Abstract:

BACKGROUND:The American Joint Committee on Cancer (AJCC) maintains that the eighth edition of its Staging Manual (AJCC8) has improved accuracy compared to the seventh (AJCC7). However, there are concerns that implementation may disrupt analysis of active clinical trials for stage III patients. We used an independent cohort of melanoma patients to test the extent to which AJCC8 has improved prognostic accuracy compared to AJCC7. METHODS:We analyzed a cohort of 1,315 prospectively enrolled patients. We assessed primary tumor and nodal classification of stage I-III patients using AJCC7 and AJCC8 to assign disease stages at diagnosis. We compared recurrence-free (RFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests. We then compared concordance indices of discriminatory prognostic ability and area under the curve (AUC) of 5-year survival to predict RFS/OS. All statistical tests were two-sided. RESULTS:Stage IIC continued to have worse outcomes than those for stage IIIA patients, with 5-year RFS of 26.5% (95%CI=12.8-55.1%) vs. 56.0% (95%CI=37.0-84.7%) by AJCC8 (P = 0.002). For stage I, removing mitotic index as T classification factor decreased its prognostic value, although not statistically significantly (RFS C-index=0.63 [95%CI=0.56-0.69] to 0.56 [95%CI=0.49-0.63], P = 0.07; OS C-index=0.48 [95%CI=0.38-0.58] to 0.48 [95%CI=0.41-0.56], P = 0.90). For stage II, prognostication remained constant (RFS C-index=0.65 [95%CI=0.57-0.72]; OS C-index=0.61 [95%CI=0.50-0.72]), and. For stage III, AJCC8 yielded statistically significantly enhanced prognostication for RFS (C-index=0.65 [95%CI=0.60-0.70] to 0.70 [95%CI=0.66-0.75], P = 0.01). CONCLUSIONS:Compared with AJCC7, we demonstrate that AJCC8 enables more accurate prognosis for patients with stage III melanoma. Restaging a large cohort of patients can enhance the analysis of active clinical trials.