Are Liquid Biopsy Tests Cost-Effective for CRC Screening?

Blood-based liquid biopsy tests for colorectal cancer (CRC) are in development and may soon hit the market, expanding potential options for patients who refuse traditional colonoscopy. But would they be a cost-effective screening tool?

Not according to an economic analysis by researchers at Columbia University Irving Medical Center in New York.

There is “intense research and patient and public interest” in blood-based cancer tests.

“However, liquid biopsy tests may not have sufficient performance and cost too much for them to be a viable strategy at this time,” corresponding author Chin Hur, MD, MPH, told Medscape Medical News.

The study was published online on November 16, 2023 in JAMA Network Open.

Better, Cheaper Liquid Biopsies Needed

The researchers developed a Markov model to compare the cost effectiveness of no screening and five CRC screening strategies: colonoscopy, liquid biopsy, liquid biopsy after nonadherence to colonoscopy, stool DNA, and fecal immunochemical test (FIT).

The model simulated a hypothetical cohort of unscreened adults at average risk for CRC with screening starting at age 45 years, in line with current US Preventive Services Task Force advice.

A strategy was considered cost effective if it had an incremental cost-effectiveness ratio (ICER) below the US willingness-to-pay threshold of $100,000 per life-year gained.

According to their model, colonoscopy was the preferred (most cost-effective) strategy with an ICER of $28,071 per life-year gained.

Offering liquid biopsy screening to adults who refuse colonoscopy was the most effective strategy in terms of number of life-years gained, but it greatly exceeded the accepted threshold of $100,000 per life-year gained coming in at $377,538 per life-year gained. The cost of liquid biopsy would have to drop by 66% for this approach to become a cost-effective option, the researchers write.

Compared with no screening, the cost of liquid biopsy would have to fall by 94% for its ICER to drop below the willingness-to-pay threshold of $100,000 per life-year gained. When compared with stool-based tests, the cost of liquid biopsy would have to drop by 43%-80% to be cost effective.

Liquid biopsy and the liquid biopsy after refusal of colonoscopy strategies had more life-years gained when polyp detection was introduced, but they did not achieve cost effectiveness at liquid biopsy’s current price even with perfect performance.

“With current estimate of performance and cost,” liquid biopsy for CRC screening is not cost effective, Hur told Medscape Medical News.

Liquid biopsy tests for CRC screening may become cost effective in the future if they are significantly less expensive or if polyp detection is introduced along with a decrease in cost, Hur said.

Making blood-based CRC screening more effective and cost effective “is more likely to depend on the ability to detect precancerous polyps than on the detection of CRC itself,” writes John Inadomi, MD, with University of Utah School of Medicine, Salt Lake City, in an invited commentary, also published online in JAMA Network Open.

The sensitivity of FIT for detecting advanced polyps is roughly 20%, whereas stool multitarget tests for blood and DNA or RNA detect 40%-45% of advanced polyps, Inadomi notes.

Blood-based tests, on the other hand, have been reported to detect 12%-16% of advanced polyps, “which is close to probability of a false-positive test,” he writes. “Because of their high cost, blood-based CRC screening will not be cost-effective unless they detect a greater proportion of advanced polyps than FIT.”

The need for follow-up colonoscopy in the case of a positive noncolonoscopy CRC screening test result is “an important concept that is not emphasized enough in clinical practice,” Inadomi adds. “Unfortunately, only 40% to 80% of people with positive noncolonoscopy screening test results follow-up with the requisite colonoscopy. Clinicians need to emphasize the necessity of the follow-up colonoscopy when discussing CRC screening options and adherence.”

Hur reported receiving consulting fees from Value Analytics outside the submitted work. Hur and co-authors Fay Kastrinos, MD, MPH, and Sheila Rustgi, MD, are supported by a grant from the National Cancer Institute. Co-author William Grady, MD, reported receiving personal fees from SEngine, Guardant Health, Freenome, Diacarta, Natera, Helio, Guidepoint, and GLG and nonfinancial support from LucidDx outside the submitted work. Grady also disclosed a patent pending for methylated gene biomarker for esophageal cancer. Co-author Yoanna Pumpalova, MD, reported receiving stock from Pfizer outside the submitted work. Inadomi reported receiving grants from Exact Sciences.