Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review.

Prostate cancer (PC) is one of the most common cancers in men. Although the overall prognosis is favorable, the management of metastatic castration-resistant prostate cancer (mCRPC) patients is challenging. Usually, mCRPC patients with progressive disease are considered for radioligand therapy (RLT) after exhaustion of other standard treatments. The prostate-specific membrane antigen (PSMA) labeled with Lutetium-177 ([177Lu]Lu-PSMA) has been widely used, showing favorable and successful results in reducing prostate-specific antigen (PSA) levels, increasing quality of life, and decreasing pain, in a multitude of studies. Nevertheless, approximately thirty percent of patients do not respond to [177Lu]Lu-PSMA RLT. Here, we only reviewed and reported the evaluated factors and their impact on survival or biochemical response to treatment to have an overview of the potentialprognostic parameters in [177Lu]Lu-PSMA RLT.

Studies were retrieved by searching MEDLINE/PubMed and GoogleScholar. The search keywords were as follows: {("177Lu-PSMA") AND ("radioligand") AND ("prognosis") OR ("predict")}. Studies discussing one or more factors which may be prognostic or predictive of response to [177Lu]Lu-PSMA RLT, that is PSA response and survival parameters, were included.

Several demographic, histological, biochemical, and imaging factors have been assessed as predictive parameters for the response to thistreatment; however, the evaluated factors were diverse, and the results mostly were divergent, except for the PSA level reduction after treatment, which unanimously predicted prolonged survival.

Several studies have investigated a multitude of factors to detect those predicting response to [177Lu]Lu-PSMA RLT. The results wereinconsistent regarding some factors, and some were evaluated in only a few studies. Future prospective randomized trials are required to detect theindependent prognostic factors, and to further determine the clinical and survival benefits of [177Lu]Lu-PSMA RLT.

European journal of nuclear medicine and molecular imaging. 2021 Mar 06 [Epub ahead of print]

Reyhaneh Manafi-Farid, Sara Harsini, Bahare Saidi, Hojat Ahmadzadehfar, Ken Herrmann, Alberto Briganti, Jochen Walz, Mohsen Beheshti

Research Center for Nuclear Medicine, Tehran University of Medical sciences, Tehran, Iran., Department of Nuclear Medicine, Klinikum Westfalen, Dortmund, Germany., Department of Nuclear Medicine, University Hospital, Essen, Germany., Urological Research Institute, Scientific Institute San Raffaele, Vita-Salute San Raffaele University, Milan, Italy., Department of Urology, Institute Paoli-Calmettes Cancer Centre, Marseille, France., Division of Molecular Imaging and Theranostics, Department of Nuclear Medicine & Endocrinology, Paracelsus Medical University, Salzburg, Austria. .