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

BACKGROUND: 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 ([(177)Lu]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 [(177)Lu]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 [(177)Lu]Lu-PSMA RLT. METHODS: 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 [(177)Lu]Lu-PSMA RLT, that is PSA response and survival parameters, were included. RESULTS: 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. CONCLUSION: Several studies have investigated a multitude of factors to detect those predicting response to [(177)Lu]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 [(177)Lu]Lu-PSMA RLT.