文章：

新辅助177镥-PSMA-617放射性配体治疗高危局限性前列腺癌：理论基础、早期临床证据与未来方向

Neoadjuvant177Lutetium-PSMA-617 Radioligand Therapy for High-Risk Localized Prostate Cancer: Rationale, Early Clinical Evidence, and Future Directions

原文发布日期：15 October 2025

DOI: 10.3390/cancers17203330

类型: Article

开放获取: 是

英文摘要：

Men with high-risk localized prostate cancer (PCa) often have poor long-term outcomes, underscoring the need for improved neoadjuvant strategies beyond the current standard of care. Radioligand therapy with177Lutetium-PSMA-617 (177Lu-PSMA-617) has emerged as a promising method to eliminate occult micrometastases while enhancing immune-mediated clearance of the primary tumor. Initial trials have affirmed the treatment’s feasibility and safety; however, they have consistently reported a lack of pathological complete response. This absence of profound initial tumor reduction necessitates further therapeutic advancements. The underlying rationale for future strategies is clear, as177Lu-PSMA-617 promotes immunogenic cell death, potentially sensitizing immunologically “cold” tumors to checkpoint inhibitors. However, caution is warranted. The synergy observed between these therapies in advanced, metastatic castration-resistant PCa stems from a different biological context, and similar outcomes cannot be presumed in treatment-naïve, localized disease without rigorous validation. Continued progress hinges on developing improved metrics for success and patient selection. Simple prostate-specific antigen reductions have demonstrated minimal correlation with significant pathological outcomes in this setting, underscoring the critical need for validated surrogate endpoints and predictive biomarkers. Ultimately, large-scale randomized trials are essential to determine whether this investigational approach impacts key clinical outcomes—namely, metastasis-free and overall survival. While the strategy is theoretically sound, its capacity to enhance cure rates for high-risk localized PCa remains unverified.

摘要翻译： 

高危局限性前列腺癌患者长期预后往往不佳，这凸显了在现有标准治疗基础上改进新辅助治疗策略的必要性。177镥-PSMA-617放射配体疗法作为一种新兴治疗手段，既能清除隐匿性微转移灶，又能增强免疫介导的原发肿瘤清除效果。初步试验已证实该疗法的可行性与安全性，但研究一致报告其未能实现病理学完全缓解。这种初期肿瘤深度缓解的缺失，表明该疗法仍需进一步优化。未来策略的理论基础明确：177镥-PSMA-617可促进免疫原性细胞死亡，可能使免疫"冷"肿瘤对检查点抑制剂敏感化。然而需要保持审慎态度——在晚期转移性去势抵抗性前列腺癌中观察到的协同效应源于不同的生物学背景，未经严格验证前，不应假定在未接受过治疗的局限性病灶中能产生相同效果。持续进展的关键在于建立更完善的疗效评估标准和患者筛选体系。单纯的前列腺特异性抗原降低已证实与显著病理结局相关性微弱，这凸显了建立经过验证的替代终点和预测性生物标志物的迫切需求。最终需要通过大规模随机试验来确定这种探索性方案能否影响关键临床结局——即无转移生存期和总生存期。虽然该策略在理论上具有合理性，但其能否提高高危局限性前列腺癌的治愈率仍有待验证。

原文链接：

Neoadjuvant177Lutetium-PSMA-617 Radioligand Therapy for High-Risk Localized Prostate Cancer: Rationale, Early Clinical Evidence, and Future Directions