The emerging role of prostate-specific membrane antigen–targeted radioligand therapy in metastatic hormone-sensitive prostate cancer

The treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has evolved in recent years towards combination therapy, enhancing survival outcomes when compared with androgen deprivation therapy (ADT) alone. However, many patients who are eligible for combination therapy are still receiving ADT monotherapy, and a significant proportion of those treated with doublet combinations still experience suboptimal outcomes. Furthermore, the value of adding docetaxel to an androgen receptor pathway inhibitor (ARPI)/ADT doublet in mHSPC has not been delineated, particularly in patients with low-volume disease, and chemotherapy toxicity and tolerability remain a major concern for patients. This review addresses the significant unmet need for additional or novel treatment strategies for mHSPC, utilizing prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in a combination regimen that uses a non-chemotherapeutic approach for the treatment of mHSPC. PSMA-targeted RLT has been shown to improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with ARPIs +/- taxanes and is now under evaluation for the treatment of mHSPC, given its demonstrated success in the mCRPC space. Thus, continued education on RLT and its use for patients with mHSPC is important to optimize patient care. This review provides a brief outline of the mHSPC treatment landscape, focusing on the challenges and unique considerations faced by healthcare professionals when treating these patients. We also evaluate the potential role of RLT in surmounting these challenges, discussing potential barriers and solutions to its integration as a treatment for mHSPC.