Pretherapeutic estimated glomerular filtration rate predicts development of chronic kidney disease in patients receiving PSMA‐targeted radioligand therapy

Abstract

Background: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT.Methods: In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m 2 ]), Tc-99mmercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMAligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up.Results: After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/ min/1.73 m 2 (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/ 46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m 2 ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/ 1.73 m 2 ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007).

Safety of Lutetium-177 prostate-specific membrane antigen-617 (PSMA-617) radioligand therapy in the setting of severe renal impairment: a case report and literature review

“…On the other hand, a single-center retrospective trial conducted by Widjaja et al evaluated 46 mCRPC patients and found that having an abnormal pretherapeutic eGFR (<90 mL/min/1.73 m 2 ) was the strongest predictor of worsening CKD. 16 The risk of kidney injury is also supported by a phase II prospective study by Violet et al 17 where grade 1–2 renal injury was observed in 10% of patients as measured by an 11.7 mL/min reduction in renal function using [ 51 Cr]Cr-ethylenediaminetetraacetic acid (EDTA) between pretherapeutic and 3-month follow-up assessment. Our patient demonstrated no worsening of his baseline renal dysfunction, and this was likely related to optimization of his renal function with ureteric stenting, personalized dosimetry, adequate hydration during treatment, and reducing the number of [ 177 Lu]Lu-PSMA-617 cycles from six to four given his excellent response to therapy.…”

Multidisciplinary Team Approach in Prostate-Specific Membrane Antigen Theranostics for Prostate Cancer: A Narrative Review

“…Patients exhibiting impaired renal function, extensive prior chemotherapy, or prolonged hematological toxicity may have a higher susceptibility to experiencing more severe myelotoxicity [50]. There is limited clinical data on patients with moderately impaired renal function (GFR 30-50 mL/min), suggesting a gap in understanding the full impact of 177 LuPSMA radioligand therapy in this subgroup [51,52]. In cases where patients began 177 LuPSMA radioligand therapy with already dimini shed kidney function, worsening renal conditions were observed, though these could also be attributed to the typical risk factors associated with chronic kidney disease [52,53].…”

“…There is limited clinical data on patients with moderately impaired renal function (GFR 30-50 mL/min), suggesting a gap in understanding the full impact of 177 LuPSMA radioligand therapy in this subgroup [51,52]. In cases where patients began 177 LuPSMA radioligand therapy with already dimini shed kidney function, worsening renal conditions were observed, though these could also be attributed to the typical risk factors associated with chronic kidney disease [52,53]. These observations indicate a crucial need for careful patient selection and monitoring within MDT, particularly for those with preexisting conditions that might elevate the risk of adverse outcomes from radioligand therapy.…”