An assessment of time toxicity in patients receiving [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate...

[177Lu]Lu-PSMA-617 (LuPSMA) improves survival and quality of life in men with metastatic castration-resistant prostate cancer but requires substantial healthcare involvement. Our analysis evaluated the time toxicity associated with LuPSMA, representing the first dedicated radioligand time toxicity assessment.

We conducted a multi-institutional retrospective study of patients initiating LuPSMA between April 2022 and March 2023. Patients were followed from first LuPSMA administration until 3 months after the final cycle, initiation of new systemic therapy, or death. Time toxicity was quantified as healthcare contact days during the at-risk interval. Associations with baseline characteristics were evaluated using negative binomial regression models. Univariate and multivariable models were performed.

The median age of 135 patients included in the study was 69 years, and the median prior systemic therapies was 4. Patients completed a median of 5 LuPSMA cycles over 7.6 months. Median healthcare contact days were 20 (IQR, 15-28), representing 9.5% (IQR, 6.4-13.9) of at-risk days. Fifteen patients (11%) experienced high time toxicity (>1 contact day per 5 days), while 42 (31%) had low time toxicity (≤1 contact day per 14 days). Among the 57 patients who received both cycle 1 and cycle 6, the mean per cycle healthcare contact days were 4 and 3.6, respectively (paired Wilcoxon signed-rank test, P = .04). Routine oncology visits comprised 32.7% of contact days, compared with 8.8% from hospitalizations. Lower baseline hemoglobin was independently associated with greater time toxicity (RR = 0.87; 95% CI, 0.79-0.96; P = .004).

In heavily pretreated patients, LuPSMA demonstrated relatively low time toxicity, supporting it as a time-efficient therapy.