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University of Lynchburg Doctoral Project Assignment Repository

Specialty

Oncology

Advisor

Dr. Lawrence Herman

Abstract

This review assesses the validity of radiographic progression-free survival (rPFS) as a surrogate endpoint for overall survival (OS) in men with taxane-naive, prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who are candidates for 177Lu-PSMA-617 over a change in androgen receptor pathway inhibitor (ARPI) therapy. A literature search of PubMed and Google Scholar identified English-language, peer-reviewed clinical studies from 2021 through 2026 evaluating 177Lu-PSMA-617 in mCRPC, excluding single case reports and pre-clinical studies. Across three randomized trials (PSMAfore, VISION, and TheraP), 177Lu-PSMA-617 consistently slowed radiographic progression, with the taxane-naive PSMAfore trial meeting its primary endpoint of rPFS and delaying PSA progression over an ARPI change. Although intention-to-treat analysis showed no OS difference due to high control-group crossover, adjusting for crossover using inverse probability of censoring weighting (IPCW) revealed a significant OS benefit with 177Lu-PSMA-617 (hazard ratio 0.59; 95% confidence interval, 0.38–0.91). Furthermore, 177Lu-PSMA-617 extended OS in post-taxane patients in VISION and improved PSA response and disease progression against cabazitaxel, without an OS difference in TheraP. Radiographic progression-free survival is a reasonable surrogate for OS in this population, where crossover prevented a clean OS comparison, but it is not equivalent to OS. This supports 177Lu-PSMA-617 as a treatment option for men wishing to delay chemotherapy, keeping taxane-based therapy available for later use.

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