Tumor diameter as a predictor of lymphatic dissemination in endometrioid endometrial cancer

Highlights

• Tumor diameter is a useful parameter for identifying low-risk endometrial patients.

• TD > 50 mm and MI of > 33% identifies possible lymphatic dissemination.

• New model reduced the number of lymphadenectomies in low-risk patients.

Abstract

Objectives

To assess the utility of tumor diameter (TD) for predicting lymphatic dissemination (LD) and determining need for lymphadenectomy following diagnosis of endometrioid endometrial cancer.

Methods

Patients diagnosed with stage I–III endometrioid endometrial cancer during 2003–2013 who underwent pelvic or para-aortic lymphadenectomy during hysterectomy were studied. Intraoperative predictors of LD included TD, grade, myometrial invasion (MI), age, body mass index, and race/ethnicity. Candidate logistic regression models of LD were evaluated for model fit and predictive power.

Results

Of 737 cancer patients, 68 (9.2%) were node-positive. Single-variable models with only continuous TD (c-statistic 0.77, 95% CI 0.71–0.83) and dichotomous TD with 50-mm cut-off (TD₅₀; c-statistic 0.73, 95% CI 0.67–0.78) were significantly more predictive than with the standard 20-mm cut-off (c-statistic 0.56, 95% CI 0.53–0.59). Overall, the most important LD predictors were TD₅₀ and MI_3rds (three-category form). The best candidate model (c-statistic 0.84, 95% CI 0.80–0.88) suggested odds of LD were five times greater for TD > 50 mm than ≤ 50 mm (OR 4.91, 95% CI 2.73–8.82) and six and ten times greater for MI > 33% to ≤ 66% (OR, 5.70; 95% CI, 2.25–14.5) and > 66% (OR 10.2, 95% CI 4.11–25.4), respectively, than ≤ 33%. Best-model false-negative (0%) and positive (57.2%) rates demonstrated marked improvement over traditional risk-stratification false-negative (1.5%) and positive (76.2%) rates (c-statistic 0.77, 95% CI 0.72–0.82).

Conclusions

Tumor diameter is an important predictor of LD. Our risk model, containing modified forms of MI and TD, yielded a lower false-negative rate and can significantly decrease the number of lymphadenectomies performed on low-risk women.

Introduction

Endometrial cancer is the most common gynecologic malignancy and fourth most common cancer in women in the United States [1]. Appropriate surgical management is important to ensure the best prognosis. Currently, the standard of care includes complete lymph node dissection for all patients at risk of lymphatic dissemination [2], [3], [4], but recent evidence suggests that nodal dissection in patients with low-risk endometrial carcinomas does not add survival benefit [5], [6], [7], [8]. The definition of low-risk patient is in question. Various investigators have defined low risk as disease confined to the uterine corpus, tumor grade I or II, endometrioid histology, and ≤ 50% invasion of the myometrium. Recently, tumor diameter (TD) was introduced as a criterion for risk assessment, but results of its use are conflicting [2], [7], [9], [10], [11], [12]. Despite controversy of the TD criterion, the most clinically utilized model for risk assessment is that proposed by the Mayo Clinic. Mayo defines low-risk patients as those with grade I or II following International Federation of Gynecology and Obstetrics (FIGO) guidelines, endometrioid histology, myometrial invasion (MI) limited to the inner half, and TD ≤ 2 cm [7]. Criteria within the Mayo risk model were demonstrated as useful for assessment of nodal dissemination of uterine cancer in a large retrospective study [9].

Recognizing the uncertain utility of the TD criterion and the need for community-based investigations, our goal for this study was to evaluate TD as a predictor of lymphatic dissemination (LD) in uterine cancer patients who underwent surgery at a community program. We also applied the currently accepted Mayo risk schema to our own population and used results of our analyses to produce new variations on this model.