Automated CT Measurement of Total Kidney Volume for Predicting Renal Function Decline after ¹⁷⁷Lu Prostate-specific Membrane Antigen-I&T Radioligand Therapy

Background Lutetium 177 (177Lu) prostate-specific membrane antigen (PSMA) radioligand therapy is a novel treatment option for metastatic castration-resistant prostate cancer. Evidence suggests nephrotoxicity is a delayed adverse effect in a considerable proportion of patients. Purpose To identify predictive markers for clinically significant deterioration of renal function in patients undergoing 177Lu-PSMA-I&T radioligand therapy. Materials and Methods This retrospective study analyzed patients who underwent at least four cycles of 177Lu-PSMA-I&T therapy between December 2015 and May 2022. Total kidney volume (TKV) at 3 and 6 months after treatment was extracted from CT images using TotalSegmentator, a deep learning segmentation model based on the nnU-Net framework. A decline in estimated glomerular filtration rate (eGFR) of 30% or greater was defined as clinically significant, indicating a higher risk of end-stage renal disease. Two-sided t tests and Mann-Whitney U tests were used to compare baseline nephrotoxic risk factors, changes in eGFR and TKV, prior treatments, and the number of 177Lu-PSMA-I&T cycles between patients with and without clinically significant eGFR decline at 12 months. Threshold values to differentiate between these two patient groups were identified using receiver operating characteristic curve analysis and the Youden index. Results A total of 121 patients (mean age, 76 years ± 7 [SD]) who underwent four or more cycles of 177Lu-PSMA-I&T therapy with 12 months of follow-up were included. A 10% or greater decrease in TKV at 6 months predicted 30% or greater eGFR decline at 12 months (area under the receiver operating characteristic curve, 0.90 [95% CI: 0.85, 0.96]; P < .001), surpassing other parameters. Baseline risk factors (ρ = 0.01; P = .88), prior treatments (ρ = -0.06; P = .50), and number of 177Lu-PSMA-I&T cycles (ρ = 0.08; P = .36) did not correlate with relative eGFR percentage decrease at 12 months. Conclusion Automated TKV assessment on standard-of-care CT images predicted deterioration of renal function 12 months after 177Lu-PSMA-I&T therapy initiation in metastatic castration-resistant prostate cancer. Its better performance than early relative eGFR change highlights its potential as a noninvasive marker when treatment decisions are pending.