{"doi":"10.3389/fonc.2021.755113","title":"High-Risk Features Are Prognostic in dMMR/MSI-H Stage II Colon Cancer","abstract":"Background High-risk features, such as T4 disease, bowel obstruction, poorly/undifferentiated histology, lymphovascular, perineural invasion, and <12 lymph nodes sampled, indicate poor prognosis and define high-risk stage II disease in proficient mismatch repair stage II colon cancer (CC). The prognostic role of high-risk features in dMMR/MSI-H stage II CC is unknown. Similarly, the role of adjuvant therapy in high-risk stage II CC with dMMR/MSI-H (≥1 high-risk feature) has not been studied in prospective trials. The aim of this analysis of the National Cancer Database is to evaluate the prognostic value of high-risk features in stage II dMMR/MSI-H CC. Methods Univariate (UVA) and multivariate (MVA) Cox proportional hazards (Cox-PH) models were built to assess the association between clinical and demographic characteristics and overall survival. Kaplan–Meier survival curves were generated with log-rank tests to evaluate the association between adjuvant chemotherapy in high-risk and low-risk cohorts separately. Results A total of 2,293 stage II CC patients have dMMR/MSI-H; of those, 29.5% ( n = 676) had high-risk features. The high-risk dMMR/MSI-H patients had worse overall survival [5-year survival and 95%CI, 73.2% (67.3–78.1%) vs . 80.3% (76.7–83.5%), p = 0.0001]. In patients with stage II dMMR/MSI-H CC, the high-risk features were associated with shorter overall survival (OS) along with male sex, positive carcinoembryonic antigen, Charlson–Deyo score >1, and older age. Adjuvant chemotherapy administration was associated with better OS, regardless of the high-risk features in dMMR/MSI-H (log-rank test, p = 0.001) or not ( p = 0.0006). When stratified by age, the benefit of chemotherapy was evident only in patients age ≥65 with high-risk features. Conclusion High-risk features are prognostic in the setting of dMMR/MSI-H stage II CC. Adjuvant chemotherapy may improve survival specifically in patients ≥65 years and with high-risk features.","journal":"Frontiers in Oncology","year":2021,"id":182352,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":300996,"name":"Renjian Jiang","orcid":"0000-0002-0910-7897","position":1,"is_corresponding":false},{"id":469426,"name":"Philip A. Philip","orcid":"0000-0002-6513-3491","position":2,"is_corresponding":false},{"id":469421,"name":"Maria Diab","orcid":"0000-0002-4809-9535","position":3,"is_corresponding":false},{"id":69837,"name":"Madhusmita Behera","orcid":"0000-0003-1121-6002","position":4,"is_corresponding":false},{"id":429974,"name":"Christina Wu","orcid":"0000-0001-5922-5392","position":5,"is_corresponding":false},{"id":429972,"name":"Olatunji B. Alese","orcid":"0000-0001-8079-4725","position":6,"is_corresponding":false},{"id":429969,"name":"Walid L. Shaib","orcid":"0000-0001-9388-0446","position":7,"is_corresponding":false},{"id":735426,"name":"Tyra M. Gaines","orcid":null,"position":8,"is_corresponding":false},{"id":573612,"name":"Glen C. Balch","orcid":"0000-0002-1575-9170","position":9,"is_corresponding":false},{"id":354302,"name":"Bassel F. El‐Rayes","orcid":"0000-0002-2661-5746","position":10,"is_corresponding":false},{"id":429973,"name":"Mehmet Akce","orcid":"0000-0003-4747-7722","position":11,"is_corresponding":false},{"id":734651,"name":"Amr Mohamed","orcid":"0000-0002-3310-6413","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-18T23:48:13.605421Z","pmid":"34760701","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":[]}