Nephro- and hepatotoxicity after radioligand therapy of metastatic castrate-resistant prostate cancer with 177Lu-PSMA-617

Objectives Radioligand therapy (RLT) with 177Lu-PSMA-617 (Lu-PSMA)(prostate-specific membrane antigen) is a novel targeted therapy for metastatic prostate cancer. There is a need for further investigation regarding renal and hepatic side effects due to this therapy. The aim of this study was to investigate the incidence and severity of nephro- and hepatotoxicity in patients who received Lu-PSMA.

Methods One hundred and nine RLT were performed in 2-month intervals in 49 hormone- and/or chemo-refractory patients (median 2 cycles; range: 1-5) with distant metastases and progressive disease (mean age: 70.8 y/o). Median PSA was 334 ng/ml (range: 4.73-5910). Mean creatinine and GFR were: 0.9 mg/dl and 67 ml /min, respectively. Twenty-eight patients had a history of chemotherapy. All patients received renal and liver function tests on the day before RLT and up to at least 2 months after the last cycle. All patients received a Tc-MAG3 scan to rule out any obstructive renal disease.

Results The patients were treated with a median of 6 GBq Lu-PSMA in each cycle. In the MAG3 scan ten patients showed obstructive renal disease, of whom two had a complete obstruction. In four patients it was necessary to place ureteral stents prior to application of Lu-PSMA. Two months after the last cycle, apart from one patient with a grade 1 nephrotoxicity, no patient showed a grade 3 or 4 nephrotoxicity. The majority of patients did not show any hepatotoxicity. No Patient developed any grade 3 or 4 hepatotoxicity.

Conclusions Severe nephro- and hepatotoxicity have not been observed in our patients. Tc-MAG3 renal scintigraphy is of importance for selecting patients who need a ureteral stent prior to RLT to avoid any severe renal injury.