By 2010, 13% of the United States population will be over 65 years old, with 2% of the population over 84. The corresponding projections for 2050 are 21% and 5%, respectively.[1] These projections underscore the aging of the population, with most recent estimates of life expectancy hitting a record high of 78.1 years.[2] With Americans living longer than ever before, physicians are already seeing larger numbers of elderly patients with cancers whose incidence increases with age, including colon cancer.
American Cancer Society estimates projected that just under 150,000 people would be diagnosed with colorectal cancer, and 50,000 people would die as a result of the disease during 2008.[3] Colon cancer is largely a disease of old age, with a median age at diagnosis of 71 years old and increasing incidence with age (Figure 1). In the 2000–2003 census period, 29% of patients were diagnosed with colon cancer between ages 75 and 84, and 12% at 85 or older. Almost three-quarters of colorectal cancer deaths occur in patients 65 or older.[3,4]
Stage III Colon Cancer: Treatment Disparities
The indication for use of fluorouracil(Drug information on fluorouracil) (5-FU)-based adjuvant chemotherapy in regional lymph node–positive (stage III) colon cancer has been well established as standard of care since the publication of a National Institutes of Health consensus statement in 1990,[5] and appears in the National Comprehensive Cancer Network (NCCN) guidelines as a category 1 recommendation (uniform consensus based on high-level evidence).[6] Randomized controlled trials have established that 5-FU–based adjuvant chemotherapy following complete resection of stage III colon cancer provides a relative reduction in subsequent mortality by approximately 30%.[7,8] However, ample evidence exists that decisions about adjuvant therapy after complete resection of colon cancer are often based on age alone.[9-12] Schrag and colleagues reported on this disparity between older and younger patients in a large retrospective cohort study utilizing the Surveillance, Epidemiology and End Results (SEER)/Medicare-linked database during the years 1991–1996. Compared to 78% of patients aged 65 to 69, 74% of those aged 70 to 74, 58% of those aged 75 to 79, and only 34% of those aged 80 to 84 received postoperative chemotherapy within 3 months of surgery. Age remained a strong predictor of chemotherapy after adjustment for potential confounders including severity of noncancer medical illness based on the Charlson/Romano comorbidity index.[12]
Similar results were obtained in a second SEER database study with direct doctor verification of the use of adjuvant therapy, and chart review for comorbidity assessment.[11] A population-based cohort study also reported a lower likelihood of administering adjuvant chemotherapy to older patients with stage III disease in the community (58% in the over-75 age group vs 84% in younger patients), even after adjustment for other prognostic factors.[9]
As to whether there has been any change in practice patterns in the past decade, the evidence is conflicting. A population-based SEER registry study did not show any sign of diminishing treatment disparity according to age over the time period spanning 1997–2002.[13] However, prospective data collection and analysis from over 85,000 patients with stage III colon cancer entered into the National Cancer Data Base—a nationwide oncology outcomes database capturing three-quarters of all newly diagnosed cases of cancer in the United States—showed a clear trend of increasing adjuvant therapy use between 1990–1991, 1995–1996, and 2001–2002 (22%, 26%, and 39% for patients 80 years and older, respectively).[14]
Adjuvant Therapy in the Elderly
Supporting Evidence
The most convincing evidence to date in favor of adjuvant chemotherapy comes from a landmark pooled analysis of seven randomized phase III trials comparing 5-FU–based chemotherapy to no postoperative adjuvant treatment for patients with resected stage II or III colon cancer.[15] The total enrollment cohort was 3,351 patients, 15.1% of whom were over 70 years old. The investigators observed a 7% absolute improvement in 5-year survival attributable to therapy, with no significant interaction between age and treatment effect. Older age had no impact on risk of recurrence but was prognostic for survival, as would be expected given the increased risk of dying from other causes with advancing age. Due to the small proportion (0.7%) of octogenarian participants, the analysis results need to be interpreted with more caution in this age group.
This concern highlights a systemic issue applicable to many published clinical trials. Elderly patient enrollment remains poor even for diseases such as colon cancer that predominantly affect the elderly.[16,17] This is either due to exclusion of elderly patients or very poor accrual of older patients despite the absence of an age cutoff in the exclusion criteria, a phenomenon that tends to be magnified in early adjuvant trials.[18]
