No Need for Intensive Follow-up of Endometrial Cancer

Pam Harrison

October 27, 2022

Women with endometrial cancer do not need to undergo intensive follow-up, say experts.

Results from the TOTEM trial show that intensive follow-up does not improve overall survival (OS) compared to a much less intensive surveillance approach, even for high-risk patients.

"[T]here is no need to routinely add vaginal cytology, laboratory, or imaging investigations to the MIN [minimalist] regimens used in this trial," conclude Paolo Zola, MD, and colleagues on behalf of the TOTEM collaborative group.

The study was published September 1, 2022 in the Journal of Clinical Oncology.

In an accompanying editorial, Amanda Fader, MD, Johns Hopkins School of Medicine, Baltimore, Maryland, and colleagues endorse the authors' recommendations.

The editorialists point out that many oncologists are still utilizing intensive surveillance despite the fact that guidelines no longer recommend this.

For example, the guidelines from the Society of Gynecologic Oncology (SGO) now only recommend symptom review and physical examination of endometrial cancer survivors, including speculum and bimanual pelvic exam every 3 to 6 months for 2 years, then every 6 months or every year after that.

The National Comprehensive Cancer Network (NCCN) guidelines also indicate that routine imaging or vaginal cytology have limited utility.

"Despite these guidelines, significant practice variability exists among oncologists, with many preferring intensive surveillance, likely stemming from the belief among patients and physicians that if a recurrence is detected early, there is a higher likelihood of disease control or improved survival," the editorialists observe.

"The TOTEM trial is an important step forward in endometrial cancer surveillance care and substantiates a minimalist approach for most endometrial cancer patients," Fader and colleagues emphasize.

The study involved patients with early-stage, low-risk disease. Because most patients with endometrial cancer are diagnosed with early-stage, low-risk disease, this study is significant, and its results validate the existing SGO and NCCN guidelines, they add.

"By re-imaging outdated surveillance practices, TOTEM trial investigators demonstrate that more effective, evidence-based survivorship care is possible with potentially fewer interventions: In this setting, doing less indeed represents progress," they conclude.

Details of the TOTEM Study Results

The TOTEM study was a multicenter trial that compared two hospital-based surveillance approaches ― intensive (INT), and minimalist (MIN) ― over the course of 5 years.

It was carried out in 42 National Health Service hospitals in Italy and France.

All patients had been surgically treated for endometrial cancer and were in complete clinical remission. They were stratified into two groups: those at low risk for relapse (LoR), and those at high risk for relapse (HiR).

"For LoR patients, the MIN follow-up regimen scheduled only 11 physical examinations...without serological, vaginal cytological, or imaging tests," the authors explain.

For high-risk patients, the INT follow-up regimen consisted of 13 visits, annual vaginal cytology, and in the first 2 years, annual chest, abdomen, and pelvic CT scans, they add.

A total of 1847 patients were included in the analysis (mean age, 63.7 years). Almost 60% of the cohort had endometrial stage IA and grade 1–2 endometrial cancer, and almost two thirds of patients were treated with surgery alone.

At 5 years, 91.3% of patients in the low-risk group were still alive, as were 85% of high-risk patients, the investigators report.

The estimated 5-year OS in the intensive surveillance arm among low-risk patients was 94.1%, compared with 96.8% of those in the minimalist surveillance arm; for high-risk patients, the estimated 5-year OS rate for those followed intensively was 85.3%, compared with 84.7% of those followed less intensively.

"Most recurrences were diagnosed during the first 2 years of follow-up," the authors note. The median time from study entry to the diagnosis of relapse was 23 months in the low-risk group, compared with only 12 months in the high-risk group.

About half of all relapses were asymptomatic. Among the patients who experienced relapse, in only about one third did the relapse occur at a single site; the majority experienced relapse at multiple sites.

The editorialists comment that the value of clinical/pelvic examinations is "dubious" in women at low risk of recurrence, as only about 10% of recurrences in the TOTEM trial were detected by examination alone. For women at higher risk of recurrence, 75% of disease relapses were distant, and most were symptomatic, "suggesting that frequent pelvic examinations for asymptomatic patients may [also] be of low yield," write Fader and colleague

The tumor marker serum CA-125 was found in only 1.6% of women who experienced recurrence, though the low rate does not necessarily negate the value of using CA-125 in endometrial cancer surveillance. The editorialists argue that elevations in CA-125 are more commonly seen in patients with disease of high-grade histology, so following CA-125 levels in patients whose levels are elevated at diagnosis may still prove useful.

J Clin Oncol. Published online September 1, 2022. Abstract, Editorial

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