Prognostic importance of prostatic specific antigen response in patients who received Lutetium-177 prostate-specific membrane antigen treatment for castration resistant prostate cancer.

Abstract

This study aims to analyze the prognostic importance of serum prostate specific antigen (PSA) response in patients who received radioligand therapy (RLT) with Lu-177 Prostate-specific membrane antigen (PSMA) for their castration-resistant prostate cancer. Thirty consecutive patients who received Lu-177 PSMA treatment for their castration-resistant prostate carcinoma were included. All the patients had undergone Ga-68 PSMA PET/CT scanning before Lu-177 PSMA therapy, which revealed multiple metastases. Patients were treated with a fixed dose (180 mCi) of Lu-177 PSMA at six to eight weeks intervals. PSA response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Serum PSA response was classified as PSA progression (25% increase over the baseline and an increase in the absolute-value PSA level by at least 5 ng per millilitre), any <50% decline or ≥50% decline. PSA response was evaluated six weeks after every cycle. Response evaluation with radiological imaging and Ga-68 PSMA PET/CT were performed before the first cycle and eight weeks after the last cycle. Thirty patients were treated with a total of 171 cycles (median 4, range 3-7) of Lu-177 PSMA. A decline in serum PSA of ≥50% was detected in ten patients (33%) while a decline in PSA of any amount was observed in fifteen (50%) patients after the first cycle. After the last cycle, a decline in PSA ≥50% and of any amount was seen in thirteen (43%) and fourteen (46%) patients, respectively. Of the fifteen patients who were not responder after the first cycle, three (20%) had a decline in PSA of any amount after the completion of the RLT. Moreover, of the 20 patients who did not have a ≥50% decline in PSA level after the first cycle, four (20%) became responder after the last cycle. Regarding serum PSA response after the first cycle, median OS was significantly higher for patients who had ≥50% decline in PSA level with 21.0±10.0 (95% CI: 1.2-40.7) months compared to patients who had not with 8.0±2.6 (95% CI: 2.7-13.2) months (P=0.012). A decline in PSA of any amount after the first cycle did not have a significant impact on median OS (12.0±1.1 vs. 6.0±2.5 months, P=0.08). The decline in serum PSA level after the last cycle of treatment had a significant impact on OS. Median OS for the decline in PSA of any amount was calculated as 13.0±1.0 (95% CI: 10.9-15.0) months for responders and 6.0±1.9 (95% CI: 2.2-9.7) months for non-responders (P=0.016). Considering ≥50% of decline as a response, median OS was 21.0±5.8 (95% CI: 9.5-32.4) months for responders and 6.0±3.0 (95% CI: 0.1-11.8) months for non-responders (P=0.026). Serum PSA level during RLT with Lu-177 PSMA remains a clinically significant factor to predict OS times. About twenty percent of patients who were not responder after the first cycle could become responder after the last cycle. However, patients without PSA response after completion of all cycles should be closely followed-up. Non-responder patients can achieve a response with further treatments.