Highlighting the NCI’s working group on biochemically recurrent prostate cancer for clinical trial considerations

Abstract

. Biochemically recurrent prostate cancer (BCR) represents a common clinical challenge following definitive local therapy. While traditionally defined by rising prostate-specific antigen (PSA) levels in the absence of metastatic disease on conventional imaging, the advent of prostate-specific membrane antigen (PSMA) PET has reshaped disease detection. PSMA imaging frequently identifies low-volume, subclinical disease not previously classified as metastatic, raising concerns about overtreatment and inappropriate extrapolation from metastatic castration-sensitive prostate cancer (mCSPC) paradigms. A National Cancer Institute Working Group convened in November 2024 to establish a framework for clinical trial development in this evolving landscape. The group proposed the term PSMA-positive BCR to distinguish this largely indolent disease state from mCSPC, emphasized the importance of paired conventional imaging, and highlighted PSA doubling time as a risk stratification tool. Given favorable long-term outcomes and limited symptoms, future trials should prioritize treatment de-escalation, novel end-points such as treatment-free survival, and improved quality-of-life measures.