Patterns of Care and Treatment Outcomes for Elderly Women With Cervical Cancer

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1 Patterns of Care and Treatment Outcomes for Elderly Women With Cervical Cancer Charu Sharma, MD 1 ; Israel Deutsch, MD 1,2 ; David P. Horowitz, MD 1 ; Dawn L. Hershman, MD 2,3,4 ; Sharyn N. Lewin, MD 2,5 ; Yu-Shiang Lu, MS 5 ; Alfred I. Neugut, MD 2,3,4 ; Thomas J. Herzog, MD 2,5 ; Clifford K. Chao, MD 1,2 ; and Jason D. Wright, MD 2,5 BACKGROUND: Cervical cancer is common in the elderly. The authors examined the patterns of care, treatment, and outcomes of elderly women with cervical cancer. METHODS: Women with cervical cancer diagnosed between 1988 and 2005 and registered in the Surveillance, Epidemiology, and End Results database were analyzed. Patients were stratified by age: <50, 50 to 59, 60 to 69, 70 to 79, and 80 years. Multivariate logistic regression models were constructed to examine treatment; cancer-specific survival was examined using Cox proportional hazards models. RESULTS: A total of 28,902 women were identified, including 2543 women 70 to 79 years old and years. For women with early stage (IB1-IIA) tumors, primary surgery was performed in 82.0% of women <50 years old compared with 54.5% of those 70 to 79 years old and 33.2% of those 80 years old (P <.0001). For women treated surgically, lymphadenectomy was performed in 66.8% of women <50 years old versus 9.1% of patients 80 years old (P <.0001). Compared with patients <50 years old, those >80 years old were less likely to undergo radical hysterectomy (odds ratio [OR], 0.10; 95% confidence interval [CI], ) and lymphadenectomy (OR, 0.11; 95% CI, ) and to receive adjuvant radiation therapy (OR, 0.06; 95% CI, ). Among women with stage IIB-IVA disease, use of brachytherapy declined with age (P <.0001). For women with stage IB1-IIA tumors, the hazard ratio for death from cancer was 1.35 (95% CI, ) for women 70 to 79 years old and 2.08 (95% CI, ) for those 80 years old compared with younger women. CONCLUSIONS: Elderly women with cervical cancer are less likely to undergo surgery, receive adjuvant radiation, and receive brachytherapy. After adjusting for treatment disparities, cancer-specific mortality is higher in older women. Cancer 2012;118: VC 2011 American Cancer Society. KEYWORDS: cervical cancer, cervical carcinoma, elderly, hysterectomy, radiation, brachytherapy, radical hysterectomy. INTRODUCTION Worldwide cervical cancer remains a major cause of cancer-associated morbidity and mortality in women. 1 Despite screening efforts, >3600 women die each year from cervical cancer in the United States. 2 Although several effective treatments exist for cervical cancer, therapy can be intensive, often involves multiple therapeutic modalities, and can be associated with substantial treatment-associated morbidity. Cervical cancer demonstrates a bimodal distribution, with peaks between 30 and 39 years of age and between 60 and 69 years of age. The older age group is becoming an increasingly prevalent portion of the US population. Demographic estimates suggest that the number of people 65 years of age or older will reach approximately 72 million, or 19% of the population, by Cancer incidence is greatest in the elderly population. Population-based data estimates that between 2003 and 2007, 54% of all new cancer cases and 70% of cancer-related deaths occurred in patients 65 years of age or older. 4 As the population continues to grow, the allocation of cancer treatment to the elderly will become an even greater concern. Despite the frequency of cancer in the elderly, treatment disparities are common. Older patients receive less aggressive cancer therapy than their younger counterparts or receive cancer care that deviates from the standards of care for several cancer sites. 5-8 In a study of elderly breast cancer patients, 26% of women aged 80 years without comorbidity Corresponding author: Jason D. Wright, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave, Eighth Floor, New York, NY 10032; Fax: (212) ; jw2459@columbia.edu 1 Department of Radiation Oncology, Columbia University College of Physicians and Surgeons, New York, New York; 2 Herbert Irving Comprehensive Cancer Center, New York, New York; 3 Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; 4 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York; 5 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York DOI: /cncr.26589, Received: July 13, 2011; Revised: August 16, 2011; Accepted: August 24, 2011, Published online October 28, 2011 in Wiley Online Library (wileyonlinelibrary.com) 3618 Cancer July 15, 2012

2 Cervical Cancer in the Elderly/Sharma et al received breast-conserving surgery alone or no surgery compared with 6% of women aged 67 to 79 years. 7 In addition to treatment delivered, age often has an independent effect on decreasing survival. 7,8 For cervical cancer, several institutional studies have demonstrated treatment-related disparities despite evidence that suggests elderly women with cervical cancer often tolerate treatment well The objective of our study was to perform a population-based analysis of the patterns of treatment and survival for elderly women with cervical cancer. We examined access to standard cervical cancer treatments stratified by stage and compared utilization for younger and older women. MATERIALS AND METHODS Data from the National Cancer Institute s Surveillance, Epidemiology, and End Results (SEER) database were used. SEER is a population-based tumor registry that records data on approximately 26% of the US population. 16 SEER is composed of several geographically distinct tumor registries. 17 Data from SEER 17 registries were used. All data were publicly available, deidentified, and exempt from institutional review board review. Women with invasive cervical cancer diagnosed between 1988 and 2005 were analyzed. Only patients with squamous cell carcinomas, adenocarcinomas, or adenosquamous carcinomas were included in the analysis. Subjects were stratified by age into the following groups for analysis: <50 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, and 80 years. Clinical and pathologic data, including race (white, black, or other), marital status, and tumor grade, were collected. Year of diagnosis was classified as 1988 to 1993, 1994 to 1999, or 2000 to Patients were categorized based on the geographic area of residence at the time of diagnosis: central (Detroit, Iowa, Kentucky, Louisiana, Utah), eastern (Connecticut, New Jersey, Atlanta, rural Georgia), or western (Alaska, California, Hawaii, Los Angeles, New Mexico, San Francisco, San Jose, Seattle). Primary treatment was classified as either surgery, radiation, or no cancer-directed therapy. Surgery was classified as 1 of the following procedure types: excision/ destruction, simple hysterectomy, radical hysterectomy, hysterectomy unspecified, or other/unknown surgery type. Performance of lymphadenectomy was noted for each subject. Receipt of radiation was recorded as external beam with or without brachytherapy (intracavitary radiation). SEER lacks data on chemotherapy, and as such this was not included. Staging information was derived from the American Joint Cancer Committee staging information and recorded extent of disease codes. Each patient s stage was determined using the revised 2009 staging criteria of the International Federation of Gynecologists and Obstetricians. 18 Each patient s vital status was recorded. Cancer-specific survival was calculated as the number of months from cancer diagnosis to date of death from cancer. Patients who were alive at last follow-up were censored. Frequency distributions between categorical variables were compared using chi-square tests. Logistic regression models were developed to describe predictors of radical hysterectomy, lymphadenectomy, adjuvant radiation, and vaginal brachytherapy. In the logistic regression analysis, we modeled all the categories of each variable controlling for all other variables in the model. Both the univariate and multivariate analyses were stratified by stage as either early stage (IB1-IIA) or advanced stage (IIB-IVA). Cox proportional hazards models were developed to examine cancer-specific survival. In Cox proportional hazards analyses, we modeled the cancer-specific mortality hazard ratios (HRs) comparing women by age and accounting for other prognostic variables and treatment. Kaplan- Meier curves were generated to examine cancer-specific survival. All analyses were performed with SAS version 9.2 (SAS Institute, Cary, NC). RESULTS A total of 28,902 women with cervical cancer were identified. The cohort included 15,790 (54.6%) women <50 years of age, 5326 (18.4%) aged 50 to 59, 3879 (13.4%) aged 60 to 69, 2543 (8.8%) who were 70 to 79 years of age, and 1364 (4.7%) 80 years of age (Table 1). The older women were more commonly nonwhite, more often lived in the eastern or central United States, and were more often unmarried (P <.05 for all). Older women more commonly had squamous cell tumors (P <.0001) and more frequently had poorly differentiated neoplasms (P <.0001). Older women were also more likely to have advanced stage disease at presentation. At diagnosis, 1058 (6.7%) women <50 years of age had stage IIIB tumors compared with 230 (16.9%) of the women in the oldest age strata (P <.0001). Table 2 displays treatment trends stratified by age and stage. Among women with early stage (IB1-IIA) tumors, primary surgery was performed in 82.0% of women <50 years of age, compared with 54.5% of Cancer July 15,

3 Table 1. Association Between Age and Clinical and Demographic Characteristics Characteristic <50 Years Years Years Years 80 Years P No. % No. % No. % No. % No. % Total 15, Race <.0001 White 12, Black Other Unknown Year of diagnosis < SEER registry <.0001 West Central East Marital status <.0001 Married Single Unknown Histology <.0001 Squamous 11, Adenocarcinoma Adenosquamous Tumor grade < Unknown Primary treatment <.0001 Surgery 11, Radiation No treatment Lymphadenectomy <.0001 No Yes Stage <.0001 IA IA IB IB IB NOS IIA IIB IIIA IIIB IVA IVB Abbreviations: NOS, not otherwise specified; SEER, Surveillance, Epidemiology, and End Results Cancer July 15, 2012

4 Cervical Cancer in the Elderly/Sharma et al Table 2. Patterns of Care for Women With Cervical Cancer Stratified by Age and Stage Characteristic <50 Years Years Years Years 80 Years P No. % No. % No. % No. % No. % Stage IB1-IIA Primary treatment <.0001 Surgery Radiation No treatment Type of surgery a <.0001 Excision/destruction Simple hysterectomy Radical hysterectomy Hysterectomy unspecified Other/unknown Lymphadenectomy <.0001 No Yes Adjuvant radiation a <.0001 No Yes Unknown Adjuvant hysterectomy b <.0001 No Yes <.0001 Stage IIB-IVA Primary treatment <.0001 Radiation Surgery No treatment Use of external beam and brachytherapy b Yes No Unknown Adjuvant hysterectomy b <.0001 No Yes a Analysis limited to patients who underwent primary surgical therapy. b Analysis limited to patients who underwent primary radiation. women aged 70 to 79 and 33.2% of those 80 years of age (P <.0001). For those women who underwent primary surgery, use of radical hysterectomy, the operative procedure of choice, decreased with age from 58.9% of patients <50 years old to 20.4% in those 80 years of age (P <.0001). Among patients treated with surgery, lymphadenectomy was undertaken in 66.8% of women <50 years of age versus 29.0% of those aged 70 to 79 years and 9.1% of patients 80 years old (P <.0001). In multivariate analysis, age remained a strong predictor of treatment for women with early stage tumors (Table 3). Compared with patients <50 years of age, women aged 70 to 79 years (odds ratio [OR], 0.32; 95% confidence interval [CI], ) and those >80 years old (OR, 0.10; 95% CI, ) were less likely to undergo radical hysterectomy. Among those women with early stage tumors who were treated surgically, women 70 to 79 years old (OR, 0.28; 95% CI, ) and those aged >80 years (OR, 0.11; 95% CI, ) were less likely to undergo lymphadenectomy. For patients with stage IB1-IIA neoplasms who underwent primary surgery and had nodal disease, women >80 years of age were less likely (OR, 0.06; 95% CI, ) to receive adjuvant radiotherapy. Other predictors of primary treatment included race, year of diagnosis, area of residence, marital status, histology, grade, and stage. Similar disparities were noted for patients with advanced stage (IIB-IVA) disease (Table 2). No cancerdirected therapy was allocated to 138 (3.9%) women <50 years of age, compared with 80 (7.3%) of those aged 70 to Cancer July 15,

5 Table 3. Multivariate Analysis of Patterns of Care for Women With Cervical Cancer Characteristic Radical Hysterectomy for All Stage IB1-IIA Patients Lymphadenectomy for Stage IB1-IIA Patients Who Underwent Surgery Radiation for Node-Positive Stage IB1-IIA Patients Who Underwent Surgery Brachytherapy for Stage IIA-IVA Patients Treated With Radiation Age <50 years Referent Referent Referent Referent years 0.80 ( ) a 0.65 ( ) a 0.87 ( ) 0.88 ( ) years 0.57 ( ) a 0.50 ( ) a 1.21 ( ) 0.77 ( ) a years 0.32 ( ) a 0.28 ( ) a 1.37 ( ) 0.73 ( ) a 80 years 0.10 ( ) a 0.11 ( ) a 0.06 ( ) a 0.46 ( ) a Race White Referent Referent Referent Referent Black 0.68 ( ) a 0.62 ( ) a 0.64 ( ) a 0.77 ( ) a Other 1.07 ( ) 1.22 ( ) a 1.23 ( ) 1.34 ( ) Unknown 0.80 ( ) 0.34 ( ) a 0.69 ( ) Year of diagnosis Referent Referent Referent Referent ( ) a 1.01 ( ) 1.48 ( ) 0.92 ( ) ( ) a 1.11 ( ) 1.63 ( ) a 0.44 ( ) a SEER registry West Referent Referent Referent Referent Central 0.84 ( ) a 0.66 ( ) a 0.82 ( ) 1.53 ( ) a East 0.91 ( ) 0.78 ( ) a 0.67 ( ) a 1.14 ( ) Marital status Married Referent Referent Referent Referent Single 0.80 ( ) a 0.84 ( ) a 1.16 ( ) 0.90 ( ) Unknown 0.55 ( ) a 0.56 ( ) a 4.27 ( ) 0.89 ( ) Histology Squamous Referent Referent Referent Referent Adenocarcinoma 1.17 ( ) a 1.30 ( ) a 0.92 ( ) 0.94 ( ) Adenosquamous 1.48 ( ) a 1.49 ( ) a 1.76 ( ) 0.95 ( ) Tumor grade 1 Referent Referent Referent Referent ( ) a 1.85 ( ) a 1.26 ( ) 1.01 ( ) ( ) a 2.38 ( ) a 1.45 ( ) 0.92 ( ) Unknown 0.69 ( ) a 0.88 ( ) 1.73 ( ) 0.90 ( ) Stage IB1 Referent Referent Referent IB ( ) a 1.09 ( ) 0.86 ( ) IB NOS 0.43 ( ) a 0.33 ( ) a 1.04 ( ) IIA 0.22 ( ) a 0.50 ( ) a 1.44 ( ) IIB Referent IIIA 0.48 ( ) a IIIB 0.53 ( ) a IVA 0.20 ( ) a Abbreviations: NOS, not otherwise specified; SEER, Surveillance, Epidemiology, and End Results. a P < years and 74 (12.1%) of the women 80 years old (P <.0001). Among women treated with radiation, use of brachytherapy, the standard of care, declined with age from 66.7% in those <50 years old to 58.9% in patients aged 70 to 79 years and to 46.3% in women 80 years old (P <.0001). Accounting for other prognostic factors, women with advanced stage tumors who were treated with radiation and were 70 to 79 years old (OR, 0.73; 95% CI, ) or 80 years old (OR, 0.46; 95% CI, ) were less likely to receive brachytherapy (Table 3). Other predictors of use of brachytherapy were race, year of diagnosis, area of residence, and stage Cancer July 15, 2012

6 Cervical Cancer in the Elderly/Sharma et al Table 4. Cox Proportional Hazards Models of Cancer-Specific Survival for Women With Cervical Cancer Characteristic Stage IB1-IIA Stage IIB-IVA Age <50 years Referent Referent years 1.00 ( ) 0.92 ( ) years 1.01 ( ) 0.94 ( ) years 1.35 ( ) a 1.12 ( ) a 80 years 2.08 ( ) a 1.47 ( ) a Race White Referent Referent Black 1.35 ( ) a 1.16 ( ) a Other 1.00 ( ) 0.76 ( ) a Unknown 0.21 ( ) a 1.64 ( ) Year of diagnosis Referent Referent ( ) a 0.96 ( ) ( ) a 0.82 ( ) a SEER registry West Referent Referent Central 1.07 ( ) 1.04 ( ) East 1.00 ( ) 0.96 ( ) Marital status Married Referent Referent Single 1.05 ( ) 1.05 ( ) Unknown 0.81 ( ) 1.12 ( ) Histology Squamous Referent Referent Adenocarcinoma 1.38 ( ) a 1.49 ( ) a Adenosquamous 1.53 ( ) a 1.09 ( ) Tumor grade 1 Referent Referent ( ) a 1.14 ( ) ( ) a 1.42 ( ) a Unknown 1.35 ( ) a 1.12 ( ) Primary treatment Surgery Referent Referent Radiation 2.21 ( ) a 1.34 ( ) a No treatment 3.49 ( ) a 3.38 ( ) a Stage IB1 Referent IB ( ) a IB NOS 1.26 ( ) a IIA 2.68 ( ) a IIB Referent IIIA 2.05 ( ) a IIIB 2.22 ( ) a IVA 3.53 ( ) a Abbreviations: NOS, not otherwise specified; SEER, Surveillance, Epidemiology, and End Results. Cancer-specific survival was then examined. Accounting for treatment disparities and other prognostic factors, elderly women were more likely to die from their tumors. For women with stage IB1-IIA tumors, the HR for death from cervical cancer was 1.35 (95% CI, Figure 1. Kaplan-Meier analysis of cancer-specific survival is stratified by age for stage IB1 (Top; P ¼.02) and stage IIIB (Bottom; P ¼.002) ) for women 70 to 79 years old and 2.08 (95% CI, ) for those 80 years old compared with younger women. Similarly, women 70 to 79 years old (HR, 1.12; 95% CI, ) and 80 years old (HR, 1.47; 95% CI, ) with stage IIB-IVA disease were more likely to die from their cancers (Table 4). In Kaplan- Meier analyses, age negatively impacted cancer-specific survival for stage IB1 (P ¼.02) and stage IIIB (P ¼.0002; Fig. 1) disease. DISCUSSION Our findings add to a growing body of literature suggesting that elderly patients with cancer are treated differently than their younger counterparts. 5-7,19 A study of nearly 23,000 patients with a variety of tumors noted that use of curative therapy declined with age and that elderly patients were more likely to forego treatment. 6 We noted Cancer July 15,

7 several treatment disparities for elderly women with cervical cancer. Compared with younger patients, women older than 70 years with early stage tumors were less likely to undergo primary surgery and less likely to receive adjuvant therapy for high-risk features, and older women with advanced stage tumors less often received high-quality radiotherapy. Even after adjusting for treatment disparities, elderly women with cervical cancer were more likely to die from their tumors than younger women. Early stage cervical cancer (stage IB-IIA) is treated either with radical hysterectomy or primary radiotherapy; survival is similar for the 2 modalities. 20 In the United States, there is a strong bias toward surgical management; >80% of women are treated surgically. 11 Despite the overall patterns of care, we noted substantial biases for the treatment of elderly women with early stage tumors. Only 55% of women aged 70 to 79 years and 33% of those aged >80 years were treated with primary surgery, compared with 82% of patients <50 years old. Even if elderly women underwent surgery, they were often not treated with radical hysterectomy, the standard of care. Despite the biases we noted in access to surgery, institutional studies have suggested that elderly women tolerate radical hysterectomy and regional lymphadenectomy well. 9,10,21,22 Further population-based studies are clearly warranted to determine the morbidity of radical hysterectomy in the elderly. The use of adjuvant treatment in early stage patients with negative prognostic features after surgery decreases the risk of locoregional recurrence and improves survival. 23,24 The Southwest Oncology Group demonstrated the superiority of chemoradiation over radiation alone for patients with high-risk features including nodal metastasis, parametrial spread, or positive margins. 24 For women at intermediate risk of recurrence with various combinations of large tumor size, deep cervical invasion, or lymphovascular space invasion, radiotherapy decreases the risk of local recurrence. 23 We noted that elderly women were less likely to receive adjuvant radiotherapy even when the indication was relatively clear. Among lymph node-positive women with early stage tumors who underwent primary surgery, patients 80 years of age were >90% less likely to receive radiation than younger women. Radiation in combination with chemotherapy is the treatment of choice for women with advanced stage cervical cancer Patterns of care studies have reported that uptake of chemotherapy has been relatively rapid, increasing from 34% in 1997 to 85% in Despite the addition of chemotherapy to treatment plans, adequate delivery of radiation remains the most important factor in disease control for advanced stage disease. The dose of radiation delivered with external beam radiation (both whole pelvic and parametrial boost) is inadequate to treat macroscopic disease and must be combined with intracavitary brachytherapy to attain adequate local control. 15 In our series, fewer than half of the women 80 years of age and only 59% of those aged 70 to 79 years received brachytherapy. Prior studies have also noted disparities in access to brachytherapy; Mitchell and coworkers noted that 11% of patients 60 to 69 years old, 20% aged 70 to 79 years, and 40% of those 80 years of age did not receive intracavitary radiation. 28 Despite the disparities in treatment with radiation, recent studies have reported that elderly women tolerate pelvic radiotherapy and brachytherapy well ,29-31 The European Organization for Research and Treatment of Cancer found that there were no age-related differences in either early or late toxicities in >1600 patients treated with pelvic radiation. 30 Even among patients >80 years of age it appears that radiotherapy is well tolerated. 31 Care should be taken to optimize radiation therapy in elderly patients who are treated. Grant and colleagues noted that 32% of women aged >75 years treated with pelvic radiotherapy did not complete therapy, and treatment interruptions occurred in 42% of patients. 32 Cisplatin-based chemotherapy is now frequently used in combination with radiation. It appears that chemoradiation is well tolerated, but further studies examining the long-term outcomes of chemoradiation in the elderly are needed. 13 Despite the inclusion of a large number of patients, we recognize several important limitations. Perhaps most importantly, SEER lacks medical comorbidities; therefore, we were unable to risk adjust our population. It is well known that performance status and comorbidity not only impact the allocation of treatment, but also exert a direct effect on survival. 5,6,33 SEER lacks data on chemotherapy, and registry data may not capture all women treated with radiotherapy. 34 Although undercoding of radiation would have been balanced among the age strata, further work is required to explore the use of chemotherapy in elderly women with cervical cancer. As central pathology review is not provided, we limited our analysis to only patients with the most common histologic subtypes of cervical cancer. Many of the effects we noted regarding treatment disparities became gradually more pronounced with age, and there was not 1 specific age cutpoint that we could define. Lastly, SEER does not capture recurrence or 3624 Cancer July 15, 2012

8 Cervical Cancer in the Elderly/Sharma et al subsequent treatment. Given this limitation, we analyzed cancer-specific survival as an endpoint. In addition to the finding that elderly women with cervical cancer are treated less aggressively than younger patients, we noted that even with standard of care therapy, older women are more likely to die from their tumors. When adjusted for stage and treatment, women >70 years of age were more likely to die from cervical cancer than their younger counterparts, suggesting that age >70 years is a negative prognostic factor in cervical cancer. Given the guarded prognosis of elderly patients with cervical cancer, our study raises the question of whether these women should be treated aggressively. Outcomes data suggest that survival for cervical cancer is in general favorable; 5-year survival for early stage tumors is 80% or greater, and even for stage IIIB neoplasms 5-year survival approaches 35% in some subsets of patients. 20,35 Given these data, treatment in the elderly should be individualized and take into account not only tumor characteristics but also comorbidities, functional status, and patient preferences. 36,37 For other tumor types, comprehensive geriatric assessment, a multidisciplinary treatment approach that includes tumor, treatment, and patient characteristics to guide treatment, have shown success and may be of value in elderly women with cervical cancer. 38 Further studies to examine the factors that underlie treatment disparities for elderly women with cervical cancer and comparative effectiveness research to individualize the management of older women with cervical cancer are needed. FUNDING SOURCES No specific funding was disclosed. CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures. REFERENCES 1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, CA Cancer J Clin. 2005;55: Jemal A, Siegel R, Xu J, Ward E. Cancer Statistics, CA Cancer J Clin. 2010;60: U.S. Population Projections Available at: tables.html Accessed on February 1, SEER Cancer Statistics Available at: Accessed on Goodwin JS, Samet JM, Hunt WC. Determinants of survival in older cancer patients. J Natl Cancer Inst. 1996;88: Samet J, Hunt WC, Key C, Humble CG, Goodwin JS. Choice of cancer therapy varies with age of patient. JAMA. 1986;255: Schonberg MA, Marcantonio ER, Li D, Silliman RA, Ngo L, McCarthy EP. Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival. J Clin Oncol. 2010;28: Wright JD, Gibb RK, Geevarghese S, et al. Cervical carcinoma in the elderly: an analysis of patterns of care and outcome. Cancer. 2005;103: Fuchtner C, Manetta A, Walker JL, Emma D, Berman M, DiSaia PJ. Radical hysterectomy in the elderly patient: analysis of morbidity. Am J Obstet Gynecol. 1992;166: Geisler JP, Geisler HE. Radical hysterectomy in patients 65 years of age and older. Gynecol Oncol. 1994;53: Trimble EL, Harlan LC, Gius D, Stevens J, Schwartz SM. Patterns of care for women with cervical cancer in the United States. Cancer. 2008;113: Brun JL, Stoven-Camou D, Trouette R, Lopez M, Chene G, Hocke C. Survival and prognosis of women with invasive cervical cancer according to age. Gynecol Oncol. 2003;91: Goodheart M, Jacobson G, Smith BJ, Zhou L. Chemoradiation for invasive cervical cancer in elderly patients: outcomes and morbidity. Int J Gynecol Cancer. 2008;18: Ikushima H, Takegawa Y, Osaki K, et al. Radiation therapy for cervical cancer in the elderly. Gynecol Oncol. 2007;107: Magne N, Mancy NC, Chajon E, et al. Patterns of care and outcome in elderly cervical cancer patients: a special focus on brachytherapy. Radiother Oncol. 2009;91: Surveillance, Epidemiology, and End Results, SEER*Stat Database: Incidence-SEER 9 Regs Limited-Use, Nov 2006 Sub ( ), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2007, based on the November 2006 submission. Available at: Accessed on October 1, Surveillance, Epidemiology, and End Results (SEER) Program, Data Quality. National Cancer Institute, Available at: Accessed on October 1, Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 2009;105: Cykert S, Dilworth-Anderson P, Monroe MH, et al. Factors associated with decisions to undergo surgery among patients with newly diagnosed early-stage lung cancer. JAMA. 2010;303: Landoni F, Maneo A, Colombo A, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet. 1997;350: Giannice R, Susini T, Ferrandina G, et al. Systematic pelvic and aortic lymphadenectomy in elderly gynecologic oncologic patients. Cancer. 2001;92: Levrant SG, Fruchter RG, Maiman M. Radical hysterectomy for cervical cancer: morbidity and survival in relation to weight and age. Gynecol Oncol. 1992;45: Rotman M, Sedlis A, Piedmonte MR, et al. A phase III randomized trial of postoperative pelvic irradiation in stage IB cervical carcinoma with poor prognostic features: followup of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys. 2006;65: Cancer July 15,

9 24. Peters WA III, Liu PY, Barrett RJ Jr, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18: Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999;17: Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340: Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340: Mitchell PA, Waggoner S, Rotmensch J, Mundt AJ. Cervical cancer in the elderly treated with radiation therapy. Gynecol Oncol. 1998;71: Minagawa Y, Kigawa J, Itamochi H, Terakawa N. The outcome of radiation therapy in elderly patients with advanced cervical cancer. Int J Gynaecol Obstet. 1997;58: Pignon T, Horiot JC, Bolla M, et al. Age is not a limiting factor for radical radiotherapy in pelvic malignancies. Radiother Oncol. 1997;42: Zachariah B, Balducci L, Venkattaramanabalaji GV, Casey L, Greenberg HM, DelRegato JA. Radiotherapy for cancer patients aged 80 and older: a study of effectiveness and side effects. Int J Radiat Oncol Biol Phys. 1997;39: Grant PT, Jeffrey JF, Fraser RC, Tompkins MG, Filbee JF, Wong OS. Pelvic radiation therapy for gynecologic malignancy in geriatric patients. Gynecol Oncol. 1989;33: Yancik R, Wesley MN, Ries LA, et al. Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study. Cancer. 1998;82: Malin JL, Kahn KL, Adams J, Kwan L, Laouri M, Ganz PA. Validity of cancer registry data for measuring the quality of breast cancer care. J Natl Cancer Inst. 2002;94: Moore DH. Cervical cancer. Obstet Gynecol. 2006;107: Extermann M, Overcash J, Lyman GH, Parr J, Balducci L. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol. 1998;16: Mayer C, Ergina P, Morin JF, Gold S. Self-reported functional status as a predictor of coronary artery bypass graft surgery outcome in elderly patients. Can J Cardiol. 2003;19: Maas HA, Janssen-Heijnen ML, Olde Rikkert MG, Machteld Wymenga AN. Comprehensive geriatric assessment and its clinical impact in oncology. Eur J Cancer. 2007;43: Cancer July 15, 2012