Molecular testing practice patterns for lung cancer based on gender: Insights into disparities and opportunities for precision medicine.
Authors: Sewanti Atul Limaye, Deepak Koppaka, Jason Chow, Padman Vamadevan, Krupa Shankar, Shivam Shingla, Daniela De Paula, Vineet Datta, Prashant Agrawal, Dadasaheb B. Akolkar, Darshana Patil, Sachin Apurwa, R.K. Choudhary, Darshit Kalpeshkumar Shah, Niyati Krunal Shah, Rajeev Vijayakumar, Rajan Datar, Shriniwas Subhash Kulkarni, James Wilson
Journal: Journal of Clinical Oncology (2025)

e20523 Background: Targeted and biomarker-driven immunotherapies have revolutionized outcomes of lung cancer, yet gender disparities may impact care. This study explores gender-specific patterns in testing, biomarker distribution, and clinical decisions in lung cancer. Methods: Genomic data from 2,743 lung cancer patients across multiple oncology centers, encompassing 3,326 NGS-based multigene variant profiling tests performed at Datar Cancer Genetics was used for this analysis. These tests utilized either tumor tissue DNA (ttDNA, n=1,395) or circulating cell-free DNA (cfDNA, n=1,931) to identify actionable alterations. Results: Median age was 63 years for men and 60 years for women. Histopathological subtypes included adenocarcinoma (86%), squamous carcinoma (9%), neuroendocrine tumors (3%), and adenosquamous carcinoma (2%). Adenocarcinoma was more common in women (90.53%) than men (82.55%), while squamous cell carcinoma was higher in men (11.77%) than women (4.26%). Adenosquamous carcinoma was rare and similar across genders (around 2%). Small cell carcinoma was more prevalent in men (2.19%) than women (1.42%). In India, lung cancer incidence is higher in men (76%), largely due to greater tobacco consumption among men than women. However, in the testing cohort, women constituted 40% of the group, suggesting a higher adoption of molecular testing among this gender. This referral bias may arise from women's higher likelihood of having targetable driver mutations as non-smokers. The data reveals gender disparities in molecular testing, with women more likely to undergo testing and show higher rates of targetable alterations. While biological differences partly explain these trends, factors like physician bias, resource access, and patient engagement, may also contribute, ultimately affecting clinical outcomes. Conclusions: Addressing barriers to molecular testing, which may include clinician gender biases, is critical for advancing equity in precision oncology. Future prospective studies are warranted to validate these findings and explore underlying reasons for observed discrepancies. By ensuring equitable access to advanced molecular testing technologies across genders, precision oncology can fully realize its potential in improving lung cancer outcomes. Distribution of tissue-based key genetic alterations across genders in lung cancer. Gene Altered Adenocarcinoma Lung Squamous Carcinoma Lung Female(N=426) Male(N=605) p-value(Chi-square test) Female(N=22) Male(N=90) p-value(Chi-square test) EGFR 49.30% 31.07% &lt;0.00001 31.82% 13.33% 0.038377 KRAS 12.44% 21.82% 0 .000112 4.55% 6.67% 0.712536 BRAF 2.82% 2.98% 0.881623 0% 0% - MET 3.99% 3.80% 0.877053 0% 5.56% 0.786588 ERBB2 2.11% 4.30% 0.056454 0% 0% - ALK 9.39% 5.95% 0.037436 4.55% 2.22% 0.545174 ROS1 3.76% 2.98% 0.489456 0.00% 0.00% - RET 0.94% 2.48% 0.070172 4.55% 1.11% 0.27555