Intensive Follow-up Does Not Improve Survival in Endometrial Cancer

Endometrial cancer is among the most common gynecological cancers in Europe. Fortunately, most patients present with operable disease which has a good prognosis, with a 5-year relative survival of 76%. After surgery ± adjuvant therapy, current guidelines recommend 5 years of follow-up, including hospital visits every 3 – 4 months during the first 2 years and then every 6 – 12 months for the remaining 3 years. However, adherence to guidelines and intensity of follow-up after treatment in clinical practice is highly variable. While randomized controlled clinical trials have investigated a reduction in the number of scheduled visits and the role of nurse-led phone follow up, the impact of intensive follow-up, including routine serum, cytological examination and imaging scans on overall survival (OS), has not been investigated.

This was addressed in the recently published TOTEM trial, which was a large, randomized, pragmatic, parallel-group trial conducted in 42 national health service hospitals in Italy and France. The study sought to investigate whether an intensive follow-up approach improves OS compared with minimalist 5-year hospital-based follow-up in patients with surgically treated endometrial cancer. Before randomization, patients were stratified by center and risk of relapse (low vs. high risk) according to FIGO classification. The minimal follow-up regimen for low-risk patients consisted of 11 visits with general and gynecological examination, but no serological, vaginal cytological, or imaging tests. By contrast, intensive follow-up for low-risk patients included 13 visits and additional annual vaginal cytology, and in the first 2 years, annual chest, abdomen, and pelvis computed tomography (CT) scans. For high-risk patients, the minimalist follow-up consisted of 13 visits and annual CT scans in the first 2 years, while the intensive follow-up regimen for these patients included 14 visits with serum cancer antigen 125 (CA-125) tests at every visit, abdomen and pelvis ultrasound examinations twice a year for 3 years, and annual vaginal cytology and CT scans.

Among 1847 patients included in the analysis, the minimal and intensive follow-up groups were well balanced, including age, stage, and histologic subtype. The median follow-up was 69 months. The overall 5-year OS rate was 91.3%, with 198 patient deaths. There was no difference in 5-year OS among patients receiving intensive vs. minimal follow-up (90.6% vs. 91.9%; hazard ratio [HR], 1.13; = 0.380). Similarly, comparison of 5-year OS in the intensive vs. minimal follow-up according to risk group showed no difference: low-risk group (94.1% vs. 96.8%, respectively; HR, 1.45; = 0.121); high-risk group (85.3% vs. 84.7%, respectively (HR, 0.99; = 0.936). In addition, subgroup analyses considering age, cancer treatment, risk of relapse, and center adherence showed no benefit of intensive follow-up.

In total, 175 patients (51 in the low-risk and 124 in the high-risk group) developed disease recurrence. Most recurrences were diagnosed during the first 2 years of follow-up, with a median time to diagnosis of the relapse of 14 months (23 months in the low-risk group and 12 months in the high-risk group). The 5-year relapse-free survival with intensive follow up vs. minimal follow up was 90.7% vs. 93.7% (HR, 1.17; = 0.194). About half of relapses were asymptomatic. The majority of the relapses were detected by visit and CT scan (50.8%). Detection of relapses in women who received the intensive follow-up was slightly higher, especially of asymptomatic relapses, but this earlier detection did not translate in OS improvements. Patients’ adherence to scheduled visits in the intensive follow-up group was slightly lower (65.5%) than those in the minimal follow-up group (69.5%; = 0.048).

The authors of the TOTEM trial concluded that the trial “clearly showed that intensive follow-up in patients treated for endometrial cancer does not improve OS, even in high-risk patients”. Furthermore, these results “add robust evidence to reinforce the existing trend in guideline recommendations to encourage a minimalist follow-up, including scheduled clinical visits and chest, abdomen, and pelvis computed tomography in the first two years for high-risk patients”.

Zola P, et al. J Clin Oncol. 2022, July 20 [Online ahead of print].