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      Predictive value of mucinous histology in colon cancer: a population-based, propensity score matched analysis

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          Abstract

          Background:

          This investigation aimed to assess whether mucinous histology impacts overall (OS) and cancer-specific survival (CSS) in colon cancer.

          Methods:

          Colon cancer patients who underwent surgery between 2004 and 2011 were identified in the Surveillance, Epidemiology, and End Results database. OS and CSS were assessed using Cox regression and propensity score methods.

          Results:

          Out of 121 628 patients, 12 863 (10.6%) had a mucinous histology. Five-year OS and CSS for mucinous adenocarcinoma were 54.4% (95% CI: 53.4–55.5%) and 66.5% (95% CI: 65.5–67.5%) compared with 60.2% (95% CI: 59.8–60.5%) and 71.9% (95% CI: 71.5–72.2%) for non-mucinous adenocarcinoma ( P<0.001). This survival disadvantage disappeared in multivariable analyses (hazard ratio (HR)=1.02, 95% CI: 0.99–1.05, P=0.269 and HR=1.03, 95% CI: 0.99–1.06, P=0.169), and after propensity score matching (OS: HR=0.99, 95% CI: 0.93–1.04, P=0.606 and CSS: HR=0.99, 95% CI:0.92–1.06, P=0.783).

          Conclusions:

          In this population-based investigation, a mucinous histology did not negatively impact survival. Hence, the present study does not provide evidence to change treatment strategies in patients with mucinous adenocarcinoma of the colon.

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          Capecitabine as adjuvant treatment for stage III colon cancer.

          Chris Twelves, Alfred Wong, Marek P. Nowacki … (2005)
          Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting. We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P<0.001). Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer. Copyright 2005 Massachusetts Medical Society.
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            Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base.

            F. Chang, John Hyngstrom, John Skibber … (2012)
            We evaluated clinical features and survival outcomes among patients with signet ring and mucinous histologies of colorectal adenocarcinoma by using data from the National Cancer Data Base (NCDB). Patients aged 18-90 years with colorectal adenocarcinoma diagnosed between 1998 and 2002 were identified from the NCDB. Site-stratified (colon vs. rectum) survival analysis was performed by multivariate relative survival adjusted for multiple clinicopathologic and treatment variables. The study included 244,794 patients: 25,546 (10%) with mucinous, 2,260 (1%) with signet ring, and 216,988 (89%) with nonmucinous, non-signet ring adenocarcinoma. Mucinous and signet ring cancers were more frequently right-sided (60% and 62%, respectively) than were nonmucinous, non-signet ring adenocarcinomas (42%, P < 0.001). Signet ring histology was associated with a higher stage (P < 0.001), and 77.2% of signet ring tumors were high-grade lesions, compared with 20% of mucinous and 17% of non-signet ring, nonmucinous adenocarcinomas (P < 0.001). After adjustment for covariates, signet ring histology was independently associated with higher risk of death [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51, and HR 1.57, CI 1.38-1.77, for tumors located in the colon and rectum, respectively]. Mucinous tumors of the rectum (HR 1.22, CI 1.16-1.29), but not the colon (HR 1.03, CI 1.00-1.06), were associated with increased risk of death. Signet ring cell adenocarcinomas of the colon and rectum and mucinous adenocarcinomas of the rectum are associated with poorer survival. These aggressive histologic variants of colorectal adenocarcinoma should be targeted for research initiatives to improve outcomes.
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              Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis.

              J. Verhulst, L Ferdinande, P Demetter … (2012)
              Mucinous adenocarcinoma (MAC) of the colorectum has been known and studied for many years. The prognostic significance of this histological subtype remains controversial. The authors reviewed the prognostic significance of mucinous differentiation in colorectal cancer. A systematic web-based search was performed using Web of Knowledge and Medline. Articles published in English, German or French which used the WHO definition of MAC and described cohort studies, case-control studies or cross-sectional studies comparing survival in patients with MAC and adenocarcinoma (AC) not otherwise specified were included. Data on first author, year of publication, country, number of patients included, prevalence of MAC, % stage IV disease, % disease located in the proximal colon, mean age at presentation, % male patients and 5-year overall survival were extracted from individual studies. A fixed-effects meta-analysis model was used for analysis. The primary outcome was survival, expressed as the HR. Differences between categorical outcome parameters were quantified using the RR and corresponding 95% CI. 44 studies and 222 256 patients were included. The RR for proximal disease versus distal disease was 1.55 (95% CI 1.53 to 1.58). Mucinous differentiation was less frequent in male subjects (RR 0.93 (95% CI 0.91 to 0.94)). Interestingly, the prevalence of stage IV disease was similar in MAC and AC (RR 0.99 (95% CI 0.96 to 1.02)). Thirty-five articles were included in the survival analysis. A worse survival in MAC versus AC was demonstrated (HR 1.05 (95% CI 1.02 to 1.08)). Conversely, three out of four studies reported a better survival in MAC with microsatellite instability (MSI). Due to heterogeneity a meta-analysis on the effect of MSI was not possible. MAC more often originates from the right colon and is less frequent in male subjects. The authors did not identify a difference in the proportion of stage IV patients at presentation. Mucinous differentiation results in a 2-8% increased hazard of death, which persists after correction for stage. More research is needed to define the interaction between mucinous differentiation, MSI and outcome.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Br J Cancer
                Journal ID (iso-abbrev): Br. J. Cancer
                Title: British Journal of Cancer
                Publisher: Nature Publishing Group
                ISSN (Print): 0007-0920
                ISSN (Electronic): 1532-1827
                Publication date (Print): 26 April 2016
                Publication date (Electronic): 15 March 2016
                Volume: 114
                Issue: 9
                Pages: 1027-1032
                Affiliations
                [1 ]Department of Surgery, Kantonsspital St. Gallen , St. Gallen 9007, Switzerland
                [2 ]Institute of Medical Biometry and Informatics, University of Heidelberg , Heidelberg 69120, Germany
                [3 ]Department of General, Visceral and Transplantation Surgery, University of Heidelberg , Heidelberg 69120, Germany
                [4 ]Department of Medical Oncology and Hematology, Kantonsspital St. Gallen , St. Gallen 9007, Switzerland
                [5 ]University Clinics for Visceral Surgery and Medicine, University Hospital Berne , Berne 3010, Switzerland
                [6 ]Study Center of the German Surgical Society, University of Heidelberg , Heidelberg, Germany
                Author notes
                [7]

                These authors contributed equally to this work.

                Article
                Publisher Item ID: bjc201657
                DOI: 10.1038/bjc.2016.57
                PMC ID: 4984906
                PubMed ID: 26977857
                SO-VID: fe0f95fd-013c-4ff9-92f7-9a35dc592f88
                Copyright © Copyright © 2016 Cancer Research UK
                License:

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                Date received : 17 November 2015
                Date revision received : 08 February 2016
                Date accepted : 14 February 2016
                Categories
                Subject: Epidemiology

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: survival,colon cancer,mucinous adenocarcinoma,surveillance, epidemiology, and end results program,seer,propensity score
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: survival, colon cancer, mucinous adenocarcinoma, surveillance, epidemiology, and end results program, seer, propensity score

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