Prognostic impact of extra-nodal extension on colon and rectal cancer should be investigated separately

We thank Luchini et al. [1.Luchini C. Nottegar A. Pea A. et al.Extranodal extension is an important prognostic parameter for both colonic and rectal cancer.Ann Oncol. 2016; 27: 955-956Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar] for replying to our comments [2.Huang Q. Qin X. Prognostic impact of extracapsular lymph node involvement in colorectal cancer.Ann Oncol. 2016; 27: 955Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar] on a recent meta-analysis [3.Veronese N. Nottegar A. Pea A. et al.Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: a systematic review with meta-analysis.Ann Oncol. 2016; 27: 42-48Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar]. A recent review by Tamas et al. [4.Tamas K. Walenkamp A.M. de Vries E.G. et al.Rectal and colon cancer: not just a different anatomic site.Cancer Treat Rev. 2015; 41: 671-679Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar] pointed out that colon and rectal cancer were different in anatomic site, embryological origin, function and metastatic patterns and further subgroup analyses would have a great effect on treatment option and prognosis evaluation of colon and rectal cancer, so we thought that the results (all-cause mortality and recurrence of disease) of colon and rectal cancer should not be combined. In addition, I2 values showed low to moderate heterogeneity across studies, but I2 statistic was a value of statistical heterogeneity; there were clinical heterogeneity and methodological heterogeneity besides statistical heterogeneity, so we thought that subgroup analyses by geographical location and types of tumor were of potential significance. Finally, for survival data, the end points and the time to reach the end points were considered in the hazard ratio (HR), but the relative risk (RR) just considered the end points, so we thought that the HR was more appropriate than RR for all-cause mortality and recurrence of disease. We respectfully admit that the outcome of subgroup analysis of five studies was not reliable enough; more high-quality studies reported that HR should be carried out to investigate the prognostic impact of extra-nodal extension on colon and rectal cancer separately. The authors have declared no conflicts of interest.