Decoding the Top Moments in Prostate Cancer From 2025

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, wound the clock back to 2025 to discuss the key findings and clinical developments that may propel the genitourinary oncology field forward. Following a breakdown of last year’s breakthroughs in kidney cancer and bladder cancer care, the hosts reviewed the biggest headlines and milestones of 2025 related to prostate cancer management and research.

Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. Together, they spoke about several major prostate cancer happenings throughout 2025, including but not limited to:

1. The FDA Approval of the Phase 3 ARANOTE Trial (NCT04736199) Regimen
   1. In June 2025, the FDA approved darolutamide (Nubeqa) for patients with metastatic castration-sensitive prostate cancer (CSPC) based on findings from the phase 3 ARANOTE trial.¹
   2. Topline data showed a median radiographic progression-free survival (rPFS) that was not reached (NR) with darolutamide vs 25 months (95% CI, 19-NR) with placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).
   3. This approval may grant easier access to darolutamide, especially for the treatment of patients who are older or who present with certain neurocognitive disorders.
2. The FDA Approval of the Phase 3 AMPLITUDE Trial (NCT04497844) Regimen
   1. December 2025 saw the FDA approval of niraparib and abiraterone acetate (Akeega) plus prednisone for adults with suspected or deleterious BRCA2-mutated CSPC.²
   2. Supporting data from the phase 3 AMPLITUDE trial showed a median rPFS that was not estimable (NE; 95% CI, 41 months-NE) in the niraparib arm vs 26 months (95% CI, 18-28) in the placebo arm among 323 patients with BRCA2-mutated disease.
   3. This approval for patients with BRCA2-mutations reinforces the importance of conducting upfront genetic testing.
3. Phase 3 PSMAddition Trial (NCT04720157)
   1. Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) significantly prolonged rPFS vs ARPI/ADT treatment alone among patients with prostate specific-membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (HR, 0.72; 95% CI, 0.58-0.90; P = .002).³
   2. Other data from ESMO Congress 2025 showed that the lutetium Lu 177 combination numerically improved the overall response rate at 85.3% (95% CI, 79.9%-89.6%) vs 80.8% (95% CI, 74.8%-85.8%) in the control arm.
   3. The safety profile observed in the trial may raise questions over whether it is worthwhile to administer all 6 cycles of lutetium Lu 177 to patients.

References

1. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. News release. FDA. June 3, 2025. Accessed January 20, 2026. https://tinyurl.com/yhde24zj
2. FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. News release. FDA. December 12, 2025. Accessed January 20, 2026. https://tinyurl.com/rcxaj98
3. Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Ann Oncol. 2025;36(suppl 2):S1627-S1628. doi:10.1016/j.annonc.2025.09.101