Response and Toxicity to the Second Course of 3 Cycles of (177)Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

SIMPLE SUMMARY: The [(177)Lu]Lu-PSMA radioligand therapy (PSMA-RLT) has emerged as a successful treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). Nevertheless, the therapeutic protocol of this treatment is still heterogeneous in many centers, in terms of the number of cycles and the interval between the cycles. Recently, we published the clinical impact of a homogeneous PSMA-RLT protocol that has been applied in our clinic since we started offering this treatment to patients with mCRPC. The outcomes were supportive and promising for analyzing the efficacy and toxicity of using the same treatment regimen in patients who benefited from the first treatment course. Based on the results, we concluded that a second course of three cycles of standardized PSMA-RLT with only a 4-week interval between the cycles is safe and offers favorable tolerability, response rates, overall survival, and progression-free survival, rendering it a promising alternative for the retreatment of mCRPC patients who have formerly responded well to PSMA-RLT. ABSTRACT: Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [(177)Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.