177Lu-PSMA-RLT of metastatic castration-resistant prostate cancer: limitations and improvements

The prevalence of metastatic castration-resistant prostate cancer (mCRPC) is increasing, and its prognosis is often poor. As a highly expressed target in mCRPC, prostate-specific membrane antigen (PSMA) is very attractive for its diagnosis and treatment. When the efficacy of chemical therapy is limited, radioligand therapy (RLT)-based on Lutetium-177 (177Lu)-PSMA has received more research as an emerging treatment. To date, most published related studies have proven this method is effective and safe. However, about 1/3 of mCRPC patients have not benefited from 177Lu-PSMA-RLT. The underlying mechanism of this phenomenon remains unclear. So based on the comprehensive research in recent years, this article proposes the possible reasons, including tumor lesions, PSMA heterogeneity, differences in DNA repair defects, and accelerated repopulation. Combining with the existing experience to give suggestions to improve the treatment efficacy, benefit more mCRPC patients.