Abstract & Commentary
Synopsis: In the classical TNM staging system for colon cancer, stage III includes patients with any size primary (T1-4) and involved regional lymph nodes. Clinically, this group is very heterogeneous and survival is variable. In an effort to determine if further stratification of stage III on the basis of nodal status (1-3 or > 3) would result in clinically important information, the National Cancer Data Base was examined. The results support the stratification into three subsets based upon nodal status. The data presented are likely to influence future modifications of the American Joint Cancer Commission’s staging manual and also in the refinement of clinical research projects in which adjuvant therapies are examined.
Source: Greene FL, et al. Ann Surgery. 2002;236: 416-421.
Traditionally, stage III colon cancer is defined on nodal involvement independent of tumor size (eg, T1-T4). However, recent reports have suggested that there is a heterogeneous survival pattern within stage III colon cancer patients, when examined in the context of T and N categories.1 Greene and colleagues used the National Cancer Data Base (NCDB), which is a large hospital cancer registry based national clinical surveillance and outcomes resource, to determine the prognostic significance of subgroup stratification based upon the number of lymph nodes found to be involved with cancer at the time of initial resection.
The NCDB captures approximately 75% of all newly diagnosed cancers in the United States. During the years 1987 to 1993, a total of 50,042 adult patients with node-positive colon cancer were reported to this national registry. This represents about one third of all stage III colon cancer during this period. From this, survival rates were calculated using a strategy dividing patients into 3 subgroups: IIIA (T1/2, N1, M0), IIIB (T3/4, N1, M0), and IIIC (any T, N2, M0). Additional characteristics were also evaluated, including tumor location, patient age, gender, ethniticity, and use of adjuvant chemotherapy.
The 5-year observed survival was 59.8% for IIIA, 42% for IIIB, and 27.3% for IIIC. A multivariate proportional hazards model identified that this subgrouping defined highly significant differences in survival, as did patient age, tumor grade, and treatment with adjuvant chemotherapy. The IIIA sub grouping (T1/2, N1 [1-3 nodes]) represented 10.7% of the population of stage III patients, whereas IIIB patients (T3/4, N1 [1-3 nodes]) were 60.5% and IIIC (any T, N2 [> 3 nodes]) were 28.8%. For each subgroup, the other independent variables indicated significant influence on survival (tumor grade, age, and the use of chemotherapy). Thus, the use of adjuvant chemotherapy was shown to enhance survival for each of the subgroups.
Comment by William B. Ershler, MD
This careful analysis of a very large database has rendered an important observation that is worthy of sustained consideration. It appears that the significant heterogeneity in observed survival for stage III patients may be, in a striking way, related to the number of involved resected nodes. Inasmuch as adjuvant therapy was shown to enhance survival for all three subgroups, a decision to withhold therapy from those in the more favorable subgroup would not be advised. On the contrary, the question of whether more intensive chemotherapy regimens should be studied in those with greater than 3 nodes (subgroup IIIC) seems relevant. Furthermore, inasmuch as the median age for patients in this registry study (and for colon patients in general) is approximately 70 years, the data might suggest that we should be particularly concerned to engage in adjuvant treatment in those with stage IIIC disease.
It remains to be seen whether the next edition of the American Joint Committee on Cancer (AJCC) staging manual will be revised to include these subgroups for stage III colon cancer, but it is very likely that it will be discussed in detail, inasmuch as Dr. Greene is the chairman of that organization. The data provide compelling evidence to further refine the staging system, and are an excellent example of the value of large-scale tumor registries.
Dr. Ershler is INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.
1. Merkel S, et al. Cancer. 2001;92:2754-2759.