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

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 [Lu] Lu-PSMA - 617 therapy.

Methods: The study included 110 patients who received ≥ 4 cycles of [Lu] 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 m post-treatment.

Conclusion: Despite treatment-related declines in eGFR levels, our findings indicate that a personalized dosimetric approach may enable extended cycles of [Lu] 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.