Arch Pathol Lab Med—Vol 124, July 2000 Prognostic Factors in Colorectal Cancer—Compton et al 979 Prognostic Factors in Colorectal Cancer College of American Pathologists Consensus Statement 1999 Carolyn C. Compton, MD, PhD; L. Peter Fielding, MD; Lawrence J. Burgart, MD; Barbara Conley, MD; Harry S. Cooper, MD; Stanley R. Hamilton, MD; M. Elizabeth H. Hammond, MD; Donald E. Henson, MD; RobertV. P. Hutter, MD; Raymond B. Nagle, MD, PhD; Mary L. Nielsen, MD; Daniel J. Sargent, PhD; Clive R.Taylor, MD, PhD; Mark Welton, MD; Christopher Willett, MD ● Background.—Under the auspices of the College of American Pathologists, the current state of knowledge re- garding pathologic prognostic factors (factors linked to outcome) and predictive factors (factors predicting re- sponse to therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of clinical (including the disci- plines of medical oncology, surgical oncology, and radia- tion oncology), pathologic, and statistical experts in colo- rectal cancer reviewed all relevant medical literature and stratified the reported prognostic factors into categories that reflected the strength of the published evidence dem- onstrating their prognostic value. Accordingly, the follow- ing 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 biologi- cally and/or clinically and repeatedly shown to have prog- nostic value for outcome and/or predictive value for ther- apy that is of sufficient import to be included in the pa- thology report but that remains to be validated in statisti- cally 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 prog- nostic 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 Accepted for publication December 17, 1999. From the Massachusetts General Hospital, Boston (Drs Compton and Willett);York Hospital, York, Pa (Dr Fielding); Mayo Clinic, Rochester, Minn (Drs Burgart and Sargent); National Cancer Institute, Bethesda, Md (Drs Conley and Henson); Fox Chase Cancer Center, Philadelphia, Pa (Dr Cooper); M. D. Anderson Cancer Center, Houston,Tex (Dr Ham- ilton); LDS Hospital, Salt Lake City, Utah (Dr Hammond); St Barnabas Medical Center, Livingston, NJ (Dr Hutter); University of Arizona,Tuc- son (Dr Nagle); Kansas Pathology Consultants, Wichita, Kan (Dr Niel- sen); University of Southern California, Los Angeles (Dr Taylor); and University of California, San Francisco (Dr Welton). Presented at the College of American Pathologists Conference XXXV: Solid Tumor Prognostic Factors: Which, How and So What?, Chicago, Ill, June 10–13, 1999. Reprints: Carolyn C. Compton, MD, PhD, Department of Pathology, Warren Building, Room 256, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114. points of variability in approach that prevented direct com- parisons among published studies and compromised the quality of the collective data. Categories of variability rec- ognized 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 experi- ence of the group. Reasons for the assignment of an indi- vidual prognostic factor to category I, II, III, or IV (cate- gories 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 rec- ommendations for improvement were made. The recom- mendations were based on the following aims: (1) to in- crease the uniformity and completeness of pathologic eval- uation 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 cat- egory of the TNM staging system); blood or lymphatic vessel invasion; residual tumor following surgery with curative in- tent (the R classification of the AJCC/UICC staging system), especially as it relates to positive surgical margins; and pre- operative 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 resec- tion specimens with nonperitonealized surfaces), and resid- ual 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 fol- lowing: 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 (infiltrat- ing vs pushing border). Factors grouped in category III in- cluded the following: DNA content, all other molecular