Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer

Abstract

Objective: Overall survival (OS) in endometrial cancer (EC) is dependent on patient-, disease-, and treatment-specific risk factors. Comprehensive risk-scoring models were developed to estimate OS in low-grade and high-grade EC.

Methods: Patients undergoing primary surgery for EC from 1999 through 2008 were stratified histologically according to the International Federation of Gynecology and Obstetrics (FIGO) as either (i) low grade: grades 1 and 2 endometrioid EC or (ii) high grade: grade 3, including non-endometrioid EC. Associations between patient-, pathological-, and treatment-specific risk factors and OS starting on postoperative day 30 were assessed using multivariable Cox regression models. Factors independently associated with OS were used to construct nomograms and risk-scoring models.

Results: Eligible patients (N=1281) included 925 low-grade and 356 high-grade patients; estimated 5-year OSs were 87.0% and 51.5%, respectively. Among patients alive at last follow-up, median follow-up was 5.0 (low grade) and 4.6years (high grade), respectively. In low-grade patients, independent factors predictive of compromised OS included age, cardiovascular disease, pulmonary dysfunction, stage, tumor diameter, pelvic lymph node status, and grade 2 or higher 30-day postoperative complications. Among high-grade patients, age, American Society of Anesthesiologists score, stage, lymphovascular space invasion, adjuvant therapy, para-aortic nodal status, and cervical stromal invasion were independent predictors of compromised OS. The two risk-scoring models/nomograms had excellent calibration and discrimination (unbiased c-indices=0.803 and 0.759).

Conclusion: Patients with low-grade and high-grade EC can be counseled regarding their predicted OS using the proposed risk-scoring models. This may facilitate institution of personalized treatment algorithms, surveillance strategies, and lifestyle interventions.

Keywords: Endometrial cancer; High grade; Low grade; Nomogram; Overall survival.

Fig. 1

A. Overall survival nomogram for low-risk patients (grades 1–2, endometrioid histology). B. Overall survival nomogram for high-risk patients (grade 3, non-endometrioid histology). Pelvic nodal status defined as ND, not done; Adeq, adequate (≥10 nodes removed); Inadeq, inadequate (<10 nodes removed); Neg, negative; and Pos, positive. Para-aortic nodal status defined as ND, not done; Adeq, adequate (≥5 nodes removed); Inadeq, inadequate (<5 nodes removed); Neg, negative; and Pos, positive. Vag BT denotes vaginal brachytherapy; RT, radiation therapy; Chemo±, chemotherapy ± radiation therapy ± vaginal brachytherapy.

Fig. 2

A. Calibration plot for 5-year overall survival (OS) probability based on the multivariable models for low-risk patients. B. Calibration plot for 5-year overall survival (OS) probability based on the multivariable models for high-risk patients. The dashed line indicates the ideal reference line where the predicted 5-year OS probabilities estimated from each model would match the Kaplan–Meier estimates of 5-year OS. Patients were grouped into quintiles according to their 5-year OS probability predicted by the final model. The vertical bars denote the 95% confidence interval for the Kaplan–Meier OS estimate derived for the patients in each quintile.