{"doi":"10.1093/jnci/djae341","title":"Response to Hu, Yang, and Sun","abstract":"We appreciate the opportunity to reply to Hu et al.’s Correspondence1 and clarify our findings regarding performance characteristics and costs that could render blood-based biomarker tests cost-effective for colorectal cancer (CRC) screening when compared with standard screening tests. Our analysis focused on establishing the minimum performance requirements for average-risk populations, to address whether new blood tests should be offered to the population at large, a central question for key US stakeholders. This is an important first step. Although we agree that it would be interesting to examine targeted use of blood tests based on patient risk—such as those with genetic or environmental risk factors—it is unlikely that a blood test that is insensitive to precursor lesions would be useful for screening high-risk populations because these individuals would likely be screened and surveilled through colonoscopy. Hu et al. suggest that we did not place enough emphasis on the detection of advanced adenomas and cumulative false positives, but our analysis did underscore the importance of detecting advanced adenomas and considered the effects of false positives. We demonstrated that increasing sensitivity to advanced adenomas from 10% to 20% improved effectiveness more than increasing CRC sensitivity from 74% to 92%. We also agree with Hu et al. that it is important to consider the impact of cumulative false-positive rates associated with repeat screening over time. Our analysis explicitly incorporated false positive tests, follow-up colonoscopies after an abnormal test, and potential complications. These costs were incorporated into total screening costs; unnecessary colonoscopies increase the cost of screening while decreasing quality of life. False-positive tests are routinely considered in all recent cost-effectiveness analyses performed by the CISNET Colorectal Working Group.2,3 As our group has shown, under the assumption of full adherence to screening, using a blood test to screen for CRC would be effective and cost-effective compared with no screening, but not relative to screening with traditional screening methods, such as fecal immunochemical test (FIT) or colonoscopy. Opting to screen for CRC with a blood test instead of colonoscopy was projected to reduce screening benefit by 34% to 50% and reduce the net monetary benefit of CRC screening by 50% to 70%. These additional costs would be borne by payers and likely passed on to consumers. It could be argued that higher adherence to a blood test may compensate for its lack of effectiveness. Current findings suggest that offering a blood test would increase one-time test adherence by about 20%.4 Previous analyses found that such a screening adherence advantage would not compensate for the lack of effectiveness—screening with a blood test would still be more expensive and less effective than stool-based and colonoscopy screening.2 Analyses using the CRC-SPIN model found that these differences widen when we assume lower adherence to follow-up colonoscopy (P. Nascimento de Lima, PhD, 2024, unpublished data). In short, high adherence to a test that performs poorly in preventing cancer can be worse than lower adherence to tests that can help prevent cancer. Although “the best test is the one that is done,” sensitivity to precursor lesions is paramount because this is the way to prevent CRC to both improve quality of life and reduce costly treatments. We agree with Hu et al. that patient preferences and adherence patterns are important considerations to be weighed alongside cost-effectiveness results. This remains challenging because we have little information regarding CRC screening behaviors over time. The best information stems from integrated health-care organizations with organized screening programs and nationally representative cross-sectional patient surveys that gather information about screening recency. In addition, receipt of colonoscopy after an abnormal test is an ","journal":"JNCI Journal of the National Cancer Institute","year":2024,"id":507973,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":776114,"name":"Carolyn M. Rutter","orcid":"0000-0002-4396-8594","position":1,"is_corresponding":false},{"id":986382,"name":"Rosita van den Puttelaar","orcid":"0000-0003-2216-6557","position":2,"is_corresponding":false},{"id":986383,"name":"Anne I. Hahn","orcid":"0000-0003-4061-2303","position":3,"is_corresponding":false},{"id":381323,"name":"Jonathan Ozik","orcid":"0000-0002-3495-6735","position":4,"is_corresponding":false},{"id":432510,"name":"Nicholson Collier","orcid":"0000-0002-2376-4156","position":5,"is_corresponding":false},{"id":6449,"name":"Ann G. Zauber","orcid":"0000-0002-1764-5994","position":6,"is_corresponding":false},{"id":282320,"name":"Iris Lansdorp‐Vogelaar","orcid":"0000-0002-9438-2753","position":7,"is_corresponding":false},{"id":310992,"name":"John M. Inadomi","orcid":"0000-0001-6776-8661","position":8,"is_corresponding":false},{"id":776115,"name":"Pedro Nascimento de Lima","orcid":"0000-0001-9057-198X","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T02:11:06.395600Z","pmid":"39718776","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}