(UroToday.com) The 2026 ASTRO Multidisciplinary Radiopharmaceutical Therapy Symposium featured a plenary session and a presentation by Dr. Mohammad Ganiyani discussing safety and efficacy of 177Lu-PSMA-617 versus established therapies in metastatic castration resistant prostate cancer (mCRPC). 177Lu-PSMA-617 delivers targeted β-radiation to prostate cancer cells, offering a distinct mechanism beyond androgen-signaling inhibition in mCRPC. Additionally, pivotal trials such as VISION [1] and Enza-P [2-3], have shown an overall survival benefit with 177Lu-PSMA-617, whereas other trials have only shown a progression free survival benefit with favorable tolerability. As its clinical use expands, comparative evidence with established systemic therapies remains limited. This meta-analysis presented by Dr. Ganiyani evaluated the pooled efficacy and safety outcomes.
This study included a systematic review and meta-analysis performed according to PRISMA guidelines to evaluate 177Lu-PSMA-617 in mCRPC. Of 456 studies screened, seven met eligibility criteria and were included in the final analysis. The selection criteria for the systematic review is as follows:
Data on progression free survival, overall survival, and grade ≥3 adverse events were extracted and pooled using a random-effects model (REML method). Hazard ratios (HRs) and risk ratios with 95% confidence intervals were calculated, heterogeneity was assessed using the I² statistic, and publication bias was evaluated using both Egger’s regression and Begg’s rank correlation.
Overall, a total of 2,526 patients from 7 randomized trials were analyzed, including 1,365 in the 177Lu-PSMA-617 arms and 1,161 in the standard of care arms. The pooled mean age was 71.2 years, including 70.8 years in the 177Lu-PSMA-617 arm and 71.8 years in the standard of care arm. A breakdown of age for each clinical trial is highlighted in the following table:
177Lu-PSMA-617 significantly improved progression free survival compared with the control group (pooled HR 0.64, 95% CI 0.50–0.81; p < 0.001):
No significant difference was observed in overall survival (HR 0.91, 95% CI 0.66–1.25; p = 0.55):
Finally, the pooled risk ratio for grade ≥ 3 adverse events was 0.98 (95% CI 0.83–1.14; p = 0.75):
However, in a pooled analysis of individual grade ≥ 3 adverse events, thrombocytopenia had a pooled risk ratio of 5.79 (95% CI 2.14-15.65, p = 0.0005) for 177Lu-PSMA-617:
By both method assessments, there was no small study effects or publication bias for any of the outcomes.
Dr. Ganiyani concluded his presentation discussing safety and efficacy of 177Lu-PSMA-617 versus established therapies in mCRPC with the following take-home points:
- 177Lu-PSMA-617 has a 36% relative reduction in risk of progression versus standard therapies in mCRPC
- There was no confirmed overall survival benefit in pooled analysis
- There was no significant difference in overall grade ≥3 toxicities between 177Lu-PSMA-617 and standard therapies. However, thrombocytopenia emerged as the primary hematologic toxicity, highlighting the need for careful baseline marrow assessment and close platelet monitoring during therapy
Presented by: Mohammad A. Ganiyani, MD, Miami Cancer Institute, Baptist Health South Florida, Miami, FL
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 American Society for Radiation Oncology (ASTRO) Multidisciplinary Radiopharmaceutical Therapy Symposium, Palm Desert, CA, Tues, Feb 17 – Wed, Feb 18, 2026.
References:
- Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.
- Emmett L, Subramaniam S, Crumbaker M, et a. [177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): An open-label, multicentre, randomized, phase 2 trial. Lancet Oncol. 2024 May;25(5):563-571.
- Emmett L, Subramaniam S, Crumbaker M, et al. Overall survival and quality of life with [177Lu]Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer (ENZA-p): Secondary outcomes from a multicentre, open-label, randomized, phase 2 trial. Lancet Oncol. 2025 Mar;26(3):291-299.