Transient prostate-specific antigen flare induced by lutetium Lu 177 vipivotide tetraxetan in patients with metastatic castration resistant prostate cancer.

Abstract

5078 Background: Prostate-specific antigen (PSA) flare, an initial rise in PSA that subsequently falls, is a well-known phenomenon in prostate cancer patients treated with hormone therapy and chemotherapy. However, its incidence, chronology, and clinical significance for treatment outcome of patients undergoing lutetium Lu 177 vipivotide tetraxetan (Lu-177), a newly FDA-approved radiopharmaceutical agent for metastatic castration-resistant prostate cancer (mCRPC), is uncertain. Our retrospective study, included mCRPC patients treated with Lu-177 between June 2022 and March 2025 at University of Kansas Cancer Center, aims to evaluate the association of PSA flare with clinical outcomes in patients with mCRPC undergoing Lu-177. Methods: PSA flare was defined as any initial increase in PSA level from baseline before start of 3 rd cycle followed by a decrease in PSA level of any degree or a decrease to less than baseline PSA level. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), PSA50 response, and disease control rate (DCR). The log-rank test was applied to compare PFS and OS between patient group with PSA flare and patient group without PSA flare. Results: The data from 158 patients were analyzed. The median age was 73.5 years old (range: 52-100). The median number of Lu-177 cycles received was 4 (range: 1-6). Forty five patients (28.5%) experienced PSA flare. The median time from treatment initiation to onset of PSA flare was 3 weeks (range: 1-9); whereas the median interval between PSA flare and PSA nadir was 14 weeks (range: 2-72). The median increase in PSA from baseline to flare was 39.1% (range: 3.3-1,133%); whereas the median decrease in PSA from flare to nadir was 70.1% (range: 8.4-98.4%). There was no statistically significant difference in PFS and OS between patient group with PSA flare and patient group without (median PFS: 8.2 vs. 5.6 months, p=0.20; median OS: 14.3 vs. 12.5 months, p=0.29). PSA50 response was observed in total of 76 patients (48.1%). In patient group with PSA flare, 48.9% of the patients achieved PSA50 response. Similarly, 48.7% of the patients achieved PSA50 response in patient group without PSA flare. Majority of patients were also assessed for radiographic response (n=139). Between patient group with PSA flare and group without PSA flare, DCR was achieved in 60% and 49.5% of the patients respectively (RR = 1.21, 95% CI: 0.88 to 1.67, p=0.26). Conclusions: The PSA flare phenomenon is not rare in mCRPC patients treated with Lu-177. Our study suggests the clinical outcome appears consistent regardless of the PSA flare. Therefore, Lu-177 should not be withdrawn early and prematurely in mCRPC patients who have an initial but isolated PSA rise following the therapy. Further studies are warranted to validate our findings.