Exercise and Molecular Testing May Improve Colorectal Cancer Survival

Regular exercise is no longer just a recommendation for general health; it is now a clinically proven intervention that can prevent cancer from returning.

Findings presented by Dr. Jeffrey Meyerhardt of the Dana-Farber Cancer Institute at the 2026 NCCN Annual Conference highlighted a shift in how doctors treat early-stage colorectal cancer. The presentation featured findings from the CO21 trial, the first randomized study to prove that a structured exercise program directly improves survival for patients with stage 2 and 3 colon cancer.

"2026 represented the first randomized behavioral intervention to impact recurrences and survival in a non-metastatic cancer population," Meyerhardt said during the session.

Exercise as a clinical tool

The CO21 study followed patients who had completed chemotherapy and randomized them into two groups: one receiving only health education materials and another enrolled in a structured exercise program (SEP). The results showed that exercise significantly altered the trajectory of the disease.

Patients in the exercise group saw an 80.3% five-year disease-free survival rate, compared to 73.9% for those who did not participate in the structured program. The data indicated that for every 16 people who exercised, one cancer recurrence was prevented. Additionally, the intervention was found to prevent one death for every 14 patients who engaged in physical activity.

The benefits extended beyond the original diagnosis. Researchers found that exercise also reduced the risk of developing new primary cancers, such as breast and prostate cancer.

Based on these findings, the NCCN Guidelines have been updated to advise that oncology teams discuss and facilitate options for patients to achieve a goal of at least 150 minutes of moderate to vigorous physical activity per week.

The role of molecular testing

While lifestyle changes are taking center stage, they are part of a broader move toward personalized medicine. Meyerhardt emphasized that 80% of patients diagnosed with colon cancer have no evidence of spread at the time of diagnosis, yet many still face recurrence.

To better predict these risks, the new guidelines recommend that all stage 2 and 3 colorectal tumors undergo molecular profiling. This testing identifies specific biomarkers, such as PI3K pathway alterations and mismatch repair (MMR) status, which dictate which supplemental treatments will be most effective.

Aspirin and targeted therapy

One of the most significant pharmaceutical updates involves the use of aspirin for a specific subset of patients.

Data from the ALASCCA trial confirmed that patients whose tumors possess a PIK3CA mutation, which acts as an "on" switch for cancer growth, benefit significantly from daily aspirin.

"To be able to know if they have a PIK3CA alteration ... you need to do testing," Meyerhardt said, noting that this represents a paradigm shift from only testing patients with advanced, metastatic disease.

Immunotherapy breakthroughs

For patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, immunotherapy is providing unprecedented results.

In the ATOMIC study, adding the immunotherapy drug Tecentriq (atezolizumab) to standard chemotherapy for stage 3 colon cancer resulted in an 86.4% three-year disease-free survival rate, compared to 76.6% for chemotherapy alone.

In the NICHE-2 study, which provided immunotherapy before surgery, 68% of patients had a complete pathologic response, meaning no live tumor was found by the time they reached the operating room.

In cases of dMMR rectal cancer, the drug Jemperli (dostarlimab) achieved a 100% clinical complete response rate in a study of 42 patients, potentially allowing some to avoid surgery altogether through "watch and wait" surveillance programs.

A personalized future

The 2026 conference findings underscore a future where colorectal cancer care is tailored to both the biological makeup of the tumor and the physical activity of the patient. By combining molecular testing with structured lifestyle interventions, clinicians are now able to offer a more comprehensive and effective path to long-term survival.

Reference:

1. “Advances in Early-Stage Colorectal Cancer: Integrating Emerging Evidence into Practice,” by Dr. Jeffrey Meyerhardt. Presented at: The NCCN 2026 Annual Conference.

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