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

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 [¹⁷⁷Lu]Lu-PSMA-617 predicted treatment response and mean survival.

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%), stable PSA (-10% ≤ dPSA ≤ + 10%) and relevant PSA increase (dPSA > 10%), along with evaluation of biochemical therapy outcome according to the Prostate-Cancer-Working-Group (PCWG3).

Two days after the first [177Lu]Lu-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).

Compared to those with increased PSA levels, patients with decreased or stable PSA levels two days after the first [¹⁷⁷Lu]Lu-PSMA-617 RLT cycle were more likely to have favorable biochemical response according to PCWG3 criteria and presented with a longer overall survival.