Medical Disclaimer
genoCDS is a clinical reference tool for qualified healthcare professionals only. Content is derived from published guidelines and regulatory sources and may contain errors or outdated information. It is not a substitute for professional medical judgment, institutional protocols, or individual patient assessment. Always verify recommendations against current primary sources before making clinical decisions. Full disclaimer →
Stage Stage III
Involvement of lymph node regions on both sides of the diaphragm (III), with or without spleen (IIIS) or extralymphatic site (IIIE). Advanced disease.
4 test recommendations across 1 clinical indication
Stage III advanced DLBCL. Full molecular workup mandatory — DHL ~10% of DLBCL, requires intensified induction.
Required — 2 tests
BCL2/BCL6/MYC FISH Panel
Double/Triple-Hit FISH
FISH panel detecting rearrangements of MYC (8q24), BCL2 (18q21), and BCL6 (3q27). MYC + BCL2 rearrangements define double-hit lymphoma (DHL); MYC + BCL2 + BCL6 define triple-hit lymphoma (THL). Both are reclassified as High-Grade B-Cell Lymphoma (HGBL) per WHO 2022 and require intensified induction (DA-EPOCH-R). Required for all newly diagnosed DLBCL.
Ordering Note
Required for all Stage III DLBCL. Results must be available before R-CHOP to avoid suboptimal therapy in DHL patients (~10% of DLBCL).
Specimen
Evidence
Cell-of-Origin Gene Expression Profiling
COO / GEP
Gene expression profiling to classify DLBCL cell-of-origin (COO) as GCB or ABC/non-GCB. GCB DLBCL has superior outcomes with R-CHOP; ABC/non-GCB benefits from pola-R-CHP (POLARIX) and novel regimens. Lymph2Cx (NanoString) is the validated clinical platform; Hans IHC algorithm is less accurate.
Ordering Note
Required. Advanced-stage non-GCB DLBCL benefits most from pola-R-CHP (POLARIX subgroup analysis) and ABC-directed clinical trials.
Specimen
Evidence
Recommended — 1 test
Comprehensive Solid Tumor NGS Panel
Comprehensive NGS
Next-generation sequencing panel covering ≥300 cancer-relevant genes, including all major NSCLC drivers (EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, HER2, FGFR), plus tumor mutational burden (TMB) and microsatellite instability (MSI). Examples include FoundationOne CDx, Tempus xT, Caris MI Transcriptome, and equivalent institutional panels. Preferred over single-gene sequential testing for efficiency and cost-effectiveness.
Ordering Note
Recommended at Stage III for comprehensive mutation profiling (EZH2, MYD88/CD79B, CREBBP/EP300, TP53). Guides trial eligibility and R/R treatment selection.
Specimen
Evidence
Optional — 1 test
Tumor Mutational Burden (TMB)
TMB
Quantitative measurement of the number of somatic mutations per megabase (mut/Mb) of tumor genome. High TMB (TMB-H, ≥10 mut/Mb per FoundationOne CDx) is an FDA-approved pan-tumor biomarker for pembrolizumab (Keytruda). In NSCLC, TMB-H correlates with improved response to immune checkpoint inhibitors independently of PD-L1 expression. TMB is typically calculated from comprehensive NGS panels (FoundationOne CDx FDA-approved for TMB). Note: TMB thresholds and clinical utility vary by assay platform — direct comparison between assays requires caution.
Ordering Note
Optional. TMB is an emerging biomarker for anti-PD-1 therapy in R/R DLBCL. Not yet standard but relevant for clinical trial enrollment.
Specimen
Evidence
Payer Coverage
Payer Coverage Summary
Coverage status as of last policy review. Prior authorization requirements and coverage criteria may change. Verify directly with each payer before ordering.
| Test | Medicare (CMS) | UnitedHealth | Anthem BCBS | Humana | Cigna | Aetna |
|---|---|---|---|---|---|---|
| Double/Triple-Hit FISH | Covered | Covered | Covered | Covered | Covered | Covered |
| COO / GEP | Prior Auth | Prior Auth | Prior Auth | Investigational | Prior Auth | Prior Auth |
| Comprehensive NGS | Covered | Covered | Covered | Prior Auth | Covered | Covered |
| TMB | Covered | Prior Auth | Covered | Prior Auth | Covered | Covered |
Coverage data last verified via automated policy research. Always confirm current policies with each payer.
Recommendations on this page are derived from publicly available guidelines (NCCN, ASCO, ESMO, FDA, OncoKB) and are paraphrased for reference. They do not constitute medical advice. Evidence levels reflect the grading systems of each respective organization and should be interpreted in clinical context. This reference is updated periodically but may not reflect the most recent guideline revisions.