Prognostic factors in colorectal cancer: College of American Pathologists consensus statement 1999

Carolyn C. Compton, L. Peter Fielding, Lawrence J. Burgart, Barbara Conley, Harry S. Cooper, Stanley R. Hamilton, M. Elizabeth H. Hammond, Donald E. Henson, Robert V.P. Hutter, Raymond B. Nagle, Mary L. Nielsen, Daniel J. Sargent, Clive R. Taylor, Mark Welton, Christopher Willett

Research output: Contribution to journalArticlepeer-review

1082 Scopus citations


Background. - Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting response to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disciplines of medical oncology, surgical oncology, and radiation oncology), pathologic, and statistical experts in colorectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the following categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence from multiple statistically robust published trials and generally used in patient management. Category IIA includes factors extensively studied biologically and/or clinically and repeatedly shown to have prognostic value for outcome and/or predictive value for therapy that is of sufficient import to be included in the pathology report but that remains to be validated in statistically robust studies. Category IIB includes factors shown to be promising in multiple studies but lacking sufficient data for inclusion in category I or IIA. Category III includes factors not yet sufficiently studied to determine their prognostic value. Category IV includes factors well studied and shown to have no prognostic significance. Materials and Methods. - The medical literature was critically reviewed, and the analysis revealed specific points of variability in approach that prevented direct comparisons among published studies and compromised the quality of the collective data. Categories of variability recognized included the following: (1) methods of analysis, (2) interpretation of findings, (3) reporting of data, and (4) statistical evaluation. Additional points of variability within these categories were defined from the collective experience of the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientific validation) were outlined with reference to the specific types of variability associated with the supportive data. For each factor and category of variability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to increase the uniformity and completeness of pathologic evaluation of tumor specimens, (2) to enhance the quality of the data needed for definitive evaluation of the prognostic value of individual prognostic factors, and (3) ultimately, to improve patient care. Results and Conclusions. - Factors that were determined to merit inclusion in category I were as follows: the local extent of tumor assessed pathologically (the pT category of the TNM staging system of the American Joint Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); regional lymph node metastasis (the pN category of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative intent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and preoperative elevation of carcinoembryonic antigen elevation (a factor established by laboratory medicine methods rather than anatomic pathology). Factors in category IIA included the following: tumor grade, radial margin status (for resection specimens with nonperitonealized surfaces), and residual tumor in the resection specimen following neoadjuvant therapy (the ypTNM category of the TNM staging system of the AJCC/UICC). Factors in category IIB included the following: histologic type, histologic features associated with microsatellite instability (MSI) (ie, host lymphoid response to tumor and medullary or mucinous histologic type), high degree of MSI (MSI-H), loss of heterozygosity at 18q (DCC gene allelic loss), and tumor border configuration (infiltrating vs pushing border). Factors grouped in category III included the following: DNA content, all other molecular markers except loss of heterozygosity 18q/DCC and MSI-H, perineural invasion, microvessel density, tumor cell-associated proteins or carbohydrates, peritumoral fibrosis, peritumoral inflammatory response, focal neuroendocrine differentiation, nuclear organizing regions, and proliferation indices. Category IV factors included tumor size and gross tumor configuration. This report records findings and recommendations of the consensus conference group, organized according to structural guidelines defined herein.

Original languageEnglish (US)
Pages (from-to)979-994
Number of pages16
JournalArchives of Pathology and Laboratory Medicine
Issue number7
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology


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