A German multicenter study evaluated the safety and efficacy of extended therapy with [¹⁷⁷Lu]Lu-PSMA in patients with metastatic castration-resistant prostate cancer (mCRPC). The study included 111 patients who received more than 6 cycles of [¹⁷⁷Lu]Lu-PSMA therapy, either as continuous treatment (43 patients) or rechallenge treatment (68 patients). The median cumulative doses were 57.4 GBq for continuous treatment and 60.8 GBq for rechallenge treatment. Overall survival from the initiation of [¹⁷⁷Lu]Lu-PSMA therapy was 31.3 months for the entire cohort, 23.2 months for the continuous treatment group, and 40.2 months for the rechallenge treatment group. The initial 50% PSA decline was significantly higher in the rechallenge group (90.4%) compared to the continuous group (61.9%). A 50% PSA decline was observed in 37.1% of patients after the first rechallenge. The rate of grades 3–4 toxicity was comparable between continuous and rechallenge treatments. Extended therapy with [¹⁷⁷Lu]Lu-PSMA was well tolerated, with few grades 3–4 adverse events. The study concluded that extended therapy with [¹⁷⁷Lu]Lu-PSMA is safe and has not been associated with increased grades 3–4 toxicity. Patients who received extended treatment experienced a favorable median survival of 31.3 months from the first administration. Response under [¹⁷⁷Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [¹⁷⁷Lu]Lu-PSMA after a treatment break. The study highlights the potential benefits of extended therapy with [¹⁷⁷Lu]Lu-PSMA in mCRPC patients, with favorable safety and efficacy profiles. The results suggest that extended treatment may be a viable option for patients with mCRPC, particularly those who have a favorable initial response to [¹⁷⁷Lu]Lu-PSMA therapy. The study also notes that extended therapy with [¹⁷⁷Lu]Lu-PSMA may be more tolerated than second-line chemotherapy such as cabazitaxel. However, the study acknowledges limitations, including potential selection bias and the short follow-up period, which may affect the assessment of long-term safety and efficacy. The findings support the use of extended [¹⁷⁷Lu]Lu-PSMA therapy in mCRPC patients, with the potential for improved survival and favorable safety profiles.A German multicenter study evaluated the safety and efficacy of extended therapy with [¹⁷⁷Lu]Lu-PSMA in patients with metastatic castration-resistant prostate cancer (mCRPC). The study included 111 patients who received more than 6 cycles of [¹⁷⁷Lu]Lu-PSMA therapy, either as continuous treatment (43 patients) or rechallenge treatment (68 patients). The median cumulative doses were 57.4 GBq for continuous treatment and 60.8 GBq for rechallenge treatment. Overall survival from the initiation of [¹⁷⁷Lu]Lu-PSMA therapy was 31.3 months for the entire cohort, 23.2 months for the continuous treatment group, and 40.2 months for the rechallenge treatment group. The initial 50% PSA decline was significantly higher in the rechallenge group (90.4%) compared to the continuous group (61.9%). A 50% PSA decline was observed in 37.1% of patients after the first rechallenge. The rate of grades 3–4 toxicity was comparable between continuous and rechallenge treatments. Extended therapy with [¹⁷⁷Lu]Lu-PSMA was well tolerated, with few grades 3–4 adverse events. The study concluded that extended therapy with [¹⁷⁷Lu]Lu-PSMA is safe and has not been associated with increased grades 3–4 toxicity. Patients who received extended treatment experienced a favorable median survival of 31.3 months from the first administration. Response under [¹⁷⁷Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [¹⁷⁷Lu]Lu-PSMA after a treatment break. The study highlights the potential benefits of extended therapy with [¹⁷⁷Lu]Lu-PSMA in mCRPC patients, with favorable safety and efficacy profiles. The results suggest that extended treatment may be a viable option for patients with mCRPC, particularly those who have a favorable initial response to [¹⁷⁷Lu]Lu-PSMA therapy. The study also notes that extended therapy with [¹⁷⁷Lu]Lu-PSMA may be more tolerated than second-line chemotherapy such as cabazitaxel. However, the study acknowledges limitations, including potential selection bias and the short follow-up period, which may affect the assessment of long-term safety and efficacy. The findings support the use of extended [¹⁷⁷Lu]Lu-PSMA therapy in mCRPC patients, with the potential for improved survival and favorable safety profiles.