A total of 82,750 subjects who had undergone colon resections were identified in the SEER data set. The 60-day unadjusted postoperative mortality for subjects with left-sided colon cancer was 3.99% (95% confidence interval [95% CI], 3.78–4.20), compared with 5.28% for those with right-sided colon cancer (95% CI, 5.08–5.49). Therefore, the 4772 subjects who died within this period of surgery were excluded from the study. Demographics of the remaining 77,978 subjects included in the study are listed in . There were 37,050 men (47.5%) and 40,928 women (52.5%), with an overall median age of 71 years. Of 77,800 subjects with race data, 64,680 (83.1%) identified themselves as white, 7135 (9.2%) as black, and 5985 (7%) as belonging to other races. Of 75,242 subjects with marital status data, 43,520 (57.8%) were married. The median survival of all subjects studied was 83 months. AJCC stage was known for 77,481 subjects and was distributed among all four stages, with 21.5% of disease being stage I, 37.7% stage II, 27.7% stage III, and 13.1% stage IV. The median tumor size at time of surgical resection was 45 mm. The tumor grade distribution was primarily moderately differentiated (grade II, 69.6%), with 10.7% being grade I and 19.8% being grade III or IV. The overall median number of lymph nodes collected in surgical specimens was 10. Of 73,324 subjects with known lymph nodal status, most had N0 lymph node involvement (60.7%), with 25.1% having N1 and 14.2% having N2 disease.
Subject and tumor characteristics of colon cancer resections in the Surveillance, Epidemiology, and End Results Program database from 1988 to 2002
Right-Versus Left-Sided Colon Cancer
Right-sided colon cancer significantly outnumbered left-sided colon cancer, with 44,544 (57.1%) of subjects having right-sided and 33,434 (42.9%) left-sided colon cancer (P<.001) (). Subjects with right-sided colon cancer were significantly older (median age of 73 vs. 69 years; P<.001) and had a significantly shorter survival time after diagnosis (78 vs. 89 months, P<.001) compared with those with left-sided colon cancer. Right-sided colon cancer subjects were less likely to be male (44.2% vs. 51.9%; P<.001) and married (55.3% vs. 61.2%; P<.001).
The majority of the right-and left-sided tumors were AJCC stage II (40.2% and 34.3% respectively). In addition, there were a far lower proportion of stage I right-sided tumors (18.2% vs. 25.9%) and a higher proportion of stage III right-sided tumors (28.8% vs. 26.3%) compared with left-sided tumors (P<.001 for χ2 test of all tumor stages). Overall, right-sided tumors were of higher grade than left-sided tumors, with 24.5% of right-sided tumors being grades III and IVvs. 13.5% of left-sided tumors (P < .001). Right-sided tumors were also larger at the time of surgery than left-sided tumors (median size 46 vs. 40 mm; P<.001).
The median number of lymph nodes examined in surgical specimens of right-sided cancers was 11 vs. 8 (P<.001) in left-sided cancer specimens. Most subjects in both cohorts had N0 lymph node involvement, 60.4% in right-sided vs. 61.3% in left-sided cancer cohorts. Overall, there was a higher percentage of right-sided cancer subjects with node-positive disease than left-sided cancer subject, a difference that was statistically significant (39.7% vs. 38.8%; P <.001). When compared by year of diagnosis, more right-sided tumors were diagnosed more recently in the study interval than left-sided tumors, as evidenced by the mean date of diagnosis of October 1995 for right-sided tumors versus June 1995 for left-sided tumors (P<.001).
Multivariate Association of Cancer Location with Mortality
The results of unadjusted and adjusted multivariate Cox survival regression analyses are listed in . The hazard ratios (HR) and 95% CIs were significant (P < .05) for all of the variables in the univariate analysis with the exception of white race, and in the multivariate analysis with the exception of subjects with grade II tumors.
Unadjusted and adjusted survival analysis of overall subject and tumor characteristics
Kaplan–Meier survival estimates for left- and right-sided colon cancer are shown in . Survival for left-sided colon cancers was 59.7% at 5 years (60 months), 41.9% at 10 years (120 months), and 29.5% at 15 years (180 months). For right-sided colon cancers, survival was 56.3% at 5 years, 37.8% at 10 years, and 24.5% at 15 years. Survival of left- and right-sided colon cancer subjects was significantly different at all three of these time points (P<.001).
Kaplan–Meier survival estimates for overall unadjusted survival of left-versus right-sided adenocarcinoma of the colon.
A Cox proportional hazard regression analysis of tumor side was performed including the variables of subject age, sex, race, marital status, AJCC stage, tumor size, histologic grade, number of lymph nodes examined, and year of diagnosis. These adjusted survival curves are shown in . Of note, nodal status was omitted because this was already accounted for in the AJCC tumor staging algorithm. Compared with subjects with left-sided colon cancer, those with right-sided cancer had a 4.2% increased mortality risk (adjusted HR = 1.042; 95% CI, 1.02–1.07; P = .001). For every increase in subject age by 1 year, mortality risk increased by 3.6%. Tumor stage was associated with the highest increase in mortality rate, with the increase in mortality over stage I being 31% for subjects with stage II cancer, 120% for those with stage III cancer, and 900% for those with stage IV cancer. Similarly, grade III and IV and N1 and N2 nodal disease (examined by univariate analysis only) were associated with worse prognosis. Being married was associated with a decreased risk of mortality, by 21%, when compared with unmarried subjects (P < .001). More recent diagnosis was associated with improved survival as well: a 1.3% reduction in mortality was experienced for every year diagnosis of colon cancer was made after 1988 (P < .001). Substratification and multivariate Cox proportional hazard regression analysis that used the above-listed variables was performed by tumor side and AJCC stage ( and ).
FIG. 2 Adjusted Kaplan–Meier survival estimates for overall survival of left-versus right-sided adenocarcinoma of the colon. Note magnified y-axis range. Multivariate Cox proportional hazard regression model includes the following variables: subject (more ...)
FIG. 3 Adjusted Kaplan–Meier survival estimates for overall survival of adenocarcinoma of the colon stratified by tumor stage for left- and right-sided tumors. Multivariate Cox proportional hazard regression model includes the following variables: subject (more ...)
The multivariate Cox proportional hazard regression analyses were repeated in different cohorts of subjects (). At subset analysis, the results did not change qualitatively. Right-sided colon cancer was associated with a statistically significant increase in HR for mortality for most subgroups tested compared with left-sided colon cancer. However, women did not have a statistically significant difference in mortality between left- and right-sided colon cancer (HR = 1.01; P = .48). Similarly, no differences in survival between right-and left-sided colon cancer with stage I or grade I were observed (stage I: HR = 1.003; P = .93; grade I: HR = 1.002; P = .96). Of note, subjects with stage II right-sided colon cancers had lower HRs than those with left-sided colon cancers (HR = .91; P<.001).
FIG. 4 Adjusted hazard ratio with 95% confidence intervals for mortality comparing right-sided colon cancers relative to left-sided colon cancers in the following cohorts: female subjects, male subjects, subjects of white race, subjects of black race, American (more ...)
Additional analysis was performed where right-sided colon cancer was further divided anatomically into two groups: cecum to ascending colon, and hepatic flexure to splenic flexure. These stratifications were compared with left-sided colon cancer (descending colon to sigmoid colon). There were 32,388 subjects with cancer between the cecum and ascending colon (41.8%), 15,055 subjects with cancer between the hepatic flexure and splenic flexure (19.4%), and 30,038 subjects with cancer between the descending colon and sigmoid colon (38.8%). Analysis of this anatomic stratification revealed that mortality risk was 8.0% greater for subjects with cancer between the hepatic flexure and splenic flexure compared with those with cancer between the descending colon and sigmoid colon (HR 1.08; 95% CI, 1.05–1.11; P < .001). Subjects with cancer between the cecum and ascending colon had a 3.7% greater mortality risk compared with those with cancer between the descending colon and sigmoid colon (HR 1.037; 95% CI, 1.01–1.06; P = .007).