Precision therapies were first approved for cancer in 1998, when trastuzumab was approved for HER2+ breast cancer, opening the door for other targeted therapies such as imatinib for Philadelphia chromosome-positive chronic myelogenous leukaemia.¹Colomer R et al. EClinicalMedicine. 2020;25. Although initially companion diagnostics were based on molecular techniques including immunohistochemistry (IHC), fluorescent in situ hybridisation (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR), more recently there has been a paradigm shift towards next-generation sequencing (NGS).¹Colomer R et al. EClinicalMedicine. 2020;25. NGS allows for the simultaneous sequencing of numerous genes at a low cost, providing oncologists with information on the mutations present in a tumour and guiding the choice of treatment.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014.

While NGS testing has been widely adopted, recommendations about its use in daily practice have not been proposed by medical societies.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014. The European Society for Medical Oncology (ESMO) has recently released the first set of guidelines on the use of NGS testing for metastatic cancers, published in Annals of Oncology.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014.

Overall, tumour multigene NGS is recommended by ESMO for use in patients with advanced non-squamous non-small cell lung cancer (NSCLC), prostate, ovarian cancer, and cholangiocarcinoma.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014.  Currently, NGS is not recommended for other cancers in clinical practice but could be used for research purposes.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014. Particularly for prostate cancer, in countries where poly (ADP-ribose) polymerase (PARP) inhibitors are available, it is recommended that NGS is performed to assess the mutational status of BRCA1/2.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014. However, larger panels are unlikely to be cost-effective so should only be used when there are specific agreements with payers.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014.

There is no current need for NGS testing with metastatic breast cancer (mBC), as PIK3CA status can be determined by RT-PCR, and HER2 testing can be accurately carried out with IHC and, where indicated, a confirming FISH.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014. However, it is vital to include mBC patients in molecular screening programmes for research; mBC patients testing positive for alterations in the AKT1^E17K, PTEN, ERBB2, ESR1 and NF1 genes may be candidates for clinical trials with novel targeted or biological therapies.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014.

Tumour multigene NGS can be an alternative to RT-PCR in metastatic colorectal cancer (mCRC) only if it does not generate extra cost compared with routine techniques, as it would allow for the detection of microsatellite instability high (MSI-H) and ERBB2 amplifications.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014. Similarly with mBC patients, clinical research centres should aim to include mCRC patients in molecular screening programmes to open access for targeted and biological agents in clinical studies.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014. Regarding cancers such as hepatocellular carcinoma and metastatic gastric cancer where patients with MSI-H and NTRK fusion-positive tumours are expected to derive benefit of targeted agents, detection of these fusions should be done with cheaper standard methods if multigene sequencing is not needed.²Mosele F et al. Ann Oncol. Doi: 10.1016/j.annonc.2020.07.014.