Impact of extended [177Lu] Lu-PSMA-617 therapy on absorbed kidney dose and CKD-EPI values: how long can therapy be safely continued?

Abstract

Purpose

This study aimed to evaluate the personalized dosimetric approach by calculating the cumulative renal absorbed dose (cRD) and assessing its impact on renal functions in patients diagnosed with metastatic castration-resistant prostate cancer who underwent four or more cycles of [¹⁷⁷Lu] Lu-PSMA − 617 therapy.

Methods

The study included 110 patients who received ≥ 4 cycles of [¹⁷⁷Lu] Lu-PSMA − 617 therapy. Whole-body static and abdominal SPECT-CT imaging was performed at 4, 24, and 96 h post-administration. Kidney function was assessed using dynamic renal scintigraphy and biochemical tests conducted prior to treatment. Estimated glomerular filtration rate (eGFR) levels were calculated using the CKD-EPI formula before each treatment cycle and at the 6th week post-treatment.

Results

Pearson correlation analysis reveal no significant relationship between cRD and CKD-EPI values (p >.05). No significant differences were observed between pre-treatment CKD-EPI levels and those measured after the 4th, 5th, 6th, 7th, and 8th cycles (p >.05). Among patients reaching a cRD of 23 Gy, a statistically significant difference was observed between pre- and post-treatment CKD-EPI values (p <.05). Of the 13 patients exceeding cRD of 28 Gy, five maintained CKD-EPI levels above 90 mL/min/1.73 m² post-treatment.

Conclusion

Despite treatment-related declines in eGFR levels, our findings indicate that a personalized dosimetric approach may enable extended cycles of [¹⁷⁷Lu] Lu-PSMA-617 therapy with manageable nephrotoxicity. Considering the significant inter-patient variability, establishing universal absorbed dose-response relationships remains challenging. Prospective multicenter studies are crucial to refining toxicity thresholds and advancing tailored treatment strategies to optimize safety and efficacy.