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© 2002 American Society for Clinical Oncology Use of Adjuvant Chemotherapy and Radiation Therapy for Rectal Cancer Among the Elderly: A Population-Based StudyByFrom the Department of Medicine, Mailman School of Public Health, and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY; and the Department of Epidemiology and Preventive Medicine, Monash Medical School, Melbourne, Australia. Address reprint requests to Alfred I. Neugut, MD, PhD, Division of Medical Oncology, New York Presbyterian Hospital, PH 18-127, 630 West 168th St, New York, NY 10032; email: ain1{at}columbia.edu
PURPOSE: Combined adjuvant fluorouracil (5-FU)–based chemotherapy with radiation is now the standard of care for locally advanced rectal cancer in the United States. We investigated the use of these treatments for stages II and III rectal cancer among the elderly and the effectiveness of these treatments on a population-based scale.
PATIENTS AND METHODS: The linked Surveillance, Epidemiology, and End-Results–Medicare database was used to identify 1,807 Medicare beneficiaries RESULTS: We found that 37% of patients received both adjuvant 5-FU and radiation therapy, 11% 5-FU alone, and 14% radiation alone. Decreasing age, increasing lymph node positivity, comorbid conditions, and nonblack race were associated with increased probability of treatment with 5-FU and radiation. Combined chemotherapy/radiation therapy was associated with improved survival for stage III (relative risk, 0.71; 95% confidence interval, 0.56 to 0.90), but not for stage II rectal cancer (relative risk, 0.89; 95% confidence interval, 0.70 to 1.14). CONCLUSION: The association of combined treatment with improved survival in node-positive disease was similar to that observed in other studies. In the absence of data from well-designed randomized controlled trials, our observational data support efforts on the part of clinicians to make appropriate referrals and provide combined treatment for elderly patients with stage III rectal cancer.
ALTHOUGH THE SURVIVAL benefits of fluorouracil (5-FU)–based adjuvant chemotherapy for node-positive colon cancer have been well established over the past decade,1-4 the optimal adjuvant regimen for surgically resected, locally advanced (T3N0M0, T4N0M0, and node-positive) rectal cancer remains less clear. Randomized controlled trials have demonstrated that radiation therapy reduces local recurrence rates, but its impact on overall survival is less clear-cut. Adjuvant chemotherapy, conversely, does seem to improve survival, particularly when used in combination with radiation therapy.5-9 Both the National Institutes of Health Consensus Conference and the National Comprehensive Cancer Network guidelines recommend the use of adjuvant chemotherapy and radiation therapy for patients with rectal cancer in stage II or stage III.4,10 Presently, most practitioners routinely use combined adjuvant chemotherapy/radiation therapy for stages II and III rectal cancer. Rectal cancer, like colon cancer, is largely a disease of older age.11 However, older patients have generally been underrepresented in clinical trials for these diseases.12-16 We have previously found that older patients with node-positive colon cancer have a survival benefit from the use of adjuvant chemotherapy similar to that demonstrated in randomized trials.17 However, we and others have also found that older patients are less likely than younger patients to receive the recommended adjuvant chemotherapy, even though most studies suggest that chemotherapy is usually well tolerated by older patients.16,18,19 In this article, we investigate the use of treatment with adjuvant 5-FU–based chemotherapy and radiation therapy among patients over 65 years of age with surgically resected stage II or III rectal cancer. In addition to identifying predictors of the use of these treatments, we assess the association of treatment with survival, taking the predictors into account by means of propensity score methodology.
This study used data from the Surveillance, Epidemiology, and End-Results (SEER) Medicare database, developed by Potosky et al20 at the National Cancer Institute in 1993. The SEER data come from tumor registries covering approximately 14% of the United States population, and provide information on tumor location, stage of disease, and demographics, and also primary surgical and radiation treatment and survival. Through an identifier, the SEER data are linked to outpatient and inpatient Medicare claims data for those over 65 years of age and those under 65 with Social Security Disability Insurance benefits. The Medicare files contain extensive diagnostic, treatment, and cost data.20
Study Population
Treatment With 5-FU
Treatment With Radiation Therapy
Sociodemographic Variables
Comorbid Disease
Determination of Survival
Statistical Analysis In the absence of randomization, simple multivariate analysis to compare two treatment groups may be insufficient to fully account for all the measured and unmeasured confounders and selection bias. The propensity score can be thought of as a measure of the likelihood that a subject will be treated on the basis solely of that subject’s covariate information. To determine the propensity scores, we constructed a logistic regression model in which the dependent variable was the treatment group and the independent variables were the predictors of treatment. The propensity score for each subject was his or her probability of being in a treatment group on the basis of the logistic regression model. When subjects are grouped into strata on the basis of their propensity scores, the treated and untreated subjects within each stratum are theoretically balanced with respect to potentially confounding covariates. Subgrouping into five propensity score strata is considered adequate to remove over 90% of the bias caused by each of the covariates.23,24 This methodology has been used for SEER-Medicare data previously.17,25
Baseline Descriptive Characteristics The descriptive statistics for our population are listed in Table 1. The cohort consisted of 1,807 (962 men and 845 women) histologically confirmed, stage II (n = 983) and stage III (n = 824) primary rectal cancer patients diagnosed between the years 1992 and 1996. The median age at diagnosis for this predominantly non-Hispanic white (88%) population was 72 years, with a range of 65 to 100 years. More than half (52%) of this cohort had at least one comorbid illness associated with a hospitalization in the time period of 1 year before diagnosis to 4 months afterward. Patients with stage II cancer did not differ from those with stage III cancer in the number of comorbid conditions.
Treatment for Rectal Cancer Of the total cohort, 51% received adjuvant chemotherapy with 5-FU–containing regimens, and 48% received radiation therapy. Specifically, 38% (n = 683) received surgery alone, 11% (n = 197) received surgery plus radiation therapy, 14% (n = 254) received surgery plus adjuvant 5-FU, and 37% (n = 673) received surgery with radiation plus adjuvant 5-FU chemotherapy. Patients with stage III disease were significantly more likely than patients with stage II disease to receive combined 5-FU chemotherapy (63.5% v 41%, respectively) and radiation (42% v 55%, respectively). The groups that received surgery plus either chemotherapy or radiation therapy alone were felt to be too small and potentially biased to be analyzed in this observational study. Thus, further analyses focused on the use of combined chemotherapy/radiation therapy.
Factors Associated With Combined Chemotherapy/Radiation Therapy
Presurgical and Postsurgical Radiation Therapy Of 673 patients who received the combined therapy, 598 (89%) received postsurgical radiation treatment, 68 (10%) received presurgical radiation, and only eight (1%) had both presurgical and postsurgical or intraoperative radiation. The timing of radiation therapy was not associated with year of diagnosis, and although age was associated with overall use of radiation, the use of presurgical versus postsurgical radiation therapy was not associated with age (data not shown).
Survival We performed both multivariate and propensity score–adjusted Cox proportional hazard models in order to calculate survival rate ratios (relative risk [RR] for mortality). The multivariate and propensity score models gave similar results; thus, we list only the propensity score results in Table 3. Combined adjuvant radiation therapy plus 5-FU–based chemotherapy was associated with a 17% reduced risk of death among all cases (RR, 0.83; 95% confidence interval [CI], 0.70 to 0.98). Stratifying by stage demonstrated effect modification. There was a survival benefit for the combined treatment in stage III cases, with a statistically significant 29% reduced risk of death (RR, 0.71; 95% CI, 0.56 to 0.90). No improvement in survival was observed among stage II cases (RR, 0.89; 95% CI, 0.70 to 1.14). Unadjusted Kaplan-Meier survival plots also demonstrate a statistically significant reduced rate of death among stage III patients receiving combined therapy compared with surgery-only patients (Figs 1 and 2).
Our study, derived from the SEER-Medicare database, provides a population-based perspective on the use of adjuvant 5-FU and radiation therapy for locally advanced rectal cancer. Between 1992 and 1996, only approximately 50% of newly diagnosed patients over the age of 65, all of whom seemed to have been eligible for adjuvant treatment, received either within 4 months of diagnosis, whereas 37% received both. As age at diagnosis increased, the use of combined chemotherapy and radiation therapy decreased. The number of lymph nodes involved with tumor increased the odds of treatment, whereas high comorbidity scores reduced it. In the years 1992 to 1996, the proportion of patients treated with adjuvant therapy did not change significantly. Our analyses show that elderly patients with stage III rectal cancer derive a significant benefit from combined adjuvant chemotherapy/radiation therapy in the form of a 29% improvement in 5-year survival, similar to that observed in randomized trials.5-9 Among these rectal cancer patients, as has been observed among colon cancer patients, the benefits of adjuvant therapy were limited to those with node-positive disease.1-4 Although radiation therapy for T3N0M0 and T4N0M0 rectal cancer may reduce local recurrence rates, the addition of chemotherapy to the adjuvant regimen did not have an overall impact on survival. The reason why studies have failed to observe a benefit among patients with less advanced disease may be that their survival is so much better without treatment that the incremental benefit of treatment is harder to detect. However, our data support the consensus that treatment should be provided to patients with node-positive disease. An inverse correlation of treatment with age has been documented for several cancers. In 1986, analysis of SEER data from New Mexico documented variations in treatment patterns on the basis of age for a variety of cancers, including colorectal cancer.26 Lower rates of treatment among the elderly over the age of 70 to 75 years compared with those 10 years younger have also been found in breast and ovarian cancer.27-29 Race as a factor in undertreatment has also been documented for colorectal cancer, prostate cancer, breast cancer, ovarian cancer, and lung cancer.29-33 However, among patients in the Veterans Affairs Medical Centers, race was not significantly associated with the use of surgery or chemotherapy.34 A recent study by Nattinger et al35 compared the SEER registry population with the general population of the United States. Although fairly representative overall, the SEER counties seem to be more affluent, more educated, and less rural than the population of the United States. They have the same density of physician resources as non-SEER counties, but fewer beds and fewer hospitals with approval from the Joint Commission on the Accreditation of Hospitals. These differences are unlikely to limit the generalizability of our data. A comparison of SEER and Medicare as sources for data on radiation therapy found that SEER did not indicate use of radiation therapy for 18% of breast cancer patients identified by Medicare as receiving radiation therapy, and that Medicare did not indicate use of radiation therapy for 7% of patients so identified by SEER.36 We used only SEER data to identify patients who received radiation therapy and may therefore have underascertained this treatment. However, if radiation therapy improves survival, this misclassification would result in underestimation of the survival benefit of treatment. The accuracy of our evaluation of comorbid disease status, an important potential determinant of treatment, depends on the accuracy of the diagnostic coding in the claims data. For the majority of comorbid diseases used in our index, agreement between claims data and abstracts of the medical record has been found to be higher than 85% and improved from 1977 to 1985.37 By the 1990s, agreement may have improved still further. In our data, comorbidity score was a significant predictor of combined treatment. An attempt to include outpatient comorbid conditions in the score made it less predictive (data not shown). Recent reports indicate that comorbid disease may not be associated with functional status.38 Patient functional status is probably a key factor in decision-making regarding adjuvant treatment. The SEER–Health Care Finance Administration database does not include variables specifically indicative of functional status, self-rated health, or psychological status, which may also affect treatment decision-making. However, all the patients in our cohort had had surgery, arguably a greater stress on functional reserves than radiation therapy or chemotherapy with 5-FU. We did not include in our analysis patients who were HMO enrollees because Medicare does not collect claims on such patients. Consequently, we do not know how this set of patients may differ in their patterns of care from those with claims-based Medicare coverage. Two studies from the National Cancer Institute describe treatment patterns in HMOs based in the San Francisco–Oakland and Seattle–Puget Sound areas. Both studies found no consistent patterns among HMO enrollees regarding adjuvant radiotherapy among women with early-stage breast cancer or among men with nonmetastatic prostate cancer.39,40 Colorectal cancer incidence rates are six times higher among persons aged 65 to 84 years than among younger people. Age is also associated with stage at diagnosis and with mortality from colorectal cancer; most colorectal cancer deaths occur in people over the age of 65.41 Although the elderly bear most of the burden of cancer, older patients have been less likely to receive the standard treatments for cancer than younger patients, even when such treatments are potentially curative. Studies of the use of potentially curative treatment for cancers of several sites have found that the likelihood of not being treated increased with age. Our own study found that increasing age was strongly inversely associated with the receipt of 5-FU–containing chemotherapy regimens in the context of node-positive colon cancer.18 Clinicians may have good reasons for treating older cancer patients less aggressively than younger ones. Elderly patients are more likely to have comorbid conditions, impairments of functional status, or living conditions (eg, living alone) that may make cancer treatment and its toxicities particularly difficult to tolerate. Both chemotherapy for lung cancer42 and radiation therapy for rectal cancer43 have been found to be more toxic in older than in younger patients. Those considerations may account in part for the underrepresentation of elderly patients in clinical trials. However, a meta-analysis of 19 drug trials found no convincing evidence that chemotherapy was, in general, more toxic or less beneficial for patients aged 70 or more than in younger patients.44 A secondary analysis of several phase II trials in advanced cancer also found no evidence of increased toxicity in those over age 65,45 although the elderly participants in these trials may have been selected, like the younger ones, for better than average overall health and functional status. Previous studies of decision-making in cancer treatment indicate that age influences both the frequency with which chemotherapy is offered as a treatment alternative and the willingness of patients to accept such treatment. In a study by Newcomb and Carbone,46 nearly 50% of those under age 65 were offered chemotherapy as a treatment option, but only 35% of those over 65 were given the same option. Of those offered chemotherapy, nearly twice as many patients over the age of 65 (33%) as under 65 rejected chemotherapy, fearing side effects. However, Begg and Carbone44 found that patients over 70 years of age had similar response rates and survival rates, and no higher levels of severely toxic effects from chemotherapy, than patients under 70. In this study, we have demonstrated, using propensity score methodology, that among patients over age 65 with node-positive rectal cancer, the difference in survival between those receiving and those not receiving adjuvant combined chemotherapy and radiation therapy is significant and similar to that described in other studies. Those with node-negative disease did not have a survival benefit. The prevention of local recurrence could not be assessed. Our data are observational, rather than experimental. They may therefore reflect uncontrolled confounding by performance status or other factors that properly affect the decision to treat or to not treat a given patient. However, their consistency with other data regarding both survival and bias in treatment decision-making suggest that they are not attributable entirely to such confounding. Moreover, trials by their nature cannot provide insight into the determinants and effectiveness (as opposed to efficacy) of treatment in actual use in the general population, as the data in our nationwide sample do. Our results reveal that, by 1992, 2 years after the National Institutes of Health Consensus Conference findings,4 adjuvant therapy of rectal cancer for patients over age 65 had reached a level that would be maintained for the next 5 years. Adoption of national recommendations had been relatively rapid (within 2 years), but limited; only one half of apparently eligible patients received therapy between 1992 and 1996. In terms of survival, adjuvant therapy for breast cancer and colorectal cancer has been one of the most important contributions of medical oncology to the health of the nation, saving more lives annually than more effective treatments for less common malignancies, such as Hodgkin’s disease and testicular cancer. However, the majority of colorectal malignancies occur in the elderly. Our data suggest that less than 50% of node-positive rectal cancer patients over age 65 years are receiving appropriate combined chemotherapy/radiation therapy, and that this treatment is associated with a 29% reduction in risk mortality, similar to that observed in randomized clinical trials. These observations are consistent with our earlier findings in colon cancer and with other reports as well. As the population continues to age, it becomes increasingly important to increase awareness among both patients and physicians that age may not diminish the benefits of chemotherapy and radiation therapy for stage III rectal cancer.
1. Moertel CG, Fleming TR, Macdonald JS, et al: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322: 352-358, 1990[Abstract]
2.
Moertel CG, Fleming TR, Macdonald JS, et al: Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: A final report. Ann Intern Med 122: 321-326, 1995 3. Zaniboni A, Labianca R, Marsoni S, et al: GIVIO-SITAC-01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma—Long term results and evaluation of the indicators of health-related quality of life. Cancer 82: 2135-2144, 1998[CrossRef][Medline]
4.
NIH Consensus Conference: Adjuvant therapy for patients with colon and rectal cancer. JAMA 264: 1444-1450, 1990 5. Gastrointestinal Tumor Study Group: Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 312: 1465-1472, 1985[Abstract]
6.
O’Connell MJ, Martenson JA, Wieand HS, et al: Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 331: 502-507, 1994
7.
Tepper JE, O’Connell MJ, Petroni GR, et al: Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: Initial results of intergroup 0114. J Clin Oncol 15: 2030-2039, 1997 8. Wagman RT, Minsky BD: Conservative management of rectal cancer with local excision and adjuvant therapy. Oncology (Huntingt) 15: 513-519, 2001[Medline] 9. Dahlberg M, Glimelius B, Pahman L: Improved survival and reduction in local failure rates after preoperative radiotherapy: Evidence for the generalizability of the results of Swedish Rectal Cancer Trial. Ann Surg 228: 493-497, 1999 10. Engstrom PF, Benson AB III, Cohen A, et al: NCCN Colorectal Cancer Practice Guidelines: The National Comprehensive Cancer Network. Oncology (Huntingt) 10: 140-175, 1996 (11 suppl)[Medline] 11. Ries LAG, Kosary CL, Hankey BF, et al: SEER Cancer Statistics Review, 1973-1996. Bethesda, MD, National Cancer Institute, 1999
12.
Hodgson DC, Fuchs CS, Ayanian JZ: Impact of patient and provider characteristics on the treatment and outcomes of colorectal cancer. J Natl Cancer Inst 93: 501-515, 2001
13.
Antman KD, Amato D, Wood W, et al: Selection bias in clinical trials. J Clin Oncol 3: 1142-1147, 1985
14.
Hutchins LF, Unger JM, Crowley JJ, et al: Underrepresentation of patients 65 years of age or older in cancer treatment trials. N Engl J Med 341: 2061-2067, 1999
15.
Taylor KM, Feldstein ML, Skeel RT, et al: Fundamental dilemmas of the randomized clinical trial process: Results of a survey of the 1,737 Eastern Cooperative Oncology Group investigators. J Clin Oncol 12: 1796-1806, 1994
16.
Sargent DJ, Goldberg RM, Jacobson SD, et al: A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 345: 1091-1097, 2001
17.
Sundararajan V, Mitra N, Grann VR, et al: Survival associated with 5-fluorouracil-based adjuvant chemotherapy among elderly patients with node-positive colon cancer. Ann Intern Med 136: 349-357, 2002 18. Sundararajan V, Grann VR, Jacobson JS, et al: Variations in the use of adjuvant chemotherapy for node-positive colorectal cancer in the elderly: A population-based study. Cancer J 7: 213-218, 2001[Medline]
19.
Schrag D, Cramer LD, Bach PB, et al: Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst 93: 850-857, 2001 20. Potosky AL, Riley GF, Lubitz JD, et al: Potential for cancer related health services research using a linked Medicare-tumor registry database. Med Care 31: 732-748, 1993[Medline] 21. Charlson ME, Pompei P, Ales KL, et al: A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 40: 373-383, 1987[CrossRef][Medline] 22. Deyo RA, Cherkin DC, Ciol MA, et al: Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45: 613-619, 1992[CrossRef][Medline] 23. Rubin DB, Thomas N: Matching using estimated propensity scores: Relating theory to practice. Biometrics 52: 249-264, 1996[CrossRef][Medline]
24.
Rubin DB: Estimating causal effects from large data sets using propensity scores. Ann Intern Med 127: 757-763, 1997
25.
Earle CC, Tsai JS, Gelber RD, et al: Effectiveness of chemotherapy for advanced lung cancer in the elderly: Instrumental variable and propensity analysis. J Clin Oncol 19: 1064-1070, 2001
26.
Samet J, Hunt WC, Key C, et al: Choice of cancer therapy varies with age of patient. JAMA 255: 3385-3390, 1986 27. Munoz KA, Harlan LC, Trimble EL, et al: Patterns of care for women with ovarian cancer in the United States. J Clin Oncol 15: 3408-3415, 1986 28. Hightower RD, Nguyen HN, Averette HE, et al: National survey of ovarian carcinoma: IV. Patterns of care and related survival for older patients. Cancer 73: 377-383, 1994[CrossRef][Medline]
29.
Greenfield S, Blanco DM, Elashoff RM, et al: Patterns of care related to age of breast cancer patients. JAMA 257: 2766-2770, 1987 30. Tropman S, Hatzell ET, Paskett E, et al: Colon cancer treatment in rural North and South Carolina. Cancer Detect Prev 23: 428-434, 1999[CrossRef][Medline] 31. Michalski TA, Nattinger AB: The influence of black race and socioeconomic status on the use of breast-conserving surgery for Medicare beneficiaries. Cancer 79: 314-319, 1997[CrossRef][Medline] 32. Klabunde CN, Potosky AL, Harlan LC, et al: Trends and black/white differences in treatment for nonmetastatic prostate cancer. Med Care 36: 1337-1348, 1998[CrossRef][Medline]
33.
Bach PB, Cramer LD, Warren JL, et al: Racial differences in the treatment of early-stage lung cancer. N Engl J Med 341: 1198-1205, 1999 34. Dominitz JA, Samsa GP, Landsman P, Provenzale D: Race, treatment, and survival among colorectal carcinoma patients in an equal-access medical system. Cancer 82: 2312-2320, 1998[CrossRef][Medline] 35. Nattinger AB, McAuliffe TL, Schapira MM: Generalizability of the surveillance, epidemiology, and end results registry population: Factors relevant to epidemiologic and health care research. J Clin Epidemiol 50: 939-945, 1997[CrossRef][Medline] 36. Du X, Freeman JL, Goodwin JS: Information on radiation treatment in patients with breast cancer: The advantages of the linked Medicare and SEER data. J Clin Epidemiol 52: 463-470, 1999[CrossRef][Medline]
37.
Fisher ES, Whaley FS, Krushat WM, et al: The accuracy of Medicare’s hospital claims data: Progress has been made, but problems remain. Am J Public Health 82: 243-248, 1992
38.
Extermann M, Overcash J, Lyman GJ, et al: Comorbidity and functional status are independent in older cancer patients. J Clin Oncol 16: 1582-1587, 1998 39. Potosky AL, Merrill RM, Riley GF, et al: Prostate cancer treatment and ten-year survival among group/staff HMO and fee-for-service Medicare patients. Health Serv Res 34: 525-546, 1999[Medline]
40.
Riley GF, Potosky AL, Klabunde CN, et al: Stage at diagnosis and treatment patterns among older women with breast cancer: An HMO and fee-for-service comparison. JAMA 281: 720-726, 1999 41. Yancik R: Cancer burden in the aged: An epidemiologic and demographic overview. Cancer 80: 1273-1283, 1997[CrossRef][Medline] 42. Findlay MP, Griffin AM, Raghavan D, et al: Retrospective review of chemotherapy for small cell lung cancer in the elderly: Does the end justify the means? Eur J Cancer 27: 1597-1601, 1991[Medline] 43. Ooi BS, Tiandra JJ, Green MD, et al: Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer: An overview. Dis Colon Rectum 42: 403-418, 1999[CrossRef][Medline] 44. Begg CB, Carbone PP: Clinical trials and drug toxicity in the elderly: The experience of the Eastern Cooperative Oncology Group. Cancer 52: 1986-1992, 1983[CrossRef][Medline]
45.
Giovanazzi-Bannon S, Rademaker A, Lai G, et al: Treatment tolerance of elderly cancer patients entered onto phase II clinical trials: An Illinois Cancer Center study. J Clin Oncol 12: 2447-2452, 1994
46.
Newcomb PA, Carbone PP: Cancer treatment and age: Patient perspectives. J Natl Cancer Inst 85: 1580-1584, 1993 Submitted August 7, 2001; accepted March 15, 2002.
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
65 years of age with stage II or III rectal cancer who underwent surgical resection between 1992 and 1996. We excluded members of a health maintenance organization in the 12 months before or 4 months after their diagnosis and those who died within 4 months of diagnosis. We used multivariate analysis to identify factors associated with combined 5-FU and radiation therapy, and propensity score methodology to determine survival benefit for those treated. 
