TY - JOUR
T1 - Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer
T2 - A pooled analysis
AU - Gunderson, Leonard L.
AU - Sargent, Daniel J.
AU - Tepper, Joel E.
AU - O'Connell, Michael J.
AU - Allmer, Cristine
AU - Smalley, Steven R.
AU - Martenson, James A.
AU - Haller, Daniel G.
AU - Mayer, Robert J.
AU - Rich, Tyvin A.
AU - Ajani, Jaffer A.
AU - Macdonald, John S.
AU - Goldberg, Richard M.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Purpose: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. Materials and Methods: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n = 200), NCCTG 86-47-51 (n = 656), and INT 114 (n = 1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. Results: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). 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, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. Conclusion: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned statistical analysis, for the "intermediate-risk" vs. the "moderately high" or "high-risk" subsets of patients.
AB - Purpose: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. Materials and Methods: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n = 200), NCCTG 86-47-51 (n = 656), and INT 114 (n = 1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. Results: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). 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, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. Conclusion: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned statistical analysis, for the "intermediate-risk" vs. the "moderately high" or "high-risk" subsets of patients.
KW - Adjuvant chemoradiation
KW - Rectal cancer
KW - Staging
UR - http://www.scopus.com/inward/record.url?scp=0036804532&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036804532&partnerID=8YFLogxK
U2 - 10.1016/S0360-3016(02)02945-0
DO - 10.1016/S0360-3016(02)02945-0
M3 - Article
C2 - 12243812
AN - SCOPUS:0036804532
SN - 0360-3016
VL - 54
SP - 386
EP - 396
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -