How often do you need to tell a lung cancer patient,
“We got the primary tumor, but it looks like the cancer has come back”?
For roughly 1 in 3 of your stage I NSCLC patients, that conversation is coming. The surgery did not fail; the biology was already ahead of you.
Occult micrometastasis drives recurrence in 30–45% of resected stage I non-squamous NSCLC patients. Until now, there was no clinically validated way to identify which patients harbored that risk before it manifested, or which patients would benefit from adjuvant therapy
No longer. RiskReveal has changed that.
The Problem
TNM Stage I Isn’t One Patient Population
TNM staging tells you what imaging and pathology can see. What matters, however, is the biological state a tumor has already reached at the time of resection. Only molecular profiling of the tumor can tell you that.
A subset of your stage I-IIA patients, those whose tumors carry a high-risk 14-gene expression profile, face a recurrence risk that is reminiscent of stage IIB or higher. It is no great surprise that they have now been documented, with randomized data, to respond to the same adjuvant chemotherapy as stages IIB-III. Now that their benefit has been documented, there is no justification to withhold potentially life-saving intervention.
Oncologists have historically relied upon outdated, now obsolete studies to maintain their belief that stage IA patients and stage IB patients with tumors <4 cm do not benefit from adjuvant intervention. One of the primary handicaps of those 20-year-old studies was that patients cured by surgery alone diluted any benefit that could have been observed with adjuvant chemotherapy. Recently published, modern data that include molecular risk stratification have now clearly demonstrated that molecular high-risk patients derive substantial benefit from adjuvant therapy even in stage IA, and therefore must be identified and treated in order to prevent thousands of unnecessary deaths in the US alone.
The Evidence
AIM-HIGH Phase 3 Randomized Trial
Published in The Lancet Respiratory Medicine, 2025
AIM-HIGH is the first Phase 3 randomized clinical trial to demonstrate a benefit from adjuvant therapy throughout stages IA-IIA NSCLC. That dramatic benefit, even in stage IA, was achieved by applying RiskReveal 14-gene molecular risk stratification to identify high-risk stage IA–IIA non-squamous NSCLC patients.
The trial enrolled 449 patients across 45 sites in the US and Europe. High-risk patients were randomized to 4 cycles of platinum-based doublet chemotherapy plus local standard of care, vs. resection alone. The primary endpoint was Disease Free Survival (DFS).
Key Outcomes
| Population | Untreated (DFS) | Treated (DFS) | Risk Reduction |
|---|---|---|---|
|
High-risk stage IA-IIA |
79% |
96% |
78% (HR 0.22) |
|
High-risk IA only |
78% |
98% |
85% (HR 0.15) |
What this means clinically
A note on timing
What this means clinically
Your stage IA patient with a high-risk molecular profile is not likely to act the way a stage IA patient is supposed to. No other risk stratification method in lung cancer outside of TNM itself has ever been as vigorously validated in as many patients as RiskReveal, which dramatically outperforms TNM in stages I-IIA. With the results of the randomized AIM-HIGH study now in hand, there is no question that these patients benefit from adjuvant therapy and therefore no need to watch these patients recur and die without an attempt at life-saving intervention.
Molecular risk stratification is also independent of EGFR mutation status. High-risk patients benefited from adjuvant chemotherapy regardless of EGFR status.
A note on timing
The benefit of adjuvant therapy has long been understood to depend on timely intervention after resection. RiskReveal results are guaranteed within 10 business days of specimen receipt and are generally available within 2-3 days. They are designed to fit within the adjuvant treatment window, unlike attempts to apply MRD testing in this scenario.
Chemotherapy-related mortality was 1%, consistent with established platinum-doublet safety profiles. 74% of patients completed all 4 cycles; 87% completed at least 3 cycles.
RiskReveal vs. Blood-Based MRD Testing
Some practices are exploring circulating tumor DNA (ctDNA) as a post-resection prognostic tool. Relative to RiskReveal, the evidence base for that approach warrants scrutiny.
| RiskReveal / AIM-HIGH | Clinically Available Blood-Based MRD (ctDNA) | |
|---|---|---|
|
Type of data available |
Phase 3, randomized, interventional |
Observational, no intervention |
|
Sites per study |
45 (US + Europe) |
Single center |
|
Number of high-risk stage I patients with outcomes included per study |
190 |
<20 |
|
Published |
Lancet Respiratory Medicine, 2025 |
J Thoracic & Cardiovascular Surgery, 2024; J Thoracic Oncology, 2026 |
|
Time to actionable assay result |
<10 days |
2-3 months or greater |
Blood-based MRD testing has never been assessed in a randomized study of early post-operative intervention. The approach retains utility for long-term recurrence surveillance. However, there is no evidence for its utility as a pre-treatment prognostic tool to help with adjuvant therapy decision making for early-stage NSCLC. Any attempt to use MRD for this purpose, which notably lacks predictive utility data, entails a delay to actionable results that renders it impractical within the most effective adjuvant chemotherapy window.
What RiskReveal Gives You — and Your Patients
Some practices are exploring circulating tumor DNA (ctDNA) as a post-resection prognostic tool. Relative to RiskReveal, the evidence base for that approach warrants scrutiny.
For high-risk patients:
A validated, randomized trial-backed method to initiate adjuvant chemotherapy consistent with NCCN guidelines for early-stage disease in which an unacceptable risk of recurrence and mortality is hidden by conventional TNM staging.
For low-risk patients:
Evidence-based reassurance. The conversation shifts from “we think you’re cured” to “your tumor biology confirms you’re low risk.”
Make sure every high-risk patient is identified and treated. Give every low-risk patient peace of mind.
Workflow Integration: When and How to Order
RiskReveal is most effectively integrated at two points in the surgical care pathway:
Point 1: Pre-Operative Discussion
This is the ideal time to introduce patients to the full breadth of modern integration of molecular technology into the management of early-stage NSCLC. Avoid a sudden, disconcerting introduction of the high risk of recurrence (even for stage IA patients) during the post-operative period by explaining up front that although surgery for lung cancer was traditionally associated with high recurrence rates, recurrence in stage IA-IIA can now be dramatically lowered by taking a two-stage approach when necessary: gold-standard surgery followed by molecular analysis of the resected tumor and a short course of well-tolerated post-operative chemotherapy when necessary for high-risk tumors to raise survival rates from the 60s to 70s into the high 90s.
Point 2: Ordering the Test Prior to the First Post-Operative Visit
Results can return before the post-operative visit, so that a full discussion of conventional and molecular analysis of the tumor can be discussed.
Ordering & Logistics
Perform
resection
resection
During the first post-op
appointment remind your
patient about RiskReveal
and order the test
Download Order Form
appointment remind your
patient about RiskReveal
and order the test
Download Order Form
Low-risk
High-risk
Discuss results
Learn More
Learn More
Discuss results
Learn More
Learn More
Routine
follow up
follow up
Refer to a medical oncologist
Perform
resection
resection
During the first post-op appointment remind your patient about RiskReveal and order the test
Download Order Form
Download Order Form
Sample Requirements
FFPE tissue block or slides. Razor Genomics provides a shipping kit with preparation and shipping instructions.
Turnaround Time
Results typically guaranteed within 10 business days of specimen receipt, often available sooner.
Insurance Coverage & Resources
Insurance & Patient Access
Razor Genomics accepts many forms of insurance. Patients with Medicare have no out-of-pocket cost. For patients with other insurance, Razor Genomics bills directly — coverage depends on the specific plan.
Patient Assistance Program are available.
For Your Colleagues
Shareable with tumor board, oncology partners, and referring physicians.
