FIT yields decline after the first round — but remain clinically meaningful over time

Even after multiple negative fecal immunochemical tests (FITs), colorectal cancer (CRC) and pre-cancerous polyp detection does not fall to zero — a finding that supports continued biennial screening and offers important guidance for clinicians counseling patients and for health systems planning colonoscopy capacity.

In a large analysis of Catalonia’s organized, population-based CRC screening program, Uri Ladabaum, MD, and colleagues found that while FIT positivity and detection rates are highest in the first round, they stabilize at lower — but still clinically meaningful — levels in subsequent rounds. The study published in the journal GUT, evaluated outcomes across seven biennial FIT rounds among 2.81 million invitees who received 8.2 million screening offers between 2010 and 2023.

Participation varied widely. Nearly half of invitees (46.2%) never completed a FIT. Longitudinal adherence patterns were categorized as consistent (29.2% completed 100% of rounds offered), frequent (8.6% completed 66%–99%), occasional (11.5% completed 33%–65%), and infrequent (4.5% completed 1%–32%). Among all invitees, FIT completion increased over successive rounds, rising from 38.6% in the first round to nearly 60% by the seventh.

As expected, the first round produced the highest yield. FIT positivity was 5.8% in round one, with a positive predictive value (PPV) for CRC of 5.1% and for high-risk CRC precursors of 20.4%. The CRC detection rate reached 2.65 per 1,000 FIT participants. After approximately three rounds, however, FIT positivity and neoplasia detection decreased and then stabilized — reflecting prior removal of prevalent neoplasia and a progressively lower-risk screening population.

The investigators also examined an “adherent cohort” of more than 400,000 individuals who entered screening at age 50–51 and completed 66%–100% of rounds offered. In this group, round one again had the highest yield (FIT positivity 4.4%, CRC PPV 3.3%, CRC detection 1.30 per 1,000). In rounds three through seven, detection rates and PPVs were lower than those seen in first-time screeners of the same age — but did not disappear.

For Dr. Ladabaum, the message is straightforward. “While the first or ‘prevalent’ round is the one with the highest yield, the results stabilized after the third or fourth rounds at levels that, in our opinion, are still clinically meaningful,” he said. “So we concluded that early stopping is not justified even after 6–7 normal biennial FIT.”

He emphasized that FIT screening should be viewed as a longitudinal strategy rather than a single event. “The message is that FIT-based screening is programmatic, and our results suggest that we ‘should keep going’ with biennial FIT even in those with multiple normal results — in the case of Catalonia, probably through the 10 maximum rounds for ages 50–69,” he said.

Whether similar conclusions apply to U.S. screening schedules — which typically recommend annual FIT beginning at age 45 — remains unclear. “The story may be different in annual programs from age 45 through 75,” Dr. Ladabaum noted. “I would imagine that after a given number of normal FIT, the yield of keeping going through up to 31 rounds is probably very low.” The current study did not address whether screening intervals could safely be lengthened after repeated negative results.

The findings also have implications for program design. “This is an incredibly important issue — and many people around the world are trying to find the answers,” Dr. Ladabaum said of improving adherence. Organized, population-based programs outperform opportunistic screening, he noted, but participation still leaves room for improvement. “The form of the invitation, whether FIT is mailed or not, endorsement by the person’s doctor, systematically addressing identifiable barriers — all these seem to matter.”

Emerging approaches may involve personalization. Dr. Ladabaum anticipates research exploring targeted outreach strategies “with the use of new technologies like artificial intelligence,” as well as refined risk prediction based on prior screening history.

For health systems, declining positivity rates over time may help forecast colonoscopy demand. “I think the PPVs we saw in later rounds are still very acceptable, and those colonoscopies are still worth doing,” he said. “The positivity rate falls a bit over rounds, so there are fewer colonoscopies per person in later rounds.”

Taken together, the data reinforce a central principle of FIT-based CRC screening: although yields decline after the first round, ongoing biennial testing continues to detect clinically meaningful disease — and early cessation in a program for ages 50-69, even after several negative biennial tests, is not supported by current evidence.