Abstract

This review aims to establish expert consensus on biomarker testing for non-small-cell lung cancer (NSCLC) in India, evaluating diagnostic practices, adherence to international guidelines, and test utility and comparing clinically validated assays with laboratory-developed tests. In round 1, experts voted on 41 statements covering various aspects of NSCLC diagnostics. Responses were graded using a 5-point Likert scale, categorizing agreement levels as high, moderate, or low based on expert consensus percentages. After thorough deliberations during round 2, consensus was reached on 32 statements underscoring the necessity for early diagnosis of NSCLC. Key issues include misdiagnosis with tuberculosis and low or delayed specialist referral rates. Although formal programs are limited by awareness, resources, and data gaps; low-dose computed tomography (LDCT) screening in community settings is advocated. Consensus was reached among experts that most lung cancers are diagnosed at advanced stages in India. The delay in diagnosis was mainly due to misdiagnosis with tuberculosis and delayed referrals to specialists for evaluation. The consensus acknowledged the need to enhance lung cancer awareness and utilization of LDCT in high-risk individuals as a screening methodology in the community.

Biomarker testing for both early-stage and advanced-stage NSCLC is recommended, with reflex testing at diagnosis, longitudinal testing at disease progression, and liquid biopsies when tissue is unavailable/inadequate. Biomarker testing for common driver mutations associated with available targeted therapies can be performed in resource-limited settings using sequential testing or hotspot panels. PD-L1 testing for all advanced-stage cases is recommended, especially when molecular driver mutations/fusions are negative. Despite longer turnaround times, next-generation sequencing (NGS) would be preferred for its comprehensive gene assessment. Multigene assays are recommended for advanced stages, and upfront broad-panel tests are ideal. Testing for EGFR, ALK, proto-oncogene ROS1, and PD-L1 is essential for NSCLC. We urge standardized histopathological and molecular practices and acknowledge challenges in NGS availability and the complexities of interpreting results. This consensus underscores the importance of streamlined approaches to enhance NSCLC diagnostics in resource-constrained settings in India.

Keywords

non-small-cell lung cancer - next-generation sequencing - biomarkers - companion diagnostic - reflex testing - targeted therapies - low-dose computed tomography

Authors' Contributions

The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and each author believes that the manuscript represents honest work. B.B.: concepts, design, literature search, manuscript preparation, manuscript editing, manuscript review; T.P.: concepts, design, literature search, manuscript preparation, manuscript editing, manuscript review; N.R.: literature search, manuscript editing, manuscript review; V.M.N.: literature search, manuscript editing, manuscript review; B.K.: literature search, manuscript editing, manuscript review; A.S.: literature search, manuscript editing, manuscript review; S.P.: literature search, manuscript editing, manuscript review; J.D.: concepts, design, literature search, manuscript preparation, manuscript editing, manuscript review; S.L.: concepts, design, literature search, manuscript preparation, manuscript editing, manuscript review.

Patient Consent

No patient data was used in this article. Hence patient consent is not applicable for this manuscript.