编者按：2026年美国临床肿瘤学会泌尿生殖系统肿瘤研讨会（ASCO-GU）盛大召开，前列腺癌领域迎来术语体系革新、多项重磅研究数据更新与治疗格局的迭代升级。会议期间，肿瘤瞭望-泌尿时讯特邀美国威尔康奈尔医学院Scott T. Tagawa教授，围绕本届大会前列腺癌领域进展及精准治疗的未来方向，展开深度解读。

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2026年ASCO GU研讨会汇聚了全球专家，共同分享泌尿生殖系统肿瘤领域的突破性研究。您对今年会议的整体印象如何？是否有让您特别关注的研究或趋势？

Scott T. Tagawa 教授：本届ASCO-GU大会上，前列腺癌领域的进展主要分为两大核心维度：一是验证性临床研究的最终数据公布，将直接改写与指导临床实践；二是大量极具潜力的早期探索性研究，虽短期内无法直接改变当前临床诊疗格局，但为长远的治疗突破奠定了坚实基础。

首先必须强调行业的核心革新：随着前列腺癌临床试验工作组第4版（PCWG4）共识的正式发布，前列腺癌的疾病术语体系迎来了重大更新—既往临床广泛使用的「去势抵抗性前列腺癌（CRPC）」，已正式更名为雄激素通路调节剂耐药（Androgen Pathway Modulator-Resistant, APMR）前列腺癌，这也是后续所有研究解读的基础。

其中最具代表性的是PEACE-3研究的最终生存数据更新。该研究为Ⅲ期随机对照临床试验，入组人群以雄激素受体信号抑制剂（ARPI）初治的APMR前列腺癌患者为主（仅少数患者既往接受过阿比特龙治疗），且无论患者既往是否接受过多西他赛化疗均可入组。研究将患者1:1随机分为两组，对照组为当时的标准治疗方案单药恩扎卢胺，试验组为恩扎卢胺联合镭[223Ra]注射液（镭-223，一种已获批多年的骨靶向α粒子发射体）。

早在几年前的欧洲肿瘤内科学会（ESMO）大会上，该研究已公布了阳性的无进展生存期（PFS）结果，同时观察到了明确的总生存期（OS）获益趋势，但受限于研究设计与生存曲线交叉的影响，当时OS未达到预设的统计学显著性标准。而本届ASCO-GU大会上公布的最终更新数据，通过对数秩检验正式证实：恩扎卢胺联合镭-223方案可为患者带来具有统计学显著性的OS获益。PEACE-3研究显示，中位随访58个月，联合组rPFS为19.4个月，单药组16.4个月（HR=0.69，P=0.0009）；最终OS联合组38.2个月，单药组32.6个月（HR=0.76，P=0.0096），死亡风险降低24%，OS延长5.6个月，TTNT、疼痛进展、SSE等次要终点均显著更优。≥3级不良事件联合组65.6%、单药组55.8%，联合组以疲劳、贫血、血小板减少、腹泻为主，加用骨保护剂可降低骨折风险，安全性可控。该方案突破既往联合困境，为骨转移为主的mCRPC一线提供更有效安全的选择。

这一结果并不意外，因为两种药物单药应用时均已被证实可为晚期前列腺癌患者带来OS获益；但联合方案的获益幅度，无论是早期数据还是本次最终结果，均表现得十分亮眼。而晚期前列腺癌患者中绝大多数合并骨转移，因此该方案具有极高的临床落地价值。

同时我们也必须正视临床试验的共性挑战：当前临床诊疗的迭代速度，已远超大型Ⅲ期临床试验的完成与数据读出速度。PEACE-3研究入组的以ARPI初治患者为主，但当前临床中绝大多数APMR患者已接受过ARPI治疗，ARPI经治人群中，新型ARPI联合镭-223是否仍能带来同等获益，目前仍无明确答案。

针对这一临床空白，目前已完成全组入组的DORA研究正在给出答案。该研究聚焦ARPI治疗进展后的APMR前列腺癌患者，头对头对比多西他赛单药与多西他赛联合镭-223的疗效与安全性。此前的随机Ⅱ期研究已证实，通过优化剂量与给药方案，两药联合不仅疗效更优，治疗毒性也更低，预计将在近期公布该研究的最终数据读出。

Oncology Frontier: What breakthrough advances in prostate cancer at this ASCO-GU congress have attracted your attention? Which studies and industry trends will have a profound impact on the clinical diagnosis and treatment of patients with prostate cancer?

Dr. Scott T. Tagawa: Advances in prostate cancer at this ASCO-GU congress fall into two core dimensions: first, the final data release of confirmatory clinical trials, which will directly rewrite and guide clinical practice; second, a large number of highly promising early exploratory studies, which, although they cannot directly change the current clinical treatment landscape in the short term, lay a solid foundation for long-term therapeutic breakthroughs.

First and foremost, we must emphasize the core innovation in the field: with the official release of the Prostate Cancer Clinical Trials Working Group 4 (PCWG4) consensus, the disease terminology system for prostate cancer has undergone a major update. The previously widely used term castration-resistant prostate cancer (CRPC) has been officially renamed Androgen Pathway Modulator-Resistant (APMR) Prostate Cancer, which forms the basis for the interpretation of all subsequent studies.

The most representative of these is the final survival data update of the PEACE-3 trial. This is a phase III randomized controlled clinical trial that enrolled predominantly androgen receptor pathway inhibitor (ARPI)-naive patients with APMR prostate cancer (only a small proportion of patients had prior abiraterone exposure), and was eligible for patients regardless of prior docetaxel chemotherapy. Patients were randomly assigned 1:1 to two groups: the control group received enzalutamide monotherapy, the standard of care at the time of trial initiation, and the experimental group received enzalutamide plus radium Ra 223 dichloride (radium-223), an approved bone-targeted alpha-particle emitter with many years of clinical use.

At the European Society for Medical Oncology (ESMO) congress a few years ago, the study had announced positive progression-free survival (PFS) results, with a clear trend of overall survival (OS) benefit. However, limited by the study design and crossing of survival curves, OS did not meet the prespecified statistical significance threshold at that time. The final updated data presented at this ASCO-GU congress, via log-rank test, formally confirmed that the enzalutamide plus radium-223 regimen delivers a statistically significant OS benefit for patients.

With a median follow-up of 58 months, the PEACE-3 trial showed a median radiographic PFS (rPFS) of 19.4 months in the combination group versus 16.4 months in the monotherapy group (HR=0.69, P=0.0009). The final median OS was 38.2 months in the combination group versus 32.6 months in the monotherapy group (HR=0.76, P=0.0096), representing a 24% reduction in the risk of death and a 5.6-month prolongation in OS. All key secondary endpoints, including time to next treatment (TTNT), time to pain progression, and symptomatic skeletal events (SSEs), were significantly improved in the combination arm. The incidence of grade ≥3 adverse events was 65.6% in the combination group and 55.8% in the monotherapy group, with fatigue, anemia, thrombocytopenia, and diarrhea being the most common events in the combination arm. The addition of bone-protective agents reduced the risk of fractures, with an overall controllable safety profile. This regimen breaks through the previous limitations of combination strategies, providing a more effective and safe first-line option for patients with bone-predominant metastatic CRPC (mCRPC).

This result is not unexpected, as both agents have individually been proven to deliver OS benefits in patients with advanced prostate cancer. However, the magnitude of benefit from the combination regimen, both in early data and this final analysis, is remarkable. Given that the vast majority of patients with advanced prostate cancer have concurrent bone metastases, this regimen has extremely high clinical translation value.

At the same time, we must face up to the common challenge of clinical trials: the iterative speed of current clinical diagnosis and treatment has far exceeded the speed of completion and data readout of large phase III clinical trials. The PEACE-3 trial enrolled predominantly ARPI-naive patients, but the vast majority of patients with APMR in current clinical practice have already received ARPI therapy. Whether novel ARPI plus radium-223 can deliver equivalent benefits in ARPI-exposed populations still has no clear answer.

To address this clinical gap, the DORA trial, which has completed full enrollment, is set to provide answers. This study focuses on patients with APMR prostate cancer who have progressed after ARPI therapy, and compares the efficacy and safety of docetaxel monotherapy versus docetaxel plus radium-223 in a head-to-head manner. A previous randomized phase II study has confirmed that by optimizing the dose and administration schedule, the combination of the two agents not only has better efficacy but also lower treatment toxicity, and the final data readout of the study is expected to be released in the near future.

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您对前列腺癌精准治疗的未来发展有何展望？在您看来，该领域下一步最核心、最关键的研究方向是什么？

Scott T. Tagawa 教授：当前的前列腺癌诊疗领域，正处于机遇与挑战并存的关键时期，我们面临两大核心问题，同时也有对应的突破方向—即便没有全新的药物问世，仅通过优化现有治疗体系，也能为患者带来显著的生存获益。

第一个核心方向，是现有治疗方案的精准化与分层化应用。目前针对APMR前列腺癌，我们已有多类成熟的治疗手段，包括新型内分泌治疗、化疗、骨靶向治疗、PARP抑制剂、分子分型指导的精准靶向治疗、前列腺特异性膜抗原（PSMA）靶向治疗等，即便没有新的治疗突破，患者的生存期已较十年前实现了大幅延长。

而未来的核心优化空间，在于通过更精准的生物标志物，筛选出各类方案的最佳获益人群，同时将现有药物前移至更合适的疾病阶段，最大化发挥治疗价值。比如通过预测性生物标志物，区分出哪些患者可以从早期联合治疗中获益，哪些患者可以豁免过度治疗，哪些患者需要提前更换治疗方案，这种精准分层，即便没有新药，也能给整个领域带来颠覆性的改变。

第二个核心方向，是全新靶点与全新作用机制药物的研发。尽管目前我们可用的前列腺癌治疗药物已达两位数，但绝大多数药物的作用机制高度同质化。比如美国已有4种获批的ARPI，中国也有多款自主研发的ARPI产品，但这类药物的作用机制均围绕AR通路，临床疗效与耐药特征高度相似。尽管绝大多数前列腺癌始终为AR驱动，我们仍有希望开发出更强效、能克服耐药的新型AR靶向药物，但对于单个患者而言，十余种同质化药物，并不意味着十余种不同的有效治疗选择，因此我们迫切需要全新靶点、全新作用机制的治疗药物。

具体到细分领域，未来最具潜力的研究方向主要分为三类：

1．更强效、可克服耐药的新型AR靶向治疗，针对ARPI耐药的患者，开发全新的AR通路干预手段；

2．细胞表面靶向治疗，包括以PSMA为代表的靶向放射性核素治疗、靶向ADC药物，进一步拓展靶向治疗的获益人群；

3．新型免疫治疗，其中最受关注的是T细胞重定向药物（双特异性抗体、T细胞衔接器），这类药物有望成为首个在前列腺癌中实现突破性疗效的免疫治疗手段，目前已有多项早期研究展现出积极的抗肿瘤活性。

总体而言，我对前列腺癌诊疗的未来充满信心，患者的生存前景会越来越光明。同时我也鼓励全球的临床医生与患者，积极参与临床试验，只有这样，我们才能更快地解答临床未被满足的需求，推动领域持续进步。

Oncology Frontier: Could you share your outlook on the future development of precision therapy for prostate cancer? In your opinion, what is the next core and most critical research direction in this field?

Dr. Scott T. Tagawa: The current field of prostate cancer diagnosis and treatment is in a critical period where opportunities and challenges coexist. We are facing two core problems, with corresponding breakthrough directions at the same time. Even without the advent of new drugs, we can bring significant survival benefits to patients only by optimizing the existing treatment system.

The first core direction is the precise and stratified application of existing treatment regimens. At present, for APMR prostate cancer, we have multiple types of mature treatment methods, including novel hormonal therapy, chemotherapy, bone-targeted therapy, PARP inhibitors, molecular profiling-guided precision targeted therapy, and prostate-specific membrane antigen (PSMA)-targeted therapy. Even without new therapeutic breakthroughs, patients' survival has been significantly prolonged compared with a decade ago.

The core room for optimization in the future lies in screening the optimal beneficiary population for each regimen through more precise biomarkers, and moving existing drugs forward to more appropriate disease stages to maximize therapeutic value. For example, through predictive biomarkers, we can distinguish which patients can benefit from early combination therapy, which patients can be exempted from overtreatment, and which patients need to change treatment regimens in advance. This precise stratification can bring disruptive changes to the entire field even without new drugs.

The second core direction is the research and development of drugs with novel targets and mechanisms of action. Although there are currently more than a dozen approved drugs for prostate cancer, the mechanisms of action of most drugs are highly homogeneous. For example, there are 4 approved ARPIs in the United States, and multiple independently developed ARPI products in China, but the mechanism of action of these drugs all revolves around the AR pathway, with highly similar clinical efficacy and resistance characteristics. Although the vast majority of prostate cancers are always AR-driven, we still have the hope to develop more potent novel AR-targeted drugs that can overcome resistance. However, for a single patient, more than ten homogeneous drugs do not mean more than ten different effective treatment options. Therefore, we urgently need therapeutic drugs with novel targets and mechanisms of action.

Specifically, the most promising research directions in the future are mainly divided into three categories:

1. More potent novel AR-targeted therapies that can overcome resistance, developing new AR pathway intervention methods for patients with ARPI resistance;

2. Cell surface-targeted therapy, including PSMA-targeted radionuclide therapy and targeted ADC drugs, to further expand the beneficiary population of targeted therapy;

3. Novel immunotherapy, among which the most watched are T-cell redirecting agents (bispecific antibodies, T-cell engagers). These drugs are expected to become the first immunotherapy to achieve breakthrough efficacy in prostate cancer, and a number of early studies have shown positive anti-tumor activity.

Overall, I am full of confidence in the future of prostate cancer diagnosis and treatment, and the survival prospects of patients will become brighter and brighter. At the same time, I encourage clinicians and patients around the world to actively participate in clinical trials. Only in this way can we more quickly address the unmet clinical needs and promote the continuous progress of the field.

Scott T. Tagawa 教授

美国威尔康奈尔医学院内科和泌尿外科教授，威尔康奈尔医学中心执业医师

研究涵盖泌尿生殖系统肿瘤和癌症患者血栓（血液凝固）的临床和转化研究。作为泌尿生殖系统肿瘤研究项目的医学主任，Scott T. Tagawa教授领导着前列腺癌、肾癌和膀胱癌以及癌症相关血栓的预防和治疗领域的临床试验。他专长于前列腺癌的药物研发和诊疗一体化。Scott T. Tagawa教授还担任泌尿生殖系统疾病管理团队的负责人和迈耶癌症中心实验治疗项目的联合负责人。他是WCM肿瘤临床试验联盟（原CALGB）的首席研究员，同时也是该联盟董事会成员和泌尿生殖系统委员会的资助成员。此外，他还担任多家期刊的编委，是众多国内外医学和科学学会的成员，并多次荣登“顶尖医生”榜单。

（来源：《肿瘤瞭望-泌尿时讯》编辑部）

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