With few exceptions, results clearly supported the stated hypothesis that ethnic disparities in colorectal cancer survival have been diminishing over time. Figure 1, showing the convergence of survival over time, best exemplifies this. The one discrepancy in this overall trend is the unchanged life expectancy for the Hawaiian group in cohort 3. A comparison with the survival curves for other causes of death within cohort 3 reveals that this effect is specific to colorectal cancer and does not reflect a general tendency for Hawaiians to die sooner.
One possible explanation for this is that Hawaiians were not utilizing medical care to treat colorectal cancer to the same degree as other ethnic groups. Our post hoc analyses did demonstrate that ethnic disparities were no longer statistically significant after controlling for treatment differences. Interestingly, however, Hawaiians did not appear to be receiving less treatment; and with respect to chemotherapy and radiation, appear to have been receiving more than the other ethnic groups. One possible explanation for this is that treatment is causing adverse effects and death. Another is that doctors see prognostic signs of severe disease that are not measured by our covariates, and therefore prescribe more treatment. That is, Hawaiians may have more advanced disease than staging alone indicates.
The implications of these findings are important. If differential screening constitutes the primary reason for ethnic survival disparities, it should be possible to achieve equally favorable outcomes in all ethnic groups. With the exception of the Hawaiians, the evidence presented here reflects a convergence in terms of screening, medical care, and colorectal cancer survival among all ethnic groups. Further efforts are needed to examine why Hawaiians do not follow the overall trend, and how to make improvements. In this regard, a Native Hawaiian cancer network called the Imi Hale is attempting, along with support from the National Cancer Institute, to increase screening for colorectal cancer in Native Hawaiians.[27]
One limitation of this study is that data are restricted to the state of Hawaii. However, even though there are clearly potential regional differences in ethnic patterns of survival, the results of this study could be important beyond Hawaii. For example, in national studies, it has been shown that African-Americans are less likely than others to receive adjuvant chemotherapy.[28] Differential treatment utilization may drive ethnic outcome disparities. The role of individual patient choice and the role of complicating co-morbid conditions in treatment selection probably play some role, and another limitation of our study is not having access to this information. In future studies, however, we hope to elucidate the impact of such factors.
To this end, an important area for future research is detailed analysis of specific treatments received by cancer patients. For example, beginning in 1988 (the start of the third cohort in the present study) colorectal cancer survival has been improved through the use of 5-fluorouracil-leucovorin as adjuvant chemotherapy.[29] This factor, as well as improving stage distribution through screening, has undoubtedly contributed to the greatly improved colorectal cancer survival rates in the third cohort. Unfortunately, the HTR does not provide adequate detail with respect to specific chemotherapy treatments, so this hypothesis could not be examined here. However, future studies incorporating expanded data sources should examine whether Hawaiians have been receiving adjuvant 5-FU-leucovorin to the same degree as others, and if not, why not (e.g., access, informed choice with refusal of recommended treatment, or co-morbid disease).
Conversely, if Hawaiians receive apparently similar adjuvant therapy (i.e., same agents, dosage, number of courses, etc.), do they benefit to the same degree as others? Also, do they show a similar degree of treatment compliance? These issues may be of particular relevance, because results from this study suggest that Hawaiians are equally likely, if not more likely, to receive treatments.
Hawaiians have been reported to have relatively high rates of diabetes, renal and vascular disease, and tend to be afflicted at a younger age. Perhaps an interaction between cancer treatment and comorbid conditions is having a negative effect on Hawaiians. We speculate that co-morbid illness might play a role in treatment selection for some individuals with colorectal cancer. Collection of ICD-9 diagnosis codes from non-HRT sources with appropriate record linkage would allow us to study this.
Other results from this study indicate that age at diagnosis is another significant predictor of survival, with older individuals having a shorter life expectancy after diagnosis. However, a comparison of hazard ratios by cause of death showed that the values were much lower for death due to colorectal cancer than for other causes. This suggests that, while age is clearly related to overall survival, it is less relevant to colorectal cancer survival. That is, colon cancer is not more deadly for older individuals than for younger ones. Similarly, sex appears to predict colorectal cancer survival. A small beneficial effect was observed for women when considering death due to colorectal cancer, but a strong effect when considering death due to other causes. The impact of co-morbid disease on survival might explain these age and gender differentials.
Stage at diagnosis represents the most important prognostic variable. In this study the SEER staging system was used so that identical analyses could be performed across all three cohorts. However, for the most recent cohort (cohort 3), TNM staging clearly improved survival predictions over the less comprehensive SEER staging. In future studies, we will use TNM staging whenever possible.