On August 5, 2025, we highlighted Decibio's latest update on MRD coverage (here). I mentioned late-breaking coverage by MolDx of the SAGA "Pathlight" MRD test. Here's some more.
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- SAGA Diagnostics is a spin-out from Lund University in Sweden. See an article at Lund University, June 2025, here.
- See a July 30 press release from SAGA about its MolDx coverage here.
- The coverage is for all breast cancer subtypes and recurring monitoring (surveillance) for "up to six years."
- See coverage at Genomeweb.
- See a Linked In article by Achyut Saroj on August 8, here.
- The Linked In article includes an embedded Elliott article.
- See the full article by Elliott et al. in Clinical Cancer Research here.
- While the webpage is dated April 14, internal text says editorial approval was February 7 and online publication February 9.
- February would have been the earliest date for a MolDx coverage submission, which requires MRD publication(s).
- The executive chairman is Roopom Banerjee. He holds a Master's from the Harvard Kennedy School and has been on the board since 2021.
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MolDx DEX Registry lists the lab as Morrisville, NC. It lists Pathlight (their only test entry on MolDx as of now) as $3652 and "covered." I suspect that is for an initial test plus set-up genomics, but I can't be sure.
- dPCR vs NGS and CMS Policy
- Since the recurring test is digital PCR rather than NGS, I think it falls outside of restrictions of CMS NGS NCD 90.2.
- The test is described as genome-informed.
- Natera recently got MolDx coverage for a genome-informed Signatera test. So this is a trend.
As of August 9, the MolDx DEX descriptor is:
- The test is a dPCR-based, tumor-informed liquid biopsy assay that is designed to detect circulating tumor DNA (ctDNA) in the blood for the purpose of detecting molecular residual disease (MRD), monitoring treatment response, or detecting cancer recurrence.
- The test entails whole genome sequencing of a patient's tumor specimen, which is then used to generate a customized multiplex dPCR assay (fingerprint) for up to 16 structural variants (SVs). This unique patient fingerprint is then used to detect the presence or absence of ctDNA.
- The test is intended to be used for patients diagnosed with solid tumor malignancies, initially focused in breast cancer (all subtypes), for multiple purposes, including neoadjuvant treatment monitoring, post-surgical MRD detection, adjuvant treatment monitoring, and post-treatment surveillance for recurrence.
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On July 19, I published a popular blog on a new proposed MolDx LCD about DCIS breast cancer test coverage (non-coverage), suggesting it might be used as a "teaching case study" for how MolDx thinks.
You can't say the same for the Pathlight coverage, since MolDx releases no info on its thought process other than the origial, four-year-old LCD and the status of "covered" for Pathlight. However, you can put together coverage statements in the press release from the company, with a detailed view of the Elliott et al. publication. This lets you infer what MolDx found acceptable.
- Analytical performance accurately classified 217 tumor and 217 control cases.
- Breast-cancer retrospective performance had 100 cases, across several BC types, and found ctDNA ahead of known distal recurrence 19/19 recurrences. (This includes postsurgical positives).
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AI CORNER
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Google Notebook LM writes a single 400 word article based on the links provided.
Direct AI output. Do not quote without checking details against original sources.
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SAGA Diagnostics has launched Pathlight MRD, an ultrasensitive liquid biopsy test designed to transform cancer care by enabling early detection of cancer recurrence. Originating from research at Lund University in Sweden, this groundbreaking test is now commercially available in the U.S. and has received Medicare coverage.
Unlike many other circulating tumor DNA (ctDNA) assays that primarily target single-nucleotide variants (SNVs), Pathlight focuses on structural variants (SVs). SVs are stable, highly tumor-specific genomic changes that reflect underlying genomic instability and provide a clearer, earlier indication of disease recurrence. This approach allows for precise molecular residual disease (MRD) tracking, especially in ER-positive (ER+) low-shedding tumors, where other assays often fall short. The assay uses whole genome sequencing (WGS) of tumor tissue to create a customized "fingerprint" of up to 16 structural variants for each patient, which is then used in digital PCR (dPCR) to detect ctDNA in blood samples.
Clinical validation, primarily through the cTdna evaluation in eaRly breAst canCER (TRACER) study published in Clinical Cancer Research, demonstrated remarkable performance. Pathlight achieved 100% sensitivity and 100% specificity in detecting early breast cancer recurrence. It provides a median lead time of 417 days (or 13.7 months) before recurrence is detected by standard clinical methods, including imaging. The test also boasts a high baseline detection rate of 96% across all early-stage breast cancer subtypes, notably 94% in ER+ disease. Furthermore, clearance of ctDNA during neoadjuvant therapy was associated with improved outcomes, enhancing residual cancer burden prognostication.
The Pathlight MRD test is now covered for Medicare beneficiaries for recurrence monitoring in the surveillance setting for up to six years in patients with stage II-III breast cancer, including all subtypes (HR+/HER2-, HER2+, and TNBC). This coverage decision, issued by Palmetto GBA’s MolDX Program, reflects a rigorous review of Pathlight’s analytical and clinical validity. The currently listed cost on the MolDX DEX Registry is $3652. This development aims to empower patients and clinicians with ultra-sensitive tools for more personalized and informed treatment decisions, moving towards smarter surveillance and long-term monitoring programs.
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Is the company a "spin-out?"
Yes, SAGA Diagnostics is a spinout company from Lund University in Sweden.
Specifically:
- It was founded in 2016 from research conducted at Lund University.
- SAGA Diagnostics is described as a "portfolio company of LU Ventures" and "a brilliant example of how research from Lund University can reach the world and improve healthcare," having started as a spinout with support from LU Ventures and LU Innovation.
- While its origins are in Sweden, SAGA's headquarters and CLIA-certified laboratory are located in Research Triangle Park, North Carolina, U.S..
The "Ultrasensitive Detection and Monitoring of Circulating Tumor DNA Using Structural Variants in Early-Stage Breast Cancer" study, published in Clinical Cancer Research by Elliott et al., describes the development and validation of a novel circulating tumor DNA (ctDNA) assay, Pathlight, that utilizes structural variants (SVs) for molecular residual disease (MRD) detection in early-stage breast cancer (EBC).
The study addresses the need for improved biomarkers in cancer diagnosis, treatment selection, and monitoring, moving beyond invasive tissue biopsies to liquid biopsies. Unlike many existing ctDNA assays that primarily target single-nucleotide variants (SNVs), this study highlights the potential of SVs, which are stable, highly tumor-specific genomic changes reflecting underlying genomic instability. The Pathlight assay workflow involves whole genome sequencing (WGS) of tumor tissue to generate a personalized "fingerprint" of up to 16 SVs per patient, followed by multiplex digital PCR (dPCR) analysis of plasma-derived cell-free DNA (cfDNA) to detect ctDNA.
Analytical validation demonstrated the assay's ultrasensitivity, achieving a 95% limit of detection (LoD95) of 0.00052% (5 parts per million) with standard cfDNA inputs, and even lower (0.00011% or 1.1 ppm) with higher inputs. It also showed 100% analytical specificity across 217 cancer-free donor samples and 217 genomic DNA samples, testing 5,268 SVs.
In a retrospective clinical evaluation of 100 EBC patients (28 TNBC, 33 ER+, 39 HER2+) undergoing neoadjuvant systemic therapy, the assay successfully generated fingerprints for 95% of participants. Key findings include:
- High baseline ctDNA detection: 96% of evaluable baseline samples showed ctDNA, with similar rates across all receptor subtypes, including 94% in ER+ disease where other assays often struggle.
- Prognostic value of on-treatment dynamics: Clearance of ctDNA prior to cycle 2 of neoadjuvant therapy was associated with improved outcomes, and persistent ctDNA detection enhanced prognostication when combined with residual cancer burden (RCB) status.
- Early detection of recurrence: ctDNA was detected prior to distant recurrence in 100% of cases (19/19) with evaluable samples, providing a median lead time of 417 days (13.7 months) before clinical detection by standard methods. Any ctDNA detection after surgery or during follow-up was strongly associated with recurrence.
The study concludes that this novel SV-based approach offers sensitive and specific ctDNA detection for treatment monitoring and prognostication in EBC. The uniqueness of SV breakpoints minimizes false positives and the selection of amplified SVs enhances sensitivity. While acknowledging limitations such as its retrospective nature, the study supports prospective trials to evaluate ctDNA-guided treatment strategies.
