Renal Function Decline After ¹⁷⁷Lu-PSMA-617 Versus Taxane-Based Chemotherapy in Patients with Metastatic...

We conducted a study to determine the effects of ¹⁷⁷Lu-PSMA-617 treatment on renal function decline in patients with metastatic castration-resistant prostate cancer (mCRPC) shortly after treatment and over long-term follow-up. Methods: The study used comparative and counterfactual analysis. Patients were eligible for inclusion if they received at least 3 but no more than 6 cycles of ¹⁷⁷Lu-PSMA-617 with androgen-deprivation therapy or completed 6 cycles of docetaxel with or without androgen-deprivation therapy. Further, the availability of serum creatinine and estimated glomerular filtration rate (eGFR) measurements within a 30-d window for each treatment cycle was required. A decline in eGFR of greater than 3 mL/min/1.73 m²/year was assessed by comparing baseline values with the posttreatment eGFR and the last available follow-up eGFR. The incidence of eGFR decline was compared between patients who received radiopharmaceutical therapy (RPT) and those who received chemotherapy after 1:1 matching, inverse probability weighting, and weighting by odds method to reduce intergroup selection bias with an additional counterfactual analysis of patients who received both treatments sequentially. Results: After propensity score adjustment using established risk factors for renal function decline, there was no difference in renal function deterioration in early posttreatment (6 mo after treatment) between patients who received RPT and those who received chemotherapy (median eGFR decreased from 82 to 80 mL/min/1.73 m² within the RPT group, P = 0.49 in both treatment groups). During long-term follow-up, the overall incidence of renal function decline increased in both groups (P = 0.044, median eGFR fall from 82 to 72 mL/min/1.73 m² in the RPT-treated group). Stratified analyses demonstrated no change among patients with preserved baseline renal function (P = 0.49), whereas patients with chronic kidney disease exhibited a significantly greater decline in renal function (P = 0.0023). Renal function remained stable over 6 cycles of RPT compared with 6 cycles of chemotherapy within the same patients. Conclusion: After adjustment of presumed risk factors, renal function decline was most prevalent in patients with lower baseline renal function. Renal function decline in patients with mCRPC, who are already susceptible to compromised renal function, may not be solely caused by ¹⁷⁷Lu-PSMA-617 therapy.