Prognostic factors in colorectal cancer - College of American PathologistsConsensus Statement 1999

Background.-Under the auspices of the College of American Pathologists, the current state of knowledge regarding pathologic prognostic factors (factor s 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 oncolo gy, and radiation oncology), pathologic, and statistical experts in colorec tal cancer reviewed all relevant medical literature and stratified the repo rted prognostic factors into categories that reflected the strength of the published evidence demonstrating their prognostic value. Accordingly, the f ollowing categories of prognostic factors were defined. Category I includes factors definitively proven to be of prognostic import based on evidence f rom multiple statistically robust published trials and generally used in pa tient management. Category IIA includes factors extensively studied biologi cally and/or clinically and repeatedly shown to have prognostic value for o utcome 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 sta tistically robust studies. Category IIB includes factors shown to be promis ing in multiple studies but lacking sufficient data for inclusion in catego ry 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 preve nted 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) rep orting of data, and (4) statistical evaluation. Additional points of variab ility within these categories were defined from the collective experience o f the group. Reasons for the assignment of an individual prognostic factor to category I, II, III, or IV (categories defined by the level of scientifi c validation) were outlined with reference to the specific types of variabi lity associated with the supportive data. For each factor and category of v ariability related to that factor, detailed recommendations for improvement were made. The recommendations were based on the following aims: (1) to in crease the uniformity and completeness of pathologic evaluation of tumor sp ecimens, (2) to enhance the quality of the data needed for definitive evalu ation of the prognostic value of individual prognostic factors, and (3) ult imately, 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 pathological ly (the pT category of the TNM staging system of the American Joint Committ ee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]); re gional lymph node metastasis (the pN category of the TNM staging system); b lood or lymphatic vessel invasion; residual tumor following surgery with cu rative intent (the R classification of the AJCC/UICC staging system), espec ially as it relates to positive surgical margins; and preoperative elevatio n 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 sp ecimens with nonperitonealized surfaces), and residual tumor in the resecti on specimen following neoadjuvant therapy (the ypTNM category of the TNM st aging system of the AJCC/UICC). Factors in category IIB included the follow ing: histologic type, histologic features associated with microsatellite in stability (MSI) (ie, host lymphoid response to tumor and medullary or mucin ous 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-associ ated proteins or carbohydrates, peritumoral fibrosis, peritumoral inflammat ory response, focal neuroendocrine differentiation, nuclear organizing regi ons, and proliferation indices. Category IV factors included tumor size and gross tumor configuration. This report records findings and recommendation s of the consensus conference group, organized according to structural guid elines defined herein.