The Effect of Primary Surgical Technique for Treatment of Endometrial Cancer and Timing of Adjuvant Radiation Therapy
Abstract
Objective: To determine if surgical approach (open, laparoscopic, robotic) influences time to initiation of adjuvant radiation therapy in women with endometrial cancer.
Methods: The National Cancer Database was used to search for patients with stage I to III endometrial cancer who received adjuvant radiation therapy from 2010-2012. Demographic, socioeconomic and clinical information was abstracted for each patient. Time to initiation of adjuvant radiation therapy was compared between groups using univariable (unadjusted) and multivariable (adjusted for all demographic and clinical variables) Cox regression models.
Results: A total of 15,480 patients were included in our study. 47.9% of patients underwent laparotomy or an unspecified surgical approach, 38.6% underwent robotic surgery, and 13.5% had a laparoscopic surgery. The distribution of time to radiation was significantly different among these groups with hazards ratios 1.0 (reference), 1.1 [95% CI 1.07, 1.15] and 1.15 [95% CI 1.02-1.06] for open, robotic and laparoscopic surgery (p<0.0001), respectively. After adjusting for covariates, younger age and worse disease status as measured by stage and grade are associated with longer wait times to radiation.
Conclusions: Women who underwent open staging surgery for endometrial cancer experienced delays from surgery to initiation of adjuvant radiation therapy as compared to women who had minimally invasive surgery.
Introduction
Endometrial cancer (EC) is the most common gynecologic malignancy in the United States, accounting for an estimated 63,230 new cases and 11,530 deaths in 2018 [1]. Women with endometrial cancer undergo surgical staging followed by adjuvant treatment as appropriate. Adjuvant radiotherapy (RT) is commonly used for patients with early-stage high-intermediate risk disease or those with advanced disease in order to prevent locoregional recurrence. The locoregional recurrence rate for early stage endometrial cancer with risk factors is up to 26% [2,3]. For patients with advanced stage disease, despite receiving systemic chemotherapy, up to 18% of patients will develop a locoregional recurrence [4].
When feasible, minimally invasive surgery is the preferred surgical modality for EC staging and treatment [5]. Laparoscopic surgical management for EC has been shown to be a safe alternative to laparotomy. Laparoscopy as compared to open techniques results in fewer short-term complications and decreased hospital length of stay [6] with similar oncological outcomes [5,7]. A meta-analysis of the literature comparing robotic-assisted laparoscopic surgery to laparotomy for EC also revealed decreased intraoperative and postoperative complication rates, decreased postoperative morbidity, improved patient-reported outcomes, including significantly shorter return to daily activities, and equivalent survival rates [8,9]. Robotic-assisted surgery for EC has also been compared with traditional laparoscopic approach and has shown equivalent short-term outcomes [10]. The use of laparoscopy and robotic-assisted surgery for EC is increasing.
Mode of surgery influences patient recovery times and therefore may influence time from surgery to adjuvant therapy. There is evidence that time intervals between diagnosis, surgery, and initiating adjuvant treatment for patients with endometrial cancer influences outcomes [11-13]. Studies have shown that a delay between hysterectomy and adjuvant RT might portend worse outcomes. Currently, literature exploring this relationship is limited. One retrospective study showed that initiating adjuvant RT more than six weeks after surgery decreased disease-specific survival for EC [11]. Others have found that local recurrence rate was associated with time interval from surgery to RT using a cutoff of nine weeks [12,13]. Given the advent of minimally invasive surgery, we sought to evaluate the impact of surgical technique on the time interval for initiating adjuvant radiation therapy for patients with endometrial cancer.
Methods
The National Cancer Database (NCDB) is a national hospitalbased cancer registry that is a joint endeavor of the American College of Surgeons and American Cancer Society. Annually, data from over 1 million patients representing 70% of all new cancer diagnoses in the United States are reported to the NCDB. Approximately 1,500 Commission on Cancer (CoC)-accredited hospitals contribute deidentified data. Data reporting is highly standardized to the CoC Registry Manuals, the American Joint Committee on Cancer and Collaborative Stage manuals, and the International Classification of Diseases for Oncology, Third Edition (ICD-O-1) [14,15]. The Institutional Review Board at the Icahn School of Mount Sinai granted exemption status for this study.
The NCDB Participant User File was used to search for patients with stage I to III EC who underwent primary surgical treatment and for whom the surgical technique was known from 2010 to 2012. Only those patients with a known cancer diagnosis prior to surgery who also received adjuvant radiotherapy were included in the study. The types of adjuvant RT delivered were external beam radiation therapy (EBRT), brachytherapy, radioisotopes, or combined EBRT with brachytherapy boost or radioisotopes. Patients who received radiation outside of the uterus, cervix, pelvis or abdomen were excluded. Demographic and socioeconomic information was abstracted for each patient, including age, year of diagnosis, race/ ethnicity, income, insurance status, and facility location. Clinical data collected included Charlson-Deyo comorbidity score, surgical approach, time to radiation, and time hospitalized. Pathologic details recorded included International Federation of Gynecology and Obstetrics (FIGO) staging and grade of disease.
Patients were categorized into three groups according to surgical approach: robotic, laparoscopic, and open or unspecified. Patients whose surgical approach was not reported were categorized as unspecified and grouped with patients who underwent open surgery by the NCDB. Demographic and clinical characteristics were compared between the groups using one-way ANOVA or Kruskal-Wallis tests for continuous measures and Chi-square tests for categorical measures. The distribution of time to adjuvant radiation by surgical approach was estimated using the Kaplan Meier method and differences between the groups were assessed using a log-rank test. Univariable (unadjusted) and multivariable (adjusted for all demographic and clinical variables) Cox regression models were estimated to assess each factor’s association with time to adjuvant radiation therapy. All analyses were conducted using SAS version 9.4 (SAS, Cary, NC).
Results
A total of 15,480 patients diagnosed with endometrial cancer from 2010 to 2012 met inclusion criteria. Of these, 47.9% had a laparotomy or unspecified surgical approach, 38.6% underwent robotic surgery, and 13.5% had a laparoscopic surgery. Although statistically significant due to the large sample size, there were no clinically significant differences between the groups based on age, income, insurance status, facility location, and Charlson-Deyo score (Table 1). The robotic group had a higher proportion of white patients compared to both the laparoscopic and open/unspecified groups. The open/unspecified group had proportionately more stage 3 and grade 3 and 4 (undifferentiated or anaplastic) patients compared to the robotic and laparoscopic groups. As expected, the length of stay in hospital was also significantly longer for open/ unspecified patients compared to patients who underwent less invasive procedures. Notably, the distribution of year of diagnosis varied by surgical group with the percentage of patients in both the robotic and laparoscopic increasing by year versus decreasing in the open/unspecified group.
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