Universal Germline Testing of Unselected Cancer Patients Detects Pathogenic Variants Missed by Standard Guidelines without Increasing Healthcare Costs.

Bryce Moulton,Gail Fulde,Derrick Haslem,Adrienne T Perkins,Lincoln Nadauld,Jessica Goldsberry,Christopher Giauque,Shawnee Snow,David Jones,Laura Sittig,Katherine Shortt,Sharanya Raghunath

doi:10.3390/cancers13225612

Abstract

Simple SummaryClinical genetic testing likely underestimates the frequency of pathogenic germline variants (PGVs) in a cancer patient population due to strict qualifications designated by practice guidelines. Accurate ascertainment of PGVs in cancer patients can be paramount to the treatment of hereditary cancer syndromes. Our prospective study aimed to (1) elucidate PGV frequency in an unselected cohort of cancer patients by offering universal germline testing regardless of eligibility by clinical guidelines and to (2) evaluate the impact of receiving such testing on cost of care. Results confirmed that over 50% of patients who harbored a PGV would not have qualified for testing under current guidelines and there was no increase in healthcare costs for patients who tested positive for a PGV. It is therefore feasible to offer universal germline testing for cancer patients in the clinic to detect PGVs without increasing healthcare costs.Purpose: To accurately ascertain the frequency of pathogenic germline variants (PGVs) in a pan-cancer patient population with universal genetic testing and to assess the economic impact of receiving genetic testing on healthcare costs. Methods: In this prospective study, germline genetic testing using a 105-gene panel was administered to an unselected pan-cancer patient population irrespective of eligibility by current guidelines. Financial records of subjects were analyzed to assess the effect of PGV detection on cost of care one year from the date of testing. Results: A total of 284 patients participated in this study, of which 44 patients (15%) tested positive for a PGV in 14 different cancer types. Of the patients with PGVs, 23 patients (52%) were ineligible for testing by current guidelines. Identification of a PGV did not increase cost of care. Conclusion: Implementation of universal genetic testing for cancer patients in the clinic, beyond that specified by current guidelines, is necessary to accurately assess and treat hereditary cancer syndromes and does not increase healthcare costs.

Highlights

IntroductionLicensee MDPI, Basel, Switzerland.Inherited germline cancer susceptibility genes are estimated to play a role in roughly4–24% of all cancers diagnosed [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]
Universal genetic testing of a pan-cancer patient population revealed that 15% of patients (44 of 284) carried a pathogenic germline variants (PGVs) in a cancer susceptibility gene, and that over half (23 of 44) of those with PGVs failed to meet current guidelines for clinical genetic testing
While it is not clear that such PGVs are responsible for the observed malignancy, this represents an opportunity for further investigation including functional validation studies in model organisms

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Inherited germline cancer susceptibility genes are estimated to play a role in roughly4–24% of all cancers diagnosed [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. The guidelines by offering universal testing to cancer patients irrespective of whether they qualified for genetic testing. Such studies carried out in cancer patients with selected cancer types, like breast [1,7,19], kidney [4], pancreatic [2,15], prostate [16], and colorectal cancer [20,25], as well as pan-cancer patient populations either selected for advanced stage [11] or unselected [10,13,14] found increased detection of pathogenic or likely-pathogenic germline variants (PGVs) in patients not eligible to receive testing. While this work provides support for universal genetic testing of cancer patient populations, there is less evidence on the impact of such testing on cost of care

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Conclusion