背景：癌症患者的强化随访，吸收了大量的卫生系统资料资源和可能是增加患者压力的一个来源，经常被提出早期发现复发的假设将转化为更好的结果。在子宫内膜癌很少进行随机对照试验来评估其作用减少了预定的就诊次数和不同的随访设置，但没有研究常规血清、细胞学或影像学随访对提高总生存率或生活质量的作用。TOTEM 研究是计划比较强化（INT）和最低限度（MIN）5 年的随访方案子宫内膜癌患者的总生存率（OS）。

Background: Intensive follow-up in cancer patients, which absorbs a lot of health system resources and can be a source of increased stress for patients, are often proposed on the assumption that an early recognition of relapse will translate in better outcomes. In endometrial cancer few randomized controlled trials were conducted to assess the role of a reduced number of the scheduled visits and of different settings of the follow-up, but did not investigate the contribution of routine serum, cytological or imaging follow-up investigations in improving overall survival or quality of life. The TOTEM study was planned to compare an intensive (INT) vs minimalist (MIN) 5- year follow-up regimen in endometrial cancer patients in terms of overall survival (OS).

方法：子宫内膜癌患者经手术治疗，影像学证实临床完全缓解，FIGO I-IV 期，按中心和低（LoR）或高（HiR）复发风险分层，然后随机分为 INT 或 MIN 基于医院的随访方案。主要研究假设是证明 INT 方案的 5年生存率从 75%提高到 80%（预期风险比，HR=0.78）。次要目标是比较两组患者的无复发生存率（RFS）、健康相关生活质量（HRQL）基线，6 个月和 12 个月，然后每年（SF-12 生理和心理测试）健康汇总表）和成本。

Methods: Patients surgically treated for endometrial cancer, in complete clinical remission confirmed by imaging, FIGO stage I-IV, were stratified by center and in low (LoR) or high (HiR) risk of recurrence and then randomized to INT or MIN hospital-based follow-up regimens. The main study hypothesis was to demonstrate an improvement from 75% to 80% (expected hazard ratio, HR = 0.78) of the 5-year OS with the INT regimen. Secondary objectives were to compare relapse free survival (RFS), health-related quality of life (HRQL) assessed at baseline, at 6 and 12 months and then yearly (with the SF-12 Physical and Mental Health Summary Scale) and costs.

结果：2008 年至 2018 年间，42 个中心随机抽取 1884 名患者，1847 名患者进入最终分析（60%LoR）。对随访计划的依从性为 75.3%，在 INT 组（74.7%）和 MIN 组（75.9%）之间相似，而 INT 组的平均记录检查次数（实验室或影像）明显高于 MIN 组（9.7 Vs 2.9，p<0.0001）。中位随访 66 个月后，总的 5 年 OS 为91.3%，INT 组和 MIN 组分别占 90.6%和 91.9%（HR=1.12，95%可信区间 0.85-1.48，p=0.429）。比较 INT和 MIN 组，5 年的 OS 是在 LoR 中分别为 94.1%和 96.8%（HR=1.48，0.92-2.37，p=0.104），和 HiR 组为 85.3%和 84.7%（HR=0.96，0.68-1.36，p=0.814）。INT 和 MIN 方案之间的 RFS 中无差异（HR=1.13，0.87-1.48，p=0.365）。在复发时，大多数妇女无症状（146/228，64.0%），其中无论是在 LoR 组（78.8%比 61.1%，p=0.070）还是 HiR 组（64%比 60%，p=0.754），INT 组的比例都高于 MIN 组。HRQL 仅适用于一些亚组患者（基线检查的 50%），且两组之间没有差异。

Results: 1884 patients were randomized in 42 centers between 2008 and 2018, and 1847 patients were available for the final analysis (60% LoR). Compliance with the follow-up scheduled visits was 75.3%, similar between INT (74.7%) and MIN (75.9%) arms, whereas the mean number of recorded exams (laboratory or imaging) was markedly higher in the INT than in the MIN arms (9.7 vs 2.9, p < 0.0001). After a median follow-up of 66 months, the overall 5-year OS was 91.3%, 90.6% in the INT and 91.9% in the MIN arms, respectively (HR = 1.12, 95%CI 0.85-1.48, p = 0.429). Comparing the INT vs MIN arms, the 5-year OS were 94.1% and 96.8% (HR = 1.48, 0.92-2.37, p = 0.104) in the LoR and 85.3% and 84.7% (HR = 0.96, 0.68-1.36, p = 0.814) in the HiR group. No relevant differences emerged in RFS between INT and MIN regimens, (HR = 1.13, 0.87-1.48, p = 0.365). At the time of the relapse most women were asymptomatic (146/228, 64.0%), with a tendency of higher proportions in the INT than in the MIN arm, both in the LoR group (78.8% vs 61.1%, p = 0.070) and in the HiR one (64% vs 60%, p = 0.754). HRQL was available only for a subgroup of patients (50% at baseline) and did not differ between arms.

结论：子宫内膜癌患者的强化随访在发现早期无症状复发方面表现出微弱且不确定的优势，没有改善OS，即使在 HiR 患者，也不影响 HRQL。不建议对这些患者进行密集的影像学检查和实验室检查。

Conclusions: Intensive follow-up in endometrial cancer treated patients showed a weak and uncertain advantage in detecting earlier asymptomatic relapses but did not improve OS, even in HiR patients, nor influenced HRQL. Frequent routine use of imaging and laboratory exams in these patients should be discouraged.