The role of PSMA-based radioligand therapy in hormone-sensitive prostate cancer

Purpose: Conventional systemic therapies are valuable options in prostate cancer (PCa); however, such treatments can determine adverse events and toxicity. The observed improvement in overall survival, coupled with PSA reduction and a favorable safety profile in the post-taxane castration-resistant PCa (CRPC) setting has prompted the consideration of PSMA-based radioligand therapy (RLT) earlier in the treatment sequence. In this review, we will describe the literature and ongoing clinical trials regarding the use of PSMA-based RLT in hormone-sensitive PCa (HSPC) including the neoadjuvant, de-novo/synchronous metastatic, adjuvant, and early BCR settings. Methods: We performed a systematic literature search on the PubMed/MEDLINE/EMBASE and clinicaltrials.gov databases for studies and protocols assessing the role of PSMA-based RLT in HSPC. Results: The literature search yielded 140 results. After screening titles and abstracts and applying inclusion and exclusion criteria, we selected 25 papers showing the potentialities of earlier RLT in HSPC, with several ongoing trials. Conclusion: Early use of PSMA-based RLT holds significant potential in HSPC patients from the neoadjuvant to the BCR setting. In these stages, the lower tumor burden, more frequent exclusive nodal involvement, and higher organ reserve may improve treatment efficacy and allow for treatment combinations while maintaining a less toxic profile.