The American Cancer Society (ACS) estimates that there will be more than 140,000 new cases of colorectal cancer in 2012.¹ Although men are more likely to develop colorectal cancer, women suffer a disproportionate mortality burden from this disease, especially older and African American women.^2–5 About 70% of colorectal cancer cases are cases of colon cancer.¹ Adequate treatment of colon cancer is important to potentially cure and/or prolong survival; therefore, differences in treatment may explain differences in survival across patients’ groups. Treatment guidelines recommend surgery followed by adjuvant chemotherapy as the standard of treatment for stage III colon cancer.^6,7 For stage II colon cancer, colectomy may be all that is required, except for adjuvant chemotherapy for patients with higher risk for recurrence. Standard chemotherapy for colon cancer at the time of this study was 5-fluorouracil (5FU)-based chemotherapy usually administered in six cycles of 21–28 days each.⁸ In a large randomized controlled trial, patients who received 5FU-based adjuvant chemotherapy had a relative risk reduction of 40% for recurrence and of 33% for mortality.⁹

Several studies have investigated whether cancer patients receive recommended treatment for their disease presentation, mostly focusing on differences by race and age.^10–15 Fewer studies have addressed the colon cancer treatment differences in regard to gender.¹⁶ To address this research gap, the objective of this study was to describe the treatment of colon cancer by gender in older patients diagnosed in Alabama. In particular, we investigated whether surgery and adjuvant chemotherapy were received and how long chemotherapy treatment lasted for Medicare beneficiaries diagnosed in a 4-year period from 2000 to 2003.

The current analysis is part of a larger study to assess cancer-directed treatment in Medicare patients with breast, colorectal, lung, or prostate cancer. The study was approved by the institutional review boards of the University of Alabama at Birmingham and the Centers for Disease Control and Prevention.

A cohort of 3435 Alabama residents 65 years old and older diagnosed with colon cancer in the period from January 1, 2000, to December 31, 2002, was identified from the Alabama Statewide Cancer Registry (ASCR). ASCR is Alabama’s population-based cancer registry which is supported by the Centers for Disease Control and Prevention’s National Program of Cancer Registries. The data collected by the ASCR have been recognized as high quality by the North American Association of Central Cancer Registries with a designation of silver certification in 2003 for case completeness greater than 90%.^17,18

We obtained 1999–2003 Medicare claims for inpatient, outpatient, and physician visits for the cohort described above. Thus, we had at least 1 year of claims data for the period before the cancer diagnosis to determine comorbid conditions, and for least 1 year of follow-up postdiagnosis to determine cancer treatment received. Because administrative claims (and, thus, the opportunity of examining treatment) are available only for beneficiaries in fee-for-service plans, we excluded 856 cases of beneficiaries who were not on fee-for-service plans. Of the remaining 2579 colon cancer patients, we excluded those with histology types not consistent with colon cancer (N = 24), not black or white (N = 21), with stage IV (N = 300), and stage 0 or missing (N = 449). The final cohort consisted of 1785 Alabama beneficiaries with stage I–III colon cancer. Compared with these, the 1650 beneficiaries excluded from analysis were more likely to be black (25.8% vs. 15.7%, p < 0.0001) and to be older than 75 years (58.2% vs. 53.5%, p = 0.005).

Of the 1785 colon cancer survivors in this study, 48.7% were male and 51.3% female, 84.3% were white and 15.7% were black, and 46.5% were 75 years old or older (Table 1). Cases were equally distributed across stage I to III disease, and about 70% had at least one comorbid condition. Approximately 25% died by the end of the follow-up period (2003) with less than 8% dying within 9 months of diagnosis. Men and women did not differ in many demographic and disease characteristics, except that women were younger than men (59.7% in 65- to 74-year-old group vs. 47% of men, p < 0.0001). However, 17.4% of the women were black compared with 14% of the men (p = 0.05), and 33.2% of the women had stage III disease versus 29.2% of the men (p = 0.09).

Overall 93.9% of the colon cancer survivors received surgery and of them 33.9% had adjuvant chemotherapy (Table 2). Of the 1182 patients with stage II–III disease who received surgery, 45.1% received chemotherapy and 41.7% received 5FU. As expected, use of chemotherapy was higher for persons with stage III colon cancer (60.4%) than for patients with stage II (25.6%) (Table 2). Moreover, among the 492 stage II and III patients receiving 5FU-based adjuvant chemotherapy, the mean number of days on treatment was 150.2 (SD = 78.07), and 28.9% received 0–4 months of 5FU with no difference by disease stage (Table 2). Moreover, more than 70% had symptoms such as anemia, nausea, emesis, or diarrhea, and about half suffered from dehydration or infection and fever (Table 3).

Women were slightly more likely than men to have surgery (95.5% vs. 92.2%, p = 0.003), and were less likely to have 5FU-based adjuvant chemotherapy (38.6% vs. 45.2%, p = 0.02). Among those who received it, women were more likely than men to have 0–4 months (32.9% vs. 24.9%, p = 0.05) and less likely to have 5–7 months of adjuvant chemotherapy (49.4% vs. 60.2%, p = 0.01) (Table 2). Women were more likely than men to experience dehydration (63.8% vs. 47.8%, p = 0.0004). They were also more likely to have symptoms or conditions unrelated to chemotherapy such as thyroid disorder (16.9% vs. 7.2%, p = 0.001) and fractures or dislocation (8.6% vs. <4.4%, p = 0.02). Other symptoms had similar frequencies for men and women (Table 3).

In the analyses adjusted for age, disease stage, existence of other comorbid conditions, and census tract socioeconomic variables, gender differences remained statistically significant except for surgery. Women had significantly lower odds of 5FU-based adjuvant chemotherapy (odds ratio [OR] 0.78, confidence interval [CI] 0.61–1.00, p = 0.049; Table 4) and higher odds of receiving fewer than 120 days of treatment (OR 1.52, CI 1.07–2.15; not shown). When controlling for side effects, however, the gender difference in receiving fewer than 120 days of 5FU was not significant (OR 1.36, CI 0.95–1.94, p = 0.09; Table 4).

No differences in treatment were found between white and black cancer survivors. Moreover, while survivors 75 years old or older were less likely to receive chemotherapy (27.4% vs. 58.8%, OR 0.24, CI 0.19–0.31), no differences were found in the duration of 5FU by age (Tables 2 and 4). In addition, having higher stages of disease was associated with higher odds of having surgery and chemotherapy, and with no significant differences in the likelihood of having chemotherapy duration of 0–4 months (Table 4). Finally, census tract variables were not associated with treatment (Table 4).

Among colon cancer cases diagnosed in Alabama in 2000–2002, we found that most received surgery and almost 42% received adjuvant 5FU chemotherapy. Among those with stage II–III disease who started this therapy, almost 30% received 0–4 months and about 70% received treatment for a longer period. Chemotherapy was used more frequently in patients with stage III colon cancer (60.4%). We also found that women were significantly less likely to receive chemotherapy compared with men and more likely to have a shorter duration of treatment. This finding is of concern because adjuvant chemotherapy for colon cancer patients with stage II and III disease significantly improves outcomes.^8,9

Our results concur with those of Paulson et al.¹⁶ who found that among 30,975 Medicare beneficiaries with colon cancer patients diagnosed in SEER areas in 1996–2002, women with stage III disease were less likely to receive adjuvant chemotherapy after surgical resection than men (51.5% vs. 59.5%, p < 0.001). However, Neugut et al.¹¹ did not find gender differences in duration of 5FU among older Medicare beneficiaries with stage III colon cancer diagnosed in 1995–1999. In an earlier time period (1992–1996), Dobie et al.¹⁵ found that female Medicare beneficiaries with stage III colon cancer were significantly less likely to receive chemotherapy and were less likely to complete chemotherapy, defined as 5 months or more, compared with men. However, the gender disparity in completion of chemotherapy was not significant after adjusting for age, stage, comorbidities, hospital readmissions, and socioeconomic information.¹⁵ We previously found similar gender differences in duration of chemotherapy among older persons diagnosed with rectal cancer in Alabama around the same time period (1999–2003).³²

The fact that women were less likely to receive adjuvant chemotherapy and have shorter duration of treatment is concerning. Poor health and older age are often reasons for underutilization of cancer treatment.^33,34 However, compared with men, women were younger and they did not have more comorbid conditions in the year before the cancer diagnosis. However, they were more likely to have thyroid disorder or fractures possibly before starting chemotherapy. Thus, women may be more likely to have some conditions that indicate frailty, making physicians reluctant to prescribe chemotherapy. Other factors that affect underuse of cancer treatments are related to beliefs in treatment efficacy, concerns about side effects, the relation with physicians, the treatment preferences of the physicians, and several other reasons that we could not ascertain in this study and that may vary by gender.^34–37 Furthermore, women were not more likely than men to come from disadvantaged neighborhoods, and thus may not have been more likely to refuse chemotherapy for economicreasons. Therefore, research into reasons why chemotherapy use in women is low warrants further research.

Once chemotherapy is started, it is important to consider the impact adverse events may have on its duration. Schrag et al.¹⁴ found that between 7% and 13% of colon cancer patients 65 years and older receiving chemotherapy were hospitalized for treatment-related adverse events such as neutropenia, mucositis, diarrhea, sepsis, and dehydration. Cen et al.²⁰ also reported high rates of chemotherapy-associated adverse events among Medicare beneficiaries with colon and rectal cancer in 2003 to 2005, especially for patients older than 70 years. All of these symptoms may cause a patient to prematurely stop treatment, leading to suboptimal outcomes. While some have reported that chemotherapy may be less tolerated in women,^38–40 Cen et al.²⁰ did not report differences in side effects by gender. Our findings, instead, showed that some side effects are more prevalent in women (e.g., dehydration) and that these may account for women having shorter courses of treatment. However, we have to consider that our findings are limited by a small sample size; investigating such gender differences in larger cohorts of colon cancer patients is thus warranted. The higher occurrence of some side effects in older women raises important questions about the administration of chemotherapy; for example, whether women are more likely than men to receive treatment doses not appropriate for their weight. Our claims data do not allow us to investigate whether this was the case, but future studies should investigate such potential differences in chemotherapy administration by gender.

Compared with previous studies of Medicare beneficiaries with colon cancer, Alabama beneficiaries received more adjuvant 5FU chemotherapy after surgery during the study period. For example, we found that among stage III colon cancer patients almost 64% had claims for chemotherapy. Neugut et al.¹¹ found that 54% of stage III colon cancer patients diagnosed in 1995–1996 received adjuvant chemotherapy. Similarly Dobie et al.¹⁵ found that 55% of stage III colon cancer Medicare beneficiaries started chemotherapy. Similar rates were found by Paulson et al.¹⁶ in the period 1996–2002. Hu et al.⁴¹ for the period 1991–2005 found that 64.4% of Medicare beneficiaries received chemotherapy, and 62% completed it. Kahn et al.⁴² found that among patients diagnosed in 2003–2005 in seven U.S. states including Alabama, 75% of those with stage III disease received chemotherapy. Among these patients, about 60% had more than 150 days of chemotherapy. We found similar patterns for rectal cancer patients in Alabama for the same time period: almost 65% of stage III rectal cancer patients had chemotherapy.³² Duration of chemotherapy is also comparable to what was found in other studies. We found that only 26% of those with stage II–III disease had less than 4 months of chemotherapy, with about 55% receiving chemotherapy for 5–7 months. Others found among stage III colon cancer patients that 64%–78% had at least 5 months (150 days) of treatment.^11,15,42

Other results of our analyses are of interest. We did not find racial differences in colon cancer treatment in this population. These findings concurred with Hofmann et al.¹² who reported no significant treatment differences among black and white colorectal cancer patients of all ages, and with Chagpar et al.¹³ who found no difference in guideline concordant care for colon cancer patients of all ages in the period 2003–2007. However, according to Dimou et al.,¹⁰ black patients were less likely than white patients to have surgical treatment for stage I cancer, although surgery is the recommended treatment for this stage. We also found differences by age in the use of chemotherapy, although we found no difference in duration of this treatment. This is similar to others,^11,13,16 although Neugut et al.¹¹ found that older patients also had shorter courses of chemotherapy. Schrag et al.¹⁴ found that patients who were older were as likely to want chemotherapy as their younger counterparts, and suggested that underutilization of chemotherapy among older patients may not be medically justified. The literature further supports this suggestion. Another study found that not receiving chemotherapy due to patient refusal was the case for less than a third of patients, while advanced age and comorbid conditions were reasons for 11.4% and 21.6% of patients, respectively.⁴³ Other explanations for decreased utilization of chemotherapy in older patients included financial and geographic barriers to care, physician knowledge and attitudes, as well as patient preferences.¹⁴

This study has several limitations. Information on treatment is derived from claims data and not from medical records. Therefore, identification of procedures depends on accurate billing and coding. However, other studies have found, for example, that use of chemotherapy can be reliably identified from these databases.⁴⁴ In addition, with these data, we cannot identify dose reductions or discontinuation of treatment prescribed by the physician. Symptoms and conditions that may be related to chemotherapy were identified for a 1-year period after diagnosis, and we cannot ascertain whether they occurred after treatment was initiated. However, we found that they were significantly more common among persons who had received chemotherapy. Lastly, during the study period 5FU-based chemotherapy with leucovorin or levamisole was the standard of care for colon cancer. Currently, 5FU remains the backbone of colorectal cancer chemotherapy, but accompanying drugs include oxaliplatin and irinotecan. We expect, however, that results are relevant to the new standard chemotherapy combinations because the side effects we described as those associated with 5FU and not the other drugs.

In conclusion, in Alabama, one of the poorest states in the United States where medical resources are more limited than in richer states, colon cancer patients received treatment comparable to or better than patients in other US states. However, our findings indicate that oncology providers may need to be alert to individual patient characteristics, including gender, which might lead to premature discontinuation of chemotherapy. In particular, attention should be given to specific side effects of therapy that may be more prevalent in women and lead to shorter courses of 5FU-based chemotherapy. Suboptimal duration of chemotherapy affects colon cancer survival.⁸ Some studies clearly show such gender mortality disparities in colon cancer patients,³ and others find no disparities when adjusting for treatment received.¹⁶ More work is needed to elucidate the role of chemotherapy in reported gender disparities of colon cancer outcomes.