Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A Meta-analysis of Observational Studies
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.
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.
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)].
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.
KeywordsRectal Cancer Adjuvant Chemotherapy Hospital Readmission Uneventful Postoperative Recovery Interstudy Heterogeneity
Conflict of interest
We declare that we have no conflict of interest.
- 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.
- 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.
- 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
- 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.
- 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.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.
- 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.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.