Survival No Better With Intensive Surveillance in Endometrial Cancer

An intensive surveillance regimen for endometrial cancer did not improve overall survival (OS) over a minimalist regimen, even in high-risk patients, results from the randomized TOTEM trial showed.

After a median follow-up of 69 months, the 5-year OS rate was 90.6% with the intensive approach versus 91.9% with the minimalist approach, which mainly included physical examinations (HR 1.13, 95% CI 0.86-1.50, P=0.380), reported Elisa Piovano, MD, PhD, of AOU Città della Salute e della Scienza di Torino, Ospedale Sant’Anna in Torino, Italy, and colleagues.

When broken down into groups of low- and high-risk patients, the estimated 5-year OS rates with the intensive versus minimalist regimens for low-risk patients were 94.1% and 96.8% (HR 1.45, 95% CI 0.91-2.33, P=0.121), and 85.3% and 84.7%, respectively, for high-risk patients (HR 0.99, 95% CI 0.69-1.40, P=0.936), they noted in the Journal of Clinical Oncology.

“These results, on the basis of a large, pragmatic, multicenter trial, have a high degree of statistical robustness and transferability to clinical practice,” Piovano and team wrote. “According to available evidence, there is no reason to routinely add vaginal cytology, laboratory, or imaging investigations to the minimalist regimens used in this trial.”

As for secondary outcomes, the 5-year relapse-free survival rate was 90.7% in the intensive regimen arm and 93.7% in the minimalist arm (HR 1.17, 95% CI 0.92-1.48, P=0.194). The hazard ratios were 1.35 (95% CI 0.91-1.99) and 1.07 (95% CI 0.80-1.44) in the low- and high-risk groups, respectively.

In an editorial accompanying the study, Anna L. Beavis, MD, MPH, and Amanda N. Fader, MD, both of the Johns Hopkins School of Medicine in Baltimore, noted that the trial was slow to meet its “accrual goal of 2,300 patients needed to demonstrate an absolute improvement from 75% to 80% in 5-year survival in the overall study population with the intensive interventions.”

“However, this is not surprising, as almost 60% of the study population (and the entire low-risk group) consisted of patients with stage IA, grade 1-2 disease,” they wrote. They also pointed out that even within the high-risk group, 77.6% of patients had stage IB disease, while only 6% of enrolled patients had stage III or IV disease.

“Therefore, patients with advanced-stage disease and higher-risk histologies were severely under-represented in the study, making it difficult to conclude the optimal surveillance strategy for those patients,” Beavis and Fader continued. “Ultimately, the TOTEM trial is a surveillance study of patients with early-stage, low-risk endometrioid cancers. Although this was a negative trial and conclusions regarding surveillance interventions could not be made for patients with advanced-stage or nonendometrioid disease, this study is impactful, as most patients are diagnosed with early-stage, low-risk disease.”

TOTEM included 1,871 patients from 42 centers in Italy and France who were surgically treated for endometrial cancer and in complete clinical remission confirmed by imaging. They were randomly assigned 1:1 to intensive or minimalist hospital-based surveillance regimens. About 36% of patients were ages 55-64, and 32% were ages 65-74.

For patients who were considered low-risk (n=1,111), the minimalist follow-up regimen included 11 physical examinations (general and gynecological examinations) without serological, vaginal cytological, or imaging tests, while the intensive follow-up regimen consisted of 13 visits, annual vaginal cytology, and, in the first 2 years, annual chest, abdomen, and pelvis CT scans.

For high-risk patients (n=736), the minimalist approach included 13 visits and annual CT scans in the first 2 years, while the intensive approach included 14 visits with serum cancer antigen 125 (CA-125) dosage at every visit, abdomen and pelvis ultrasound examinations twice a year for 3 years, and then annual vaginal cytology and CT scans.

Piovano and colleagues found that adherence to follow-up schedules was slightly lower in the intensive arm (65.5%) than in the minimalist arm (69.5%), with similar differences in low- and high-risk groups. They suggested that this “suboptimal” adherence to scheduled visits and examinations within the intensive arm “is not only a limitation of the study but also an indicator of poor acceptability and feasibility of these intensive regimens.”