High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [¹⁷⁷Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer.

尽管尝试了包括手术在内的治愈性局部治疗，但高危局限性前列腺癌仍然是一种致命疾病，复发率、转移率和死亡率很高。疾病复发被认为是局部控制失败和隐匿性微转移的结果。术前新辅助策略对许多癌症有效，但迄今为止，没有一种策略对前列腺癌有效。基于前列腺特异性膜抗原 （PSMA） 的治疗诊断学是前列腺癌中一个令人兴奋且快速发展的领域。新型静脉注射放射性核素疗法 [¹⁷⁷Lu]Lu-PSMA-617 （镥 PSMA） 已被证明可有效治疗男性转移性去势抵抗性前列腺癌，靶向全身表达 PSMA 的细胞。当作为新辅助治疗时，镥 PSMA 也可能改善高危局部疾病男性的长期肿瘤学结局。放疗的一个组成部分可能是癌细胞死亡的免疫原性形式。镥 PSMA 可导致癌细胞死亡，导致肿瘤抗原释放并诱导肿瘤特异性全身免疫反应。这种靶向放射性配体治疗有可能通过直接靶向表达 PSMA 的细胞来治疗局部和全身性肿瘤部位，但也可能通过这种全身免疫反应间接发挥作用。在选定的患者中，镥 PSMA 可能与全身免疫疗法联合使用，以增强抗肿瘤 T 细胞反应，这可能会在前列腺癌中产生持久的免疫力。