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EVIDENCE-BASED ANSWER:
Yes. Any occult blood on a fecal occult blood test (FOBT) should be investigated further because colorectal cancer mortality decreases when positive FOBT screenings are evaluated (strength of recommendation: A, systematic review, evidence-based guidelines).
Follow-up of positive screening results lowers colorectal cancer mortality
No studies directly compare the need for colonoscopy when various numbers of stool samples are positive for occult blood on an FOBT. However, a Cochrane review of 4 randomized controlled trials (RCTs) with more than 300,000 patients examined the effectiveness of the FOBT for colorectal cancer screening.1 Each study varied in its follow-up approach to a positive FOBT.
Two RCTs offered screening with FOBT or standard care (no screening) and immediately followed up any positive results with a colonoscopy. The screened group had lower colorectal cancer mortality (N=46,551; risk ratio [RR]=0.75; 95% confidence interval [CI], 0.62-0.91) than the unscreened group (N=61,933; RR=0.84; 95% CI, 0.73-0.96).
Another trial screened with FOBT or standard care and offered colonoscopy if 5 or more samples were positive on initial testing or one or more were positive on repeat testing. The screened group showed reduced colorectal cancer mortality (N=152,850; RR=0.87; 95% CI, 0.78-0.97).
The final trial examined screening with FOBT compared with standard care and inconsistently offered repeat FOBT or sigmoidoscopy with double-contrast barium enema if any samples were positive on initial testing, which resulted in decreased colorectal cancer mortality for the screened group (N=68,308; RR=0.84; 95% CI, 0.71-0.99).
