Huge underuse of germline testing for cancer patients

By | June 7, 2023

CHICAGO Fewer than 7 percent of newly diagnosed cancer patients are tested for germline gene mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such tests could indicate that targeted therapies would be beneficial and have implications for close relatives who may carry the same genes.

The finding that so few newly diagnosed cancer patients were tested comes from an analysis of data on more than 1.3 million individuals in two US states. Data were taken from the Surveillance, Epidemiology, and Outcomes (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Alison Kurian, MD, department of medicine, Stanford University School of Medicine, Stanford, California.

Addressing the problem requires “innovative care delivery,” including streamlining pre-test counseling, making post-test counseling more widely available, and employing long-term follow-up to monitor patient outcomes, he suggested. .

“I think this is the time for creative solutions of different kinds,” he said. She suggested that lessons could be learned from the use of telehealth during the COVID-19 pandemic. She also noted that “there have been some interesting studies on the placement of genetic counselors in cancer clinics.”

Kurain presented the study here at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting on June 5. The study was simultaneously published in Journal of the American Medical Association.

The current findings represent “a missed opportunity to reduce the cancer burden at the population level,” say experts writing in an accompanying editorial.

“Physicians should recommend the test to their patients and provide them with the information they need to make informed decisions about whether to get tested,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center , New York City, write in their editorial.

They also suggest new approaches to broadening access, such as the use of point-of-care testing, teleconsulting and, in the future, chatbots to answer patient questions.

“With increased emphasis on overcoming both healthcare system and patient-level barriers to genetic cancer susceptibility testing for cancer patients, treatment outcomes will improve, and cancer diagnoses and related deaths in family members will be prevented,” they conclude.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, Michigan, referring to breast cancer as an example, said progress has “stagnant” in recent years.

The study found a higher rate of genetic testing among newly diagnosed breast cancer patients, at just over 20%.

Cobain argued that this was still too low. He pointed out that “a recent study suggested that more than 60% of people with an incident cancer diagnosis would meet the criteria for genetic testing under the National Comprehensive Cancer Network’s guidelines.

“This could be because tests are not being offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” he suggested.

A compelling reason to conduct genetic testing for newly diagnosed breast cancer patients is that it can demonstrate that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase), which “may have a direct impact on cancer-related mortality,” he pointed out.

“We need greater awareness and access to resources for genetic testing for breast cancer patients, especially for racial and ethnic minorities,” she said.

Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients of racial and ethnic minorities than among white patients. He said such a finding “increases patient and physician anxiety” and there may be “unclear optimal management recommendations for these patients.”

Study details

Germline genetic testing is “increasingly essential for cancer treatment,” Kurain said at the meeting.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARPs and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

He stressed that in clinical practice, tests have “evolved rapidly”. Panels include more and more genes. In addition, the cost of these tests is decreasing and the guidelines have become “more expensive”.

However, “little is known about the use and results of genetic testing,” Kurian noted.

The team then embarked on the SEER-GeneLINK initiative, which involved 20-year-old patients who were diagnosed with cancer between January 1, 2013 and March 31, 2019 and who were referred to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic testing results had been reported by the four labs that performed the most testing on patients in the two states. Findings were classified as pathogenic, benign, or VUS.

Findings were classified based on current testing and/or management guidelines as related to breast/ovarian cancer, gastrointestinal cancer, other inherited cancers, or those with no testing or management guidelines.

Kurian reported that out of an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of these, approximately half (51.9%) were women and the majority (86.3%) were 50 years of age or older.

Many of these patients (61.4%) were non-Hispanic white, and just under half (49.8%) were considered to be in medium or high poverty, as determined using US Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) patients during the study period.

Women were more likely to undergo germline mutation testing than men, at 13.9% vs 2.2%, as were patients aged 2049, at 22.1% vs 8.2%. for those aged 5069 and older, and 3.3% for those aged 70 and older.

The number of genes tested for increased from a median of two in 2013 to 34 in 2019. Rates of VUS increased more than those for pathological variants and substantially more in non-white patients.

In 2019, the ratio of VUS to disease variants was 1.7 among white patients, versus 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

Most identified pathological variants that were related to diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

As for specific cancer diagnoses, Kurian said that over the study period, testing rates consistently exceeded 50 percent among only male breast cancer patients.

There have been rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates rose from 1.0% to 19.0% over the same period and for prostate cancer, rates increased from 0.1% to 4.0%. He suggested that these rate increases could be related to the approval of PARP inhibitors for use in these indications.

However, there was a small change in germline mutation testing rates for patients with lung cancer, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0 %.

The findings also revealed racial and ethnic differences in tests after controlling for age, cancer type and year. Over the study period, 8.0% of white patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

For male and female breast cancer and ovarian cancer specifically, the testing rates were 31% among white patients, 22% for Asian patients, 25% for black patients, and 23% for hispanic patients (P < .001).

Kurian acknowledged the study is limited by a lack of testing from other labs and direct-to-consumer testing data, though a recent survey suggested this accounts for less than 5 percent of all germline genetic testing.

He also noted that the SEER registries do not collect family history or tumor sequencing data.

The study was funded by the National Institutes of Health and the Centers for Disease Control and Prevention. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae and Myriad Genetics. Other authors report numerous relationships with the industry. Cobain has relationships with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics and Immunomedics. Schrag has relationships with Merck (Inst), JAMA, AACR (Inst) and Grail (Inst). Stadler has relationships with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics and Regeneron Pharmaceuticals.

American Society of Clinical Oncology (ASCO) 2023: Abstract 10500. Submitted June 5, 2023.

JAMA Oncol. Published online June 5, 2023. Full text, editorial

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