Molecular Profiling for Stage II Colon Cancer

February 2012, Vol 3, No 1 - Meeting Highlights


San Francisco, CA—Approximately 80% of patients with stage II colon cancer will be cured by surgery alone, but 20% will still relapse. Oncologists struggle with the question of which patients could benefit from adjuvant chemotherapy to reduce this risk, and which patients can be safely observed, without further treatment.

Molecular factors of the tumor can help define high-risk stage II disease; however, no agreement exists about which of the currently available molecular assays are most useful for this purpose. At the 2012 Gastrointestinal Cancers Symposium, George J. Chang, MD, FACS, Associate Medical Di­rector, Colorectal Center, University of Texas M.D. Anderson Cancer Center, Houston, and Neal J. Meropol, MD, Chief, Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH, debated this question.

Table
 Molecular Tests for Stage II Colon Cancer
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Dr Chang described the current assays, by risk (Table). In all the assays, prognosis is independent of standard high-risk clinical criteria. But molecular profiling does improve treatment efficiency, he said.

 

Limitations of the Assays
“Although these assays are emerging as tools that can classify patients with stage II colon cancer based on their risk for recurrence, an inherent limitation of each is its lack of predictive ability,” Dr Chang noted. “In an ideal world, we could identify patients who can be predicted to benefit from chemotherapy. But in the real world, we can identify patients at high risk for recurrence, and, therefore, those who have the greatest need for adjuvant chemotherapy benefit. And, we can identify patients at low risk for recurrence who may safely be observed.”

The number needed to treat for a low-risk patient with stage II cancer is 50 compared with 20 for high-risk patients. In the latter case, the benefit is similar to that obtained by oxaliplatin in a patient with stage III cancer, which is considered very reasonable, Dr Chang said.

According to Dr Meropol, “What matters is the absolute benefit of chemotherapy at each level of risk.” This is hard to determine, especially when the estimated relapse risk varies in each of the assays. Although he did not dismiss the benefit of these assays, he did note their limitations:

  • Validation sets are small or not representative of real patient populations
  • No well-validated genetic platforms identify patients at “very high risk”
  • There is a small or uncertain impact of chemotherapy in the “high-risk” groups
  • The predictive value of the assays has not been demonstrated
  • The impact of oxaliplatin in “high-risk” groups is uncertain
  • It is unclear how to integrate testing for microsatellite stability status (another determinant of favorable/unfavorable prognosis) into the classifier
  • It is unclear how to address discordance between clinical and molecular results.

“The available tests also do not obviate the need for consideration of patient preferences in adjuvant therapy decision-making,” Dr Meropol added. Future research should focus, he said, on expanding the identification of patients who will not relapse, improving the identification of those at highest risk, improving adjuvant therapy, and predicting the harms of chemotherapy for individual patients, so that the impact on quality-adjusted survival can be estimated.