Section snippets

Patients receiving subsequent therapy

Initially, we assessed the number of patients in the control groups who underwent any subsequent treatment (including surgery, radiotherapy, or systemic therapy) after a disease-free survival event. Among the 15 perioperative ICI trials examined, only eight trials provided data on the number of patients receiving any subsequent therapy. In the melanoma clinical trials, 62 (89·8%) of 69 patients (CheckMate 76K) and 282 (87·3%) of 323 patients (EORTC 18071) who had a disease-free survival event

Patients receiving subsequent systemic therapy

We examined the number of patients who underwent systemic therapy following disease-free survival events in the control group. Among the 15 perioperative ICI trials examined, 13 provided data on the number of patients receiving subsequent systemic therapy. In the melanoma trials, 44 (38·2%) of 115 patients (KEYNOTE-716), 49 (71·0%) of 69 (CheckMate 76K), and 218 (72·2%) of 302 (KEYNOTE-054) who experienced a disease-free survival event received systemic therapy. In the NSCLC trials, 131 (61·8%)

Patients receiving subsequent immunotherapy

We then reviewed the proportion of patients receiving subsequent systemic immunotherapy among the patients who experienced a disease-free survival event in the control or non-experimental group. In the melanoma trials KEYNOTE-716 and KEYNOTE-054, which were the only trials with a built-in cross-over, 35 (30·4%) of 115 patients (KEYNOTE-716) and 195 (64·6%) of 302 (KEYNOTE-054) with a disease-free survival event received ICI as subsequent therapy. In the NSCLC trials, 102 (48·1%) of 212 patients

Non-immune subsequent systemic therapy

Relapses after surgery in some types of cancers are typically aggressive and surveillance or local therapies are not recommended. An example is urothelial carcinoma, for which regular radiology monitoring within adjuvant trials should enable early detection, necessitating timely intervention.⁵ Chemotherapy has been considered the global standard of care for the management of patients with metastatic urothelial carcinoma and is globally available. Therefore, upon relapse, most patients should

Real-world scenarios after recurrence

To further understand the vast range of scenarios following tumour relapses, we created a visualisation of real-world instances of reporting subsequent therapies in perioperative trials, specifically focusing on renal cell carcinoma from KEYNOTE-564 (appendix p 3), the only pure adjuvant immunotherapy trial in solid cancers with an overall survival benefit. Our point was to illustrate that analyses of subsequent therapies are time-dependent and complex. For instance, by capturing subsequent

Discussion

Only a subset of patients seem to receive subsequent therapies in perioperative trials, suggesting some unmet needs in practice, from education and health-system organisation to accessibility to standard and innovative treatments. Potential gaps in clinical trials data collection are also possible and could be attributed to challenges in keeping track of patients in long-term clinical trials, or even entering data appropriately.11, 12 A review by Fitzpatrick and colleagues¹³ showed that longer

中文翻译：

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多种癌症类型的围手术期免疫治疗试验中后续治疗的前景

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接受后续治疗的患者

最初，我们评估了对照组中在无病生存事件后接受任何后续治疗（包括手术、放疗或全身治疗）的患者人数。在检查的 15 项围手术期 ICI 试验中，只有 8 项试验提供了接受任何后续治疗的患者人数的数据。在黑色素瘤临床试验中，69 名患者中有 62 名 （89·8%） （CheckMate 76K） 和 323 名患者 （EORTC 18071） 中有 282 名 （87·3%） 有无病生存事件

接受后续全身治疗的患者

我们检查了对照组在无病生存事件后接受全身治疗的患者人数。在检查的 15 项围手术期 ICI 试验中，13 项提供了接受后续全身治疗的患者人数的数据。在黑色素瘤试验中，115 名患者中有 44 名 （38·2%） （KEYNOTE-716），69 名患者中有 49 名 （71·0%） （CheckMate 76K），和 302 名患者中有 218 名 （72·2%） （KEYNOTE-054） 经历了无病生存事件接受了全身治疗。在 NSCLC 试验中，131 例 （61·8%）

接受后续免疫治疗的患者

然后，我们回顾了对照组或非实验组经历无病生存事件的患者接受后续全身免疫治疗的患者比例。在黑色素瘤试验 KEYNOTE-716 和 KEYNOTE-054 中，这是唯一具有内置交叉的试验，115 名患者中有 35 名 （30·4%） （KEYNOTE-716） 和 302 名患者中有 195 名 （64·6%） （KEYNOTE-054） 有无病生存事件接受 ICI 作为后续治疗。在 NSCLC 试验中，212 名患者中有 102 名 （48·1%）

非免疫性后续全身治疗

某些类型的癌症术后复发通常具有侵袭性，不建议进行监测或局部治疗。一个例子是尿路上皮癌，对于这种癌，在辅助试验中定期进行放射学监测应该能够及早发现，需要及时干预。⁵ 化疗被认为是转移性尿路上皮癌患者管理的全球标准护理，并且在全球范围内可用。因此，在复发时，大多数患者应该

复发后的真实场景

为了进一步了解肿瘤复发后的广泛情况，我们创建了围手术期试验中报告后续治疗的真实世界实例的可视化，特别关注 KEYNOTE-564 中的肾细胞癌（附录 p 3），这是唯一具有总生存期获益的实体癌纯辅助免疫治疗试验。我们的目的是为了说明后续疗法的分析是时间依赖性和复杂的。例如，通过捕获后续

 讨论

在围手术期试验中，似乎只有一部分患者接受了后续治疗，这表明实践中存在一些未满足的需求，从教育和卫生系统组织到标准和创新治疗的可及性。临床试验数据收集中可能存在的潜在差距，这可能归因于在长期临床试验中跟踪患者，甚至适当输入数据方面的挑战。11， 12 Fitzpatrick 及其同事¹³ 的一项审查表明，更长的