Early Experience of Rechallenge 177Lu-PSMA Radioligand Therapy After an Initial Good Response in Patients with Advanced Prostate Cancer

Abstract

Our aim was to retrospectively evaluate the feasibility of rechallenge ¹⁷⁷Lu-prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) radioligand therapy. Methods: Rechallenge radioligand therapy was defined as subsequent treatment with ¹⁷⁷Lu-PSMA after initial exposure with an excellent response followed by progression. Biochemical, radiographic, clinical antitumor response, and adverse events were analyzed. Prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival were calculated. Results: Eight patients underwent a median of 2 (range: 1-4) cycles of rechallenge with ¹⁷⁷Lu-PSMA for imaging and therapy. A maximum PSA decrease of 50% was achieved in 3 patients (37.5%). Radiographic response was favorable in 3 patients, whereas 4 exhibited progressive disease. Eastern Cooperative Oncology Group performance status was stable during therapy in all patients. No grade 4 toxicity was noticed, and grade 3 toxicity occurred in 3 patients (37.5%). The median PSA-PFS and overall survival were 3.2 mo (95% confidence interval, 2.6-3.7 mo) and 14.0 mo (95% confidence interval, 6.2-21.8 mo), respectively. Conclusion: In a small patient cohort with an initial excellent response, ¹⁷⁷Lu-PSMA rechallenge is still active, with lower efficacy and higher toxicity.

Keywords: 177Lu-PSMA; PSMA; prostate cancer; radioligand therapy; rechallenge.