Purpose Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety
and efcacy of radioligand therapy (RLT) targeting prostate-specifc membrane antigen (PSMA) in men with metastatic
castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples
treated in everyday practice.
Methods We analyzed prospectively collected registry data regarding lutetium-177 (177Lu)-PSMA-617 RLT of 254 consecu tive men with mCRPC seen in everyday academic practice. Since 177Lu-PSMA-617 was experimental salvage treatment
following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated
(median age 70 years; prior taxanes 74.0%, 188/254), with late–end-stage disease (visceral metastasis in 32.7%, 83/254).
Primary endpoints were response to RLT, defned by changes from baseline serum prostate-specifc antigen (PSA) concen tration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with Kaplan–Meier statistics, and
caregiver-reported and patient-reported safety. Unless noted, median (minimum–maximum) values are given.
Results Patients received 3 (1–13) 177Lu-PSMA-617 activities (6.5 [2.5–11.6] GBq/cycle) every 5.7 (3.0–11.0) weeks. Best
response was≥50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confdence interval [95%CI]
4.4–6.6) months and OS, 14.5 (95%CI 11.5–17.5) months. In multivariable Cox proportional-hazards modeling, response
to the initial≤2 RLT administrations was the strongest signifcant prognosticator related to OS (hazard ratio 3.7 [95%CI
2.5–5.5], p<0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade
3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%).
RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%).
Conclusions In a large, prospectively observed “real-world” cohort with late-stage/end-stage mCRPC and conventional
treatment failure, 177Lu-PSMA-617 RLT was efective, safe, and well-tolerated. Early biochemical disease control by such
therapy was associated with better OS. Prospective study earlier in the disease course may be warranted
