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Time to Treat Exercise Like a Therapy? Here’s How

How often are you asked, “Is there anything else I can do to keep my cancer from coming back?”

For the first time, Phase III evidence says yes.

The CHALLENGE trial (CCTG CO.21), presented at ASCO 2025 and published in NEJM, shows that a 3-year, structured exercise program can reduce recurrence by 28% and improve overall survival by 37% in stage II/III colon cancer survivors.

This is a non-pharmacologic, disease-modifying intervention — with survival-grade data.

Let’s call it what it clinically functions as:

Exercizumab (Name credit: Dr. Nina Sanford) - a long-acting, tapering, survival-enhancing agent, delivered through movement.

What The Trial Got Right

1. Survival as a Primary Endpoint

Unlike most survivorship studies, this trial reported hard endpoints: recurrence and survival - with enough follow-up to be meaningful.

889 patients randomized
3-year structured exercise vs. health education control
55 centers across 6 countries
Median follow-up: 8.2 years

Statistically Significant Results:

🔻 28% reduction in recurrence/new primary (DFS), HR 0.72, p=0.02
🔻 37% reduction in all-cause mortality (OS), OS HR 0.63
DFS improvements driven by reductions in liver recurrence (3.6% vs. 6.5%) and new primary cancers (5.2% vs. 9.7%).

This is Phase III, survival-grade evidence - not a surrogate, not a signal.

2. Behaviorally Intelligent Design

This was a structured, titrated regimen, not a "walk more" recommendation:

Individualized prescriptions from certified physical activity consultants
Behavior support: biweekly (year 1) → monthly (years 2–3)
Target: +10 MET-hours/week from baseline during the first 6 months, sustained for 3 years

It was prescribed, monitored, and adjusted - like any long-term therapeutic.

3. Rigor and Global Applicability

Dynamic minimization ensured balance across stage, BMI, fitness, site
Baseline characteristics were balanced - no significant biomarker differences
Conducted across Canada, Australia, US, UK, France with consistent results

Where the Limits Are

1. Selection Bias

Patients had to complete chemo and pass a 6-minute walk — selecting for fitter survivors. Still, 40% were obese and <40th percentile in fitness for age. This was a typical survivor population, not athletes.

2. Musculoskeletal Events

18.5% in the exercise group reported mostly mild/moderate MSK events vs. 11.5% in control - expected in previously deconditioned patients.
The takeaway: gradual ramp-up, trained supervision, and anticipatory guidance matter.

3. Subjective Secondary Endpoints

Fatigue and VO₂ max carry bias risk. But recurrence and mortality were adjudicated — hard endpoints remain solid.

4. Adherence Data and Dose Ambiguity

Adherence waned over 3 years, yet still delivered:

Increases of 5.2–7.4 MET-hours/week
Improved VO₂max by 1.3–2.7 ml/kg/min
Gains in 6-minute walk distance (13–30 meters)
Dose-response data needs more clarity, but the intervention worked.

5. Implementation Burden – and Opportunity

Yes, it requires trained professionals and infrastructure. And no, cost-effectiveness data isn’t available yet- further delaying any systemic changes.

We already know that nearly 40% of reported barriers to implementing exercise programs exist at the organizational level — missing structures, missing staff. That won’t change overnight.

This is where you matter most. You don’t need a system. You need conviction.

How to Use This, Now

1. Screen smartly

If they’re fit for 3-month surveillance scans, they’re likely fit to start activity. Use:

ECOG 0–2
6-minute walk test
Screen for comorbid flags (e.g., CHF, severe arthritis, uncontrolled neuropathy)

Refer to cardio-onc or physiatry if uncertain — but default to inclusion, not avoidance.

2. Prescribe concretely

“Try to stay active” is vague.

Prescribe: 150–300 min/week of moderate aerobic activity
Add: "Prefer structured or supervised support. Reassess in 3 months."

Write it into the survivorship care plan — like any other prescription.

3. Monitor like a medication

What’s not measured is ignored.
Add “exercise adherence” to survivorship templates. Ask:

“How many minutes/week are you currently doing?”
“What’s making it harder or easier?”
“Do you need support to maintain this?”

Treat behavioral tracking like labs. It drives accountability.

4. Refer intentionally

Survivors need oncology-literate professionals. But even if those resources aren’t available yet - start anyway. Start small.

Download this editable patient guide to help you begin.

⬇️DOWNLOAD HERE

It includes referral resources and tools to connect patients with trained specialists and evidence-based programs.

Bottom Line

The CHALLENGE trial offers practice-shifting results with Phase III data, durable DFS and OS gains, and low toxicity.

This is Exercizumab - and it belongs in every oncologist’s toolkit.

But benefit needs your clinical buy-in, workflow integration, and team-based survivorship care.

The next time a patient asks, “Is there anything else I can do?” - You’ll have a plan - a proven, survival-extending intervention that may be prescribed like any other adjuvant therapy.

It’s not easy. It's not perfect. But it works.

Best,
Shruti Agarwal, PhD
Together4Cancer

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The Compass is your practical briefing on what’s working in oncology care - strategy, science, and systems. No fluff. Just implementation.