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

Abstract

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 ([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. 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 [177Lu]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 [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.

PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

“…Moreover, in the present study, response was assessed only using the PSA change after two cycles of 177 Lu-PSMA-RLT. Although easily to obtain in clinical routine and demonstrating a high predictive value for later outcome [13], Han et al recently revealed significant discordance between PSA and follow-up PSMA-PET/CTs for response assessment pooling 10 different studies [35]. Nonetheless future studies should also include follow-up PSMA-PET/CTs for response assessment (including early biochemical response and OS) to further define the value of changes in PET parameters, such as delta values of PSMA-TV, TL-PSMA or occurrence of new metastases for subsequent outcome.…”

“…In addition, the ongoing prospective VISION phase-3 trial further investigates the clinical value of PSMA RLT and hence may further boost the use of RLT in mCRPC patients [12]. Most studies demonstrated PSA response in about half of the enrolled subjects, whereas 30% of the patients still suffered from progressive disease (PSA increase of >25%) [13]. Therefore, predictors for identifying such high-risk individuals are intensively sought, and multiple studies have already investigated the use of PSMA-ligand PET/CT for late outcome, e.g., in terms of overall survival (OS).…”

Outcome of 177Lu-PSMA Radionuclide Treatment in Advanced Prostate Cancer and Its Association With Clinical Parameters

“…Recently, a meta-analysis revealed that increased ALP and CRP had worse OS, whereas baseline PSA, PLT, and WBC had no impact on OS. 33 Besides, the impact of baseline LDH, Hg, age, and prior chemotherapy is controversial based on the meta-analysis. Tumor burden is also a critical point for therapy of choice since the CHAARTED study showed that low volume M1 disease did not benefit from DTX as much as high volume disease.…”

Salvage Radioligand Therapy with Repeated Cycles of 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer with Diffuse Bone Marrow Involvement

“…To refine therapeutic reasoning in RLT, early denominators of treatment efficacy are highly desired. Various predictive factors for both response and outcome have been put forth, mainly based on retrospective evidence from heterogeneous patient groups [34].…”