ASCO has published updated guidance on the use of adjuvant therapy in the management of stage II colon cancer, providing clinicians with a newer evidence-based framework that can be used in shared decision-making with patients.1
Need for Updated Guidance
“How to approach patients with stage II colon cancer has been a continuous issue since the realization of the benefit of adjuvant therapy in stage III disease in the 1990s,” said Jeffrey A. Meyerhardt, MD, MPH, of Dana-Farber Cancer Institute, and Guideline Chair.
Jeffrey A. Meyerhardt, MD, MPH
The choice of treatment for stage II colon cancer is often based on a lengthy conversation with patients, Dr. Meyerhardt added, particularly since treatment data from interventional trials are not always straightforward or clear. Likewise, treatment decisions for the disease are typically based on careful analysis and discussion of the risks of harm vs benefits associated with therapy. “Oncologists are torn between not wanting to overtreat patients with drugs that can have short- and long-term toxicities but also not undertreat if chemotherapy can reduce the risk of recurrences,” he said.
In 2004, ASCO published a guideline on adjuvant therapy for stage II colon cancer, but since then, new evidence has emerged on the roles of fluoropyrimidine-based adjuvant chemotherapy and adjunct oxaliplatin in the management of the disease.2 The ASCO guideline expert panel sought to develop newer recommendations for oncologists based on the latest clinical data.
The 2004 ASCO guideline recommended against routine use of adjuvant chemotherapy in patients with stage II colon cancer, based on dismal 5-year survival outcomes from a meta-analysis. In the update, the guideline panel supports this previous recommendation, citing strong evidence showing that the harms of routine adjuvant chemotherapy use in this population outweigh the potential benefits.
Additionally, the updated ASCO guideline recommends against offering adjuvant chemotherapy to patients at low risk of experiencing disease recurrence. These low-risk patients, according to the committee, include those with stage IIA (T3) tumors with at least 12 sampled lymph nodes of the surgical specimen, tumors without perineural or lymphatic invasion, poor or undifferentiated tumor grade, tumor perforation, clinical intestinal obstruction, and less than grade BD3 tumor budding.
In contrast, the guideline recommends that clinicians offer adjuvant chemotherapy to patients with stage IIB and IIC colon cancer through a shared decision-making approach. Additionally, the guideline recommends adjuvant chemotherapy for patients with stage IIA disease who have high-risk clinical features. The authors state that the number of risk factors should be incorporated into the shared decision-making process, however, given that patients with at least one risk factor are at an increased risk of experiencing recurrence.
The guideline noted that the use of adjuvant fluoropyrimidine-alone chemotherapy is not routinely recommended for the management of disease in patients with tumors that exhibit mismatch repair deficiency/high microsatellite instability. The guideline also states that little evidence exists to support adding oxaliplatin to fluoropyrimidine-based chemotherapy in patients with high-risk stage II colon cancer. Despite this, the expert panel does recommend oxaliplatin-containing chemotherapy in patients with mismatch repair deficiency/high microsatellite instability who have T4 tumors and/or other high-risk features, but this decision should be made between both patients and clinicians after a discussion of the lack of documented survival benefit and possible harms.
One of the challenges in stage II colon cancer is how to define high-risk stage II disease, Dr. Meyerhardt explained, as often it is a composite of multiple factors including T4 disease, lymphovascular invasion, poor differentiation, inadequate lymph node sample, clinical bowel obstruction, and clinical bowel perforation. “It is likely those are not all the same in terms of prognosis or where adjuvant chemotherapy should be used,” he added. “But in the guidelines, we are able to outline where the data exist for each of these features.”
Dr. Meyerhardt and colleagues also updated the guideline with recommendations on therapy and when to consider adding oxaliplatin to fluoropyrimidine. Specifically, the guideline recommends that adjuvant oxaliplatin-containing chemotherapy could be offered for 3 or 6 months in patients eligible for adjuvant doublet chemotherapy. This decision, the guideline committee noted, should be made following a discussion with the patient on the benefits and risks of harm with the proposed treatment duration.
On a concluding note, the expert panel acknowledged that circulating tumor DNA is increasingly used in stage II colon cancer, particularly as an emerging predictive variable for prognosis. “While we recognize this usage, at this point the data are really prognostic,” Dr. Meyerhardt said. Critical to this discussion is whether circulating tumor DNA can guide treatment decisions on whether to offer adjuvant therapy to patients with stage II colon cancer, he said. “And that is where data are lacking and really need to be explored to guide clinicians.”
1. Baxter NN, Kennedy EB, Bergsland E, et al: Adjuvant therapy for stage II colon cancer: ASCO guideline update. J Clin Oncol. December 2021 (early release online).
2. Benson AB, Schrag D, Somerfield MR, et al: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22:3408-3419, 2004.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, December 23, 2021. All rights reserved.