The Society of Nuclear Medicine and Molecular Imaging (SNMMI) published a new consensus statement in the Journal of Nuclear Medicine that provides recommendations for the selection and management of patients with metastatic castration-resistant prostate cancer (mCRPC) who are being treated with 177Lu-PSMA radionuclide therapy.
177Lu-PSMA-617 is approved by the US Food and Drug Administration for the treatment of patients with mCRPC after disease progression on taxane-based chemotherapy and at least 1 prior line of androgen receptor pathway inhibitors (ARPIs). SNMMI convened an autonomous workgroup comprising a multidisciplinary panel of health care professionals to review 4 prospective phase 2/3 clinical trials that used 177Lu-PSMA-617 and develop consensus recommendations.
Regarding patient selection, the workgroup recommends that PSMA PET (18F-DCFPyL or 68Ga-PSMA-11) should be performed within 3 months of treatment or reported disease progression on the most recent therapy to ensure that the current disease state is represented. 18F-FDG PET is not required as a standard patient selection tool, they added, and patients should be imaged with either contrast-enhanced CT or MRI to identify PSMA-negative disease.
As for treatment sequencing, the workgroup deemed 177Lu-PSMA after chemotherapy and ARPI as “appropriate,” while administration after ARPI and before chemotherapy is “rarely appropriate.” Additionally, they noted the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC) with 177Lu-PSMA is “rarely appropriate.”
Included in the consensus statement is a section on the current clinical struggles that physicians face when administering 177Lu-PSMA, including subsections for the role of androgen receptor-targeted therapies, the role of Radium-223, treatment-related toxicities, when to consider cessation of treatment, exceptional responders and restarting treatment, and imaging during treatment.
“How to determine when to stop treatment remains a difficult decision,” statement authors wrote. “We look forward to the potential use of PSMA [radionuclide therapy] in prechemotherapy mCRPC or other settings pending the full results of ongoing trials,” they added, listing the PSMAfore, SPLASH, and ECLIPSE trials in the prechemotherapy setting; PSMAddition in the mCSPC setting; and numerous nonregistration trials evaluating 177Lu-PSMA-617 in combination with immunotherapy, chemotherapy, ARPIs, and DNA damage repair pathways.