Although chemotherapy hasn’t been shown to benefit people with stage II colon cancer as a group, doctors have assumed those patients whose tumors had high risk features for poor survival might live longer if they did get chemo after surgery.
Now, a new study that looked at nearly 44,000 Medicare patients is challenging that assumption.
Medicare patients 66 and older with high risk stage II colon cancer didn’t do better when they received chemotherapy according to an analysis of information in the SEER-Medicare database. Whether or not they had chemo, their chance of being alive five years after diagnosis was about 56%.
A research team at the University of Wisconsin analyzed Surveillance, Epidemiology, and End Results (SEER) cancer registries linked to Medicare claims data from 1992 though 2005 for patients with stage II and III colon cancer. Their goal was to find out whether, using the large number of patients in that database who were being treated in the community, they could prove that adjuvant chemotherapy made a difference in the percentage of patients who lived at least five years after their cancer diagnosis.
The team’s primary outcome was 5-year overall mortality, meaning death from any cause during the five years following a diagnosis of colon cancer.
Overall, they had information on 43,032 people, including 24,847 with stage II colon cancer and 18,135 with stage III.
Poor prognostic clinical features available in the SEER-Medicare data included:
- colon obstruction at the time of diagnosis
- colon perforation
- T4 tumor — tumor that penetrates the outermost layer of the intestines or invades nearby organs
- poorly differentiated pathology — cells that look very different from normal colon cells under the microscope.
- fewer than 12 lymph nodes examined
Information about two other factors that have a poor prognosis in colon cancer were not available to study:
- CEA level before surgery
- peritumoral lymphatic/venous invasion
While five-year survival was higher for all stage II patients with no poor prognostic features than for those whose tumor had at least one high risk issue, getting chemotherapy didn’t make a difference in the percentage of patients — high risk or not — who were alive five years after their diagnosis.
In considering these numbers remember that they apply to people who did not die from any cause five years after diagnosis, not only from colon cancer, and they are based on people 66 and older who are more likely to die than younger individuals. They cannot tell any individual their risk of dying from colon cancer.
Poor prognostic features didn’t play a large role in choosing patients for chemotherapy. About 20% of patients in both the stage II risk groups received chemo. Instead, people who were younger, male, married, and not have other health problems were more likely to be treated with chemotherapy after surgery.
The team, led by Erin S. O’Connor, M.D., concluded,
In conclusion, we ﬁnd that patients with stage II colon cancer,even those with any of six identiﬁed poor prognostic features, do not have a signiﬁcant survival beneﬁt from chemotherapy. Given the frequent use ofchemotherapy in this generalizable population of older adults, this suggests that, in practice, many patients may be receiving chemotherapy with a disadvantageous risk-beneﬁt ratio. Given the statistical power of this study, clinicians may wish to counsel high-risk older adults with colon cancer that any possible survival beneﬁt is likely less than 2% at 5 years.
In an editorial accompanying the study, Neal Merapol, M.D., reminds us that, “We we must not divert attention from discovery of more effective treatments.” Dr. Merapol writes,
The study by O’Connor et al suggests that in a real-world setting,adjuvant treatment of older patients with stage II colon cancer and high-risk clinical features does not improve survival. Is this example of comparative effectiveness research sufﬁcient to guide clinical practice?
Given consistency with clinical trial data and the lack of compelling data to the contrary, this report must be viewed as more than merely hypothesis-generating, and should discourage routine use of adjuvant treatment in this patient population
During a JCO Podcast, Leonard B. Saltz, M.D., head of the Colorectal Oncology Section at Memorial Sloan Kettering Cancer Center, discusses the O’Connor study and stage II challenges faced by doctors and patients.
Meropol, Ongoing Challenge of Stage II Colon Cancer, Journal of Clinical Oncology, published online before print July 25, 2011.
What This Means for Patients
This study adds additional information to that available for colon cancer patients who are trying to make a good decision about whether or not to have chemotherapy after surgery for stage II colon cancer.
While based on a large number of patients treated in real-world settings, it cannot provide a definitive answer for every patient:
- Patients in the study were all older than 65.
- Since the information only went through 2005, few patients treated with oxaliplatin are likely included.
- Risk factors are clinical ones. The study doesn’t include molecular markers, such as microsatellite instability, that are know to improve survival in stage II.
ASCO Recommendations on the Use of Adjuvant Chemotherapy for Stage II Colon Cancer published in 2004 say,
Recommendations: The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology.
Conclusion: Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.
Discuss risks and benefits of chemotherapy for stage II colon cancer with your doctor.