A study showed adjuvant exercise reduces colon cancer recurrence rates. However, the crucial detail is that the benefit was seen in patients undergoing structured, intense exercise with trainers, not just those given a pamphlet and told to walk more. This suggests the intervention's intensity and social component are critical.
In a study of neoadjuvant Dostarlamab for MSI-high tumors, 100% of rectal cancer patients achieved a clinical complete response, compared to 82% of colon cancer patients. Experts find this high degree of discordance surprising and currently lack a clear biological explanation, as such differences are not typically observed in the metastatic setting.
While the STELR-303 trial of zanzalidinib plus atezolizumab in MSS colorectal cancer was technically positive, showing a 1.5-month median overall survival benefit, experts are not enthusiastic. They view the magnitude of benefit as slight and are concerned about increased toxicity, questioning its clinical meaningfulness and potential adoption into practice.
A significant real-world barrier to implementing superior neoadjuvant immunotherapy strategies is the referral pattern in community settings. Medical oncologists often don't see patients until after surgery is completed, by which point the opportunity to give neoadjuvant treatment and potentially avoid chemotherapy or major surgery has been lost.
While ctDNA testing offers powerful prognostic information, some patients decline it. The key reason is the anxiety associated with receiving a positive result after adjuvant therapy when there is no standard-of-care intervention for MRD positivity. For these patients, the psychological burden of knowing about likely recurrence without a clear action plan outweighs the benefit.
A retrospective analysis of the CALGB 80702 trial yielded a provocative finding: the COX-2 inhibitor celecoxib provided no benefit to the overall population but was associated with a 40% reduction in recurrence risk specifically in patients who were ctDNA-positive after surgery. This suggests a potential targeted use for an old, inexpensive drug in a high-risk population.
Despite the ATOMIC trial (adjuvant FOLFOX + atezolizumab) being practice-changing and included in NCCN guidelines for stage 3 MSI-high colon cancer, experts from major academic centers would not use it. They cite the high toxicity of chemotherapy and superior data from neoadjuvant immunotherapy trials like NICHE2, which achieve excellent outcomes without any chemotherapy.
Clinical trial data provides a clear directive for using MRD testing. The DYNAMIC study showed that for stage 2 colon cancer, a ctDNA-guided approach halved chemotherapy use with identical outcomes. In contrast, the DYNAMIC-3 study found that de-escalating chemo for high-risk stage 3 patients based on a negative ctDNA result led to worse outcomes.