMA and CD3, and CRISPR-based gene editing approaches. PSA decline, rPFS, and overall survival remain primary endpoints, with ctDNA and PSMA-PET emerging as early response biomarkers.
Disease Burden & Epidemiology
Prostate cancer is the most common non-skin cancer and the second leading cause of cancer death in men in the United States. The American Cancer Society estimates approximately 299,000 new diagnoses and 35,000 deaths in the US annually. Globally, prostate cancer is the second most commonly diagnosed cancer in men, with approximately 1.4 million new cases per year. Incidence is strongly age-dependent: the median age at diagnosis is 67, and more than 60% of cases are diagnosed in men aged 65 and older. Risk is substantially higher in Black men, who have a 1.7-fold greater incidence rate and 2.1-fold greater mortality rate than white men β€” disparities driven by both biological and socioeconomic factors. Approximately 85% of prostate cancers are localized or regional at diagnosis, associated with an essentially 100% five-year survival rate; however, metastatic disease carries a five-year survival rate of approximately 32%. The rise of PSMA-PET imaging has transformed staging precision, and germline testing for BRCA1/2, ATM, and CDK12 mutations is now recommended for all patients with metastatic disease due to therapeutic implications.
Key Research Trends & Landmark Studies
The VISION trial established 177Lu-PSMA-617 (lutetium vipivotide tetraxetan, Pluvicto) as the first radioligand therapy for PSMA-positive mCRPC, demonstrating a 38% reduction in risk of death versus best supportive care plus standard of care and achieving FDA approval in 2022. The PROfound trial showed that olaparib (PARP inhibitor) doubled radiographic progression-free survival in mCRPC patients with homologous recombination repair gene mutations (BRCA1/2, ATM), establishing germline and somatic testing as a treatment-guiding standard. The ARAMIS trial demonstrated darolutamide plus ADT as superior to ADT alone in non-metastatic CRPC, while ARASENS showed the darolutamide/docetaxel/ADT triplet combination as a new standard for metastatic hormone-sensitive prostate cancer. Currently active trials include PSMAddition (lutetium in hormone-sensitive disease), TALAPRO-3 (talazoparib plus enzalutamide in HRR-mutated hormone-sensitive disease), and multiple bispecific T-cell engager (BITE) antibody studies in mCRPC.
Patient Guide: How to Find & Join a Trial
Men with newly diagnosed prostate cancer should request complete molecular characterization before initiating treatment: Gleason grade group, clinical stage, PSA density, and ideally genomic risk classification (Oncotype DX GPS, Decipher, Polaris) for localized disease. For metastatic disease, germline genetic testing for BRCA1/2, ATM, CDK12, and MLH1/MSH2 is recommended for all patients and determines eligibility for PARP inhibitor and immunotherapy trials. PSMA-PET/CT imaging is increasingly available and should be requested before treatment initiation to accurately assess disease extent β€” PSMA expression is also required for lutetium radioligand therapy trials. Academic urology and genitourinary oncology programs at comprehensive cancer centers offer the broadest trial access; community urology practices increasingly participate in sponsored trials and can screen patients locally. Patients on active surveillance for low-risk localized disease may also qualify for chemoprevention and lifestyle intervention trials.