Melanoma Prognosis: Accuracy of the American Joint Committee on Cancer Staging Manual Eighth Edition

Abstract

Background: The American Joint Committee on Cancer (AJCC) maintains that the eighth edition of its Staging Manual (AJCC8) has improved accuracy compared with 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 with AJCC7.

Methods: We analyzed a cohort of 1315 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 of 5-year survival to predict RFS and OS. All statistical tests were two-sided.

Results: Stage IIC patients continued to have worse outcomes than stage IIIA patients, with a 5-year RFS of 26.5% (95% confidence interval [CI] = 12.8% to 55.1%) vs 56.0% (95% CI = 37.0% to 84.7%) by AJCC8 (P = .002). For stage I, removing mitotic index as a T classification factor decreased its prognostic value, although not statistically significantly (RFS concordance index [C-index] = 0.63, 95% CI = 0.56 to 0.69; to 0.56, 95% CI = 0.49 to 0.63, P = .07; OS C-index = 0.48, 95% CI = 0.38 to 0.58; to 0.48, 95% CI = 0.41 to 0.56, P = .90). For stage II, prognostication remained constant (RFS C-index = 0.65, 95% CI = 0.57 to 0.72; OS C-index = 0.61, 95% CI = 0.50 to 0.72), and for stage III, AJCC8 yielded statistically significantly enhanced prognostication for RFS (C-index = 0.65, 95% CI = 0.60 to 0.70; to 0.70, 95% CI = 0.66 to 0.75, P = .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.

Figure 1.

Recurrence-free survival (RFS) probability of stage I–III melanoma patients using American Joint Committee on Cancer Staging Manual Seventh Edition (AJCC7) and Eighth Edition (AJCC8). A) Stage IA and IB melanoma patients using AJCC7. B) Stage IIA, IIB, and IIC melanoma patients using AJCC7. C) Stage IIIA, IIIB, and IIIC melanoma patients using AJCC7. D) Stage IA and IB melanoma patients using AJCC8. E) Stage IIA, IIB, and IIC melanoma patients using AJCC8. F) Stage IIIA, IIIB, IIIC, and IIID melanoma patients using AJCC8. The Kaplan-Meier curves were generated for each substage with data from patients enrolled in the Interdisciplinary Melanoma Cooperative Group database at NYU Langone Health. The curves were compared, and P values were calculated using a two-sided log-rank test. The 5-year RFS probabilities with corresponding 95% confidence intervals for each substage are reported for both staging systems in the tables on the right.

Figure 2.

Overall survival (OS) probability of stage I–III melanoma patients using American Joint Committee on Cancer Staging Manual Seventh Edition (AJCC7) and Eighth Edition (AJCC8). A) Stage IA and IB melanoma patients using AJCC7. B) Stage IIA, IIB, and IIC melanoma patients using AJCC7. C) Stage IIIA, IIIB, and IIIC melanoma patients using AJCC7. D) Stage IA and IB melanoma patients using AJCC8. E) Stage IIA, IIB, and IIC melanoma patients using AJCC8. F) Stage IIIA, IIIB, IIIC, and IIID melanoma patients using AJCC8. The Kaplan-Meier curves were generated for each substage with data from patients enrolled in the Interdisciplinary Melanoma Cooperative Group database at NYU Langone Health. The curves were compared, and P values were calculated using a two-sided log-rank test. The 5-year OS probabilities with corresponding 95% confidence intervals for each substage are reported for both staging systems in the tables on the right.

Figure 3.

Recurrence-free survival (RFS) probability of stage IIC and IIIA melanoma patients using American Joint Committee on Cancer Staging Manual Seventh Edition (AJCC7) and Eighth Edition (AJCC8). A) Stage IIC and IIIA melanoma patients using AJCC7. B) Stage IIC and IIIA melanoma patients using AJCC8. The Kaplan-Meier curves were generated for each substage with data from patients enrolled in the Interdisciplinary Melanoma Cooperative Group database at NYU Langone Health. The curves were compared, and P values were calculated using a two-sided log-rank test.