Impact of TNM Stage on Survival and Disease Control in Adjuvant Rectal Cancer Pooled Analysis

Heather Jones, MD
University of Pennsylvania Cancer Center
Last Modified: November 4, 2001

Presenter: L.L. Gunderson
Affiliation: Institution: Oncology, Mayo Clinic, Rochester, MN

Background
This study attempts to evaluate the TMN staging and the MAC staging as predictors of outcome such as overall survival and patterns of failure for patients with rectal cancer who have undergone adjuvant therapy. The study evaluates patients from 3 randomized studies in North America.

Materials and Methods

Eligible patients on NCCTG 79-47-51 (N=200), NCCTG 86-47-51 (N=656) and INT 114 (N=1695) had data merged for analysis.

All patients received postop radiation (RT) and 96% were randomized to receive concomitant and maintenance chemotherapy (CT).

5yr follow-up was available in 94% of patients and 7yr FU in 84%.

Overall and disease-free survival (OS, DFS) and time to local and distant relapse were estimated using cumulative incidence methodology.

Results

Both OS and DFS were dependent on TN stage Three risk groups of patients were defined: 1) intermediate- T3N0, T1-2N1 2) moderately high- T4N0, T1-2N2, T3N1 and 3) high- T3N2, T4N1, T4N2.

For Group 1, 5yr OS was 74% and 81% and 5yr DFS 66% and 74%

For Group 2, 5yr OS ranged from 61% to 69%

For Group 3, 5 yr OS ranged from 33% to 48%

Similar differences by TN stage were seen for cumulative incidence rates of local relapse and distant metastases

Author's Conclusions
Patients with only a single high-risk factor of either extension beyond the rectal wall or nodal involvement have improved OS, DFS and disease control when compared to those with both high risk factors. For the purposes of future trial design, it may be appropriate to perform separate studies for the "intermediate risk" subsets of T3N0 and T1-2N1 vs the "moderately high" or "high risk" subsets in view of differential survival and rates of relapse.

Clinical/Scientific Implications
This is a very interesting study that would seem to indicate that the TMN and MAC are not clear prognostic indicators of functional outcome as previously believed. Even more interesting is the independent prognostic factor of T stage in the Nodal groups. This study clearly demonstrates that there is a selective group of N2 patients with disease confined to the rectal wall that has better overall survival and disease- free survival than traditionally would be predicted.