HONOLULU – Tumor testing for the triage of women with high-grade serous ovarian cancer to confirmatory genetic testing for BRCA mutations appears feasible, according to a cost-effectiveness analysis.
In fact, based on a Markov Monte Carlo simulation model developed to compare a tumor-testing approach with a universal germline testing approach, tumor testing yields an incremental cost-effectiveness ratio (ICER) of $127,000 per year of life gained, Janice S. Kwon, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
“This is well in excess of [the $50,000 to $100,000 that] would be considered an acceptable threshold in the United States,” saidof the University of British Columbia, Vancouver, Canada.
“We predict that tumor testing will be a cost-effective method of triage in women with high-grade serous ovarian cancer for confirmatory genetic testing to identify BRCA mutation carriers, assuming high sensitivity and acceptable cost of tumor testing,” she said.
In many areas around the world, germline testing is recommended for all women with high-grade serous ovarian cancer (HGSOC) because they have a 20% chance of carrying a BRCA 1 or 2 mutation.
“However, we all know that the referral rate for genetic testing is far from optimal, and furthermore, there are costs incurred to the healthcare system for resources utilized for genetic counseling and testing,” she said.
Tumor testing for triage is an alternative approach.
“If you consider 100 women with high-grade serous ovarian cancer and follow them through the conventional pathway in which all of them are referred for germline testing, you would expect to find 20 mutation carriers. If you take those same 100 women and apply tumor testing first, then 25 are expected to have a mutation in the tumor, Dr. Kwon said.
“If [all 25] are referred for germline testing, you would expect to find the same number of BRCA mutation carriers but with far less resource utilization.”
The remaining 75 are not expected to have a mutation in the tumor, and they may not need to be referred for confirmatory genetic testing unless there is a compelling family history or panel testing reveals a concerning mutation, she explained.
Since a randomized trial to compare these two strategies is not feasible, Dr. Kwon and her colleagues performed the current cost-effectiveness analysis.
The Markov simulation model was used to estimate the number of BRCA mutation carriers from index cases and their first degree relatives, and the number of cancer cases averted among first degree relatives, assuming they would undergo risk-reducing surgery.
“We conducted extensive sensitivity analyses to account for uncertainly around various parameters and we modeled a time horizon of 50 years,” Dr. Kwon noted. “We know that there are approximately 10,000 new [HGSOC] cases diagnosed in the United States every year, and we assumed that for every woman with [HGSOC], there was at least 1 female first-degree relative who would benefit from genetic testing.”
The model showed that applying tumor testing first would lead to a substantial reduction in the number of women undergoing germline mutation testing, but the number of BRCA mutation carriers identified would be comparable with the two strategies – assuming that the sensitivity of tumor testing is less than 100%, she said.
“As expected, the average lifetime costs associated with germline testing would be less than that for tumor testing, and even though you would expect that more first-degree relatives would be identified as BRCA mutation carriers after universal germline testing for index cases, the life expectancy gain for those first-degree relatives is averaged over the entire cohort at risk, and therefore the average incremental gain or benefit was actually quite small,” she said, noting that this yielded the ICER of $127,000 per year of life gained.
Based on this finding, tumor testing would be the preferred strategy, she added.
Sensitivity analysis around the sensitivity and specificity of tumor testing showed that tumor testing would be cost effective if its sensitivity is above 97%, and that tumor testing is cost-effective as long as it costs less than a third of the cost of germline testing – including genetic counseling.
Dr. Kwon has received research funding from AstraZeneca.
SOURCE: Kwon J et al., SGO 2019: .