SEARCH

SEARCH BY CITATION

Keywords:

  • outcome assessment;
  • colonic neoplasms;
  • standards;
  • survival analysis;
  • multivariate analysis;
  • health care disparities

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. Data Sources
  6. RESULTS
  7. DISCUSSION
  8. Acknowledgements
  9. FUNDING SOURCES
  10. REFERENCES

BACKGROUND:

The objective of the current study was to examine the impact of adherence to guidelines on stage-specific survival outcomes in patients with stage III and high-risk stage II colon cancer. The National Comprehensive Cancer Network (NCCN) has established working, expert consensus, and evidence-based guidelines for organ-specific cancer care, including care of patients with colon cancer.

METHODS:

Patients who were diagnosed with colon adenocarcinoma between 1998 and 2002 were selected from within the National Cancer Data Base. The cohort was limited to patients who received their first course of treatment at the reporting facility. Pathologic variables, including tumor depth, lymph node status, and evidence of metastatic disease, were used to restage patients, and the patients were divided into low-risk and high-risk categories on the basis of criteria defined by the NCCN. Relative survival rates were calculated for the entire cohort, stratified according to adherence versus nonadherence to NCCN treatment guidelines.

RESULTS:

In univariate analysis of treatment adherence patterns for both patient subgroups (high-risk stage II and stage III), several factors were associated with a higher rate of nonadherence in both groups, including older age (P < .001); Medicaid, Medicare, or uninsured status versus private insurance (P < .001); and subsequent treatment at a facility other than the facility at which the cancer was first diagnosed (P < .001). In multivariate analysis, multiple factors were associated with differences in relative survival, although analyses that included the year of diagnosis did not demonstrate significant differences over time.

CONCLUSIONS:

The current study documented practice patterns in a heterogeneous population of patients with colon cancer and demonstrated a survival benefit for patients with stage III and high-risk stage II colon cancer who received treatment that adhered to NCCN guidelines. These data validate the current NCCN practice guidelines for colon cancer and support the concept of guideline-based metrics that can be compared across institutions to assess the quality of cancer care and to compare the quality of cancer care among institutions. Cancer 2013. © 2012 American Cancer Society.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. Data Sources
  6. RESULTS
  7. DISCUSSION
  8. Acknowledgements
  9. FUNDING SOURCES
  10. REFERENCES

Multimodality treatment guidelines for colon cancer have been revised frequently as data accumulate on the optimal selection and timing of treatment. The National Comprehensive Cancer Network (NCCN) is a nonprofit organization that has established working, expert consensus, and evidence-based guidelines for organ-specific cancer care, including care of patients with colon cancer.1 Stage-based treatment for colon cancer has been subjected to significant scrutiny over the last decade, and several large trials have examined the benefits of multimodality care for this disease.2-7 The current NCCN guidelines for colon cancer recommend that patients with stage I and low-risk stage II disease undergo surgery alone; that patients with high-risk stage II disease and all patients with stage III disease undergo surgical resection and receive adjuvant chemotherapy unless there are obvious contraindications; and that patients with stage IV disease be offered some combination of chemotherapy with or without surgical resection.1

There is clear evidence that adjuvant chemotherapy in patients with stage III colon cancer is associated with improved survival outcomes.3, 4, 8-15 However, the optimal treatment of patients with high-risk stage II disease (defined by tumor depth, histologic grade, margin status, and number of lymph nodes retrieved) has been the subject of considerable study and is a topic of ongoing controversy. Many studies have demonstrated an overall survival benefit from the addition of adjuvant chemotherapy to surgery, but some have not. Thus, although the NCCN guidelines recommend adjuvant chemotherapy for patients with high-risk stage II disease, a significant proportion of such patients do not receive adjuvant chemotherapy.

The objective of the current study, which expands on a previous study by our group that evaluated practice variation with respect to adherence to NCCN recommendations within the National Cancer Data Base (NCDB),16 was to examine the impact of adherence to guidelines on stage-specific survival outcomes in patients with stage III and high-risk stage II colon cancer. We examined factors associated with survival to identify subgroups of patients who may benefit from improved access to or delivery of cancer care.

Data Sources

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. Data Sources
  6. RESULTS
  7. DISCUSSION
  8. Acknowledgements
  9. FUNDING SOURCES
  10. REFERENCES

The NCDB is a program of the Commission on Cancer of the American College of Surgeons and the American Cancer Society that accumulates outcomes data from more than 1500 commission-accredited cancer programs in the United States and Puerto Rico. Reporting hospitals range from small community hospitals to National Cancer Institute-designated comprehensive cancer centers. The database captures approximately 70% of all cancer diagnoses within the United States, offering a large, hospital-based sampling of current clinical practice.17-19

Definition of Patient Cohort

The International Classification of Disease for Oncology, third edition (ICD-O-3) codes associated with a diagnosis of adenocarcinoma of the colon (ICD-O-3 topography codes C180 and C182-199 and morphology codes 8140-8144, 8210, 8211, 8220, 8221, 8260-8263, 8480-8481, 8490, and 8550) were used to select patients from within the NCDB who were diagnosed with colon adenocarcinoma between 1998 and 2002. The cohort was limited to patients who received their first course of treatment at the reporting facility. Pathologic variables, including tumor depth, lymph node status, and evidence of metastatic disease, were used to restage patients according to the American Joint Committee on Cancer staging system (6th edition).

Patients with stage II disease were subdivided into low-risk and high-risk categories on the basis of criteria defined by the NCCN: Patients were considered to have high-risk disease if they had T4 depth of invasion, histologic grade ≥3, R1 or R2 margin status, or if <12 lymph nodes were retrieved. Several other selection criteria also were used to restrict the cohort and minimize the potential for selection or reporting bias. Patients were excluded if they were aged >80 years or if they had received treatment at an institution where the overall rate for recommending chemotherapy for stage III cancer was <20%, suggesting that an institution may have under reported this treatment variable (as previously described16). Patients with missing or incomplete treatment information were excluded from the analysis (Fig. 1).

thumbnail image

Figure 1. Selection of the patient (pt) cohort is illustrates. Chemo indicates chemotherapy.

Download figure to PowerPoint

The definition of adherence or nonadherence to NCCN guidelines in this study is based on stage-based NCCN recommendations for colon cancer. The current NCCN guidelines for colon cancer recommend that patients with stage I and low-risk stage II disease undergo surgery alone; that patients with high-risk stage II disease and all patients with stage III disease undergo surgical resection and receive adjuvant chemotherapy unless there are obvious contraindications; and that patients with stage IV disease be offered some combination of chemotherapy with or without surgical resection.1 Therefore, patients who received treatment in accordance with these recommendations were categorized as “adherent,” and those who did not receive treatment according to these recommendations were categorized as “nonadherent.”16

Statistical Analyses

To assess cancer-specific causes of death, relative survival was used as a means of estimating disease-specific survival.20 Relative survival analysis is a validated method for performing survival studies that provides an objective measure of survival in cancer patients when comorbidities or issues complicating treatment do not exist. Relative survival is best defined as the ratio of the observed survival rate (including all causes of death) among an established cohort of cancer patients to the expected survival rate of a similar cohort of individuals who do not have cancer. Five-year relative survival was presented according to cancer stage and whether or not treatment adhered to NCCN guidelines. Propensity scores also were used to adjust for potential confounding in the analysis of treatment outcome.21, 22 Specifically, several models were created to compare the effects of adherent versus nonadherent treatment on relative survival within groups stratified by propensity scores incorporating sex, age, race, insurance, facility type, year of diagnosis, and class of case; pooled, stratum-specific estimates were computed for groups with similar propensity scores. We also included the propensity score, as a summary measure of all potential confounders, as 1 of the covariates in the multivariable regression models.

Two-level, stage-specific, hierarchical generalized linear regression models were used to analyze the influence of multiple factors on relative survival for patients with stage III and high-risk stage II disease and to evaluate the influence of various demographic factors. All reported P values were 2-sided, and values < .05 were considered statistically significant. Statistical analyses were performed using the Stata 10 software package (Stata Corp, College Station, Tex). Forest plots were generated using SigmaPlot 10 for Windows (Systat Software, Inc., Chicago, Ill).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. Data Sources
  6. RESULTS
  7. DISCUSSION
  8. Acknowledgements
  9. FUNDING SOURCES
  10. REFERENCES

After the application of defined inclusion and exclusion criteria (Fig. 1), the final study cohort consisted of 167,434 patients. The baseline patient characteristics are listed in Table 1. The distribution according to sex did not differ by stage, and 50.7% of patients overall were men. Younger patients were more likely to present with more advanced disease (51.1% of patients with stage IV disease were aged <65 years). The bulk of patients across all stages were Caucasian (81.2%), and most patients had Medicare coverage (47.4%) or private insurance coverage (43%). Most patients (81.2%) had a median household income (as measured per zip code) >$$30,000 per year. Patients most commonly received treatment at community cancer centers (52%); the remaining patients were treated at academic hospitals (29.2%) or community hospitals (18.8%). Most patients received their treatment at the hospital of initial diagnosis (81.4%).

Table 1. Patient Characteristics Stratified by Cancer Stage
 Percentage of Patients 
CharacteristicStage I, n = 34,476Stage II Low-Risk, n = 18,192High Risk, n = 28,592Stage III, n = 48,758Stage IV, n = 37,416Total, n = 167,434
  • a

    Other government includes federal insurance programs, such as Veterans Affairs, TRICARE/Military, and Public Health Service.

Men51.249.849.550.352.250.7
Age, y      
 <508.411.98.713.515.211.8
 50-6431.831.629.33435.932.9
 65-7438.335.738.434.332.835.6
 ≥7521.520.823.718.216.219.6
Race/ethnicity      
 Caucasian83.880.782.980.678.681.2
 African American9.711.710.111.514.211.5
 Hispanic2.93.93.83.83.73.6
 Other3.63.73.24.23.53.7
Insurance status      
 Uninsured1.53.12.834.43
 Medicaid233.13.44.53.3
 Medicare5147.952.74542.747.4
Other governmenta0.40.50.40.40.50.4
 Private42.742.638.245.144.443
 Unknown2.532.83.13.53
Median annual household income      
 <$30,00012.213.314.113.815.113.7
 $30,000- $45,99943.344.145.743.74444.1
 ≥$46,00039.437.635.637.435.737.1
 Unknown5.154.65.15.25
Year of diagnosis      
 199817.41819.818.918.518.5
 199918.518.219.31918.918.8
 200019.819.420.119.719.219.7
 200122.121.42121.321.721.5
 200222.22319.821.121.721.5
Treatment facility      
 Community hospital18.717.22118.917.818.8
 Community cancer center54515452.548.552
 Academic hospital27.331.82528.633.829.2
Treatment facility and facility where disease diagnosed      
 Same facility83.182.383.780.478.981.4
 Different facilities16.917.716.319.621.118.6
 Adherent treatment96.46735.773.663.468.8

Rates of adherence to NCCN treatment guidelines were 96.4% for patients with stage I disease, 67% for patients with low-risk stage II disease, 35.7% for patients with high-risk stage II disease, 73.6% for patients with stage III disease, and 63.4% for patients with stage IV disease. The highest rate of nonadherence occurred in the high-risk stage II group (under treatment), followed by stage IV (under treatment), low-risk stage II (over treatment), and stage III (under treatment); the treatment of stage I disease was highly compliant with guidelines.16

The relative survival rates of patients for the entire cohort, stratified according to adherence versus nonadherence to NCCN treatment guidelines, are illustrated in Figure 2. Nonadherence to current NCCN guidelines was associated with a decreased 5-year relative survival rate (54.5% vs 67.7%). Next, we examined stage-specific relative survival rates stratified by adherence to current NCCN guidelines, specifically focusing on patients with stage III and high-risk stage II disease. Among patients with high-risk stage II disease, the 5-year relative survival rate was lower with nonadherence (ie, no adjuvant chemotherapy; 77.5% vs 84.9%) (Fig. 3A). A similar trend was noted for patients with stage III disease who did not receive adherent treatment (5-year relative survival rate, 50.9% vs 68.8%) (Fig. 3B). Overall survival also was calculated with identical stage-specific survival trends observed as well as similar hazard ratios (HRs) in multivariate analyses (data not shown).

thumbnail image

Figure 2. This chart illustrates the relative survival of patients (pts) with colon cancer who received treatment (tx) in accordance (adherent) or not in accordance (nonadherent) with National Comprehensive Cancer Network guidelines.

Download figure to PowerPoint

thumbnail image

Figure 3. The relative survival of patients (pts) with colon cancer who received treatment in accordance (adherent) or not in accordance (nonadherent) with National Comprehensive Cancer Network guidelines is illustrated by disease stage for (A) patients with high-risk stage II disease and (B) patients with stage III disease.

Download figure to PowerPoint

On multivariate analysis of relative survival in patients with high-risk stage II disease and stage III disease (Table 2, Fig. 4), multiple factors were associated with differences in relative survival. In both patient subgroups, the factors associated with decreased survival included male gender, African American ethnicity, lack of insurance, Medicaid coverage, and Medicare coverage. Age ≥75 years also was associated with decreased relative survival in patients with stage III disease. In both patient subgroups, residence in an area code with a median annual income ≥$30,000 was associated with improved relative survival, as was treatment at a comprehensive cancer center and treatment at the same facility where the colon cancer initially was diagnosed. There was a trend toward increased relative survival in later years compared with earlier years of diagnosis both in patients with high-risk stage II disease and in patients with stage III disease, most likely representing the evolution of practice patterns and available treatment options over time. In both groups, patients who did not receive treatment in accordance with NCCN guidelines (ie, “under treated”) had an increased risk of death.

Table 2. Multivariate Relative Survival Analysis by Disease Stage
 HR (95% CI)
VariableHigh-Risk Stage IIStage III
  • Abbreviations: CI, confidence interval; HR, hazard ratio.

  • a

    Other government includes federal insurance programs, such as Veterans Affairs, TRICARE/Military, and Public Health Service.

  • b

    These values are statistically significant.

Men vs women1.11 (1.04-1.18)b1.09 (1.05-1.12)b
Age, y  
 <501.00 (Referent)1.00 (Referent)
 50-641.02 (0.91-1.15)1.02 (0.96-1.07)
 65-740.89 (0.77-1.03)1.04 (0.97-1.11)
 ≥751.12 (0.95-1.30)1.17 (1.08-1.26)b
Race/ethnicity  
 Caucasian1.00 (Referent)1.00 (Referent)
 African American1.44 (1.31-1.59)b1.15 (1.09-1.21)b
 Hispanic0.93 (0.78-1.11)0.95 (0.87-1.04)
 Asian/Pacific Islander0.72 (0.54-0.97)b0.84 0.75-0.94)b
Insurance  
 Private1.00 (Referent)1.00 (Referent)
 Uninsured1.70 (1.43-2.01)b1.39 (1.27-1.53b
 Medicaid1.91 (1.64-2.23)b1.73 (1.60-1.88)b
 Medicare1.67 (1.49-1.87)b1.30 (1.23-1.37)b
 Other governmenta1.58 ((1.01-2.47)b1.22 (0.95-1.57)
Annual income  
 <$30,0001.00 (Referent)1.00 (Referent)
 $30,000-$46,0000.90 (0.83-0.99)b0.88 (0.83-0.92)b
 >$46,0000.76 (0.68-0.84)b0.78 (0.74-0.82)b
Treatment facility  
 Community hospital1.00 (Referent)1.00 (Referent)
 Community cancer center0.91 (0.84-0.99)b0.94 (0.90-0.98)b
 Academic hospital0.94 (0.85-1.03)0.89 (0.84-0.93)b
Year of diagnosis  
 19981.00 (Referent)1.00 (Referent)
 19990.97 (0.88-1.07)1.01 (0.96-1.07)
 20000.93 (0.84-1.03)0.93 (0.89-0.99)b
 20010.89 (0.80-0.98)b0.92 (0.87-0.97)b
 20021.02 (0.92-1.13)0.95 (0.90-0.99)b
Treatment  
 Adherent1.00 (Referent)1.00 (Referent)
 Nonadherent1.43 (1.32-1.54)b1.88 (1.82-1.95)b
Treatment facility and facility where disease diagnosed  
 Different facility1.00 (Referent)1.00 (Referent
 Same facilities0.73 (0.66-0.80)b0.82 (0.78-0.85)b
thumbnail image

Figure 4. Multivariate analysis of factors that affected relative survival is illustrated in patients with high-risk stage II colon cancer and patients with stage III colon cancer. Govt indicates government.

Download figure to PowerPoint

To elucidate the specific factors underlying trends in adherence to treatment recommendations, univariate analysis was used to examine adherence patterns in both patient subgroups (high-risk stage II and stage III). Several factors were associated with a higher rate of nonadherence in both groups, including older age (P < .001); Medicaid, Medicare, or uninsured status versus private insurance (P < .001); and subsequent treatment at a facility other than the facility at which the cancer was first diagnosed (P < .001).

We noted that the HRs for relative survival associated with nonadherent versus adherent treatment were similar regardless of the specific propensity-adjusted application examined (Table 3). In addition, the propensity-adjusted estimates were similar to the multivariate HRs for relative survival, which were estimated for nonadherent versus adherent treatment without propensity scores (high-risk stage II: HR, 1.43; 95% confidence interval [CI], 1.33-1.54; stage III: HR, 1.88; 95% CI, 1.82-1.95).

Table 3. Hazard Ratios for Relative Survival Associated With Nonadherent Treatment Versus Adherent Treatment With and Without Adjustment by Propensity Scores
 High-Risk Stage IIStage III
VariableHR (95% CI)PHR (95% CI)P
  1. Abbreviations: CI, confidence interval; HR, hazard ratio; standardized mortality or morbidity ratio.

Univariate analysis1.66 (1.54-1.80)< .0011.57 (1.46-1.69)< .001
Multivariate analysis1.43 (1.33-1.54)< .0011.88 (1.82-1.95)< .001
Propensity scores    
 As a covariate1.44 (1.33-1.55)< .0011.88 (1.82-1.95)< .001
 Strata1.44 (1.33-1.55)< .0011.89 (1.82-1.95)< .001
 Weight: Reverse1.49 (1.39-1.61)< .0011.82 (1.76-1.89)< .001
Weight: SMR1.49 (1.39-1.61)< .0011.82 (1.76-1.89)< .001

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. Data Sources
  6. RESULTS
  7. DISCUSSION
  8. Acknowledgements
  9. FUNDING SOURCES
  10. REFERENCES

The current findings in this large, hospital-based analysis demonstrate a relative survival benefit for patients with stage III and high-risk stage II colon cancer who receive treatment according to the NCCN guidelines. Although several trials support the survival benefits of adjuvant chemotherapy for patients with stage III disease,3, 8-12 the recommendations in favor of adjuvant chemotherapy for patients with high-risk stage II disease are based on compiled data from several studies, suggesting that there is a subset of such patients who may benefit from adjuvant therapy.2, 8-10, 23, 24 Our data offer additional evidence to support the current NCCN recommendations on the effectiveness of adjuvant chemotherapy in heterogeneous populations that extend the results of well controlled clinical trials. The current analysis also identified several other factors associated with an increased risk of death in both patients with stage III disease and those with high-risk stage II disease, including male gender, African Americans race, insurance status other than private insurance (ie, Medicare, Medicaid, other government insurance, or lack of insurance), lower household income, treatment at a community hospital, and treatment at an institution other than the hospital of diagnosis.

The current recommendations for adjuvant treatment of high-risk stage II colon cancer are based on composite data from several different studies, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-04,6 NSABP C-05,25 and NSABP C-077 trials as well as the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (the MOSAIC trial), all of which demonstrated a benefit from adjuvant chemotherapy with 5-fluorouracil and leucovorin.3 The Intergroup 0035 study demonstrated a trend toward lower recurrence rates among patients with stage II colon cancer who received adjuvant fluorouracil plus levamisole but did not demonstrate improvements in overall survival.5 A Surveillance, Epidemiology, and End Results (SEER)/Medicare study of patients with stage II disease did not demonstrate a significant increase in survival with adjuvant treatment but did demonstrate a trend in that direction.15 To our knowledge, the Quick and Simple and Reliable (QUASAR) study is the most contemporary study to specifically evaluate the benefit of adjuvant chemotherapy for patients with stage II colon cancer and identified a small but measurable benefit in overall survival and a clinically significant reduction in recurrence risk with the addition of 5-fluorouracil–based adjuvant chemotherapy.23 Pooled analysis of the NSABP C-01 through C-05 trials demonstrated improved overall survival in patients with both stage II and stage III disease who received adjuvant 5-fluorouracil and leucovorin.10 The combined observations from NSABP C-0710 as well as the International Multicenter Pooled Analysis of B2 Colon Cancer (IMPACT B-2) tria,2 contributed to the NCCN adoption of their current recommendations for adjuvant treatment patients with stage III disease and patients with high-risk stage II disease when possible. However, the formal NCCN recommendations for the treatment of patients who have high-risk stage II disease with adjuvant chemotherapy is based on several pooled analyses of the literature.26-28

The recently published pooled analysis of the NSABP C-01 through C-05 trials, including 2273 patients with colon cancer (rectal cancer excluded), reported outcomes consistent with our current study findings.24 In the pooled analysis, improved overall survival was observed with adjuvant chemotherapy both in patients with stage II disease (HR, 0.65; 95% CI, 0.48-0.71) and in patients with stage III disease (HR, 0.65; 95% CI, 0.55-0.75). These results, as well as our own findings, demonstrate a much greater effect than that observed by the Adjuvant Colon Cancer Endpoint (ACCENT) study group, which compiled data from 18 trials of adjuvant chemotherapy in patients with stage II and III colon cancer.29 These differences may reflect differences in patient populations or selection criteria. In the NSABP pooled analysis,24 the factors associated with poor outcomes were age >60 years, male gender, African American race, and having <12 lymph nodes examined. Our findings are similar, with consistent trends in relative survival demonstrating an increased risk of death associated with age >75 years, male gender, and African American race. In addition, our analysis indicated an increased risk of death for patients with insurance status other than private insurance among patients who had stage III and high-risk stage II disease and did not received treatment in adherence to NCCN guidelines (ie, with surgery alone). Similar survival trends relating to insurance status and demographic factors have been noted in several other studies.30-34

These survival benefits associated with adherence to NCCN guidelines, which call for patients who have high-risk stage II disease to receive adjuvant chemotherapy, are in contrast to the results reported by O'Connor et al,35 who examined data in the SEER-Medicare database from the same time period and reported no survival benefit associated with chemotherapy in patients with high-risk stage II disease (HR, 1.03; 95% CI, 0.94-1.13).35 SEER accumulates data from specific geographic areas that cover 26% of the US population and documents cancer incidence and survival in 15 population-based registries.36 An earlier analysis of SEER-Medicare data (1991-1996), which examined outcomes from 3151 patients with low-risk stage II colon cancer (T3N0M0), reported a 5-year survival rate of 75% for patients who underwent surgery but did not receive adjuvant chemotherapy and 78% for patients who received adjuvant chemotherapy. In this earlier SEER analysis, the HR for survival was 0.91 (95% CI, 0.77-1.09), and the survival advantage from adjuvant chemotherapy did not reach statistical significance despite a trend toward improved outcomes.15 Our current findings demonstrating a survival benefit from adjuvant chemotherapy in patients with high-risk stage II disease may reflect cohort differences and/or differences in patient-selection practices between the SEER-Medicare data base and the NCDB. The most obvious difference is patient age, because 45% of patients in the NCDB analysis were aged <65 years, and our selection criteria excluded all patients aged >80 years. In addition, our data demonstrated poorer survival outcomes in patients with Medicare than in patients with private insurance, a group that was excluded from the previous SEER analysis. These differences in patient selection may contribute to our overall improved survival statistics for each stage of disease compared with the survival statistics in previously reported studies.

When we examined the factors that influenced adherence to NCCN treatment recommendations, our findings on univariate analysis suggested that, in both patients with high-risk stage II disease and those with stage III disease, adherence to NCCN guidelines was worse with increasing age, insurance status other than private insurance, and treatment at a facility other than that in which the colon cancer initially was diagnosed.

Recently, several groups have examined trends in racial disparities among patients with colon cancer. A study of the SEER database by Robbins et al37 that spanned the same time frame as our current study demonstrated increasing disparities between blacks and whites in colon cancer survival relating to differences in the stage of diagnosis and resultant outcomes. These differences may be related to differences in access to and receipt of adjuvant chemotherapy. Although referral rates may be the same for black patients and white patients, differences in these 2 groups in terms of actual treatment with adjuvant therapy have been reported.37 The current analysis is not an intention-to-treat analysis and reflects the actual treatment received by patients, which also may contribute to the racial disparities identified.

In terms of access to care, other groups have previously documented differences in cancer outcomes based on insurance status.38, 39 A recent evaluation of the Ohio Cancer Incidence Surveillance System demonstrated higher mortality and unfavorable survival outcomes in Medicaid patients compared with non-Medicaid patients who had various malignancies, including colon cancer.40 Those studies support the hypothesis that multiple factors influence the use of and access to health resources and that these factors may be associated with measurable survival outcomes.

The current study has several limitations, including the possibility of variations in practice patterns and chemotherapy regimens administered over the period covered by the study (1998-2002). However, multivariate analyses that included year of diagnosis did not demonstrate significant differences over time (Table 2). In addition, specific pathologic data fields were absent (eg lymphovascular invasion and microsatellite stability/instability) as well as clinical data noting whether the tumors were obstructing and/or emergent surgery was required. Therefore, the low-risk and high-risk categorization of patients with stage II disease in this analysis does not include all criteria used in the current clinical setting. However, such misclassification of high-risk patients as low-risk would likely result in minimizing differences in outcomes. In addition, the NCDB is a hospital-based database that includes a younger cohort of patients with various types of insurance who were not previously included in the other studies and spans a broad range of hospital settings. Our selection criteria created an analytic cohort limited to patients aged <80 years, almost half of whom were aged <65 years, which may have influenced the magnitude of the treatment effects observed in our analysis. Given that measures of baseline health indices, including comorbidities, were not available, it is possible that baseline health factors may have contributed to treatment decisions and were reflected in the relative survival differences. Furthermore, our analysis was not an intent-to-treat analysis, and outcomes relating to adjuvant chemotherapy reflect situations in which adjuvant chemotherapy actually was received by the patient.

Overall, the current analysis documents practice patterns in a heterogeneous population of patients with colon cancer and demonstrates a survival benefit for patients with stage III and high-risk stage II colon cancer who received treatment that adhered to NCCN guidelines. These data validate the current NCCN practice guidelines for colon cancer and support the concept of guideline-based metrics that can be compared across institutions to assess the quality of cancer care and to compare the quality of cancer care among institutions.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. Data Sources
  6. RESULTS
  7. DISCUSSION
  8. Acknowledgements
  9. FUNDING SOURCES
  10. REFERENCES

This research was supported in part by Support Grant CA016672 from the National Institutes of Health to The University of Texas MD Anderson Cancer Center.

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. Data Sources
  6. RESULTS
  7. DISCUSSION
  8. Acknowledgements
  9. FUNDING SOURCES
  10. REFERENCES
  • 1
    National Comprehensive Cancer Center (NCCN). NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. Fort Washington, PA: NCCN; 2012. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. [Accessed December 4, 2012.]
  • 2
    Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. J Clin Oncol. 1999; 17: 1356-1363.
  • 3
    Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009; 27: 3109-3116.
  • 4
    Laurie JA, Moertel CG, Fleming TR, et al. Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic. J Clin Oncol. 1989; 7: 1447-1456.
  • 5
    Moertel CG, Fleming TR, Macdonald JS, et al. Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer. J Clin Oncol. 1995; 13: 2936-2943.
  • 6
    Wolmark N, Rockette H, Mamounas E, et al. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999; 17: 3553-3559.
  • 7
    Yothers G, O'Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011; 29: 3768-3774.
  • 8
    Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004; 350: 2343-2351.
  • 9
    Haller DG, Catalano PJ, Macdonald JS, et al. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol. 2005; 23: 8671-8678.
  • 10
    Kuebler JP, Wieand HS, O'Connell MJ, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007; 25: 2198-2204.
  • 11
    Saltz LB, Niedzwiecki D, Hollis D, et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol. 2007; 25: 3456-3461.
  • 12
    Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005; 352: 2696-2704.
  • 13
    Van Cutsem E, Labianca R, Bodoky G, et al. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009; 27: 3117-3125.
  • 14
    Ychou M, Raoul JL, Douillard JY, et al. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802). Ann Oncol. 2009; 20: 674-680.
  • 15
    Schrag D, Rifas-Shiman S, Saltz L, Bach PB, Begg CB. Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer. J Clin Oncol. 2002; 20: 3999-4005.
  • 16
    Chagpar R, Xing Y, Chiang YJ, et al. Adherence to stage-specific treatment guidelines for patients with colon cancer. J Clin Oncol. 2012; 30: 972-979.
  • 17
    Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008; 15: 683-690.
  • 18
    Steele GD Jr, Winchester DP, Menck HR. The National Cancer Data Base. A mechanism for assessment of patient care. Cancer. 1994; 73: 499-504.
  • 19
    Winchester DP, Stewart AK, Phillips JL, Ward EE. The National Cancer Data Base: past, present, and future. Ann Surg Oncol. 2010; 17: 4-7.
  • 20
    Dickman PW, Sloggett A, Hills M, Hakulinen T. Regression models for relative survival. Stat Med. 2004; 23: 51-64.
  • 21
    Shah BR, Laupacis A, Hux JE, Austin PC. Propensity score methods gave similar results to traditional regression modeling in observational studies: a systematic review. J Clin Epidemiol. 2005; 58: 550-559.
  • 22
    Suh HS, Hay JW, Johnson KA, Doctor JN. Comparative effectiveness of statin plus fibrate combination therapy and statin monotherapy in patients with type 2 diabetes: use of propensity-score and instrumental variable methods to adjust for treatment-selection bias. Pharmacoepidemiol Drug Saf. 2012; 21: 470-484.
  • 23
    Quasar Collaborative G, Gray R, Barnwell J, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007; 370: 2020-2029.
  • 24
    Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05. A baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010; 17: 959-966.
  • 25
    Wolmark N, Bryant J, Smith R, et al. Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05. J the Natl Cancer Inst. 1998; 90: 1810-1816.
  • 26
    Benson AB 3rd, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004; 22: 3408-3419.
  • 27
    Figueredo A, Charette ML, Maroun J, Brouwers MC, Zuraw L. Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidence-based care's gastrointestinal cancer disease site group. J Clin Oncol. 2004; 22: 3395-3407.
  • 28
    Gill S, Loprinzi CL, Sargent DJ, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol. 2004; 22: 1797-1806.
  • 29
    Sargent D, Sobrero A, Grothey A, et al. Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2009; 27: 872-877.
  • 30
    Rhoads KF, Cullen J, Ngo JV, Wren SM. Racial and ethnic differences in lymph node examination after colon cancer resection do not completely explain disparities in mortality. Cancer. 2012; 118: 469-477.
  • 31
    Richards CA, Kerker BD, Thorpe L, et al. Increased screening colonoscopy rates and reduced racial disparities in the New York Citywide campaign: an urban model. Am J Gastroenterol. 2011; 106: 1880-1886.
  • 32
    Laiyemo AO, Doubeni C, Pinsky PF, et al. Race and colorectal cancer disparities: health-care utilization vs different cancer susceptibilities. J Natl Cancer Inst. 2010; 102: 538-546.
  • 33
    Berry J, Caplan L, Davis S, et al. A black-white comparison of the quality of stage-specific colon cancer treatment. Cancer. 2010; 116: 713-722.
  • 34
    Etzioni DA, El-Khoueiry AB, Beart RW Jr. Rates and predictors of chemotherapy use for stage III colon cancer: a systematic review. Cancer. 2008; 113: 3279-3289.
  • 35
    O'Connor ES, Greenblatt DY, LoConte NK, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011; 29: 3381-3388.
  • 36
    National Cancer Institute; Surveillance, Epidemiology, and End Results (SEEER) Program. SEER Cancer Statistics Review 1975-2008. Bethesda, MD: National Cancer Institute; 2009.
  • 37
    Robbins AS, Siegel RL, Jemal A. Racial disparities in stage-specific colorectal cancer mortality rates from 1985 to 2008. J Clin Oncol. 2012; 30: 401-405.
  • 38
    Robbins AS, Pavluck AL, Fedewa SA, Chen AY, Ward EM. Insurance status, comorbidity level, and survival among colorectal cancer patients age 18 to 64 years in the National Cancer Data Base from 2003 to 2005. J Clin Oncol. 2009; 27: 3627-3633.
  • 39
    Kelz RR, Gimotty PA, Polsky D, Norman S, Fraker D, DeMichele A. Morbidity and mortality of colorectal carcinoma surgery differs by insurance status. Cancer. 2004; 101: 2187-2194.
  • 40
    Koroukian SM, Bakaki PM, Raghavan D. Survival disparities by Medicaid status: an analysis of 8 cancers. Cancer. 2012; 118: 4271-4279.