The kidneys are recognised organs at risk during prostate-specific membrane antigen (PSMA)–targeted radioligand therapy. While clinically overt nephrotoxicity appears uncommon in late-line metastatic castration-resistant prostate cancer (mCRPC), the longitudinal trajectory of renal function following ¹⁷⁷LuLu-PSMA I p < 0.001). Baseline renal vulnerability was independently associated with lower absolute eGFR values (− 6.76 mL/min/1.73 m² per RRI unit; p < 0.001) but did not modify the rate of decline. Within the administered activity range and using population-based dose estimates, no clear dose–response relationship was detected; this finding should be interpreted in the context of the narrow activity range studied and the absence of patient-specific dosimetry. Reconstructed pre-treatment trajectories demonstrated stable renal function prior to therapy (β = +0.06 mL/min/month; p = 0.30), whereas post-treatment eGFR declined significantly (β = −0.60 mL/min/month; p < 0.001). Restricted analyses limited to the first 12 months showed similar slopes, with no evidence of non-linearity. Clinically significant renal decline occurred in 16 patients (15%), most frequently within the first year following treatment initiation. In this retrospective mCRPC cohort treated with ¹⁷⁷LuLu-PSMA I&T, a measurable decline in renal function was observed over time, although the observational design precludes causal attribution to radioligand therapy. Clinically significant renal deterioration remained relatively uncommon. Baseline renal vulnerability influenced overall renal reserve but not the rate of decline, and no clear dose–response relationship was detected within the administered activity range. Extrapolation of these findings to earlier-line settings should be considered hypothesis-generating. These findings support baseline renal assessment and longitudinal monitoring as PSMA-targeted radioligand therapy expands to earlier disease settings.
Cockcroft et al. (Tue,) studied this question.