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Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A Meta-analysis of Observational Studies

  • Healthcare Policy and Outcomes
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The survival benefit of administering adjuvant chemotherapy (AC) in colorectal cancer is well established, as is the impact of its timing. Although various factors have been associated with treatment delay, their implications remain controversial. We determined clinicopathological factors associated with delay in transition to AC via systematic review and meta-analysis.

Methods

Studies assessing factors for delay in initiating AC were identified from MEDLINE, EMBASE, and Cochrane Databases. Studies were included only if relevant clinicopathological factors were adequately described and appropriate comparative groups were balanced. For each study, the odds ratio (OR) and 95 % confidence interval (CI) were estimated, regarding response to early versus delayed AC initiation.

Results

We identified 15 eligible studies involving 67,537 patients. Twelve studies were multicentre studies and three were single-center cohort studies. Meta-analysis demonstrated age >75 years [4 studies, OR = 1.44 (95 % CI 1.32–1.58)], marital status-single [3 studies, OR = 1.32 (95 % CI 1.20–1.44)], low socioeconomic status (SES) [7 studies, OR = 1.67 (95 % CI 1.32–2.12)], worse comorbidity status [5 studies, OR = 1.47 (95 % CI 1.14–1.90)], low tumour grade [7 studies, OR = 1.06 (95 % CI 1.02–1.11)], prolonged length of stay [3 studies, OR 2.37 (95 % CI 2.10–2.68)], and readmission [3 studies, OR = 3.23 (95 % CI 1.66–6.26)] were significant predictors of delayed initiation of AC. Laparoscopy compared to an open surgical approach was a significant predictor of earlier AC initiation [5 studies, OR = 0.70 (95 % CI 0.51–0.97)].

Conclusions

Laparoscopy is associated with earlier initiation of AC, encouraging its increased adoption. Social isolation and low SES merit consideration of approaches that counter the lack of social support and deprivation to improve cancer outcomes.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. (2011);61(2):69–90. doi:10.3322/caac.20107.

    Article  PubMed  Google Scholar 

  2. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–502. doi:10.1016/S0140-6736(13)61649-9.

    Article  PubMed  Google Scholar 

  3. 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(9604):2020–9. doi:10.1016/S0140-6736(07)61866-2.

    Article  PubMed  Google Scholar 

  4. Bosset J-F, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23. doi:10.1056/NEJMoa060829.

    Article  CAS  PubMed  Google Scholar 

  5. Fisher B, Gunduz N, Coyle J, Rudock C, Saffer E. Presence of a growth-stimulating factor in serum following primary tumor removal in mice. Cancer Res. 1989;49(8):1996–2001. http://www.ncbi.nlm.nih.gov/pubmed/2702641. Accessed 5 Aug 2014.

  6. Colorectal cancer | Guidance and guidelines | NICE. http://www.nice.org.uk/guidance/cg131. Accessed 30 Oct 2014.

  7. Rectal Cancer Treatment (PDQ®) - National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/rectal/HealthProfessional/page4. Accessed 30 Oct 2014.

  8. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305(22):2335–42. doi:10.1001/jama.2011.749.

    Article  CAS  PubMed  Google Scholar 

  9. Mayer EK, Chow A, Vale JA, Athanasiou T. Appraising the quality of care in surgery. World J Surg. 2009;33(8):1584–93. doi:10.1007/s00268-009-0065-8.

    Article  PubMed  Google Scholar 

  10. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 6 Aug 2014.

  11. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2127453&tool=pmcentrez&rendertype=abstract. Accessed 8 Nov 2014.

  12. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12. http://www.ncbi.nlm.nih.gov/pubmed/10789670. Accessed 11 July 2014.

  13. Strouch MJ, Zhou G, Fleshman JW, Birnbaum EH, Hunt SR, Mutch MG. Time to initiation of postoperative chemotherapy: an outcome measure for patients undergoing laparoscopic resection for rectal cancer. Dis Colon Rectum. 2013;56(8):945–51. doi:10.1097/DCR.0b013e318290ce30.

    Article  PubMed  Google Scholar 

  14. Simpson GS, Smith R, Sutton P, et al. The aetiology of delay to commencement of adjuvant chemotherapy following colorectal resection. Int J Surg Oncol. 2014;2014:670212. doi:10.1155/2014/670212.

    PubMed Central  CAS  PubMed  Google Scholar 

  15. Hendren S, Birkmeyer JD, Yin H, Banerjee M, Sonnenday C, Morris AM. Surgical complications are associated with omission of chemotherapy for stage III colorectal cancer. Dis Colon Rectum. 2010;53(12):1587–93. doi:10.1007/DCR.0b013e3181f2f202.

    Article  PubMed  Google Scholar 

  16. Tsai W-S, Hsieh P-S, Yeh C-Y, et al. Impact of chemotherapy-related prognostic factors on long-term survival in patients with stage III colorectal cancer after curative resection. Int J Clin Oncol. 2013;18(2):242–53. doi:10.1007/s10147-011-0370-8.

    Article  CAS  PubMed  Google Scholar 

  17. Ahmed S, Ahmad I, Zhu T, et al. Early discontinuation but not the timing of adjuvant therapy affects survival of patients with high-risk colorectal cancer: a population-based study. Dis Colon Rectum. 2010;53(10):1432–8. doi:10.1007/DCR.0b013e3181e78815.

    Article  PubMed  Google Scholar 

  18. Bayraktar UD, Chen E, Bayraktar S, et al. Does delay of adjuvant chemotherapy impact survival in patients with resected stage II and III colon adenocarcinoma? Cancer. 2011;117(11):2364–70. doi:10.1002/cncr.25720.

    Article  PubMed  Google Scholar 

  19. Berglund A, Cedermark B, Glimelius B. Is it deleterious to delay the start of adjuvant chemotherapy in colon cancer stage III? Ann Oncol. 2008;19(2):400–2. doi:10.1093/annonc/mdm582.

    Article  CAS  PubMed  Google Scholar 

  20. Cheung WY, Neville B, Earle CC. Etiology of delays in the initiation of adjuvant chemotherapy and their impact on outcomes for Stage II and III rectal cancer. Dis Colon Rectum. 2009;52(6):1054–63. doi:10.1007/DCR.0b013e3181a51173.

    Article  PubMed  Google Scholar 

  21. Czaykowski PM, Gill S, Kennecke HF, Gordon VL, Turner D. Adjuvant chemotherapy for stage III colon cancer: does timing matter? Dis Colon Rectum. 2011;54(9):1082–9. doi:10.1097/DCR.0b013e318223c3d6.

    Article  PubMed  Google Scholar 

  22. Day AR, Middleton G, Smith RVP, Jourdan IC, Rockall TA. Time to adjuvant chemotherapy following colorectal cancer resection is associated with an improved survival. Colorectal Dis. 2014;16(5):368–72. doi:10.1111/codi.12570.

    Article  CAS  PubMed  Google Scholar 

  23. Hershman D, Hall MJ, Wang X, et al. Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer. Cancer. 2006;107(11):2581–8. doi:10.1002/cncr.22316.

    Article  PubMed  Google Scholar 

  24. Lima ISF, Yasui Y, Scarfe A, Winget M. Association between receipt and timing of adjuvant chemotherapy and survival for patients with stage III colon cancer in Alberta, Canada. Cancer. 2011;117(16):3833–40. doi:10.1002/cncr.25954.

    Article  PubMed  Google Scholar 

  25. Merkow RP, Bentrem DJ, Mulcahy MF, et al. Effect of postoperative complications on adjuvant chemotherapy use for stage III colon cancer. Ann Surg. 2013;258(6):847–53. doi:10.1097/SLA.0000000000000312.

    Article  PubMed  Google Scholar 

  26. Rayson BD, Urquhart R, Cox M, Grunfeld E. Original contribution adherence to clinical practice guidelines for adjuvant chemotherapy for colorectal cancer in a Canadian Province: a population-based analysis. J Oncol Pract. 2012;1:253–260.

    Article  Google Scholar 

  27. Tevis SE, Kohlnhofer BM, Stringfield S, et al. Postoperative complications in patients with rectal cancer are associated with delays in chemotherapy that lead to worse disease-free and overall survival. Dis Colon Rectum. 2013;56(12):1339–48. doi:10.1097/DCR.0b013e3182a857eb.

    Article  PubMed  Google Scholar 

  28. Van der Geest LGM, Portielje JEA, Wouters MWJM, et al. Complicated postoperative recovery increases omission, delay and discontinuation of adjuvant chemotherapy in patients with Stage III colon cancer. Colorectal Dis. 2013;15(10):e582–91. doi:10.1111/codi.12288.

    Article  PubMed  Google Scholar 

  29. Gantt G, Ashburn J, Kiran RP, Khorana A, Kalady MF. Laparoscopy mitigates adverse oncological effects of delayed adjuvant chemotherapy for colon cancer. Surg Endosc. 2014. doi:10.1007/s00464-014-3697-1.

    Google Scholar 

  30. Yu S, Shabihkhani M, Yang D, et al. Timeliness of adjuvant chemotherapy for stage III adenocarcinoma of the colon: a measure of quality of care. Clin Colorectal Cancer. 2013;12(4):275–9. doi:10.1016/j.clcc.2013.08.002.

    Article  PubMed  Google Scholar 

  31. Massarweh NN, Haynes AB, Chiang Y-J, et al. Adequacy of the National Quality Forum’s Colon Cancer Adjuvant Chemotherapy Quality Metric: Is 4 months soon enough? Ann Surg. 2014. doi:10.1097/SLA.0000000000000859.

    Google Scholar 

  32. Hensler T, Hecker H, Heeg K, et al. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun. 1997;65(6):2283–91. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=175317&tool=pmcentrez&rendertype=abstract. Accessed 5 Aug 2014.

  33. Harless W, Qiu Y. Cancer: A medical emergency. Med Hypotheses. 2006;67(5):1054–9. doi:10.1016/j.mehy.2006.04.032.

    Article  PubMed  Google Scholar 

  34. Shahir MA, Lemmens VEPP, van de Poll-Franse L V, Voogd AC, Martijn H, Janssen-Heijnen MLG. Elderly patients with rectal cancer have a higher risk of treatment-related complications and a poorer prognosis than younger patients: a population-based study. Eur J Cancer. 2006;42(17):3015–21. doi:10.1016/j.ejca.2005.10.032.

    Article  CAS  PubMed  Google Scholar 

  35. Surgery for colorectal cancer in elderly patients: a systematic review. Colorectal Cancer Collaborative Group. Lancet. 2000;356(9234):968-74. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11041397. Accessed 7 Aug 2014.

  36. Esteva M, Ruiz A, Ramos M, et al. Age differences in presentation, diagnosis pathway and management of colorectal cancer. Cancer Epidemiol. 2014;38(4):346–53. doi:10.1016/j.canep.2014.05.002.

    Article  PubMed  Google Scholar 

  37. Kennedy RH, Francis EA, Wharton R, et al. Multicenter Randomized Controlled Trial of Conventional Versus Laparoscopic Surgery for Colorectal Cancer Within an Enhanced Recovery Programme: EnROL. J Clin Oncol. 2014. doi:10.1200/JCO.2013.54.3694.

    Google Scholar 

  38. Chan A, Woods R, Kennecke H, Gill S. Factors associated with delayed time to adjuvant chemotherapy in stage iii colon cancer. Curr Oncol. 2014;21(4):181–6. doi:10.3747/co.21.1963.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Malietzis G, Scuppa D, Nachiappan S, et al. Myopenia is associated with delay and failure to transition to adjuvant chemotherapy in stage III colorectal cancer: P241. Color Dis. 2014.

  40. Malietzis G. Giacometti M. Lee G.H. Kennedy R.H. Glynne-Jones R. Anyamene N. Aziz O. Jenkins J.T. Preoperative neutrophil to lymphocyte ratio independently predicts failure to proceed with adjuvant chemotherapy in stage III colorectal cancer. 2013:S507. doi:10.1016/S0959.

  41. Borras JM, Albreht T, Audisio R, et al. Policy statement on multidisciplinary cancer care. Eur J Cancer. 2014;50(3):475–80. doi:10.1016/j.ejca.2013.11.012.

    Article  PubMed  Google Scholar 

  42. Popescu RA, Schäfer R, Califano R, et al. The current and future role of the medical oncologist in the professional care for cancer patients: a position paper by the European Society for Medical Oncology (ESMO). Ann Oncol. 2014;25(1):9–15. doi:10.1093/annonc/mdt522.

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgery, St Marks Hospital, Harrow, Middlesex, UK

    George Malietzis MRCS, Andrew C. Currie MRCS, Robin H. Kennedy FRCS & John T. Jenkins FRCS

  2. Department of Surgery and Cancer, Imperial College, London, UK

    George Malietzis MRCS, Aamer Mughal, Andrew C. Currie MRCS, Robin H. Kennedy FRCS, Thanos Athanasiou FECTS & John T. Jenkins FRCS

  3. Centre for Cancer Treatment, Mount Vernon Hospital, Northwood, Middlesex, UK

    Nicola Anyamene FRCP

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  1. George Malietzis MRCS
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Correspondence to John T. Jenkins FRCS.

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Malietzis, G., Mughal, A., Currie, A.C. et al. Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A Meta-analysis of Observational Studies. Ann Surg Oncol 22, 3793–3802 (2015). https://doi.org/10.1245/s10434-015-4479-2

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  • DOI: https://doi.org/10.1245/s10434-015-4479-2

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