Track 1

DR LOVE: Neal, what do we know about the impact of adjuvant chemotherapy on patients with Stage II colon cancer?

DR MEROPOL: The management of Stage II colon cancer is a difficult decision-making scenario, insofar as the prognosis is good with surgery alone and the potential benefit of adjuvant therapy for the population as a whole is marginal. If you were to treat all patients who have Stage II colon cancer with adjuvant therapy, the absolute benefit would probably be in the range of five percent or less for the most active chemotherapy regimen (Andre 2004; de Gramont 2005).

The challenges are in defining which patients are at the greatest risk of relapse from the group of patients with Stage II disease and in selecting those patients for adjuvant therapy because their potential for benefit is greater.

Patients have different values with regard to the tradeoffs of the potential benefits and side effects. This requires a discussion about the option of adjuvant therapy — the potential hazards, which are well defined, and the potential benefits, which are less well defined for any individual.

The doctor and patient have to come to an agreement and understanding about what is best for that individual patient. With regard to your question about whether all patients with Stage II colon cancer should be referred to a medical oncologist, my answer is that all of those patients should engage in a discussion about adjuvant therapy and whether it’s right for them.

Track 2

DR LOVE: When we ask oncologists nationally, “What are you likely to recommend to a woman who has a 10 or 20 percent risk of relapse from breast cancer?” the vast majority say they’re likely to recommend chemotherapy, but in colon cancer, far fewer docs say they would treat a patient with colon cancer and the same risk for relapse (6.1). What do you think explains these differences?

DR MEROPOL: I believe part of it is cultural and part of it is data driven. With regard to the data in breast cancer, prospective randomized studies involving thousands of patients have conclusively shown and defined the small benefit from the addition of adjuvant therapy for an individual who’s at low risk of relapse.

In colon cancer, we don’t have those kinds of data. We have extrapolations from a higher-risk situation and pooled analyses that either show no benefit or marginal benefit (Benson 2004; Figueredo 2004; Gill 2004).

The most compelling data with regard to patients with Stage II colon cancer are from the MOSAIC trial, in which patients with Stage II disease seem to have a benefit of a few percent in three- and four-year disease-free survival with FOLFOX over 5-FU/leucovorin (Andre 2004; de Gramont 2005; [6.2]).

The overall survival data have not been reported yet. So we don’t have the long-term follow-up, but we do know there’s an attendant risk of long-term neurotoxicity, which affects decisions about the use of this therapy when the gain is marginal in terms of overall survival.

Track 6

DR LOVE: We asked 150 people who had received adjuvant chemotherapy for colorectal cancer in the last five years, “How much benefit would you want to receive in order to go through chemotherapy again?” Approximately one third of them would go through chemotherapy again for a one percent reduction in relapse rate, and more than half of them would go through therapy for a three percent reduction (6.3).

DR WOLMARK: I believe that from a biologic standpoint, we have no reason to think that Stage II patients are a unique subset relative to their responsiveness to adjuvant therapy. It’s just that they’re at lower risk for recurrence.

What your analysis, Neil, has shown is very useful. The heterogeneity between breast and colon cancer does not lie in the tumor or in the patient. Patients want to be treated for the same low risk, whether they have breast or colon cancer. The heterogeneity lies in the fact that, traditionally, the medical oncologist who specializes in colorectal cancer is less enthusiastic about adjuvant therapy.

The irksome part from my perspective is not that all Stage II patients should be treated — it’s that all Stage II patients should be apprised of the benefit of adjuvant chemotherapy.

I believe what we need to resolve this issue is a tool that allows us to evaluate patients beyond the traditional factors we’ve used to decide which patients with early-stage colorectal cancer to treat. We need an assay equivalent to Oncotype DX™, and I believe we’re making significant progress relative to that.

DR HOCHSTER: I agree that every patient with Stage II cancer would benefit from seeing a medical oncologist. Even if they decide against adjuvant therapy, they reap other benefits, such as discussions about the risk of colorectal cancer for relatives and how they can be screened. Patients also need to know how their health-related issues for the next 25 years will be different as a result of their having colorectal cancer, particularly in terms of future screening so that if they’re the one patient in five who develops recurrence, we can capture it when it’s likely to be curative.

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Editor and Moderator:
Neil Love, MD