Classification and regression tree (CART) analysis of endometrial carcinoma: Seeing the forest for the trees☆
Introduction
Endometrial carcinoma is the most common gynecologic malignancy in the Western world, with a generally favorable 5-year overall survival rate of 80–85% [1], but there are still many controversies with regard to extent of staging and treatment. The International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging system was changed from a clinical to surgical system in 1988, and was most recently updated in 2009 [2], [3], [4]. It is well accepted that surgical staging should include a hysterectomy and bilateral salpingo-oophorectomy, but the role and extent of lymph node dissection are highly debated [5]. Do all patients require lymphadenectomy? Should pelvic and para-aortic lymph nodes be excised? If lymph node dissection is not therapeutic, can it guide adjuvant treatment decisions? How do grade and tumor subtype impact survival or the need to perform a lymph node dissection? Who if anyone needs adjuvant therapy?
Classification and regression tree (CART) analysis is an innovative and powerful statistical technique with significant clinical utility [6]. CART analysis is a tree-building technique in which several “predictor” variables are tested to determine how they impact the “outcome” variable, such as overall survival. It has many advantages over more traditional methods, such as multivariate regression; it is inherently non-parametric, can handle highly skewed data, and does not require much input or categorization of the data, as is needed for other multivariate modeling methods. The resulting trees from CART analysis are clear and easy to interpret. Given the many controversies in endometrial cancer, CART analysis provides a promising statistical technique that can assist in identifying important predictors of overall survival and homogeneous subsets of patients with regards to outcome.
Our primary objectives were to evaluate what clinicopathologic factors influenced overall survival in women with endometrial carcinoma undergoing primary surgical staging and to determine if the surgical effort to assess para-aortic lymph nodes at staging surgery impacted overall survival. In other words, where is the value added to the patient beyond a total hysterectomy and adnexectomy when it comes to staging?
Section snippets
Methods
After institutional review board approval, we identified all patients diagnosed with endometrial cancer at Memorial Sloan-Kettering Cancer Center from January 1993 through December 2011 who had lymph nodes excised at the time of surgical staging and evaluated by pathology. Removal of lymph nodes was at surgeon discretion, and stage assignment was based on all available pathologic information. Tumor types included: endometrioid adenocarcinoma, carcinosarcoma, clear cell, serous, and other. Tumor
Results
During the study period, 1920 patients met inclusion criteria and had surgically staged endometrial carcinoma including evaluation of at least one lymph node (Table 1); 880 patients were excluded because lymph nodes were not sampled. The median age was 62 (range, 21–92). FIGO (1988) stage distribution was as follows: stage I, 1313; stage II, 114; stage III, 397; and stage IV, 96. The majority of patients (1433) had endometrioid adenocarcinoma histology, but we also included carcinosarcoma, 128;
Discussion
In an effort to see the big picture and determine what truly matters in overall survival of women with endometrial carcinoma undergoing primary staging surgery, this innovative CART analysis emphasized the importance of proper stage assignment category (I–IV) and grade (a binary system of low-grade [1], [2] vs. high-grade [3], which included all serous carcinomas, clear cell carcinomas, and carcinosarcomas) in impacting overall survival. The surgical staging of all patients in this study
Conclusions
In the midst of several ongoing controversies in the staging and treatment of endometrial carcinoma, our CART analysis is an innovative attempt at seeing the forest for the trees. Utilizing commonly available clinicopathologic variables and limiting investigator selection bias of variables and cut-offs, we have found that what really matters in endometrial cancer overall survival is stage assignment category (I–IV) and final grade (a binary system of low grade [1], [2] vs. high grade [3], with
Conflict of interest statement
There are no conflicts of interest.
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Funding source: Funded in part by the Cancer Center Core Grant P30 CA008748. The core grant provides funding to institutional cores, such as Biostatistics and Pathology, which were used in this study.