Advertisement

Annals of Surgical Oncology

, Volume 22, Issue 12, pp 3793–3802 | Cite as

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

  • George Malietzis
  • Aamer Mughal
  • Andrew C. Currie
  • Nicola Anyamene
  • Robin H. Kennedy
  • Thanos Athanasiou
  • John T. Jenkins
Healthcare Policy and Outcomes

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.

Keywords

Rectal Cancer Adjuvant Chemotherapy Hospital Readmission Uneventful Postoperative Recovery Interstudy Heterogeneity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

We declare that we have no conflict of interest.

Disclosure

None.

References

  1. 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.CrossRefPubMedGoogle Scholar
  2. 2.
    Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–502. doi: 10.1016/S0140-6736(13)61649-9.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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. 6.
    Colorectal cancer | Guidance and guidelines | NICE. http://www.nice.org.uk/guidance/cg131. Accessed 30 Oct 2014.
  7. 7.
    Rectal Cancer Treatment (PDQ®) - National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/rectal/HealthProfessional/page4. Accessed 30 Oct 2014.
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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. 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. 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. 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.CrossRefPubMedGoogle Scholar
  14. 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.PubMedCentralPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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. CrossRefGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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. 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.CrossRefPubMedGoogle Scholar
  31. 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. 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. 33.
    Harless W, Qiu Y. Cancer: A medical emergency. Med Hypotheses. 2006;67(5):1054–9. doi: 10.1016/j.mehy.2006.04.032.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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. 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.CrossRefPubMedGoogle Scholar
  37. 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. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  39. 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.Google Scholar
  40. 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. 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.CrossRefPubMedGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • George Malietzis
    • 1
    • 2
  • Aamer Mughal
    • 2
  • Andrew C. Currie
    • 1
    • 2
  • Nicola Anyamene
    • 3
  • Robin H. Kennedy
    • 1
    • 2
  • Thanos Athanasiou
    • 2
  • John T. Jenkins
    • 1
    • 2
  1. 1.Department of SurgerySt Marks HospitalHarrowUK
  2. 2.Department of Surgery and CancerImperial CollegeLondonUK
  3. 3.Centre for Cancer TreatmentMount Vernon HospitalNorthwoodUK

Personalised recommendations