背景：癌症患者的強化隨訪，吸收了大量的衛生係統資料資源和可能是增加患者壓力的一個來源，經常被提出早期發現複發的假設將轉化為更好的結果。在子宮內膜癌很少進行隨機對照試驗來評估其作用減少了預定的就診次數和不同的隨訪設置，但沒有研究常規血清、細胞學或影像學隨訪對提高總生存率或生活質量的作用。TOTEM 研究是計劃比較強化（INT）和最低限度（MIN）5 年的隨訪方案子宮內膜癌患者的總生存率（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：子宮內膜癌患者經手術治療，影像學證實臨床完全緩解，FIGO I-IV 期，按中心和低（LoR）或高（HiR）複發風險分層，然後隨機分為 INT 或 MIN 基於醫院的隨訪方案。主要研究假設是證明 INT 方案的 5年生存率從 75%提高到 80%（預期風險比，HR=0.78）。次要目標是比較兩組患者的無複發生存率（RFS）、健康相關生活質量（HRQL）基線，6 個月和 12 個月，然後每年（SF-12 生理和心理測試）健康彙總表）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.
結果：2008 年至 2018 年間，42 個中心隨機抽取 1884 名患者，1847 名患者進入最終分析（60%LoR）。對隨訪計劃的依從性為 75.3%，在 INT 組（74.7%）和 MIN 組（75.9%）之間相似，而 INT 組的平均記錄檢查次數（實驗室或影像）明顯高於 MIN 組（9.7 Vs 2.9，p<0.0001）。中位隨訪 66 個月後，總的 5 年 OS 為91.3%，INT 組和 MIN 組分別占 90.6%和 91.9%（HR=1.12，95%可信區間 0.85-1.48，p=0.429）。比較 INT和 MIN 組，5 年的 OS 是在 LoR 中分別為 94.1%和 96.8%（HR=1.48，0.92-2.37，p=0.104），和 HiR 組為 85.3%和 84.7%（HR=0.96，0.68-1.36，p=0.814）。INT 和 MIN 方案之間的 RFS 中無差異（HR=1.13，0.87-1.48，p=0.365）。在複發時，大多數婦女無症狀（146/228，64.0%），其中無論是在 LoR 組（78.8%比 61.1%，p=0.070）還是 HiR 組（64%比 60%，p=0.754），INT 組的比例都高於 MIN 組。HRQL 僅適用於一些亞組患者（基線檢查的 50%），且兩組之間沒有差異。
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.
結論：子宮內膜癌患者的強化隨訪在發現早期無症狀複發方麵表現出微弱且不確定的優勢，沒有改善OS，即使在 HiR 患者，也不影響 HRQL。不建議對這些患者進行密集的影像學檢查和實驗室檢查。
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.
