Intensive follow-up of surgically treated patients with endometrial cancer also does not improve overall survival

Results from the TOTEM study showed no improvement in overall survival (OS) and early detection of recurrence in patients who underwent surgery for endometrial cancer and followed up with an intensive 5-year regimen, regardless of recurrence risk. Based on the results of this large, randomized, pragmatic, multicenter study, there is no reason to routinely add vaginal cytology, laboratory, or imaging to the minimal follow-up protocol used in the study. The results add to strong evidence that reinforces the existing trend in guideline recommendations to encourage minimal follow-up, including regular clinical visits and computed tomography scans of the chest, abdomen and pelvis in high-risk patients in the first two years. The findings were published on July 20, 2022 in the Journal of Clinical Oncology by Dr. Elisa Piovano from the AOU Città della Salute e della Scienza di Torino, Ospedale Sant’anna and TOTEM Collaborative Group.

Endometrial cancer is the most common gynecological cancer in Europe, the authors wrote in a background article. The 5-year relative survival rate in this population was 76%, with earlier diagnosis explaining the relatively high survival rate. According to current guidelines, after treatment, patients are followed for 5 years, with hospital visits every 3-4 months for the first 2 years and every 6-12 months for 5 years. However, despite the lack of evidence to support the effectiveness of follow-up in improving survival or quality of life (QoL), follow-up requires a considerable investment in clinical resources. Furthermore, few people follow these guidelines. Intensive follow-up protocols are widely used, at least in southern Europe.

In this context, a number of randomized controlled studies have been published involving settings that reduce the number of planned visits and follow-up, but have never investigated routine serum, cytology, or imaging Examine the effect on improving OS or quality of life. In the absence of clear evidence from randomized studies, the strength of follow-up regimens following surgical treatment of endometrial cancer varies widely in clinical practice. To reduce this uncertainty, the research team conducted a randomized study to test whether intensive versus minimal follow-up protocols could improve OS in patients undergoing surgery for endometrial cancer.

TOTEM study conducted in 42 hospitals in Italy and France in patients with endometrial cancer undergoing surgery, clinical complete remission, International Federation of Gynaecology and Obstetrics stage I-IV . After stratification by center and risk of recurrence (low or high), patients were randomized 1:1 to intensive or minimal hospital follow-up. This study demonstrated a 5% absolute improvement in 5-year OS with the intensive regimen.

A total of 1,871 patients were randomized between November 2008 and July 2018, and 1,847 patients (98.7%) were available for final analysis, of which 60% were low risk. After a median follow-up of 69 months, the 5-year OS was 90.6% in the intensive group and 91.9% in the minimalist group (hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.86 to 1.50, p = 0.380). No differences in OS were found in subgroup analyses, taking into account age, treatment, risk of recurrence, and center compliance with scheduled follow-up. The probability of detecting recurrence was slightly higher in the intensive treatment group (HR 1.17, 95% CI, 0.92 to 1.48; p = 0.194).

The authors comment that the main advantages of their study are the large sample size and long follow-up. An important feature of this study is its representation of the real population. However, some degree of underrepresentation and misclassification of recurrence risk cannot be excluded from non-endometrioid histology, especially for the low-risk group that may contain some p53-mutated patients, an unfavorable prognosis unknown at the time of TOTEM. Factor studies are envisaged.

The authors concluded that the TOTEM study clearly showed that intensive follow-up of surgically treated endometrial cancer did not improve OS, even in high-risk patients. These findings are highly statistically robust and transferable to clinical practice.

Source: ESMO