Treating Colon Cancer in Patients with Diabetes

Abstract & Commentary

By William B. Ershler, MD

Synopsis: In a retrospective review of consecutive patients with colon cancer, the presence of diabetes mellitus was found to confer negative prognostic information with regard to overall, and cancer-specific, survival. Notably, it was in patients with stage II disease that the presence of diabetes was of most importance.

Source: Huang Y-C, et al. Diabetes mellitus negatively impacts survival of patients with colon cancer, particularly in stage II disease. J Cancer Res Clin Oncol. DOI 10.1007/s00432-010-0879-7, available on-line, 2010.

Cancer patients with pre-existing diabetes mellitus are known to have less-favorable outcomes,1 and several previous reports have indicated this to be the case with colon cancer.2-5 Whether this is simply the result of less-aggressive management or a consequence of altered tumor properties in patients with diabetes is unclear. To address this, Huang and colleagues performed a retrospective study aimed to determine the effects of diabetes on overall survival (OS) and cancer-specific survival (CSS) in patients with newly diagnosed colon cancer, with particular focus on the impact of diabetes on survival at each stage of colon cancer.

From January 1999 to January 2008, 2,762 consecutive patients diagnosed with colon cancer in Taipei Veterans General Hospital were enrolled. The general characteristics, as well as presence of diabetes prior to colon cancer diagnosis were identified. Cox proportional hazard analyses were used to define the significance of selected prognostic factors, and survival was analyzed using the Kaplan-Meier method with log-rank test.

A total of 469 patients (17%) had diabetes at diagnosis of colon cancer. Patients with diabetes had baseline characteristics comparable to those without diabetes, with the exception that the patients with diabetes were older (> 65 years). The five-year OS for the entire cohort was 55.1% (86.9%, 77.8%, 60.6% and 10.5% for stages I, II, III, and IV, respectively). The 5-year CSS was 61.2% (98.5%, 87.6%, 66.1%, and 11% for stages I, II, III, and IV, respectively). Patients with diabetes had significantly worse OS (HR = 1.31, p = 0.001) and CSS (HR = 1.24, p = 0.013) when compared to those without diabetes. The 5-year OS was 48.9% for patients with diabetes and 56.4% without diabetes. Similarly, the CSS rate for those with diabetes was 55.7% compared to 62.2% for those without. Differences in OS and CSS were statistically significant for stage II (p < 0.001) and stage III (p = 0.049) but not significant for those with stage I or IV disease. In multivariate analysis, controlling for other variables that could explain the less-favorable outcomes experienced by diabetic patients with stage II disease (age, tumor size, bowel perforation at time of diagnosis, bowel obstruction at diagnosis, poorly differentiated histology), the presence of diabetes remained a significant independent prognostic variable.

Commentary

Thus, as described in several prior publications, the presence of diabetes confers a less-favorable prognosis for those with colon cancer. What is remarkable is that the difference in OS and CSS is primarily observed for those with stage II disease. Why this would be the case remains a matter of conjecture. The authors speculate that this may imply a biologic influence of insulin or insulin-like growth factor (IGF) which, in turn, may be more relevant for those with minimal residual microscopic disease. Such has previously been proposed as relevant in the biology of colon cancer,2 as well as other tumors.6,7 However, this and other mechanisms remain to be clarified, and it is still quite possible that the presence of diabetes and associated comorbidities somehow influence management decisions. However, it would seem if this were the case, it would not just be stage II, but all stages of colon cancer that would be influenced. There is a message here that hopefully will be the subject of additional investigation.

For now, clinicians should be aware that diabetes significantly and negatively impacts OS and CSS in patients with colon cancer, and other cancers as well. For colon cancer, this is particularly significant for patients with stage II disease.

References

1. Barone BB, Yeh HC, Snyder CF, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008;300:2754-2764.

2. Meyerhardt JA, Catalano PJ, Haller DG, et al. Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol. 2003;21:433-440.

3. Polednak AP. Comorbid diabetes mellitus and risk of death after diagnosis of colorectal cancer: a population-based study. Cancer Detect Prev. 2006;30: 466-472.

4. van de Poll-Franse LV, Houterman S, Janssen-Heijnen ML, Dercksen MW, Coebergh JW, Haak HR. Less aggressive treatment and worse overall survival in cancer patients with diabetes: A large population based analysis. Int J Cancer. 2007;120:1986-1992.

5. Will JC, Galuska DA, Vinicor F, Calle EE. Colorectal cancer: Another complication of diabetes mellitus? Am J Epidemiol. 1998;147:816-825.

6. Hammarsten J, Hogstedt B. Hyperinsulinaemia: A prospective risk factor for lethal clinical prostate cancer. Eur J Cancer. 2005;41:2887-2895.

7. Goodwin PJ, Ennis M, Pritchard KI, et al. Fasting insulin and outcome in early-stage breast cancer: Results of a prospective cohort study. J Clin Oncol. 2002;20:42-51.