Tumor Size, an Additional Prognostic Factor to Include in Low-Risk Endometrial Cancer: Results of a French Multicenter Study.

BACKGROUND: Additional tools are needed to improve the selection of women with early-stage endometrial cancer (EC) at increased risk of nodal metastases and/or recurrence to adapt surgical staging and adjuvant therapies. The aim of this study was to assess the impact of EC tumor size on nodal status and recurrence-free survival (RFS) according to European risk groups for recurrence. METHODS: Data of 633 women with early-stage EC who received primary surgical treatment between 2001 and 2012 were abstracted from a multicenter database. Optimal tumor size cut-offs were determined by a minimal p value approach according to final nodal status. Logistic regression was used to determine the impact of defined tumor size on nodal involvement, and the Kaplan-Meier method was used to estimate the survival distribution. RESULTS: The number of women with final low-, intermediate-, and high-risk EC was 302, 204, and 127, respectively. Tumor size was correlated with nodal status and RFS in women with low-risk EC, while no correlation was found for women with intermediate/high-risk EC. Tumor size ≥35 mm emerged as the optimal threshold for a higher rate of nodal involvement (odds ratio 4.318, 95 % CI 1.13-16.51, p = 0.03) and a lower RFS (p = 0.005) in women with low-risk EC. CONCLUSION: Tumor size is an independent prognostic factor of lymph node involvement in women with low-risk EC and could be a valuable additional histological criterion for selecting women at increased risk of lymph node metastases to better adapt surgical staging.

A Predictive Model Using Histopathologic Characteristics of Early-Stage Type 1 Endometrial Cancer to Identify Patients at High Risk for Lymph Node Metastasis.

BACKGROUND: This study aimed to develop a predictive model using histopathologic characteristics of early-stage type 1 endometrial cancer (EC) to identify patients at high risk for lymph node (LN) metastases. METHODS: The data of 523 patients who received primary surgical treatment between January 2001 and December 2012 were abstracted from a prospective multicenter database (training set). A multivariate logistic regression analysis of selected prognostic features was performed to develop a nomogram predicting LN metastases. To assess its accuracy, an internal validation technique with a bootstrap approach was adopted. The optimal threshold in terms of clinical utility, sensitivity, specificity, negative predictive values (NPVs), and positive predictive values (PPVs) was evaluated by the receiver-operating characteristics (ROC) curve area and the Youden Index. RESULTS: Overall, the LN metastasis rate was 12.4 % (65/523). Lymph node metastases were associated with histologic grade, tumor diameter, depth of myometrial invasion, and lymphovascular space involvement status. These variables were included in the nomogram. Discrimination of the model was 0.83 [95 % confidence interval (CI) 0.80-0.85] in the training set. The area under the curve ROC for predicting LN metastases after internal validation was 0.82 (95 % CI 0.80-0.84). The Youden Index provided a value of 0.2, corresponding to a cutoff of 140 points (total score in the algorithm). At this threshold, the model had a sensitivity of 0.73 (95 % CI 0.62-0.83), a specificity of 0.84 (95 % CI 0.82-0.85), a PPV of 0.40 (95 % CI 0.34-0.45), and an NPV of 0.95 (95 % CI 0.94-0.97). CONCLUSION: The results show that the risk of LN metastases can be predicted correctly so that patients at high risk can benefit from adapted surgical treatment.

Implications of a two-step procedure in surgical management of patients with early-stage endometrioid endometrial cancer.

OBJECTIVE: Since European Society for Medical Oncology (ESMO) recommendations and French guidelines, pelvic lymphadenectomy should not be systematically performed for women with early-stage endometrioid endometrial cancer (EEC) preoperatively assessed at presumed low- or intermediate-risk. The aim of our study was to evaluate the change of our surgical practices after ESMO recommendations, and to evaluate the rate and morbidity of second surgical procedure in case of understaging after the first surgery. METHODS: This retrospective single-center study included women with EEC preoperatively assessed at presumed low- or intermediate-risk who had surgery between 2006 and 2013. Two periods were defined the times before and after ESMO recommendations. Demographics characteristics, surgical management, operative morbidity, and rate of understaging were compared. The rate of second surgical procedure required for lymph node resection during the second period and its morbidity were also studied. RESULTS: Sixty-one and sixty-two patients were operated for EEC preoperatively assessed at presumed low-or intermediate-risk before and after ESMO recommendations, respectively. Although immediate pelvic lymphadenectomy was performed more frequently during the first period than the second period (88.5% vs. 19.4%; p<0.001), the rate of postoperative risk-elevating or upstaging were comparable between the two periods (31.1% vs. 27.4%; p=0.71). Among the patients requiring second surgical procedure during the second period (21.0%), 30.8% did not undergo the second surgery due to their comorbidity or old age. For the patients who underwent second surgical procedure, mean operative time of the second procedure was 246.1±117.8 minutes. Third operation was required in 33.3% of them because of postoperative complications. CONCLUSION: Since ESMO recommendations, second surgical procedure for lymph node resection is often required for women with EEC presumed at low- or intermediate-risk. This reoperation is not always performed due to age/comorbidity of the patients, and presents a significant morbidity.

Severe Obesity Impacts Recurrence-Free Survival of Women with High-Risk Endometrial Cancer: Results of a French Multicenter Study.

BACKGROUND: Studies focusing on the impact of obesity on survival in endometrial cancer (EC) have reported controversial results and few data exist on the impact of obesity on recurrence rate and recurrence-free survival (RFS). The aim of this study was to assess the impact of obesity on surgical staging and RFS in EC according to the European Society of Medical Oncology (ESMO) risk groups. METHODS: Data of 729 women with EC who received primary surgical treatment between January 2000 and December 2012 were abstracted from a multicenter database. RFS distributions according to body mass index (BMI) in each ESMO risk group were estimated using the Kaplan-Meier method. Survival was evaluated using the log-rank test, and the Cox proportional hazards model was used to determine influence of multiple variables. RESULTS: Distribution of the 729 women with EC according to BMI was BMI < 30 (n = 442; 60.6 %), 30 ≤ BMI < 35 (n = 146; 20 %) and BMI ≥ 35 (n = 141; 19.4 %). Nodal staging was less likely to be performed in women with a BMI ≥ 35 (72 %) than for those with a BMI < 30 (90 %) (p < 0.0001). With a median follow-up of 27 months (interquartile range 13-52), the 3-year RFS was 84.5 %. BMI had no impact on RFS in obese women in the low-/intermediate-risk groups, but a BMI ≥ 35 was independently correlated to a poorer RFS (hazard ratio 12.5; 95 % confidence interval 3.1-51.3) for women in the high-risk group. CONCLUSION: Severe obesity negatively impacts RFS in women with high-risk EC, underlining the importance of complete surgical staging and adapted adjuvant therapies in this subgroup of women.

A risk scoring system to determine recurrence in early-stage type 1 endometrial cancer: a French multicentre study.

BACKGROUND: To develop a risk scoring system (RSS) to determine recurrence in women with early-stage type 1 endometrial cancer (EC). METHODS: Data of 396 women with early-stage type 1 EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from multicentre database (training set). A risk model for predicting recurrence was developed and internally validated with the bootstrap technique. The RSS was externally validated using data from an independent population. RESULTS: Overall, the recurrence rate was 12.1 %. The median follow-up and initial time to recurrence were 34 (range 1-152) and 26 (range 1-151) months, respectively. Recurrence was associated with five variables: age ≥60 years, histological grade III, primary tumor diameter >2 cm, depth of myometrial invasion ≥50 %, and the positive lymphovascular space involvement status. These variables were included in the RSS and assigned scores. A total score of 6.5 points corresponded to the optimal threshold of the RSS. For women with a score <6.5 or ≥6.5, the recurrence rates were 8.4 % (30/357) and 48.7 % (19/39) in the training set, respectively. At this threshold, the diagnostic accuracy of the RSS was 87 %. Areas under the curve of the receiver-operating characteristics for predicting recurrence at internal and external validation were 0.74 [95 % confidence interval (CI) 0.71-0.77] and 0.82 (95 % CI 79-85), respectively. CONCLUSIONS: This RSS identified two subsets of women with low and high risk of recurrence among women with early-stage type 1 EC. It could be helpful to better define indications for nodal staging and adjuvant therapy.