These Two Simple Interventions May Cut CRC Recurrence Risk

Medscape

4 days ago

This transcript has been edited for clarity.
Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, Virginia.
New guidelines have lowered the age to begin screening for colon cancer to 45 years old. Although this change is positive, we're still seeing advanced cancer in younger patients who haven't been screened in time.
Once diagnosed, these patients undergo surgery and chemotherapy and often return to us asking, 'What can I do now to help myself?'
Two recent studies highlight interventions that are simple, affordable, and actionable today: exercise and aspirin. Let's take a closer look at the results.
Exercise's Risk Reduction Potential
The idea that exercise reduces cancer recurrence and mortality is supported by observational data. The mechanistic effects behind this have been ascribed to metabolic growth factors, inflammatory changes, immune function changes, and perhaps even positive impact on sleep.
A study just published in The New England Journal of Medicine examined structured exercise after adjuvant chemotherapy for colon cancer. The phase 3 randomized CHALLENGE trial, mostly conducted at Canadian and Australian centers, recruited patients with resected stage II or III colon cancer (9.8% and 90.2%, respectively) who had completed adjuvant chemotherapy. Patients with recurrences within a year of diagnosis were excluded, as they were more likely to have highly aggressive, biologically active disease.
Patients were randomized to receive healthcare education materials alone or in conjunction with a structured exercise program over a 3-year follow-up period.
The exercise intervention, delivered in person or virtually, focused on increasing recreational aerobic activity over baseline by at least 10 metabolic equivalent task (MET). An increment of 10 MET hours per week is not too vigorous. It is essentially the equivalent of adding about 45-60 minutes of brisk walking or 25-30 minutes of jogging 3-4 times a week.
Patients were asked to increase MET over the first 6 months and then maintain or further increase the amount over the next 2.5 years. They were permitted to structure their own exercise program by choosing the type, frequency, intensity, and duration of aerobic exercise.
The primary endpoint was disease-free survival, with secondary endpoints assessing overall survival, patient-reported outcomes, and other outcomes. Although designed to detect differences at 3 years, follow-up was also performed out to 5 and 8 years.
At a median follow-up of 7.9 years, exercise reduced the relative risk of disease recurrence, new primary cancer, or death by 28% ( P =.02). This benefit persisted — and even strengthened — over time, with disease-free survival increasing by 6.4 and 7.1 percentage points at 5 and 8 years, respectively.
Musculoskeletal adverse events were slightly higher in the exercise group compared with the health education group (18.5% vs 11.5%, respectively), but only 10% were directly attributed to the exercise.
There are considerations when interpreting these results. First, there was an attrition over time for compliance and training. It would be interesting to see whether that impacted the results. Second, it's unclear whether patient pedigree or a genomic pathway may predispose to a benefit here for the exercise group.
But overall, this phase 3 trial provides class 1 evidence supporting exercise as a low-cost, high-impact intervention to reduce cancer recurrence.
Adjuvant Aspirin in Colon Cancer Subset
That's a perfect segue into another recent study looking at the effects of adjuvant aspirin on the prevention of recurrence.
The ALASCCA trial— conducted across centers in Sweden, Denmark, Finland, and Norway — assessed patients with stage I-III rectal cancer or stage II-III colon cancer. It focused on a subset of patients with an oncogenic abnormality called PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha).
PIK3CA occurs in approximately a third of colon cancers and is associated with significant chemotherapy resistance and a higher rate of disease progression.
Of the included patients, 1103 (37%) had alterations in the PIK3CA pathway. Researchers randomized patients to receive either 160 mg of aspirin or placebo daily for 3 years, starting within 3 months of surgery.
Among patients with PIK3CA mutations, aspirin dramatically reduced the risk for time to recurrence by nearly 50% at 3 years ( P =.044). Adverse events associated with aspirin were minimal, including one case each of gastrointestinal bleeding, hematoma, and allergic reaction.
There is no evidence that higher aspirin doses provide greater prevention of colorectal cancer recurrence. The 160 mg use in the current study is fairly normal, roughly equivalent to two low-dose (81 mg) aspirin tablets.
Now, it's worth noting that the use of aspirin for the primary prevention of cardiovascular disease was initially recommended by the US Preventive Task Services Force in 2016. This recommendation was then recanted in 2022, when the same group reported limited net benefit to this approach.
Two Proactive Actions
These studies highlight two interventions — exercise and aspirin — that are low cost, accessible, and appeal to patients eager to help prevent their cancer from recurring.
Exercise is broadly beneficial and can be recommended immediately.
For aspirin, patients should work with their oncologist to determine their PIK3CA mutation status, as this subgroup appears to benefit the most.
These findings offer patients meaningful, proactive interventions they can apply to support their recovery and reduce the risk of recurrence. Hopefully these new findings will help guide your clinical conversations.
I'm Dr David Johnson. Thanks for listening.