Latest Cancer TreatmentsDr. Mohammadreza Dabiri
Dr. Mohammadreza Dabiriفارسی
Physician lesson

Molecular tests and biomarkers needed before treatment, by cancer

A physician's checklist: order these tests before writing the first prescription

Updated: 28 October 20261 min read21 references

Key points

  • Starting chemotherapy before molecular results arrive permanently worsens the treatment pathway in many cancers; for example, immunotherapy before the EGFR status is known in lung cancer.
  • In advanced non-squamous lung cancer, metastatic prostate cancer, ovarian cancer and biliary tract cancer, NGS (a multigene panel) is recommended [1].
  • Hereditary (germline) genetic testing is recommended for all patients with ovarian cancer, pancreatic cancer, breast cancer (age 65 or under, and most other patients) and metastatic prostate cancer, not only those with a family history [3, 6, 7, 9].
  • In acute leukaemia, FLT3 and NPM1 results should arrive within a few days so that a targeted drug can be added to induction [10].
  • Order MMR/MSI in every colorectal and endometrial cancer: both for Lynch syndrome and for immunotherapy [5, 8, 19].

Solid tumours

Tests needed before treatment (summary)
CancerWhich testWhy
Advanced non-small cell lung cancer (non-squamous, and squamous in never-smokers or young patients)EGFR, ALK, ROS1, BRAF V600E, KRAS G12C, MET exon 14, RET, NTRK, HER2 (preferably NGS on DNA and RNA) + PD-L1 [1, 2]First-line targeted drug; with a targetable mutation, first-line immunotherapy has no place
Operable lung cancer (stage IB to IIIA)EGFR, ALK and PD-L1Adjuvant osimertinib for EGFR [14], adjuvant alectinib for ALK [15]
Breast cancerER, PR, HER2 (IHC and ISH; report HER2-low and HER2-ultralow) [4], Ki-67; germline BRCA1/2 genetics [3]; in metastatic HR-positive disease: PIK3CA, AKT1, PTEN and ESR1 [1]; in metastatic triple-negative disease: PD-L1Anti-HER2 treatment, T-DXd in HER2-low disease, adjuvant olaparib, second-line targeted drugs
Colorectal cancerAll: MMR/MSI [5, 19]; metastatic: KRAS and NRAS (exons 2 to 4), BRAF V600E, HER2 amplification [5]Lynch syndrome; immunotherapy in MSI-H; anti-EGFR only in RAS wild type; anti-BRAF
Stomach and gastro-oesophageal junction cancerHER2, MMR/MSI, PD-L1 (CPS), claudin 18.2 [16]Trastuzumab, immunotherapy and zolbetuximab
Pancreatic cancerGermline genetics for all (BRCA1/2, PALB2, ATM, Lynch) [6]; MSI; in KRAS wild type: NRG1 and NTRK fusions [1]Maintenance olaparib and platinum; immunotherapy in MSI-H; family counselling
Ovarian cancer (high-grade serous and other non-mucinous types)Germline BRCA1/2 for all; if negative, tumour BRCA and HRD [7]Maintenance PARP inhibitor
Endometrial cancerMMR (IHC), p53, POLE (molecular classification); HER2 in serous tumours [8]Choice of adjuvant treatment; immunotherapy in dMMR; Lynch
Metastatic and high-risk prostate cancerGermline genetics (especially BRCA2) [9]; tumour HRR and MSI [1]PARP inhibitor and family counselling
Stage 3 and 4 melanomaBRAF V600Dabrafenib-trametinib in the adjuvant and metastatic settings [17]
Advanced biliary tract cancerNGS: FGFR2, IDH1, HER2, BRAF, MSI, NTRK [1]Second-line targeted drugs
Advanced bladder (urothelial) cancerFGFR3 alterations [18]Erdafitinib after previous treatment

Wherever a guideline recommends NGS, testing genes one by one uses up the tissue and may miss uncommon mutations [1].

Preserve the tissue sample

Keep a small biopsy (especially a lung needle biopsy) first for diagnosis and molecular tests. If there is not enough tissue, a liquid biopsy (ctDNA) helps for EGFR and other lung cancer mutations, but a negative result does not exclude a mutation [1].

Haematological malignancies

Tests needed before treatment
DiseaseWhich testWhy
Acute myeloid leukaemiaKaryotype, FISH, NPM1, FLT3-ITD/TKD (urgent), CEBPA, IDH1/2, TP53, myeloid NGS panel [10]ELN 2022 risk group; midostaurin or quizartinib, ivosidenib; transplant decision
Acute promyelocytic leukaemia (APL)PML::RARA (urgent) and coagulation testsStart ATRA at the first suspicion, before the result
Chronic lymphocytic leukaemia17p deletion (FISH) and TP53 mutation before every line of treatment; IGHV status once [11]Choosing between a BTK inhibitor and venetoclax, and avoiding chemoimmunotherapy
Chronic myeloid leukaemiaQuantitative BCR::ABL1 (IS) and transcript type before treatment [12]Monitoring molecular response and the possibility of stopping the drug
MyelomaFISH on purified plasma cells: del(17p), t(4;14), t(14;16), ‎1q+‎ [13]R2-ISS staging and choice of treatment intensity
Myelodysplastic syndromeKaryotype and NGS panel [20]IPSS-M, transplant decision, targeted drug (for example in del(5q) or SF3B1 mutation)

Related tools

AML risk group (ELN 2022) · CLL-IPI · Myeloma R2-ISS · IPSS-R · Lesson on reading trials and biomarkers

Common questions

What should I do if the patient is unwell before the EGFR result arrives?

In non-squamous lung cancer without a result, chemotherapy alone (without immunotherapy), adding immunotherapy once the result is negative, is a reasonable option; starting immunotherapy and then moving to osimertinib increases the risk of severe immune side effects (especially pneumonitis and hepatitis) [21].

Who should order hereditary genetic testing?

The treating physician can order the test with pre-test counselling; a positive result needs genetic counselling and testing of relatives [3, 7].

References

21 references
Show all references, 9 with a study cardClose the reference list

Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.

  1. 1
    Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working GroupMosele MF, Westphalen CB, Stenzinger A, et al · Ann Oncol · 2024;35:588-606
    Study cardDOIPubMed Back to text: 1 2 3 4 5 6 7 8
  2. 2
    Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular PathologyLindeman NI, Cagle PT, Aisner DL, et al · Arch Pathol Lab Med · 2018;142:321-346
    DOIPubMed Back to text
  3. 3
    Germline Testing in Patients With Breast Cancer: ASCO-Society of Surgical Oncology GuidelineBedrosian I, Somerfield MR, Achatz MI, et al · J Clin Oncol · 2024;42:584-604
    DOIPubMed Back to text: 1 2 3
  4. 4
    Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO-College of American Pathologists Guideline UpdateWolff AC, Somerfield MR, Dowsett M, et al · J Clin Oncol · 2023;41:3867-3872
    DOIPubMed Back to text
  5. 5
    Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical OncologySepulveda AR, Hamilton SR, Allegra CJ, et al · J Clin Oncol · 2017;35:1453-1486
    DOIPubMed Back to text: 1 2 3
  6. 6
    Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical OpinionStoffel EM, McKernin SE, Brand R, et al · J Clin Oncol · 2019;37:153-164
    Study cardDOIPubMed Back to text: 1 2
  7. 7
    Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO GuidelineKonstantinopoulos PA, Norquist B, Lacchetti C, et al · J Clin Oncol · 2020;38:1222-1245
    DOIPubMed Back to text: 1 2 3
  8. 8
    ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinomaConcin N, Matias-Guiu X, Vergote I, et al · Int J Gynecol Cancer · 2021;31:12-39
    DOIPubMed Back to text: 1 2
  9. 9
    Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019Giri VN, Knudsen KE, Kelly WK, et al · J Clin Oncol · 2020;38:2798-2811
    DOIPubMed Back to text: 1 2
  10. 10
    Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELNDöhner H, Wei AH, Appelbaum FR, et al · Blood · 2022;140:1345-1377
    Study cardDOIPubMed Back to text: 1 2
  11. 11
    iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLLHallek M, Cheson BD, Catovsky D, et al · Blood · 2018;131:2745-2760
    Study cardDOIPubMed Back to text
  12. 12
    European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemiaHochhaus A, Baccarani M, Silver RT, et al · Leukemia · 2020;34:966-984
    Study cardDOIPubMed Back to text
  13. 13
    Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY ProjectD'Agostino M, Cairns DA, Lahuerta JJ, et al · J Clin Oncol · 2022;40:3406-3418
    DOIPubMed Back to text
  14. 14
    Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung CancerWu YL, Tsuboi M, He J, et al · N Engl J Med · 2020;383:1711-1723
    DOIPubMed Back to text
  15. 15
    Alectinib in Resected ALK-Positive Non-Small-Cell Lung CancerWu YL, Dziadziuszko R, Ahn JS, et al · N Engl J Med · 2024;390:1265-1276
    Study cardDOIPubMed Back to text
  16. 16
    Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trialShitara K, Lordick F, Bang YJ, et al · Lancet · 2023;401:1655-1668
    Study cardDOIPubMed Back to text
  17. 17
    Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated MelanomaLong GV, Hauschild A, Santinami M, et al · N Engl J Med · 2017;377:1813-1823
    DOIPubMed Back to text
  18. 18
    Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial CarcinomaLoriot Y, Matsubara N, Park SH, et al · N Engl J Med · 2023;389:1961-1971
    Study cardDOIPubMed Back to text
  19. 19
    Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relativesGenet Med · 2009;11:35-41
    DOIPubMed Back to text: 1 2
  20. 20
    Molecular International Prognostic Scoring System for Myelodysplastic SyndromesBernard E, Tuechler H, Greenberg PL, et al · NEJM Evid · 2022;1:EVIDoa2200008
    Study cardDOIPubMed Back to text
  21. 21
    Severe immune-related adverse events are common with sequential PD-(L)1 blockade and osimertinibSchoenfeld AJ, Arbour KC, Rizvi H, et al · Ann Oncol · 2019;30:839-844
    DOIPubMed Back to text

This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.

Printed from the website; the full and up-to-date version: https://drdabiri.com/en/learn/pretreatment-biomarker-testing/

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