We conducted our analysis from the perspective of a third-party payer; we specifically used Medicare reimbursement to provide conservative cost estimates. We used only 2005 direct costs and did not use charges billed or indirect costs such as travel, lost time from work, or patient pharmaceutical expenses (Table 3). When Medicare costs were not available, we estimated costs by adjusting local charges using a cost-to-charge ratio of 60%. Baseline costs were varied across clinically reasonable ranges in sensitivity analyses. The costs of cancer surveillance, surgical complications, and morbidity from adjuvant therapy were not included in the model. Furthermore, the costs related to the initial evaluation and work-up of the newly diagnosed patient was not included in the model because this expense would be the same in each strategy.
Costs related to total abdominal hysterectomy included costs for operating room time, operating room supplies, surgeon's fees, pathology fees, postanesthesia care unit fees, anesthesiology fees, and a 3-day hospital stay. The total cost of hysterectomy was $21,200. Patients who underwent hysterectomy and lymphadenectomy had slightly higher surgeon's fees and therefore a total cost of $21,700. Frozen section added slightly more costs because of increased pathology fees and increased co-surgeon's fees ($22,100).
The cost of whole pelvic radiation therapy included evaluation by a radiation oncologist with radiation dosimetry, simulation costs, professional fees for administering the radiation, and facility fees. A conservative estimate of $6,800 was used for the 5-week course of treatment. The cost of brachytherapy included evaluation by a radiation oncologist with radiation dosimetry, simulation costs, professional fees for administering the radiation, handling fees, and facility fees. A conservative estimate of $4,000 was used for the five high-dose rate treatments. Costs related to chemotherapy included the costs of the chemotherapy agents, infusion, laboratory, intravenous fluids, and associated support medications (Table 3).
Recurrence rates with each strategy were entered into the model (Table 4), and cost-effectiveness ratios were calculated. Cost-effectiveness was defined as the overall cost of implementing a strategy per patient cure. We defined cure (effectiveness) as the percentage of patients who were disease-free at 5 years (5-year disease-free survival). Sensitivity analyses were performed to evaluate the effects of uncertainty inherent in the model. All modeling and calculations were performed with a decision analysis program (DATA 3.5, TreeAge Pro Software, Williamston, MA).
Under our baseline assumptions, using 10,000 hypothetical patients diagnosed annually with grade 1 endometrial cancer, we compared the three surgical strategies (surgical staging, frozen section, and no staging) (Table 5). Surgical staging was the least expensive strategy at a cost of $240.4 million per 10,000 patients. The 5-year disease-free survival, a surrogate for effectiveness, was 87.9% for patients in the surgical staging strategy. Both frozen section and no staging had similar 5-year disease-free survival (87.3% and 86.7%, respectively), but both strategies were more expensive than surgical staging, costing $252.4 million and $255.8 million, respectively. The cost-effectiveness ratio or cost per disease-free survivor was lowest for the surgical staging strategy ($27,337), compared with frozen section ($28,913) or no staging ($29,513). The surgical staging strategy yielded 64 additional disease-free patients per 10,000 patients compared with frozen section and 126 additional disease-free patients compared with no staging.
The use of lymphadenectomy and radiotherapy differed significantly for each strategy. Patients in the surgical staging strategy were surgically staged in 89% of cases, compared with 36% in those undergoing frozen section as a triage method for determining the need for lymphadenectomy. These results are consistent with previously reported surgical experiences using these strategies. Radiation therapy was administered to 32% of patients in the no staging strategy compared with 23% of patients undergoing frozen section. Patients in the surgical staging strategy received radiation therapy less frequently (13%). Surgically staged patients received brachytherapy alone 56% of the time compared with 16% of patients in the frozen section strategy. The remaining patients received combination therapy with brachytherapy and whole pelvic radiation therapy.
A series of one-way sensitivity analyses were performed to evaluate the impact of a single estimate while all other estimates remained the same. We specifically evaluated the cost of brachytherapy and whole pelvic radiation therapy because these costs may vary significantly according to insurance providers and region of the country. The baseline cost of brachytherapy was $4,000, and we varied this cost from $2,000 to $20,000. As the cost of brachytherapy decreases, the total cost and cost-effectiveness ratios for each strategy decrease, but surgical staging remains the most cost-effective strategy. Of note, if the cost of brachytherapy were estimated to be $20,000, the total cost of the surgical staging strategy increases $20.9 million while the frozen section and no staging strategies increase $36.3 million and $50.9 million, respectively. We also varied the baseline cost of whole pelvic radiation therapy from $3,000 to $30,000. Decreasing the cost of whole pelvic radiation therapy to $3,000 does not affect the cost-effectiveness ratios, and surgical staging remains the most cost-effective strategy. However, if the cost of whole pelvic radiation therapy is increased to $30,000, the incremental costs increase dramatically for frozen section and no staging ($44.2 million and $73.8 million, respectively) compared with surgical staging ($13.3 million).
We also wanted to evaluate the expected outcomes of observation in surgical stage I patients. In the baseline model, we estimated that 95% of surgical stage I patients would be observed while 5% of patients would receive brachytherapy for high-risk factors. In a one-way sensitivity analysis, we evaluated the outcomes if all surgical stage I patients were observed and found that the costs, efficacy, and cost-effectiveness ratios were essentially unchanged. Furthermore, we estimated that 5-year disease-free survival was 95% in surgical stage I patients who were observed, compared with 98% in surgical stage I who received brachytherapy. In a two-way sensitivity analysis, we varied the 5-year disease-free survival estimates of observation and brachytherapy from 80% to 99% and found that the surgical staging strategy remains the least costly and most effective strategy under all estimates.
In this decision analysis evaluating women with grade 1 endometrial cancer, we demonstrate that comprehensive surgical staging is the least costly and most effective strategy for this patient population. Despite the support for routine comprehensive surgical staging of patients with endometrial cancer by most organizations, arguments concerning the value of lymphadenectomy still persist. It is clear that several management strategies are effective because the disease-free survival estimates are quite similar, but surgical staging dramatically decreases the use of radiation therapy without negatively impacting survival. Furthermore, the decreased use of radiation therapy should improve the quality of life of women by avoiding complications, decreasing morbidity, and allowing quicker return to a normal lifestyle.
Over the last decade, several studies have evaluated the costs associated with the management of early endometrial cancer.17–21 Although the results from these studies cannot be directly compared with those presented in this analysis, it does provide some interesting perspective on the cost-effectiveness of adjuvant treatment after surgical staging. Barnes et al17 performed a cost analysis and evaluated different treatment strategies using accumulated hospital charges. They concluded that staging all patients and withholding teletherapy except for patients with extrauterine disease was associated with the lowest cost. In Fanning's original analysis,18 he concluded that surgical staging and brachytherapy was the most cost-effective strategy for women with early surgical stage endometrial cancer. In a subsequent study, Fanning et al19 evaluated the use of brachytherapy versus observation in patients with intermediate-risk surgical stage IC and II cancer. The authors concluded that withholding brachytherapy decreases costs and complications with a 3% decrease in survival. Collectively, these studies demonstrate that, as the use of radiation therapy increases, so does the cost, but this increased cost is generally not associated with a significant effect on survival, especially in patients who undergo comprehensive surgical staging. This finding was again supported in our current study and, specifically, in those patients (grade 1 tumors) who often are not offered comprehensive surgical staging. Recently, a retrospective study was reported which evaluated the costs associated with a gynecologic oncologist being involved for lymphadenectomy with a gynecologist who performed a hysterectomy.22 In this small study, the authors demonstrated increased payor costs for women undergoing surgical staging with both a gynecologist and gynecologic oncologist compared with a gynecologic oncologist alone.
Given that adjuvant radiotherapy has not been demonstrated to improve overall survival in patients with surgical stage I endometrial cancer,5,6,23,24 the decision to recommend adjuvant radiation therapy must be made with information regarding the role of local disease control balanced with the costs and morbidity of the treatment. Because of this lack of survival advantage afforded by radiation therapy, several institutions withhold teletherapy in patients with surgically staged endometrial cancer confined to the uterus.5,6,23,24 This management strategy is further supported by the fact that most recurrences in surgical stage I patients are local and therefore curable by salvage radiation.15,25–27 We acknowledge that a surgical staging philosophy is not universally accepted and is the means by which the expense in the surgical staging group is minimized. However, we believe that published data supports this schema due to excellent survival rates in these patients with minimization of costs. Furthermore, the results of the sensitivity analysis that varied the outcome (5-year disease-free survival) of surgical stage I endometrial cancer patients documented no decrease in the cost-effectiveness ratios, supporting the rationale of surgical staging without adjuvant radiation therapy for patients with surgical stage I disease.
As with any cost-effectiveness model, potential criticisms related to the design of the model and the clinical estimates entered into the model must be addressed. We have attempted to use accurate data to design the model and use conservative estimates especially with costs. Although the estimated costs of whole pelvic radiation therapy and brachytherapy used in the model are much lower than previous reports, significant costs are still incurred in the frozen section and no staging strategies. Another limitation of this study is the fact that the rate and costs of complications were not included in the model. From previously published data, we believe that the morbidity caused by pelvic and para-aortic lymphadenectomy for endometrial cancer is relatively low4 and therefore would not significantly impact the model. However, the additional morbidity of adjuvant teletherapy after hysterectomy is not negligible,28 and the costs associated with the management and long-term consequences of these complications would likely increase the overall costs of patients receiving radiation therapy. As such, the lack of inclusion of complications in our model would likely underestimate the difference in costs between comprehensive staging and the other strategies for the management of grade 1 endometrial cancer. We believe that one of the strengths of this study is that a specific population (patients with grade 1 endometrial cancer) is being investigated. Importantly, the results of this decision analysis do not apply to high-risk histologies such as papillary serous or clear cell.
As with any cost-effectiveness model, the results should only be used as an adjunct to clinical judgment because these analyses are unable to address all relevant factors that are used to formulate treatment plans. However, we believe that these data suggest that, for the management of grade 1 endometrial cancer, comprehensive surgical staging in all patients is less costly and more efficacious than other strategies. It is important for physicians and patients to recognize that expert surgical management of endometrial cancer may improve survival and minimize costs to society. It is our hope that continued research into the effectiveness and costs of surgical staging in patients with endometrial cancer will clearly define the role of lymphadenectomy.
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© 2007 The American College of Obstetricians and Gynecologists
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