| Coverage Policy Manual | |
| Policy #: | 2022020 |
| Category: | Laboratory |
| Initiated: | August 2022 |
| Last Review: | October 2025 |
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| Tumor-informed Circulating Tumor DNA Testing (e.g., Signatera) for Cancer Management | |
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| Description: |
The purpose of tumor-informed ctDNA testing in individuals with cancer is to predict disease course to inform treatment decisions and to monitor for recurrence following treatment.
Signatera is a tumor-specific ctDNA test. Tumor tissue obtained from either a diagnostic biopsy or surgically resected tissue is used to identify 16 single nucleotide variants found in the tumor but not in normal tissue and are likely to be present in all tumor cells regardless of tumor evolution. A custom assay of 16 tumor-specific clonal, somatic variants is generated for the individual and the resulting tumor signature can be monitored throughout the individual’s disease course. When the test is used for detection of recurrence following curative treatment, plasma samples with 2 or more out of these 16 variants detected above a predefined confidence threshold are deemed to be ctDNA-positive. When the test is used to monitor treatment response, evaluation is based on whether ctDNA levels increase or decrease from a baseline measurement. The test is intended to be used in conjunction with radiological assessment.
Regulatory Status
Signatera is a laboratory developed test regulated under CLIA. Signatera has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA), but has received 3 Breakthrough Device Designations from FDA:
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Policy/ Coverage: |
Effective August 15, 2022
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
Tumor-informed circulating tumor DNA testing (e.g., Signatera) does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness for all indications.
For members with contracts without Primary Coverage Criteria, tumor-informed circulating tumor DNA testing (e.g., Signatera) is considered Not Medically Necessary or is investigational and is not covered for all indications. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
This evidence review was created in April 2022 with a search of the PubMed database. The most recent literature update was performed through March 11, 2022.
Tumor-Informed Circulating Tumor DNA Testing with Signatera in Individuals with Colorectal Cancer
Four nonrandomized studies, 3 of which were noncomparative, examined the association of Signatera testing to prognosis in individuals with colorectal cancer (CRC). They differed in their study designs, populations (e.g., stage of disease), frequency and timing of standard care, outcome measures, and timing of follow up. Three studies evaluated the association between positive ctDNA results and prognosis in CRC. These studies did not provide comparisons of ctDNA testing to standard methods of risk stratification for therapy selection, monitoring response to therapy, or early relapse detection. One retrospective study compared Signatera testing to other surveillance strategies in individuals with resected colorectal cancer (Fakih, 2022). There are no randomized controlled trials, and no studies in which Signatera testing was used to guide treatment decisions.
Reinert et al enrolled 125 individuals with stage I to III colorectal cancer in a validation study of the Signatera assay (Reinert, 2019). Plasma samples were collected before surgery, at 30 days following surgery, and every 3 months for up to 3 years. The recurrence rate at 3 years was 70% in individuals with a positive ctDNA test (7 of 10) compared to 11.9% (10 of 84) of those with a negative ctDNA test. In multivariate analyses, ctDNA status was associated with recurrence after adjusting for clinicopathological risk factors including stage, lymphovascular invasion, and microradical resection status.
Henriksen et al assessed the added benefit of serial ctDNA analysis; with samples taken at diagnosis, following surgery, during adjuvant therapy, and at follow up (Henriksen, 2022).
Loupakis et al evaluated the association of ctDNA with Signatera on survival outcomes in 112 individuals who had undergone resection for metastatic (stage IV) CRC (Loupakis, 2021). The study included an analysis of the sensitivity of Signatera testing to digital droplet PCR testing but not to standard methods to identify recurrence, such as CEA and imaging.
Fakih et al directly compared Signatera testing to other surveillance strategies in individuals with resected CRC in a retrospective observational study (Fakih, 2022). This study was unique in that it used NCCN recommended guidelines for surveillance and ctDNA testing was performed at the same interval as standard surveillance with CEA and imaging. Test characteristics for Signatera were not significantly different from standard imaging techniques. Estimates were imprecise, with wide confidence intervals.
Tumor-Informed Circulating Tumor DNA Testing with Signatera in Individuals with Breast Cancer
Two noncomparative studies reported the association of Signatera testing with survival outcomes in breast cancer. There are no randomized controlled trials (RCTs), and no studies in which Signatera testing was used to guide treatment decisions.
Coombes et al evaluated Signatera for disease surveillance in 49 individuals who had received surgery and adjuvant therapy for stage I to III breast cancer of various subtypes (Coombes, 2019). Signatera detected ctDNA in 16 of 18 individuals who subsequently relapsed, and the presence of ctDNA test was associated with poorer prognosis.
Magbanua et al evaluated ctDNA clearance as a predictor of response to neoadjuvant chemotherapy (NAC) in 84 individuals with nonmetastatic breast cancer who were enrolled in the I-SPY2 trial (Magbanua, 2021). In the population as a whole, ctDNA positivity decreased during the course of NAC, from 73% before treatment (T0), to 35% at 3 weeks (T1), to 14% at the inter-regimen time point (T2), and down to 9% after NAC (T3). Hazard ratios for recurrence at each of these timepoints indicate that positive predictive value increased over time.
Major limitations of both studies include a lack of comparison to standard methods of monitoring, and heterogeneity in the study populations.
Tumor-Informed Circulating Tumor DNA Testing with Signatera in Individuals with Bladder Cancer
Two nonrandomized studies have reported an association between Signatera testing and prognosis in bladder cancer.
Christensen et al assessed the association of ctDNA with prognosis in 68 individuals with localized advanced bladder cancer (Christensen, 2019).
Powles et al reported the association of a positive Signatera test to treatment response in 581 individuals who had undergone surgery for urothelial cancer and were enrolled in a RCT of atezolizumab versus observation (Powles, 2021). Study participants who were positive for ctDNA had improved disease-free survival and overall survival in the atezolizumab arm versus the observation arm (disease-free survival hazard ratio = 0.58 [95% CI, 0.43–0.79]; p=.0024 and overall survival hazard ratio = 0.59 [95% CI, 0.41–0.86]). No difference in disease-free survival or overall survival between treatment arms was noted for patients who were negative for ctDNA.
The major limitation of these studies was lack of comparison to other tests used for the same purpose.
Tumor-Informed Circulating Tumor DNA Testing with Signatera in Individuals with Non-Small Cell Lung Cancer
The evidence for the use of Signatera to detect relapse in NSCLC following surgery is limited to a subgroup analysis of 24 individuals enrolled in TRACERx, a longitudinal cohort study of tumor sampling and genetic analysis in individuals with NSCLC (Abbosh, 2017)). Of 14 individuals with confirmed relapse, 13 (93%) had a positive ctDNA test (defined as at least 2 single-nucleotide variants detected). Of 10 individuals with no relapse after a median follow up of 775 days, (range 688 to 945 days), 1 had a positive ctDNA test (10%).
Major limitations include no comparison to standard surveillance methods and imprecise estimates due to the small sample size. Additionally, the commercially available Signatera has been updated since this publication.
Tumor-Informed Circulating Tumor DNA Testing with Signatera in Individuals with Esophageal Cancer
One noncomparative retrospective study reported the association of Signatera testing measured before and after surgery with relapse and recurrence in 17 individuals with esophageal adenocarcinoma (Ococks, 2021). Patients who were ctDNA-positive before surgery had significantly poorer disease-free survival (DFS) (p<.042), with a median DFS of 32.0 months vs. 63.0 months in ctDNA-negative preoperative patients. This study was limited by the very small number sample size, and its retrospective design.
Tumor-Informed Circulating Tumor DNA Testing with Signatera in Individuals with Solid Tumors Receiving Immunotherapy
Bratman et al evaluated Signatera to predict treatment response in 106 individuals receiving pembrolizumab for solid tumors, including squamous cell cancer of head and neck, triple negative breast cancer, high-grade serous ovarian cancer, malignant melanoma, and mixed solid tumors (Bratman, 2020).
Lower-than-median ctDNA levels at baseline were associated with improved overall survival (adjusted hazard ratio [HR] 0.49, 95% CI 0.29 to 0.83) and progression free survival (adjusted HR 0.54, 95% CI 0.34 to 0.85). Among participants with at least 2 ctDNA measurements, any rise in ctDNA levels during surveillance above baseline was associated with rapid disease progression and poor survival (median overall survival 13.7 months), whereas among 12 patients whose ctDNA cleared during treatment, overall survival was 100% at a median follow up of 25.4 months (range 10.8 to 29.5 months) following the first clearance.
This single-center study is limited by its small sample size and variability in results across different tumor types. The study did not include a comparison of monitoring with ctDNA to standard methods of monitoring response such as repeat imaging.
Practice Guidelines and Position Statements
National Comprehensive Cancer Network
National Comprehensive Cancer Network guidelines do not specifically address tumor-informed ctDNA testing for any of the cancer types included in this review. The guidelines on colon cancer state: "The panel believes that there are insufficient data to recommend the use of multigene assays, Immunoscore or post-surgical ctDNA to estimate risk of recurrence or determine adjuvant therapy" (NCCN, 2022).
Ongoing and Unpublished Clinical Trials
Summary of Key Trials
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2023. No new literature was identified that would prompt a change in the coverage statement.
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through April 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Chidharla et al published a systematic review of 23 studies (N = 3568) investigating the use of ctDNA as a biomarker for minimal residual disease in patients with CRC after curative-intent surgery (Chidharla, 2023). The results of this analysis demonstrated that ctDNA positivity after surgery was associated with a significantly higher risk of recurrence, with a pooled hazard ratio (HR) of 7.27 for all stages of CRC. Furthermore, post-adjuvant chemotherapy ctDNA positivity was associated with an even higher risk of recurrence (pooled HR, 10.59).
Kotani et al analyzed presurgical and postsurgical ctDNA levels in a large (N = 1039) prospective study that included patients with stage II to IV resectable CRC (Kotani, 2023). After a median follow-up of 16.74 months, postsurgical ctDNA positivity at 4 weeks after surgery was associated with a significantly higher risk of recurrence (HR, 10.0; 95% CI, 7.7 to 14; p<.0001), and identified patients with high-risk stage II or III CRC who derived a benefit from adjuvant chemotherapy (HR, 6.59; 95% CI, 3.53 to 12.3; p<.0001). For both outcomes, trends were observed across all pathological stages evaluated.
Powles et al reported the association of a positive Signatera test to treatment response in 581 individuals who had undergone surgery for urothelial cancer and were enrolled in a RCT of atezolizumab versus observation (Powles, 2021). Study participants who were positive for ctDNA had improved disease-free survival (DFS) and overall survival in the atezolizumab arm versus the observation arm (DFSHR, 0.58 [95% CI, 0.43 to 0.79]; p=.0024 and overall survival HR, 0.59 [95% CI, 0.41 to 0.86]). No difference in DFS or overall survival between treatment arms was noted for patients who were negative for ctDNA. At 2-year follow up, ctDNA status remained prognostic and no relapses were observed in the ctDNA-negative patients at baseline and after neoadjuvant therapy (Svabados, 2022).
The guideline on colon cancer states: "There is currently insufficient evidence to recommend use of circulating tumor DNA (ctDNA) assays outside of a clinical trial. De-escalation of care is not recommended based on ctDNA results. Participation in clinical trials is encouraged" (NCCN, 2023).
The guideline on breast cancer states that for recurrent/stage IV disease: "Tissue or plasma-based circulating tumor DNA (ctDNA) assays may be used. Tissue-based assays have greater sensitivity, but ctDNA may reflect tumor heterogeneity more accurately." Additionally, "For HR-positive/HER2-negative breast cancer, assess for PIK3CA mutations with tumor or liquid biopsy to identify candidates for alpelisib plus fulvestrant. PIK3CA mutation testing can be done on tumor tissue or ctDNA in peripheral blood (liquid biopsy). If liquid biopsy is negative, tumor tissue testing is recommended." The relevant discussion for these recommendations is pending an update (NCCN, 2023).
Additional 2024 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Christensen et al assessed the association of ctDNA with prognosis in 68 individuals with localized advanced bladder cancer who were receiving neoadjuvant chemotherapy before cystectomy (median follow-up of 21 months) (Christensen, 2019). Data from a 68-month follow-up of this cohort were reported by Lindskrog et al (Lindskrog, 2023). Additionally, Lingskrog et al reported on the association of ctDNA with prognosis in a separate cohort of 102 patients who did not receive neoadjuvant chemotherapy and had ctDNA testing before and after cystectomy (median follow-up of 72 months). Results demonstrated that ctDNA was prognostic regardless of whether or not patients received neoadjuvant chemotherapy before cystectomy.
The guideline on non-small cell lung cancer (NSCLC) states the following in their section on molecular and biomarker analysis (NCCN, 2024):
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2025. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Chidharla et al published a systematic review of 23 studies (N = 3568) investigating the use of ctDNA as a biomarker for minimal residual disease in patients with CRC after curative-intent surgery; of which 3 of the included studies used the Signatera ctDNA assay(Chidharla, 2023). The results of this analysis demonstrated that ctDNA positivity after surgery was associated with a significantly higher risk of recurrence, with a pooled hazard ratio (HR) of 7.27 for all stages of CRC. Furthermore, post-adjuvant chemotherapy ctDNA positivity was associated with an even higher risk of recurrence (pooled HR, 10.59). Two additional systematic reviews by international author groups had similar findings (Hoang, 2025; Zhou, 2025).
Kotani et al analyzed presurgical and postsurgical ctDNA levels in a large (N = 1039) prospective study that included patients with stage II to IV resectable CRC (Kotani, 2023). After a median follow-up of 16.74 months, postsurgical ctDNA positivity at 4 weeks after surgery was associated with a significantly higher risk of recurrence (HR, 10.0; 95% CI, 7.7 to 14; p less than .0001), and identified patients with high-risk stage II or III CRC who derived a benefit from adjuvant chemotherapy (HR, 6.59; 95% CI, 3.53 to 12.3; p less than .0001). For both outcomes, trends were observed across all pathological stages evaluated. An updated analysis was published with data through June 2024 (Nakamura, 2024). This analysis included patients with stage II to III colon cancer or stage IV CRC and had a median follow-up of 23 months. Similar to the previous analysis, ctDNA positivity at 4 weeks after surgery was associated with a significantly higher risk of recurrence (disease free survival [DFS] HR, 11.99; p less than .0001), and identified patients with high-risk stage II or III CRC who derived a benefit from adjuvant chemotherapy (HR, 0.23; p less than .0001).
Molinari et al analyzed post-neoadjuvant therapy and postsurgical ctDNA levels in a retrospective study of 33 patients with stage II to III rectal cancer (Molinari, 2024). After a median follow-up of 60 months, post-neoadjuvant therapy ctDNA positivity was associated with a significantly higher risk of recurrence (HR, 7.82), as was ctDNA positivity at 2 to 12 weeks post-surgery (HR, 19.65). Estimates were imprecise, with wide confidence intervals.
Slater et al prospectively analyzed ctDNA levels in patients with resectable stage I to III CRC before and after surgery, post-adjuvant chemotherapy, every 3 months for year 1 and every 6 months in years 2 and 3 (Slater, 2024). A total of 1203 patients were enrolled, of whom plasma samples were available for 214 patients; the median follow-up was 30.3 months. The 2-year RFS was 91.1% in patients with ctDNA not detected postoperatively and 50.4% in those with ctDNA detected (HR, 6.5; p less than .0001). The negative predictive value, sensitivity, and specificity were 88.5%, 41.7%, and 90.8%, respectively. The TRACC Part C study is currently investigating the potential de‐escalation of adjuvant chemotherapy in patients with undetectable postoperative ctDNA.
Zhang et al published a systematic review investigating the prognostic value of ctDNA in early-stage triple-negative breast cancer (TNBC) (Zhang, 2025). Twenty publications were included in the analysis, though only 4 studies specifically investigated the Signatera assay. Results demonstrated that post-neoadjuvant (before or after surgery) ctDNA positivity was associated with increased risk of disease recurrence (HR, 4.12, 95% CI, 2.81 to 6.04; p less than .00001) as well as worse overall survival (HR, 3.26; 95% CI, 1.88 to 5.63; p less than .0001).
Ben-David et al retrospectively assessed whether ctDNA status before cystectomy and during surveillance is predictive of recurrence in patients with bladder cancer (Ben-David, 2024). A total of 112 patients were included with a median follow-up of 8 months. Detectable ctDNA before surgery was found in 59 patients, and was associated with worse prognosis (Kaplan-Meier analysis, p less than .0001). Additionally, patients with undetectable ctDNA before surgery had comparable RFS regardless of whether they received neoadjuvant therapy before surgery. Patients with detectable ctDNA that remained persistently detectable after surgery had the worst prognosis, with RFS rates of 33% at 6 months and 16% at 12 months.
Sfakianos et al retrospectively assessed whether ctDNA status before cystectomy and during surveillance is predictive of recurrence in patients with bladder cancer (Sfakianos, 2025). A total of 167 patients were included with a median follow-up of 10 months. Detectable ctDNA before surgery was found in 26 of 65 patients (40%) with available plasma samples. Among those receiving upfront surgery, patients with detectable ctDNA had shorter DFS (HR, 10.61; 95% CI, 1.01 to 1434; p=.03). Likewise, detectable ctDNA during the window of 1 to 12 weeks after surgery was associated with shorter DFS (HR, 6.93; p less than .001) as well as during surveillance (more than 12 weeks after surgery if no adjuvant therapy was administered or 2 or more weeks after the completion of adjuvant therapy; HR, 23.02; p less than .001).
Mukherjee et al examined the association between ctDNA and prognosis in a Phase II study of 22 patients with localized esophageal or gastroesophageal junction adenocarcinoma treated with induction chemotherapy and preoperative chemoradiation (Mukherjee, 2025). With a median follow-up of 15.8 months, ctDNA data were available for 10 patients, and 7 were eligible for survival analysis. Among them, patients who cleared ctDNA post-surgery (n=5) had significantly better overall survival (25.9 vs. 10.1 months; p=.012) and progression-free survival (PFS; 25.9 vs. 7.6 months; p=.0082) than those with persistent ctDNA (n=2).
Valenza et al published a systematic review evaluating ctDNA as a predictive biomarker of pathologic complete response in patients with solid tumors who are treated with neoadjuvant immune checkpoint inhibitor (ICI) therapy (Valenza, 2025). Thirteen trials (N = 380) were included, of which only 2 trials specifically evaluated Signatera. Among the 380 patients, 74 received ICI monotherapy and 306 received an ICI in combination with chemotherapy or targeted therapy. Overall, 144 of 380 (38%) patients achieved pathologic complete response after neoadjuvant treatment, and 262 of 380 (73%) had ctDNA clearance after neoadjuvant ICI therapy. The estimated sensitivity of ctDNA clearance for pathologic complete response was 0.98 (95% CI, 0.86 to 1.00), and the estimated specificity of ctDNA persistence for lack of pathologic complete response was 0.53 (95% CI, 0.37 to 0.69).
The guideline on bladder cancer states the following regarding muscle-invasive bladder cancer/resectable: "The Panel recognizes that some ultrasensitive circulating tumor DNA (ctDNA) assays may have prognostic value after cystectomy. However, to date, the Panel has concluded that there are insufficient data for ctDNA results to determine the course of surveillance or therapy after complete surgical resection." For advanced disease, the guideline notes the following: "Studies have demonstrated that ultrasensitive ctDNA assays may track the response to therapy and progression. However, there are insufficient data that changes in therapy based on ctDNA significantly improve outcomes. Additionally, there are no data to date that ctDNA clearance should be used to make decisions to alter or discontinue therapy" (NCCN, 2025).
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| References: |
Abbosh C, Birkbak NJ, Wilson GA, et al.(2017) Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. Apr 26 2017; 545(7655): 446-451. PMID 28445469 Ben-David R, Tillu N, Cumarasamy S, et al.(2024) Longitudinal Tumor-informed Circulating Tumor DNA Status Predicts Disease Upstaging and Poor Prognosis for Patients Undergoing Radical Cystectomy. Eur Urol Oncol. Oct 2024; 7(5): 1105-1112. PMID 38521660 Bratman SV, Yang SYC, Iafolla MAJ, et al.(2020) Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer. Sep 2020; 1(9): 873-881. PMID 35121950 Chidharla A, Rapoport E, Agarwal K, et al.(2023) Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis. Int J Mol Sci. Jun 16 2023; 24(12). PMID 37373376 Christensen E, Birkenkamp-Demtroder K, Sethi H, et al.(2019) Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma. J Clin Oncol. Jun 20 2019; 37(18): 1547-1557. PMID 31059311 Coombes RC, Page K, Salari R, et al.(2019) Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res. Jul 15 2019; 25(14): 4255-4263. PMID 30992300 Fakih M, Sandhu J, Wang C, et al.(2022) Evaluation of Comparative Surveillance Strategies of Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen Levels in Patients With Resected Colorectal Cancer. JAMA Netw Open. Mar 01 2022; 5(3): e221093. PMID 35258578 Henriksen TV, Tarazona N, Frydendahl A, et al.(2022) Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior of Recurrences. Clin Cancer Res. Feb 01 2022; 28(3): 507-517. PMID 34625408 Hoang T, Choi MK, Oh JH, et al.(2025) Utility of circulating tumor DNA to detect minimal residual disease in colorectal cancer: A systematic review and network meta-analysis. Int J Cancer. Aug 15 2025; 157(4): 722-740. PMID 40293388 Kotani D, Oki E, Nakamura Y, et al.(2023) Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat Med. Jan 2023; 29(1): 127-134. PMID 36646802 Loupakis F, Sharma S, Derouazi M, et al.(2021) Detection of Molecular Residual Disease Using Personalized Circulating Tumor DNA Assay in Patients With Colorectal Cancer Undergoing Resection of Metastases. JCO Precis Oncol. Jul 2021; 5. PMID 34327297 Magbanua MJM, Swigart LB, Wu HT, et al.(2021) Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival. Ann Oncol. Feb 2021; 32(2): 229-239. PMID 33232761 Molinari C, Marisi G, Laliotis G, et al.(2024) Assessment of circulating tumor DNA in patients with locally advanced rectal cancer treated with neoadjuvant therapy. Sci Rep. Nov 28 2024; 14(1): 29536. PMID 39604448 Moreno C, Kim DH, Bartel TB, et al.(2018) ACR Appropriateness Criteria Colorectal Cancer Screening. J Am Coll Radiol. May 2018; 15(5S): S56-S68. PMID 29724427 Mukherjee S, Fujiwara Y, Fountzilas C, et al.(2025) Trifluridine/Tipiracil and Oxaliplatin as Induction Chemotherapy in Resectable Esophageal and Gastroesophageal Junction Adenocarcinoma: A Phase II Study. Cancer Med. Apr 2025; 14(7): e70835. PMID 40200573 Nakamura Y, Watanabe J, Akazawa N, et al.(2024) ctDNA-based molecular residual disease and survival in resectable colorectal cancer. Nat Med. Nov 2024; 30(11): 3272-3283. PMID 39284954 Natera.(2021) FDA Grants Two New Breakthrough Device Designations for Nateras Signatera MRD Test. March 24, 2021. https://www.natera.com/company/news/fda-grants-two-new-breakthrough-device-designations-for-nateras-signatera-mrd-test/. Accessed April 5, 2022 National Comprehensive Cancer Network (NCCN).(2022) Guidelines on Colon Cancer. Version 1.2022. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed April 5, 2022. National Comprehensive Cancer Network (NCCN).(2025) Guidelines on Bladder Cancer Version 1.2025. www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 14, 2025 Ococks E, Sharma S, Ng AWT, et al.(2021) Serial Circulating Tumor DNA Detection Using a Personalized, Tumor-Informed Assay in Esophageal Adenocarcinoma Patients Following Resection. Gastroenterology. Nov 2021; 161(5): 1705-1708.e2. PMID 34284036 Powles T, Assaf ZJ, Davarpanah N, et al.(2021) ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature. Jul 2021; 595(7867): 432-437. PMID 34135506 Reinert T, Henriksen TV, Christensen E, et al.(2019) Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. Aug 01 2019; 5(8): 1124-1131. PMID 31070691 Sfakianos JP, Basu A, Laliotis G, et al.(2025) Association of Tumor-informed Circulating Tumor DNA Detectability Before and After Radical Cystectomy with Disease-free Survival in Patients with Bladder Cancer. Eur Urol Oncol. Apr 2025; 8(2): 306-314. PMID 39013741 Slater S, Bryant A, Aresu M, et al.(2024) Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study. Clin Cancer Res. Aug 15 2024; 30(16): 3459-3469. PMID 38864835 Terasawa T, Tadano T, Abe K, et al.(2025) Single-round performance of colorectal cancer screening programs: a network meta-analysis of randomized clinical trials. BMC Med. Feb 21 2025; 23(1): 110. PMID 39985068 Thomas DE, Horvat N, Fowler KJ, et al.(2025) ACR Appropriateness Criteria Colorectal Cancer Screening: 2024 Update. J Am Coll Radiol. May 2025; 22(5S): S190-S201. PMID 40409877 Valenza C, Saldanha EF, Gong Y, et al.(2025) Circulating tumor DNA clearance as a predictive biomarker of pathologic complete response in patients with solid tumors treated with neoadjuvant immune checkpoint inhibitors: a systematic review and meta-analysis. Ann Oncol. Jul 2025; 36(7): 726-736. PMID 40187491 Zhang D, Jahanfar S, Rabinowitz JB, et al.(2025) Role of circulating tumor DNA in early-stage triple-negative breast cancer: a systematic review and meta-analysis. Breast Cancer Res. Mar 12 2025; 27(1): 38. PMID 40075528 Zhou Q, Chen X, Zeng B, et al.(2025) Circulating tumor DNA as a biomarker of prognosis prediction in colorectal cancer: a systematic review and meta-analysis. J Natl Cancer Cent. Apr 2025; 5(2): 167-178. PMID 40265088 |
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| Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants. | |
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