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: it tracks up to 16 somatic variants selected from sequencing of your resected tumor, and a draw is called positive when at least two of those variants are detected in plasma. A positive result after curative-intent surgery therefore indicates molecular residual disease (MRD), meaning tumor-derived DNA is still circulating. Both draws were run on the same assay with the same tumor-specific panel, so the values are directly comparable. The level rose roughly 3.4-fold, from 12.4 to 41.7 mean tumor molecules per mL, over about twelve weeks. A positive draw followed by a higher positive draw is the pattern most consistent with residual disease that is growing.

What it supports

In stage II and III colon cancer, ctDNA detected after surgery is one of the strongest known predictors of recurrence, stronger than T stage, nodal status or CEA. In the GALAXY cohort of CIRCULATE-Japan and in earlier prospective series, most patients who were ctDNA-positive after surgery and did not receive adjuvant therapy went on to recur, while ctDNA-negative patients had low recurrence rates. The DYNAMIC trial in stage II colon cancer used exactly this signal to decide who receives adjuvant chemotherapy: ctDNA-positive patients were treated and ctDNA-negative patients were spared it, without loss of recurrence-free survival. Your results place you in the group for which adjuvant treatment was offered in that trial.

What it does not show

ctDNA does not localize disease. It cannot tell you whether residual cells are in the liver, the peritoneum, the lungs or elsewhere, or how large any deposit is. A negative CT is expected at this stage, because CT generally detects lesions only once they reach several millimeters, while ctDNA can be positive months before anything is visible. The median lead time of ctDNA over imaging in published colorectal data is roughly eight to nine months. A normal CEA does not argue against the ctDNA result: CEA is elevated in only a portion of recurrences and is far less sensitive. None of these tests conflict; they measure different things at different thresholds.

Where the uncertainty sits

Two draws establish a direction. A false-positive call on a tumor-informed assay is uncommon, and a rising value makes a technical artifact less likely, but a confirmatory draw before committing to treatment is reasonable if it does not delay a decision. Timing matters: the benefit of adjuvant chemotherapy is greatest when it starts within roughly eight weeks of surgery, and Maya is now four months out, so the evidence for treating at this point comes from MRD-directed studies rather than from the classic adjuvant trials. Mismatch repair status is essential and does not appear in her records: dMMR/MSI-high tumors respond poorly to fluoropyrimidine alone and may be candidates for immunotherapy-based approaches or trials, and the result also determines whether Lynch syndrome testing is indicated.

What I would raise with your team

First, whether the rising ctDNA is being weighed in the adjuvant decision or whether the recommendation still rests on stage and imaging alone. Second, the regimen and duration being considered, typically CAPOX or FOLFOX, and how the delayed start affects the expected benefit. Third, whether a PET-CT or liver MRI would add information before treatment, and what the surveillance schedule will be. Fourth, eligibility for MRD-directed trials, which often require ctDNA positivity and no visible disease, the exact situation described here. Bring both printed 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. Given that I am four months past surgery, what benefit would you expect from starting CAPOX or FOLFOX now?
  3. Has my tumor been tested for mismatch repair or MSI status, and how would that result change the plan?
  4. Would a PET-CT or liver MRI change anything before we decide, and when will my next Signatera draw be?
  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.