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 2026）已圆满落幕，会上多项泌尿生殖系统肿瘤领域的重磅研究公布，为临床实践更新了关键循证依据。其中，针对初治晚期肾细胞癌的CYTOSHRINKⅡ期随机试验公布了研究结果，为免疫联合放疗的治疗模式提供了重要探索。本刊特邀加拿大麦克马斯特大学Juravinski癌症中心Aly-Khan A.Lalani教授解读研究核心设计、临床实践启示及领域前沿进展。

 

Aly-Khan A.Lalani教授：我在本次大会上公布的是CYTOSHRINK试验的首批研究结果，这是一项由研究者发起的多中心、开放标签、随机Ⅱ期临床试验，研究于2019年启动，核心目的是评估初治新发晚期肾细胞癌患者中，在免疫检查点抑制剂（ICI）标准治疗基础上，早期联合立体定向体部放疗（SBRT）的疗效与安全性。

 

本研究采用2:1的分层随机化设计，入组患者按国际转移性肾细胞癌数据库联盟（IMDC）风险分层（中危/高危）分层后，随机分配至干预组与对照组。对照组接受晚期肾细胞癌一线标准治疗—纳武利尤单抗联合伊匹木单抗双免疫方案；干预组则先接受1个周期的双免疫诱导治疗，序贯针对原发灶行SBRT（放疗剂量30~40 Gy，分5次分割完成），放疗结束后继续完成剩余周期的双免疫治疗，后续以纳武利尤单抗单药进行维持治疗。

 

研究的主要终点设定为1年无进展生存率，次要终点包括研究者评估的客观缓解率（ORR）、总生存期（OS）、患者生活质量（QoL）等，同时研究预设了关键的探索性生物标志物分析，相关结果将在后续陆续公布。

 

Oncology Frontier:Could you briefly introduce the core research you presented at this ASCO-GU congress?

 

Dr.Aly-Khan A.Lalani:What I presented at this congress is the first set of results from the CYTOSHRINK trial，an investigator-initiated，multicenter，open-label，randomized phase II clinical trial launched in 2019.The core objective of the study is to evaluate the efficacy and safety of early combination of Stereotactic Body Radiation Therapy(SBRT)on top of standard-of-care immune checkpoint inhibitor(ICI)therapy in patients with treatment-naive de novo advanced renal cell carcinoma.

 

The study adopted a 2:1 stratified randomization design.Enrolled patients were stratified by the International Metastatic Renal Cell Carcinoma Database Consortium(IMDC)risk category(intermediate-risk/high-risk)before being randomly assigned to the intervention group and the control group.The control group received the first-line standard treatment for advanced renal cell carcinoma–the dual immunotherapy regimen of nivolumab plus ipilimumab.The intervention group first received 1 cycle of induction dual immunotherapy，followed by SBRT to the primary tumor(a radiation dose of 30 to 40 Gy delivered in 5 fractions).After the completion of radiotherapy，patients continued to receive the remaining cycles of dual immunotherapy，followed by nivolumab monotherapy as maintenance treatment.

 

The primary endpoint of the study was set as the 1-year progression-free survival(PFS)rate.Secondary endpoints included investigator-assessed objective response rate(ORR)，overall survival(OS)，patient quality of life(QoL)，etc.Meanwhile，the study prespecified key exploratory biomarker analyses，the relevant results of which will be released sequentially in the follow-up.

 

Aly-Khan A.Lalani教授：通过对本次试验数据的全面分析，我们总结了几点对临床实践极具参考价值的核心发现。首先，本研究的患者入组依从性与参与意愿极佳。研究于2020年2月正式启动入组，恰逢新冠疫情爆发前期，后续受疫情防控相关措施影响，入组工作曾短暂暂停数月，但仍顺利完成了预设的入组目标。其次，在试验过程中我们发现，入组患者确诊时普遍处于疾病晚期，且基线临床特征存在显著的组间不均衡：干预组患者的整体肿瘤负荷更高，其中肾脏原发肿瘤体积显著大于对照组，同时干预组合并骨转移、肝转移的患者占比更高，基线预后特征较对照组更差。即便存在基线水平的不利因素，两组的主要终点——1年无进展生存率仍基本相当。我们针对完成4个周期纳武利尤单抗联合伊匹木单抗治疗的患者进行了符合方案集（PP集）分析，结果显示该人群整体预后更优，组间疾病进展或死亡风险比（HR）约为1.07。

 

亚组分析结果显示，相较于IMDC高危患者，中危患者从干预方案中获得的获益趋势更为显著，但该差异未达到统计学显著性—这主要是由于高危患者的入组样本量有限，导致统计结果的置信区间（CI）较宽，统计效能不足。

 

目前研究的总生存期数据仍在持续随访中，尚未成熟。而在肿瘤缓解维度，我们观察到了极具临床价值的信号：尽管两组的整体ORR相近，但截至本本次大会，干预组仍维持持续缓解状态的患者比例达50%，而对照组仅为10%。这一结果提示，双免疫早期联合SBRT的治疗模式，能够为获益人群带来更深、更持久的肿瘤缓解。

 

Oncology Frontier:What core insights can you share regarding the implications of this study for clinical practice，as well as the safety profile of the treatment regimen?

 

Dr.Aly-Khan A.Lalani:Through comprehensive analysis of the trial data，we have summarized several core findings with great reference value for clinical practice.First of all，the study had excellent patient enrollment compliance and willingness to participate.The study officially launched enrollment in February 2020，just before the outbreak of the COVID-19 pandemic.Although enrollment was briefly suspended for several months due to subsequent pandemic prevention and control measures，we still successfully completed the prespecified enrollment target.

 

Second，during the trial，we found that enrolled patients were generally at an advanced stage of the disease at diagnosis，with significant imbalance in baseline clinical characteristics between the groups:patients in the intervention group had a higher overall tumor burden，among which the volume of the primary renal tumor was significantly larger than that in the control group.Meanwhile，the intervention group had a higher proportion of patients with concurrent bone metastases and liver metastases，with worse baseline prognostic characteristics than the control group.Even with these unfavorable factors at baseline，the 1-year PFS rate，the primary endpoint of the study，was still largely comparable between the two groups.We conducted a per-protocol(PP)set analysis of patients who completed 4 cycles of nivolumab plus ipilimumab treatment，and the results showed that this population had an overall better prognosis，with a hazard ratio(HR)for disease progression or death of approximately 1.07 between the groups.

 

Subgroup analysis showed that，compared with IMDC high-risk patients，intermediate-risk patients had a more prominent trend of benefit from the intervention regimen，but the difference did not reach statistical significance.This was mainly due to the limited sample size of high-risk patients enrolled，which resulted in a wide confidence interval(CI)of the statistical results and insufficient statistical power.

 

At present，the overall survival data of the study are still under continuous follow-up and not yet mature.In terms of tumor response，we observed a signal with great clinical value:although the overall ORR was similar between the two groups，as of the date of this congress，the proportion of patients maintaining a durable response in the intervention group reached 50%，compared with only 10%in the control group.This result suggests that the treatment paradigm of early dual immunotherapy combined with SBRT can bring deeper and more durable tumor responses to the beneficiary population.

 

Aly-Khan A.Lalani教授：首先针对我们开展的CYTOSHRINK试验，后续我们将持续推进长期随访工作，重点关注患者的OS、QoL、疾病进展后的后续治疗模式、进展后接受减瘤性肾切除术患者的临床结局等核心指标；尤为重要的是，研究预设的生物标志物探索工作正在稳步开展，相关结果非常值得期待，有望为该治疗模式的优势人群筛选提供关键依据。

 

本次ASCO-GU 2026大会公布了诸多泌尿生殖系统肿瘤领域的突破性进展，亮点纷呈。其中尿路上皮癌领域的成果尤为瞩目，尤其是肌层浸润性膀胱癌（MIBC）围手术期治疗的方案优化探索，比如维恩妥尤单抗（EV）联合帕博利珠单抗的无化疗围手术期方案，展现出极具前景的疗效与可控的安全性，为不适合顺铂化疗的MIBC患者提供了全新的治疗选择。

 

而在肾癌领域，我们期待未来能有更多创新治疗方案与联合策略落地临床。后续我将重点关注肾癌辅助治疗阶段的双药联合方案、一线治疗失败后的后线联合治疗策略，以及这些方案在真实世界临床实践中的应用价值与长期生存获益。

 

Oncology Frontier:During this ASCO-GU congress，what studies do you think deserve key attention，and what exploratory directions may have an important impact on the future development of the field?

 

Dr.Aly-Khan A.Lalani:First，for the CYTOSHRINK trial we conducted，we will continue to advance long-term follow-up in the future，focusing on core endpoints including patients’OS，QoL，subsequent treatment patterns after disease progression，and clinical outcomes of patients who received cytoreductive nephrectomy after progression.Most importantly，the prespecified biomarker exploration work is being carried out steadily，and the relevant results are highly anticipated，which are expected to provide a key basis for the identification of the optimal patient population for this treatment paradigm.

 

ASCO-GU 2026 has presented numerous breakthrough advances in the field of genitourinary oncology，with many highlights.Among them，the achievements in the field of urothelial carcinoma are particularly remarkable，especially the exploration of optimized perioperative treatment regimens for muscle-invasive bladder cancer(MIBC).For example，the chemotherapy-free perioperative regimen of Enfortumab Vedotin(EV)combined with pembrolizumab has shown promising efficacy and controllable safety，providing a brand-new treatment option for MIBC patients who are ineligible for cisplatin-based chemotherapy.

 

In the field of renal cancer，we expect more innovative treatment regimens and combination strategies to be translated into clinical practice in the future.Going forward，I will focus on dual-drug combination regimens in the adjuvant setting of renal cancer，later-line combination treatment strategies after first-line treatment failure，as well as the application value and long-term survival benefits of these regimens in real-world clinical practice.

 

Aly-Khan A.Lalani教授

拉拉尼博士是麦克马斯特大学的助理教授

Juravinski癌症中心的肿瘤内科医生。他在波士顿的丹娜-法伯癌症研究所完成了泌尿生殖系统肿瘤专科医师培训。他还完成了哈佛大学陈曾熙公共卫生学院的临床疗效项目。其学术研究方向为临床试验设计和转化医学。