Prompt PSA changes as a prognostic marker for response to PSMA-radioligand therapy.

Introduction We investigated whether prompt changes in prostate-specific-antigen (PSA) levels within two days after the first cycle of prostate-specific-membrane-antigen radioligand therapy (PSMA-RLT) with 177LuLu-PSMA-617 predicted treatment response and mean survival. Methods In a retrospective study of 76 metastatic castration resistant prostate cancer (mCRPC) patients, we evaluated pretreatment PSA-values and their relative changes in PSA (dPSA) two days later. We tested for correlations between dPSA with long-term biochemical response (BCR) to treatment, using a priori criteria for relevant PSA decrease (dPSA 10%), along with evaluation of biochemical therapy outcome according to the Prostate-Cancer-Working-Group (PCWG3). Results Two days after the first 177LuLu-PSMA-617 cycle, 32 (42%) of the patientsshowed PSA decrease, of whom 19 (59%) had experienced a partial response according toPCWG3 criteria. Of the 37 patients with stable PSA, 17 (46%) showed partial response totreatment according to PCWG3 criteria. Among the seven patients with PSA increase, three(43%) showed partial response. Pearson correlation analysis showed statistically significantcorrelations between dPSA on day 2 and relative Nadir for the first two treatment cycles.Patients with PSA decrease or stable PSA compared to those with an increase of PSA two daysafter cycle 1 lived longer on average (399, 405 and 225 days, respectively). Conclusion Compared to those with increased PSA levels, patients with decreased or stable PSA levels two days after the first 177LuLu-PSMA-617 RLT cycle were more likely to have favorable biochemical response according to PCWG3 criteria and presented with a longer overall survival.