Effectiveness of Intensive Versus Minimalist Follow-Up Regimen on Survival in Patients With Endometrial Cancer (TOTEM Study): A Randomized, Pragmatic, Parallel Group, Multicenter Trial

Paolo Zola, Giovannino Ciccone, Elisa Piovano, Luca Fuso, Daniela Di Cuonzo, Anna Castiglione, Eva Pagano, Elena Peirano, Fabio Landoni, Enrico Sartori, Fabrice Narducci, Oscar Bertetto, Annamaria Ferrero, TOTEM Collaborative Group

J Clin Oncol

https://doi.org/10.1200/JCO.22.00471

Abstract

Purpose: In the absence of clear evidence from randomized trials, the intensity of follow-up regimens after surgical treatment of endometrial cancer is highly variable in clinical practice. To reduce this uncertainty, we conducted a randomized trial to test whether an intensive (INT) versus a minimalist (MIN) follow-up regimen improves overall survival (OS) in patients undergoing operation for endometrial cancer. Methods: The TOTEM study was a large, pragmatic randomized trial, conducted in 42 hospitals (in Italy and France) including patients surgically treated for endometrial cancer, in complete clinical remission, International Federation of Gynecology and Obstetrics stage I-IV. After stratification by center and risk of relapse (low or high), patients were randomly assigned (1:1) to INT or MIN hospital-based follow-up regimens. The study was powered to demonstrate an absolute improvement of 5% of the 5-year OS with the INT regimen. Results: In total, 1,871 patients were randomly assigned between November 2008 and July 2018, and 1,847 patients (98.7%) were available for the final analysis (60% low risk). After a median follow-up of 69 months, the 5-year OS was 90.6% in the INT and 91.9% in the MIN arms (hazard ratio, 1.13, 95% CI, 0.86 to 1.50, P = .380). No differences in OS were found in subgroup analyses considering age, cancer treatment, risk of relapse, and degree of adherence of the center to the scheduled follow-up. The probability of detecting a relapse was slightly higher in the INT arm (hazard ratio, 1.17; 95% CI, 0.92 to 1.48; P = .194). Conclusion: An INT follow-up in endometrial cancer-treated patients does not improve OS, even in high-risk patients. According to available evidence, there is no need to routinely add vaginal cytology, laboratory, or imaging investigations to the MIN regimens used in this trial.