MolDx issues a bonanza - a triplet - of new proposed LCDs.
Two provide defined coverage. One general NGS LCD for heme malignancies, one for whole genome mapping in heme neoplasms.
The renal biomarker LCD finds that there is much activity in the field but that the power or utility of the stratification biomarkers do NOT yet meet MolDx standards for coverage. Expect brisk comments or updated literature. (The request is dated 2022. Some citations go to 2025. Guidelines are cited.)
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#1 =======================================
DL40425 Link
MolDX: Next-Generation Sequencing for Hematologic Malignancies and Suspected Hematologic Malignancies [107 refs]
Request: Montgomery. 11/18/2025.
Request: Russler-Germain 5/13/2026
#2 ======================================
DL40429 Link
MolDX: Transcriptional Biomarkers for Therapeutic Decision-Making in Renal Carcinoma [38 refs]
Request: Davicioni 5/11/2022
#3 =======================================
DL40407 Link
MolDX: Genome-Wide Molecular Methodologies for the Detection of Copy Number Alterations and Structural Variants in Hematologic Neoplasms [37 refs]
Request: Polizio 12/22/2023
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DL40407 — Genome-Wide Molecular Methodologies for CNAs and Structural Variants in Hematologic Neoplasms
This draft provides limited positive coverage for genome-wide methods that detect copy-number alterations (CNAs) and structural variants (SVs) in hematologic neoplasms. Coverage applies when the result is needed for guideline-based diagnosis or clinical management at initial diagnosis, progression, or relapse, and generally only when equivalent CNA/SV information has not already been obtained through another genome-wide test or multiple conventional methods such as karyotyping, FISH, CMA, and NGS. There are sensible exceptions—for example, an initial rapid PML::RARA or BCR::ABL test, or a prior conventional workup that was negative. The test must pass MolDX TA for analytical validity, clinical validity, clinical utility, and performance comparable or superior to established methods. The important conceptual move is that MolDX explicitly recognizes newer single-workflow genome-wide approaches such as WGS, optical genome mapping (OGM), and genomic proximity mapping (GPM) as potentially replacing combinations of traditional cytogenetic methods rather than merely being added on top of them. MRD/therapy-response testing is excluded.
DL40425 — NGS for Hematologic Malignancies and Suspected Hematologic Malignancies
This is a broader positive-coverage LCD for multigene NGS testing in confirmed or strongly suspected hematologic malignancies. Testing can be covered at initial diagnosis, progression/transformation, or clinical relapse when it is needed either to establish WHO/ICC classification or to make an immediate management decision—such as targeted therapy, treatment intensity, or stem-cell transplant eligibility. The policy applies to both hotspot panels and comprehensive genomic profiling, but requires that the assay contain the genomic content necessary for its intended use, that substantially duplicative testing has not already been performed, and that the assay be used in its validated population and successfully complete MolDX TA for AV/CV/CU. Solid tumors, ctDNA, germline testing, MRD, and response monitoring are outside the LCD. MolDX's evidence conclusion is unusually affirmative: it states that multigene NGS has established clinical utility across myeloid, lymphoid, and histiocytic neoplasms and is reasonable and necessary when the stated criteria are met.
DL40429 — Transcriptional Biomarkers for Therapeutic Decision-Making in Renal Carcinoma
This draft reaches the opposite immediate result: transcriptional and proteomic biomarker classifiers for RCC are presently noncovered. MolDX nevertheless lays out a prospective pathway to coverage: a test would need to address a genuine treatment choice, materially improve recurrence/metastasis risk prediction or predict response to a specific accepted therapy beyond existing clinical-pathologic information, be independently validated, demonstrate CV/CU in peer-reviewed literature, pass MolDX TA, and perform at least as well as any covered comparator. The evidence review finds current studies inadequate—often retrospective or outdated, dominated by clear-cell RCC, limited by incomplete clinical-pathologic data and tumor heterogeneity, and insufficient to show that the classifiers add clinically meaningful information beyond stage, grade, histology, and established nomograms or actually improve management and outcomes. The rapidly changing RCC treatment landscape, particularly immunotherapy, further weakens older evidence.
Brief comparison
The three drafts share a very recognizable MolDX framework: a clearly defined intended-use population, avoidance of redundant testing, demonstrated incremental clinical value, validation in the intended population, and successful MolDX TA establishing AV/CV/CU. The two hematologic LCDs, however, conclude that the evidence has crossed the reasonable-and-necessary threshold and therefore establish conditional positive coverage. DL40425 covers the broader NGS molecular-profiling function; DL40407 is more specifically a modernization of cytogenetics, allowing genome-wide technologies to substitute for a bundle of karyotype/FISH/CMA-type testing. By contrast, the RCC LCD effectively says the concept is plausible but the evidence has not yet crossed the line: prognostic association alone is not enough; MolDX wants demonstrated incremental information that changes a therapeutic decision and ultimately improves patient management or outcomes.
