Lymph Node Excision

This is a retrospective study using the National Cancer Institute Surveillance, Epidemiology, and End Results Program, a publicly available and deidentified population-based tumor registry covering approximately 28% of the U.S. population.⁹ The data entry to this database is performed by registered staff personnel with rigorous quality control.¹⁰ The institutional review board at the University of Southern California exempted this study as a result of the use of publicly available, deidentified data.
The data set extraction was performed by using SEER*Stat 8.3.2 to use the SEER18 cases for malignancies in “Corpus Uteri/Uterus NOS.” Within the extracted cases, women aged younger than 50 years with stage I endometrioid endometrial cancer diagnosed between 1983 and 2013 who had ovarian conservation at hysterectomy were included in the study cohort. This age cutoff was chosen based on mean age of spontaneous menopause in the North American population.^{11 (link)} Sarcoma or metastatic tumors to the uterus from another origin, no or unknown hysterectomy status, neoadjuvant radiotherapy, no or unknown ovarian conservation status, stage II–IV or unknown stage, nonendometrioid histology types, and age 50 years or older were excluded from the analysis.
To identify the subsequent ovarian cancers, an ovarian cancer data set was generated from the section for malignancies in “Ovary” in the same study period. Then, the ovarian cancer data set was linked with the endometrial cancer data set by sorting according to the unique database identification number. The same study identification numbers between the two data sets were considered secondary primary cancer, as described and validated previously.^{12 (link)}The chronologic time sequence of the endometrial cancer diagnosis date and the ovarian cancer diagnosis date were examined among the secondary primary cancer cases. Then, 1) women in whom primary ovarian cancer was diagnosed before the date of endometrial cancer and 2) women with synchronous endometrial and ovarian cancers were excluded from the study. Ovarian cancers diagnosed 6 months or later after an endometrial cancer diagnosis were considered subsequent ovarian cancers. The cutoff value of a 6-month time interval between the two cancer diagnoses is based on the rationale that endometrial cancer is commonly diagnosed by endometrial sampling before hysterectomy and ovarian cancer is generally diagnosed at the time of subsequent hysterectomy. Nearly 90% of women with endometrial cancer undergo hysterectomy within 4 months of diagnosis.^{13 (link)-15 (link)}Among the eligible cases for analysis, patient demographics, tumor information, treatment patterns, and survival outcome were ascertained from the database. Patient demographics included age, year and month of diagnosis, ethnicity, marital status, and registration area. Tumor information included cancer stage, histologic subtype, tumor grade, and tumor size. For treatment patterns, use of hysterectomy, oophorectomy, pelvic lymphadenectomy, and postoperative radiotherapy was abstracted. For survival, cause-specific survival and overall survival were examined.
Recorded cancer stage was reclassified using the American Joint Committee on Cancer 7th surgical–pathologic staging classification schema.¹⁶ The International Classification of Diseases for Oncology, 3rd Revision codes for disease site histology validation and World Health Organization histologic classification were used for grouping histologic subtypes as reported previously.^{5 (link)} Women with surgical codes for hysterectomy without oophorectomy were classified as having undergone ovarian conservation as described previously.^{5 (link),7 (link),8 (link)}Endometrial cancer-specific survival was defined as the time interval between the endometrial cancer diagnosis and the death from endometrial cancer. Overall survival was defined as the time interval between the endometrial cancer diagnosis and the death from any reason (all-cause). This definition was also applied to the ovarian cancer cases. Cause of death in this database is linked with the National Death Index and the state mortality records.¹⁷ The primary study endpoint was the cumulative incidence of subsequent ovarian cancer after ovarian conservation in women aged younger than 50 years with stage I endometrioid endometrial cancer. The secondary study objective was to examine tumor characteristics and outcome of subsequent ovarian cancer. Kaplan-Meier method was used to construct cumulative risk curves for subsequent ovarian cancer¹⁸ ; and statistical significance between the curves was examined with a log-rank test for univariable analysis. In addition, a Cox proportional hazard regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for subsequent ovarian cancer risk.¹⁹ Based on our recent study,^{5 (link)} we estimated eligible cases for this study to be approximately 1,300–1,500. We also assumed the subsequent ovarian cancer risk to be less than 1–2% after ovarian conservation at the time of hysterectomy.^{20 (link)} Thus, we did not perform multivariable analysis because it may result in over-adjustment. All hypotheses were two-tailed, and P<.05 was considered statistically significant. SPSS 24.0 was used for the analysis. The Strengthening the Reporting of Observational Studies in Epidemiology guidelines were used to outline the performance of this observational study.^{21 (link)}