Assessment of nephrotoxicity following lutetium-177 PSMA I&T radioligand therapy: a comparative study with docetaxel chemotherapy.

Abstract

To compare changes in estimated glomerular filtration rate (eGFR) following Lutetium-177 prostate-specific membrane antigen I&T radioligand therapy (¹⁷⁷Lu-PSMA I&T) and docetaxel chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). This retrospective multicenter analysis included 145 patients treated with ¹⁷⁷Lu-PSMA I&T and 39 patients treated with docetaxel. Inclusion required ≥ 4 cycles of ¹⁷⁷Lu-PSMA I&T or ≥ 10 docetaxel administrations and ≥ 12 months of eGFR follow-up. Docetaxel patients were excluded if ¹⁷⁷Lu-PSMA I&T was initiated within 12 months after therapy initiation. Patients were stratified by treatment sequence (docetaxel only, pre-chemo and post-chemo ¹⁷⁷Lu-PSMA I&T). Linear mixed models (LMM) assessed longitudinal eGFR changes with adjustment and matching for baseline renal risk factors (arterial hypertension, diabetes mellitus, age ≥ 65 years, prior platinum-based chemotherapy). Median age (interquartile range, IQR) was 75.0 (67.0–77.0) years in the docetaxel group, 81.5 (77.5–87.0) years in the pre-chemo ¹⁷⁷Lu-PSMA I&T subgroup (<i>n</i> = 58), and 75.5 (71.0–78.3) years in the post-chemo ¹⁷⁷Lu-PSMA I&T subgroup (<i>n</i> = 87). Mean eGFR declined over time in both pre- and post-chemo ¹⁷⁷Lu-PSMA I&T subgroups compared with docetaxel-treated patients, with significant differences emerging earlier in the pre-chemo subgroup (from 3 months) and later in the post-chemo subgroup (from 12 months), persisting through follow-up. At 12 months, severe eGFR decline (≥ 30%) was more frequent after ¹⁷⁷Lu-PSMA I&T than docetaxel (pre-chemo: 32.8% vs. 2.6%, OR = 18.5; post-chemo: 31.0% vs. 2.6%, OR = 17.1; both <i>p</i> < 0.001). LMM confirmed a significant time-dependent eGFR decline with ¹⁷⁷Lu-PSMA I&T versus docetaxel (entire cohort β=-1.56; pre-chemo β=-1.41; both <i>p</i> < 0.001). ¹⁷⁷Lu-PSMA I&T is associated with a gradual, time-dependent decline in renal function compared with docetaxel, independent of prior chemotherapy exposure and baseline renal risk factors. These findings highlight the importance of baseline renal assessment and longitudinal kidney function monitoring, particularly as ¹⁷⁷Lu-PSMA RLT is increasingly considered earlier in the treatment course.