Interlesional response heterogeneity is associated with the prognosis of abiraterone treatment in metastatic castration-resistant prostate cancer.

Abstract

Interlesional response heterogeneity (ILRH) poses challenges to the treatment of metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no prospective clinical trials exploring the prognostic significance of ILRH on paired positron emission tomography/computed tomography (PET/CT) in the context of abiraterone therapy. In this prospective study, we enrolled patients with mCRPC treated with abiraterone (ClinicalTrials.gov: NCT05188911; ChiCTR.org.cn: ChiCTR2000034708). 68Ga-prostate-specific membrane antigen (PSMA)+18F-fluorodeoxyglucose (FDG) PET/CT and circulating tumor DNA (ctDNA) monitoring were performed at baseline and week 13. Patients were grouped by their early ILRH measurement. The primary endpoint was to evaluate the predictive role of ILRH for conventional progression-free survival (PFS) through the concordance index (C-index) assessment. Conventional PFS was defined as the time from medication to conventional radiographic progression, clinical progression, or death. Ultimately, 33 patients were included with a median follow-up of 28.7months. Baseline+week 13 PSMA PET/CT revealed that 33.3% of patients showed ILRH. Those patients with hetero-responding disease had significantly different PFS compared to the responding and non-responding groups (hazard ratio: responding group= reference, hetero-responding group= 4.0, non-responding group= 5.8; p<0.0001). The C-index of ILRH on paired PSMA PET/CT (0.742 vs. 0.660) and FDG PET/CT (0.736 vs. 0.668) for conventional PFS was higher than that of PSA response. In an exploratory analysis, PSMA-/FDG+ lesions at week 13 were identified as a strong surrogate for poor conventional PFS (p= 0.039). ILRH on both baseline+week 13 PSMA and FDG PET/CT strongly associated with conventional PFS. This study was funded by the Ministry of Science and Technology of China and Shanghai.