Frequency and Effect of Adjuvant Radiation Therapy Among Women With Stage I Endometrial Adenocarcinoma

Department of Radiation Oncology, Huntsman Cancer Hospital and University of Utah Medical Center, Salt Lake City 84112-5560, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 06/2006; 295(4):389-97. DOI: 10.1001/jama.295.4.389
Source: PubMed


The benefit of adjuvant radiation therapy (RT) in stage I endometrial adenocarcinoma remains controversial despite several phase 3 trials.
To evaluate the frequency and effect of adjuvant RT on overall and relative survival within a large US population database.
A retrospective analysis that used data from the Surveillance, Epidemiology, and End Results program of the US National Cancer Institute from January 1, 1988, to December 31, 2001. A total of 21,249 patients with American Joint Committee on Cancer stage IA-C node-negative endometrial adenocarcinoma comprised the study population.
Overall survival curves were constructed using Kaplan-Meier method and compared via stratified log-rank test within T stage/grade combinations, adjusted for age. Relative survival was performed to assess the effects of age, race, stage, grade, whether nodes were examined, and whether adjuvant RT was administered.
Of 21,249 women, 4080 received adjuvant RT (19.2%) and 17,169 did not receive adjuvant RT (80.8%). The mean age at diagnosis was 63.2 years (range, 14-99 years). Adjuvant RT significantly improved overall survival for patients with stage IC/grade 1 (P<.001) and stage IC/grades 3 and 4 (P<.001). Cox proportional hazards regression analysis revealed a statistically detectable association of adjuvant RT with improved relative survival in patients with stage IC/grade 1 and stage IC/grades 3 and 4 (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.31-0.63; P<.001; and HR, 0.72; 95% CI, 0.57-0.92; P = .009; respectively). A separate analysis of those patients with a surgical lymph node examination at the time of total abdominal hysterectomy and bilateral salpingo-oophorectomy revealed similar estimates (HR, 0.59; 95% CI, 0.39-0.90; P = .01; and HR, 0.73; 95% CI, 0.55-0.96; P = .02; respectively).
As the largest reported population analysis to date of adjuvant RT in early stage endometrial adenocarcinoma, our study reveals a statistically significant association between improved overall and relative survival and adjuvant RT in stage IC disease (grades 1 and 3-4). Future work is needed to continue to delineate clinical and biological factors, which can guide treatment decisions and account for disparities in outcome between varied subsets of patients.

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    • "In contrast to the four randomized controlled trials showing no survival benefit with adjuvant radiation therapy in early endometrial cancer, in an analysis of over 21,000 women from the Surveillance, Epidemiology, and End Results (SEER) database, stage IC grades 1 and 3 showed improved overall and relative survival from adjuvant radiation with hazards ratios of 0.44 (P < 0.001) and 0.72 (P = 0.009), respectively [61]. Despite randomized controlled trials showing no survival benefit with adjuvant radiation in early endometrial cancer, these data elucidate the importance of identifying an early-stage, high-risk population that might benefit from adjuvant therapy. "
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    ABSTRACT: Although the contemporary management of endometrial cancer is straightforward in many ways, novel data has emerged over the past decade that has altered the clinical standards of care while generating new controversies that will require further investigation. Fortunately most cases are diagnosed at early stages, but high-risk histologies and poorly differentiated tumors have high metastatic potential with a significantly worse prognosis. Initial management typically requires surgery, but the role and extent of lymphadenectomy are debated especially with well-differentiated tumors. With the changes in surgical staging, prognosis correlates more closely with stage, and the importance of cytology has been questioned and is under evaluation. The roles of radiation in intermediate-risk patients and chemotherapy in high-risk patients are emerging. The therapeutic index of brachytherapy needs to be considered, and the best sequencing of combined modalities needs to balance efficacy and toxicities. Additionally novel targeted therapies show promise, and further studies are needed to determine the appropriate use of these new agents. Management of endometrial cancer will continue to evolve as clinical trials continue to answer unsolved clinical questions.
    Full-text · Article · Jun 2013 · Obstetrics and Gynecology International
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    • "It is estimated that between 34 to 58% of all patients with endometrial cancer will have an indication for external beam radiation at some point in the course of their disease [1]. There is no doubt that adjuvant radiotherapy reduces the risk of pelvic failure after surgery for early endometrial cancer and there is some evidence that it improves survival in high-risk stage I cases [2] [3]. Randomised trials have, however, failed to show a survival advantage from radiotherapy in intermediate-risk stage I patients and the role of postoperative radiotherapy in this large group remains controversial [4e7]. "
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    ABSTRACT: To describe the use of adjuvant radiotherapy for endometrial cancer in Ontario, and identify factors associated with its use, and to determine whether variation in the use of radiation is associated with differences in survival. This was a retrospective, population-based, cohort study of all patients who had a hysterectomy for endometrial cancer in Ontario between 1992 and 2003. We used multiple logistic regression to identify health system-related factors associated with the use of radiotherapy, while controlling for disease- and patient-related factors. Survival and cancer cause-specific survival were compared among regions of the province with higher and lower rates of use of radiotherapy. The study population included a total of 9411 women with a median age of 63 years. Overall, 26.2% received adjuvant radiotherapy. Patients living further from regional cancer centres were slightly less likely to receive radiation (P = 0.02). Patients who had their surgery during longer prevailing waiting times for radiotherapy were less likely to receive radiation (P = 0.04). The use of radiotherapy varied widely from 18.0 to 34.3% among the catchment areas of provincial radiotherapy centres (P < 0.0001). In the overall population, there was no difference in survival among regions with higher and lower rates of use of radiotherapy. However, in the subgroup of cases with clear cell and serous carcinomas, both overall survival and cancer cause-specific survival were significantly lower in regions with lower rates of use of radiotherapy (P < 0.05). This difference remained significant after controlling for other factors (P < 0.05; hazard ratio 1.43; 95% confidence limits 1.06-1.93). Health system-related factors unrelated to patients' needs affect the use of adjuvant radiotherapy in Ontario. Lower rates of use of adjuvant radiotherapy are associated with lower rates of survival in patients with serous and clear cell carcinomas.
    Full-text · Article · Mar 2012 · Clinical Oncology
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    • "The vagina is the most common site of recurrence, and whole pelvic radiotherapy, vaginal cuff brachytherapy, or both types of radiation therapy may follow surgical treatment. Radiation therapy significantly decreases the risk of local regional recurrence and has been associated with improved survival in patients with stage IC disease [2-4]. "
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    ABSTRACT: A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer. A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation. The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities. EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer.
    Full-text · Article · Jul 2010 · Radiation Oncology
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