Benefit of radiotherapy and lymphadenectomy questioned in early-stage endometrial cancer

NEW YORK (Reuters Health) - Improved survival among women with stage I-II endometrial cancer who undergo radiotherapy and lymphadenectomy may be attributable in large part to selective application of these therapies in healthier patients, according to a new analysis of SEER (Surveillance, Epidemiology, and End Results) data.

"Publication bias is the tendency to report positive findings, and we all want treatments that can improve survival," Dr. Loren K. Mell told Reuters Health. "Unfortunately, we can be easily misled and pat ourselves on the back too soon when healthier patients happen to get the treatment we hope is beneficial."

In the case of early-stage endometrial cancer, randomized trials have not found evidence that radiotherapy and lymphadenectomy prolong survival, whereas population-based studies and retrospective cohort studies have, Dr. Mell, from University of California San Diego, La Jolla, and colleagues explain in their report in the Journal of the National Cancer Institute online October 11.

To investigate this disparity, the researchers used data from SEER 1988-2006 to determine the cause-specific effects of radiotherapy and lymphadenectomy in 58,172 women with stage I and II endometrial cancer.

Among these women, there were 2589 deaths from endometrial cancer, 3019 deaths from secondary malignancies, and 8015 deaths from other causes, according to the report.

Overall, women who underwent whole pelvic radiation therapy (WPRT) were more likely to die from endometrial cancer than women who had no radiotherapy (adjusted hazard ratio, 1.66). This increased risk was highest among women 31 to 40 years (aHR, 3.84) and lowest in women 81 to 90 years (aHR, 1.21).

Vaginal brachytherapy and lymphadenectomy were associated with increased endometrial cancer mortality in stage I patients but lower endometrial cancer mortality in stage II patients.

On the other hand, WPRT was associated with significantly decreased non-cancer mortality in intermediate- and high-risk patients with stage I or II disease (pooled HR, 0.82), as was lymphadenectomy in all stage I-II patients (HR, 0.84).

"On the whole, we interpret these findings as evidence that the associations between WPRT and lymphadenectomy and improved overall survival reported in other SEER studies is largely due to the selection of healthier patients with higher-risk disease for these interventions, rather than effects of the treatments per se," the researchers conclude.

"Once the average patient with early stage endometrial cancer has undergone a hysterectomy, mortality from causes other than endometrial cancer becomes her biggest health threat," Dr. Mell added. "Healthier patients tend to get more intensive treatment (e.g., extended lymph node dissection, radiotherapy) and that's why it appears that these treatments are associated with longer survival in studies, especially non-randomized studies."

"Be careful when you see a study that claims there is a survival benefit to treatment, especially when the rate of competing non-cancer mortality is high," Dr. Mell cautioned. "This is especially true of non-randomized trials but it goes for randomized trials too."

"We need better strategies to identify patients at high risk of non-cancer mortality and tailor our clinical trials appropriately to specific populations," Dr. Mell concluded. "This is my view and is quite contrary to the prevailing wisdom that claims that we should generalize clinical trial populations to make the studies representative to a wide population."

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