Lutetium-177-PSMA-617 in low-volume hormone sensitive metastatic prostate cancer, a prospective pilot study.

177Lu-PSMA-617 radioligand-therapy is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression.

In this prospective study (NCT03828838), we analyzed toxicity, radiation doses and treatment effect of 177Lu-PSMA in low-volume mHSPC patients.

Ten progressive mHSPC patients following local treatment, with a maximum of ten metastatic lesions on 68Ga-PSMA-11 PET (PSMA-PET) and serum-PSA doubling time <6 months received two cycles of 177Lu-PSMA. Whole-body SPECT/CT and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory(-toxicity) and quality of life were monitored until week 24 after cycle two; the end of study (EOS). All patients underwent PSMA-PET at screening, eight weeks after cycle one, 12 weeks after cycle two and at EOS.

All patients received two cycles of 177Lu-PSMA without complications. No treatment related grade III-IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation related toxicity. Moreover, all target lesions received higher radiation dose than the OAR. All ten patients showed altered PSA kinetics, postponed androgen-deprivation therapy and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET-imaging until EOS and two others had only minimal residual disease.

177Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume metastatic hormone-sensitive prostate cancer patients.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Apr 21 [Epub ahead of print]

Bastiaan Michael Privé, Steffie M B Peters, Constantijn H J Muselaers, Inge M van Oort, Marcel J R Janssen, Michiel Sedelaar, Mark W Konijnenberg, Patrik Zamecnik, Maike J M Uijen, Melline G M Schilham, Annemarie Eek, Tom W J Scheenen, J Fred Verzijlbergen, Winald R Gerritsen, Niven Mehra, Linda G W Kerkmeijer, Robert Jan Smeenk, Diederik M Somford, Jean-Paul A van Basten, Sandra Heskamp, Jelle Barentsz, Martin Gotthardt, J Alfred Witjes, James Nagarajah

Dept. of Radiology and Nuclear Medicine, Radboudumc ., Dept. of Medical Imaging, Radboudumc., Urology, Radboud University Nijmegen Medical Centre., urology, Radboud University Nijmegen Medical Centre., Dept. of Radiology and Nuclear Medicine, Radboudumc., Department of Urology, Radboud University Nijmegen Medical Centre., Radiologyand nuclear medicine, Radboud University Medical Centre Nijmegen., Medical Oncology, Radboud University Medical Centre., Medical Oncology, Radboud University Nijmegen Medical Centre., Dept. of Radiation Oncology, Radboudumc., Urology, Canisius-Wilhelmina Ziekenhuis., Department of Medical Imaging, Radboud University Nijmegen Medical Centre., Medical Imaging, Radboud University Nijmegen Medical Centre., Radiology and Nuclear Medicine, Radboud University Nijmegen Medical Centre., Radboud University Nijmegen Medical Centre., Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center.