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Adjuvant Chemotherapy for Stage II Right-Sided and Left-Sided Colon Cancer: Analysis of SEER-Medicare Data

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Survival benefit from adjuvant chemotherapy is established for stage III colon cancer; however, uncertainty exists for stage II patients. Tumor heterogeneity, specifically microsatellite instability (MSI), which is more common in right-sided cancers, may be the reason for this observation. We examined the relationship between adjuvant chemotherapy and overall 5-year mortality for stage II colon cancer by location (right- vs left-side) as a surrogate for MSI.

Methods

Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified Medicare beneficiaries from 1992 to 2005 with AJCC stage II (n = 23,578) and III (n = 17,148) primary adenocarcinoma of the colon who underwent surgery for curative intent. Overall 5-year mortality was examined with Kaplan–Meier survival analysis and Cox proportional hazards regression with propensity score weighting.

Results

It was found that 18 % of stage II patients (n = 2941) with right-sided cancer and 22 % (n = 1693) with left-sided cancer received adjuvant chemotherapy. After adjustment, overall 5-year survival benefit from chemotherapy was observed only for stage III patients (right-sided: hazard ratio [HR], 0.64; 95 % CI, 0.59–0.68; p < .001 and left-sided: HR, 0.61; 95 % CI, 0.56–0.68; p < .001). No survival benefit was observed for stage II patients with either right-sided (HR, 0.97; 95 % CI, 0.87–1.09; p = .64) or left-sided cancer (HR, 0.97; 95 % CI, 0.84–1.12; p = .68).

Conclusions

Among Medicare patients with stage II colon cancer, a substantial number receive adjuvant chemotherapy. Adjuvant chemotherapy did not improve overall 5-year survival for either right- or left-sided colon cancers. Our results reinforce existing guidelines and should be considered in treatment algorithms for older adults with stage II colon cancer.

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References

  1. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA. 1990;264:1444–50.

    Article  Google Scholar 

  2. Benson AB, 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19.

    Article  PubMed  Google Scholar 

  3. Schrag D, Rifas-Shiman S, Saltz L, Bach PB, Begg CB. Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer. J Clin Oncol. 2002;20:3999–4005.

    Article  CAS  PubMed  Google Scholar 

  4. O’Connor ES, Greenblatt DY, LoConte NK, Gangnon RE, Liou JL, Heise CP, et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol. 2011;29:3381–8.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Lanza G, Jr., Maestri I, Ballotta MR, Dubini A, Cavazzini L. Relationship of nuclear DNA content to clinicopathologic features in colorectal cancer. Mod Pathol. 1994;7:161–5.

    PubMed  Google Scholar 

  6. Bufill JA. Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990;113:779–88.

    Article  CAS  PubMed  Google Scholar 

  7. Iacopetta B. Are there two sides to colorectal cancer? Int J Cancer. 2002;101:403–8.

    Article  CAS  PubMed  Google Scholar 

  8. Glebov OK, Rodriguez LM, Nakahara K, Jenkins J, Cliatt J, Humbyrd CJ, et al. Distinguishing right from left colon by the pattern of gene expression. Cancer Epidemiol Biomarkers Prev. 2003;12:755–62.

    CAS  PubMed  Google Scholar 

  9. Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, Laurberg S, Laiho P, Aaltonen LA, et al. Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut. 2005;54:374–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Gervaz P, Bucher P, Morel P. Two colons-two cancers: paradigm shift and clinical implications. J Surg Oncol. 2004;88:261–6.

    Article  PubMed  Google Scholar 

  11. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med. 2003;349:247–57.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609–18.

    Article  CAS  PubMed  Google Scholar 

  13. Hemminki A, Mecklin JP, Jarvinen H, Aaltonen LA, Joensuu H. Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology. 2000;119:921–8.

    Article  CAS  PubMed  Google Scholar 

  14. Malesci A, Laghi L, Bianchi P, Delconte G, Randolph A, Torri V, et al. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res. 2007;13:3831–9.

    Article  CAS  PubMed  Google Scholar 

  15. Samowitz WS, Curtin K, Ma KN, Schaffer D, Coleman LW, Leppert M, et al. Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol Biomarkers Prev. 2001;10:917–23.

    CAS  PubMed  Google Scholar 

  16. Poynter JN, Siegmund KD, Weisenberger DJ, Long TI, Thibodeau SN, Lindor N, et al. Molecular characterization of MSI-H colorectal cancer by MLHI promoter methylation, immunohistochemistry, and mismatch repair germline mutation screening. Cancer Epidemiol Biomarkers Prev. 2008;17:3208–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816–9.

    Article  CAS  PubMed  Google Scholar 

  18. Kim H, Jen J, Vogelstein B, Hamilton SR. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol. 1994;145:148–56.

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Thibodeau SN, French AJ, Cunningham JM, Tester D, Burgart LJ, Roche PC, et al. Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res. 1998;58:1713–8.

    CAS  PubMed  Google Scholar 

  20. Potosky AL, Riley GF, Lubitz JD, Mentnech RM, Kessler LG. Potential for cancer related health services research using a linked Medicare-tumor registry database. Med Care. 1993;31:732–48.

    Article  CAS  PubMed  Google Scholar 

  21. Warren JL, Klabunde CN, Schrag D, Bach PB, Riley GF. Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population. Med Care. 2002;40:IV-3–18.

    Google Scholar 

  22. Lo NS, Sarr MG. Mucinous cystadenocarcinoma of the appendix. The controversy persists: a review. Hepatogastroenterology. 2003;50:432–7.

    Google Scholar 

  23. Bradley CJ, Given CW, Dahman B, Fitzgerald TL. Adjuvant chemotherapy after resection in elderly Medicare and Medicaid patients with colon cancer. Arch Intern Med. 2008;168:521–9.

    Article  PubMed  Google Scholar 

  24. Dobie SA, Baldwin LM, Dominitz JA, Matthews B, Billingsley K, Barlow W. Completion of therapy by Medicare patients with stage III colon cancer. J Natl Cancer Inst. 2006;98:610–9.

    Article  PubMed  Google Scholar 

  25. Meguid RA, Slidell MB, Wolfgang CL, Chang DC, Ahuja N. Is there a difference in survival between right- versus left-sided colon cancers? Ann Surg Oncol. 2008;15:2388–94.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Benedix F, Kube R, Meyer F, Schmidt U, Gastinger I, Lippert H. Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum. 2010;53:57–64.

    Article  PubMed  Google Scholar 

  27. Weiss JM, Pfau PR, O’Connor ES, King J, LoConte N, Kennedy G, et al. Mortality by stage for right- vs. left-sided colon cancer: Analysis of SEER-Medicare data. J Clin Oncol. 2011;29:4401–9.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Morris AM, Baldwin LM, Matthews B, Dominitz JA, Barlow WE, Dobie SA, et al. Reoperation as a quality indicator in colorectal surgery: a population-based analysis. Ann Surg. 2007;245:73–9.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Ash AS, Ellis RP, Pope GC, Ayanian JZ, Bates DW, Burstin H, et al. Using diagnoses to describe populations and predict costs. Health Care Financ Rev. 2000;21:7–28.

    CAS  PubMed  Google Scholar 

  30. Fenton JJ, Cai Y, Green P, Beckett LA, Franks P, Baldwin LM. Trends in colorectal cancer testing among Medicare subpopulations. Am J Prev Med. 2008;35:194–202.

    Article  PubMed  Google Scholar 

  31. Rosenbaum PR, Rubin DB. The Central Role of the Propensity Score in Observational Studies for Causal Effects. Biometrika. 1983;70:41–55.

    Article  Google Scholar 

  32. Rubin DB. Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1997;127:757–63.

    Article  CAS  PubMed  Google Scholar 

  33. Rubin DB. The design versus the analysis of observational studies for causal effects: parallels with the design of randomized trials. Stat Med. 2007;26:20–36.

    Article  PubMed  Google Scholar 

  34. D’Agostino RB, Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17:2265–81.

    Article  PubMed  Google Scholar 

  35. Imbens GW. The role of the propensity score in estimating dose-response functions. Biometrika. 2000;87:706–10.

    Article  Google Scholar 

  36. Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05. A baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010;17:959–66.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27:3109–16.

    Article  CAS  PubMed  Google Scholar 

  38. Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007;370:2020–9.

    Article  PubMed  Google Scholar 

  39. Gill S, Loprinzi CL, Sargent DJ, Thomé SD, Alberts SR, Haller DG, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol. 2004;22:1797–806.

    Article  CAS  PubMed  Google Scholar 

  40. Figueredo A, Charette ML, Maroun J, Brouwers MC, Zuraw L. Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidence-based care’s gastrointestinal cancer disease site group. J Clin Oncol. 2004;22:3395–407.

    Article  PubMed  Google Scholar 

  41. Sargent D, Sobrero A, Grothey A, O’Connell MJ, Buyse M, Andre T, et al. Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2009;27:872–7.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Mamounas E, Wieand S, Wolmark N, Bear HD, Atkins JN, Song K, et al. Comparative efficacy of adjuvant chemotherapy in patients with Dukes’ B versus Dukes’ C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol. 1999;17:1349–55.

    CAS  PubMed  Google Scholar 

  43. Sharif S, O’Connell MJ, Yothers G, Lopa S, Wolmark N. FOLFOX and FLOX regimens for the adjuvant treatment of resected stage II and III colon cancer. Cancer Invest. 2008;26:956–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Wolmark N, Rockette H, Mamounas E, Jones J, Wieand S, Wickerham DL, et al. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999;17:3553–9.

    CAS  PubMed  Google Scholar 

  45. Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, et al. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol. 1993;11:1879–87.

    CAS  PubMed  Google Scholar 

  46. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. J Clin Oncol. 1999;17:1356–63.

    Google Scholar 

  47. Flejou J-F, Andre T, Chibaudel B, Scriva A, Hickish T, Tabernero J, et al. Effect of adding oxaliplatin to adjuvant 5-fluorouracil/leucovorin (5FU/LV) in patients with defective mismatch repair (dMMR) colon cancer stage II and III included in the MOSIAC study. J Clin Oncol. 2013;31(suppl): abstr 3524.

    Google Scholar 

  48. Jernvall P, Makinen MJ, Karttunen TJ, Makela J, Vihko P. Microsatellite instability: impact on cancer progression in proximal and distal colorectal cancers. Eur J Cancer. 1999;35:197–201.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

The authors thank Research Specialist Lauren Weeth-Feinstein, MPH, for her assistance in formatting and proofing this manuscript. This project also received funding from the University of Wisconsin Carbone Cancer Center (UWCCC) Support Grant from the National Cancer Institute, Grant No. P30 CA014520. This project was also supported by the Health Innovation Program, the UW School of Medicine and Public Health from The Wisconsin Partnership Program, and the Community‐Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR) through the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000427. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, the National Institutes of Health, and the Centers for Disease Control and Prevention, or their Contractors and Subcontractors is not intended nor should be inferred. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement No. U55/CCR921930-02 awarded to the Public Health Institute. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database.

Disclosures

Dr. Weiss was supported by the Agency for Healthcare Research and Quality (AHRQ)/National Research Service Award (NRSA) T-32 Institutional Training Program Grant No. 5-T32-HS00083.

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Authors and Affiliations

  1. Department of Medicine, University of Wisconsin School of Medicine and Public Health (UWSMPH), Madison, WI, USA

    Jennifer M. Weiss MD, MS & Noelle K. LoConte MD

  2. Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health (UWSMPH), Room 4230, 1685 Highland Avenue, Madison, WI, 53705-2281, USA

    Jennifer M. Weiss MD, MS

  3. Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health (UWSMPH), Madison, WI, USA

    Jessica Schumacher PhD, Glenn O. Allen MPH & Maureen A. Smith MD, MPH, PhD

  4. Department of Surgery, University of Wisconsin School of Medicine and Public Health (UWSMPH), Madison, WI, USA

    Heather Neuman MD, MS, Caprice C. Greenberg MD, MPH & Maureen A. Smith MD, MPH, PhD

  5. Division of Oncology, University of Wisconsin School of Medicine and Public Health (UWSMPH), Madison, WI, USA

    Noelle K. LoConte MD

  6. Department of Family Medicine, University of Wisconsin School of Medicine and Public Health (UWSMPH), Madison, WI, USA

    Maureen A. Smith MD, MPH, PhD

  7. University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health (UWSMPH), Madison, WI, USA

    Jennifer M. Weiss MD, MS, Heather Neuman MD, MS, Noelle K. LoConte MD, Caprice C. Greenberg MD, MPH & Maureen A. Smith MD, MPH, PhD

  8. Wisconsin Surgical Outcomes Research Program, University of Wisconsin School of Medicine and Public Health (UWSMPH), Madison, WI, USA

    Heather Neuman MD, MS & Caprice C. Greenberg MD, MPH

  9. Department of Surgery, University of Minnesota, Minneapolis, MN, USA

    Erin O’Connor Lange MD, MSPH

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  1. Jennifer M. Weiss MD, MS
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  2. Jessica Schumacher PhD
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Correspondence to Jennifer M. Weiss MD, MS.

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Weiss, J.M., Schumacher, J., Allen, G.O. et al. Adjuvant Chemotherapy for Stage II Right-Sided and Left-Sided Colon Cancer: Analysis of SEER-Medicare Data. Ann Surg Oncol 21, 1781–1791 (2014). https://doi.org/10.1245/s10434-014-3631-8

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  • DOI: https://doi.org/10.1245/s10434-014-3631-8

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