Early discontinuation of ¹⁷⁷ Lu-PSMA-617 after ≤ 3 doses in prostate cancer: A single-center retrospective cohort study.

e17074 Background: 177 Lu-PSMA-617 is an FDA-approved radioligand therapy for prostate cancer. In clinical practice, some patients discontinue therapy early. We characterized treatment delivery and reasons for early discontinuation among patients receiving ≤3 doses of 177 Lu-PSMA-617 at a tertiary academic center. Methods: We performed a single-center retrospective cohort study at Indiana University of prostate cancer patients treated with 177 Lu-PSMA-617 from March 23, 2022 to December 17, 2025 who received ≤3 doses. Reasons for early treatment discontinuation were abstracted from the medical record. Descriptive statistics were used. Results: A total of 103 of 276 patients (37.3%) discontinued 177 Lu-PSMA-617 after ≤3 doses (1: 23.3%, 2: 34.0%, 3: 42.7%). Median age at 177 Lu-PSMA-617 initiation was 74 years (range, 50-92). Median follow-up from 177 Lu-PSMA-617 start to last contact was 3 months (range, 0-22). The median interval between doses was 42 days (range, 39-133). Dose delays were uncommon (n = 8, 7.8%) and were primarily related to intercurrent medical events, including acute kidney injury, infections (osteomyelitis, COVID-19, urinary tract infection), procedural needs (ureteral stent exchange, gangrenous cholecystectomy), symptomatic back pain, or anemia. Dose reductions were rare (n = 2, 1.9%) and occurred in the setting of pancytopenia and extensive bone metastases. The most common reason for early discontinuation were progression in 80 patients (77.7%). Grade ≥3 cytopenia contributed to discontinuation in 18 patients (17.5%), including cytopenia alone in 14 (13.6%) and cytopenia + progression in 4 (3.9%). Among those with grade ≥3 cytopenia (n = 18), thrombocytopenia was most frequent (83.3%), followed by anemia (61.1%) and leukopenia (16.7%). Among these 18 patients, 14 (77.8%) had extensive bone metastases prior to treatment (≥10 bone lesions). Baseline hematologic abnormalities were common, including anemia in 13 (72.2%) patients, thrombocytopenia in 3 (16.7%), and leukopenia in 1 (5.6%). One patient had significant comorbidities contributing to treatment intolerance, including renal failure, heart failure, neuroendocrine carcinoma, and stage 3 chronic kidney disease. At most recent follow-up 90.3% of patients were dead of prostate cancer, 1.0% were dead of other causes (sepsis), and 8.7% were alive with disease. Conclusions: In a real-world single-center cohort, most early discontinuations of 177Lu-PSMA-617 after ≤3 doses were due to disease progression, while grade ≥3 cytopenias accounted for nearly one-fifth of discontinuations and were predominantly thrombocytopenia, frequently occurring in patients with extensive bone metastases and baseline cytopenias. Earlier identification of patients at high risk for progression or marrow toxicity may help optimize patient selection, supportive care, and treatment completion.