What a written review looks like

Fictional example. Not a real patient. Not medical advice.

This is the shape of what Kim sends back: a plain reading of the result, the limits of that reading, and the questions to take into your appointment.

The situation: Maya R., 58, Stage II colon cancer

Maya R. is 58. Four months ago she had a laparoscopic right hemicolectomy for a pT3 N0 M0 (stage IIA) adenocarcinoma of the ascending colon. Twenty-four lymph nodes were examined, all negative, and margins were clear. She did not receive adjuvant chemotherapy. Her first Signatera draw, six weeks after surgery, was positive at 12.4 MTM/mL. A second draw twelve weeks later was 41.7 MTM/mL. Her CEA has stayed within the normal range, and a contrast CT of the chest, abdomen and pelvis showed no evidence of disease.

The question she sent

My Signatera went up but my CT is clear and my CEA is normal. Does this mean the chemo decision is already made for me? What should I be asking my oncologist?

What the result shows

Signatera is a tumor-informed assay: its published 16-variant method tracks variants selected from the resected tumor, with at least two detected variants required for a positive call. The actual report should be checked for the assay version and reporting criteria. A positive postoperative result is consistent with molecular residual disease and is associated with increased recurrence risk. Assuming both reports used the same tumor-specific panel and comparable methods, the measured ctDNA concentration increased about 3.4-fold, from 12.4 to 41.7 MTM/mL. That is concerning, but MTM/mL measures circulating tumor DNA, not tumor volume. Shedding, clearance, sampling and analytical variability can affect the value; two draws do not establish a tumor growth rate.

What it supports

Postoperative ctDNA positivity is strongly associated with increased recurrence risk. GALAXY, a prospective observational study using Signatera, found associations between ctDNA positivity and recurrence, and between chemotherapy and improved outcomes in ctDNA-positive patients. Treatment was not randomized, so selection bias and other differences between patients limit conclusions about chemotherapy benefit. DYNAMIC used a different tumor-informed assay, based on Safe-SeqS, not Signatera. It randomized stage II patients to ctDNA-guided or standard management, reduced chemotherapy use, and met its two-year recurrence-free-survival noninferiority endpoint; five-year outcomes were similar. It did not randomize ctDNA-positive patients to chemotherapy versus observation, so it did not prove chemotherapy benefit specifically for that subgroup or validate treatment choices based on Signatera MTM/mL values. These findings make the result important to discuss, not a treatment decision by itself.

What it does not show

ctDNA does not locate disease or measure the size of a deposit. A negative CT can coexist with positive ctDNA because disease may be below imaging detection thresholds. Some colorectal cancer cohorts have reported ctDNA detection months before radiologic recurrence. One longitudinal study reported a mean lead time of 8.7 months, but that is not a universal interval or a prediction for Maya. The interval depends on the assay, blood-draw and imaging schedules, disease site and patient population. A normal CEA does not exclude residual or recurrent disease. These results can differ without contradicting one another.

Where the uncertainty sits

Two draws document an increase in measured ctDNA, but do not establish its cause. Whether repeat testing would clarify the result, and how it would affect management, needs discussion with the treating team. Adjuvant chemotherapy is generally started within approximately six to eight weeks of surgery when indicated and recovery permits. Observational studies associate longer delays with worse outcomes, but eight weeks is not a proven cutoff beyond which benefit disappears. Neither DYNAMIC nor GALAXY establishes the benefit of starting treatment approximately four months after surgery solely because ctDNA remains positive. MMR/MSI status is an important missing result. Stage II dMMR/MSI-high tumors generally have a more favorable prognosis, and fluoropyrimidine-only adjuvant chemotherapy is not routinely recommended because benefit has not been demonstrated. If chemotherapy is chosen because of additional high-risk features, ASCO recommends an oxaliplatin-containing regimen. Immunotherapy is not established postoperative treatment for this stage IIA, ctDNA-positive, imaging-negative scenario; trial eligibility is a separate question. Abnormal MMR/MSI results guide Lynch syndrome evaluation, sometimes with additional tumor testing before germline testing. ctDNA is prognostic, but does not by itself establish which treatment will improve outcomes.

What I would raise with your team

First, how the ctDNA result fits with the full pathology, MMR/MSI status and other recurrence-risk features. Second, what evidence supports treatment, observation or a clinical trial in this setting, including the time elapsed since surgery. Third, whether any additional imaging would answer a specific clinical question or change management, rather than assuming PET-CT or liver MRI is routinely needed. Fourth, whether an MRD-directed trial is available and whether Maya meets its current eligibility criteria. Bring both Signatera reports with collection dates, the full surgical pathology report, and any MMR or MSI result.

Questions for the appointment

  1. Is my rising ctDNA part of your recommendation about adjuvant chemotherapy, or is the recommendation based on stage and CT alone?
  2. What evidence supports treatment versus observation or a clinical trial here, and how does the time since surgery affect that evidence?
  3. Has my tumor been tested for mismatch repair or MSI status, and how would that result change the plan?
  4. Would additional imaging or a repeat ctDNA test change management, and what surveillance schedule do you recommend?
  5. Am I eligible for any ctDNA-positive, MRD-directed clinical trials, and would enrolling change my standard options?

Records and testing to bring

The name, values and dates in this example are invented. No real patient's results appear here. What is real is the structure: what the result shows, what it does not, and what to ask next.

Focused Report Reviews start at $250 for one report and one focused question. Kim Lockheimer, PhD, DFM confirms scope, fee and delivery date before sending an invoice. Send a report at /biomarker-intelligence.