A controversial, big-budget breast cancer screening trial that has been chronically unable to attract enough female participants since its debut in 2017 got a vote of confidence from a special working group of the National Cancer Institute (NCI) on March 17.
The Tomosynthesis Mammography Imaging Screening Trial (TMIST) should continue, but with modification, the expert group concluded in its report.
The randomized trial, with an estimated cost of $100 million, compares two kinds of mammography screenings for breast cancer in healthy women. One group of patients is screened with digital breast tomosynthesis, also known as 3-D mammography; the other is screened with the older, less expensive 2-D digital technology.
Tomosynthesis is already considered superior in detecting small cancers and reducing callbacks and is increasingly being used in the real world, leading some experts in the field to say that TMIST is critically hampered by women’s and radiologists’ preference for 3-D mammography.
At a meeting of an NCI advisory board in September 2020, there was a suggestion that the federal agency may kill the trial.
But at the latest meeting, the working group proposed that the trial should live on.
One of the main problems with the trial has been recruitment; the recommended changes discussed at the meeting include reducing the number of women needed in the study (from 165,000 to 102,000), which would allow patient “accrual to be completed more quickly,” the working group noted. In addition, the target date for completing patient accrual would be moved to 2023, 3 years after the original completion date of 2020.
The group’s recommendations now go to NCI staff for scientific review. The NCI will then decide about implementing the proposed changes.
The trial, which is the NCI’s largest and most expensive screening study, has never come close to targeted monthly enrollment. It was enrolling fewer than 1,500 patients per month over a 2-year period, instead of the projected 5,500 per month, Philip Castle, PhD, MPH, director of the NCI’s Division of Cancer Prevention, said last year. He called for a review of TMIST’s “feasibility and relevance” in view of the increasing use of tomosynthesis in the United States, as well as other factors.
The new technology has been “rapidly adopted” by facilities in North America, the working group noted. As of December 2020, approximately 74% of breast cancer screening clinics in the United States had at least one tomosynthesis or 3-D system; 42% of the mammography machines were 3-D.
This trend of increasing use of 3-D machines might be too much for TMIST to surmount, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, in Seattle, who chaired the working group.
“We are worried the challenges [to patient accrual] may persist due to the increasing adoption of three-dimensional breast tomosynthesis in the United States over time,” she said during the working group’s virtual presentation of the report to the NCI’s Clinical Trials and Translational Research Advisory Committee.
Committee member Smita Bhatia, MD, PhD, of the University of Alabama at Birmingham, wondered, “What are the ongoing barriers that [TMIST investigators] are going to face beside recruitment?”
Dr. Davidson answered by speaking, again, about market penetration of tomosynthesis machines and suggested that the recruitment problems and the availability of 3-D mammography are intertwined.
“Is this a technology that has or will arrive, at which point it may not be very easy to put the genie back in the bottle?” she asked.
That question has already been answered – widespread use of tomosynthesis is here to stay, argued Daniel Kopans, MD, of Harvard Medical School, Boston, who invented digital breast tomosynthesis but no longer benefits financially from his invention because the patent has expired.
“The horse is out of the barn,” Dr. Kopans said in an interview. By the time the study results are available, digital mammography will be a tool of the past, he said.
TMIST is a trial “that should never have been started in the first place, and it’s failing,” he said. “I was hoping they [the NCI] would say, ‘Let’s stop this because there’s not enough accrual.’ But it looks like they’re not.”
“TMIST is a waste of money,” said Dr. Kopans, repeating a criticism he has made in the past.