Trial Between Two Follow up Regimens With Different Test Intensity in Endometrial Cancer Treated Patients

Impact of different follow-up regimens on health-related quality of life and costs in endometrial cancer patients: Results from the TOTEM randomized trial

To investigate whether intensive follow-up (INT) after surgery for endometrial cancer impact health-related quality of life (HRQoL) and healthcare costs compared to minimalist follow-up (MIN), in the absence of evidence supporting any benefit on 5-year overall survival. In the TOTEM trial, HRQoL was assessed using the SF-12 and the Psychological General Well-Being (PGWB) questionnaires at baseline, after 6 and 12 months and then annually up to 5 years of follow-up. Costs were analyzed after 4 years of follow-up from a National Health Service perspective, stratified by risk level. The probability of missing data was analyzed for both endpoints. 1847 patients were included in the analyses. The probability of missing data was not influenced by the study arms (MIN vs INT OR: 0.97 95%CI: 0.87-1.08). Longitudinal changes in HRQoL scores did not differ between the two follow-up regimens (MIN vs INT SF-12 PCS: -0.573, CI95%: -1.31; 0.16; SF-12 MCS: -0.243, CI95%: -1.08; 0.59; PGWB: -0.057, CI95%: -0,88; 0,77). The mean cost difference between the intensive and minimalist arm was €531 for low-risk patients and €683 for high-risk patients. In the follow-up of endometrial cancer after surgery, a minimalist treatment regimen did not affect quality of life and was cost-saving in both low-risk and high-risk recurrence patients. As previous results showed no survival benefit, a minimalist approach is justified. The relevant proportion of missing data on secondary outcomes of interest could be a critical point that deserves special attention.

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

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.