Long-term outcome of (177)Lu-PSMA-617 radioligand therapy in heavily pre-treated metastatic castration-resistant prostate cancer patients

OBJECTIVE: Investigators have extensively explored the short-term safety and efficacy data on (177)Lu-PSMA-617 radioligand therapy (RLT) in mCRPC patients. However, scarce literature is reported on the long-term outcome of these patients. The current goal of this study is focused on the long-term outcome of mCRPC patients treated with (177)Lu-PSMA-617 RLT. METHODS: Among 135 patients, 121 mCRPC patients fulfilled the eligibility criteria and were included in the final analysis. Patients received a median of 3 cycles of (177)Lu-PSMA-617 RLT at 6 to 12-week intervals. Primary endpoint included overall survival (OS) and secondary endpoints involved progression-free survival (PFS), predictive factors of OS and PFS, PSA response rate, molecular response, clinical response, and toxicity assessment. RESULTS: The median administered cumulative activity was 20 GBq (3.7–37 GBq). The median follow-up duration was 36 months (6–72 months). The estimated median PFS and OS were 12 months (mo) (95% CI: 10.3–13 mo) and 16 mo (95% CI: 13–17 mo), respectively. Any PSA decline and PSA decline >50% was achieved in 73% and 61% of the patients, respectively. Multivariate analysis revealed only failure to achieve >50% PSA decline as a significant factor associated with a poor PFS. Prognostic factors associated with reduced OS included, failure to experience >50% PSA decline, heavily pre-treated patient cohort who received >2 lines of prior treatment options, and patient sub-group treated with ≥2 lines of chemotherapy. Patients re-treated with additional treatment options after attaining (177)Lu-PSMA refractory disease showed a remarkably prolonged OS. A significant clinical benefit was achieved post (177)Lu-PSMA-617 RLT. The most common toxicities observed were fatigue (34.7%), followed by nausea (33%), and dry mouth (24.7%). CONCLUSION: The current study supports the short-term safety and efficacy results of high response rates, prolonged PFS and OS, improved quality of life, and low treatment-related toxicities in patients treated with (177)Lu-PSMA-617 radioligand therapy.