Missed opportunities: Germline testing following tumor sequencing

Tumor next generation sequencing (NGS) may identify potential germline DNA mutations associated with cancer susceptibility. We describe the frequency of tumor NGS results in patients meeting ESMO 2019 recommendations for germline genetic testing (GT) and reasons for not undergoing germline GT.

A retrospective study (Sept. 2019-Feb. 2022) in a large, urban healthcare system identified patients meeting ESMO guidelines for potentially actionable germline mutations on NGS.

Of 3470 patients who underwent tumor NGS, 326 (9.4 %) had at least one potential actionable germline mutation. Of eligible patients, 189 (58.0 %) did not receive germline GT. Reasons for not undergoing GT include: 127 (67.2 %), not referred for GT; 30 (15.9 %), referred but did not attend genetic counseling; 32 (16.9 %), declined, died before GT, had insufficient samples, lacked insurance or lost to follow-up. Among 127 patients not referred for germline GT (39.0 % of the total eligible cohort), the most common cancer types were lung (33.0 %), colorectal (9.4 %), and cancer of unknown primary (9.4 %). Overall, 64 (50.4 %) patients not referred for germline GT had mutations in BRCA1/2 and/or Lynch syndrome genes. Of 137 patients who underwent germline GT, 86 (62.8 %) had positive GT.

In this cohort, 60 % of the eligible population by ESMO criteria did not receive GT, most commonly due to lack of referral (over 2/3 of patients). Further, 50 % of patients not referred for GT had mutations in commonly known genes (i.e., BRCA1/2). Education on germline eligibility and reflex clinical protocols are needed to ensure patients receive germline GT.