American Joint Committee on Cancer Tumor Staging System Predicts the Outcome and Metastasis Pattern in Conjunctival Melanoma

Abstract

Purpose: To assess the predictive value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, and histologic features for outcomes and metastasis patterns in conjunctival melanoma (CM).

Design: Retrospective, single-center cohort study.

Participants: Eighty-three patients with CM were treated at Shanghai Ninth People's Hospital between 2000 and 2021.

Methods: We reviewed the clinical and histologic parameters and used Kaplan-Meier survival curves and Cox proportional hazards regression models for risk factor analyses.

Main outcome measures: Time to nodal/distant metastasis, disease-specific survival, metastatic pattern, and metastatic site.

Results: At presentation, 5 patients (6%) had clinical tumor (cT)1 disease, 34 patients (41%) had cT2 disease, and 44 patients (53%) had cT3 disease. Four patients (5%) had nodal metastasis (N1), and none had distant metastasis (M1). During follow-up, 12 patients (14%) developed nodal metastasis, 29 patients (35%) developed distant metastasis, and 26 patients (31%) died of disease. The brain, liver, and lung were common distant metastasis sites. Higher cT category was associated with increased risks of distant metastasis (P < 0.001) and disease-specific death (P = 0.002). The separate analysis of primary and recurrent tumors at presentation showed that the patients with cT3 tumors had a higher risk of distant metastasis than those with cT2 tumors. Greater tumor thickness, ulceration, and the presence of regression were correlated with distant metastasis. Previously unreported mutations were detected in the tumor suppressor genes FAT atypical cadherin 4 (FAT4) and spleen associated tyrosine kinase (SYK). Among the 29 patients who developed distant metastasis, we analyzed 2 patterns of metastasis: Eleven patients (38%) developed nodal metastasis before distant metastasis, and 18 patients (62%) developed distant metastasis without previously known nodal metastasis. The patients with cT3 tumors were more likely to follow the latter metastasis pattern (P = 0.02).

Conclusions: Conjunctival melanoma presented with mostly advanced stages and high rates of distant metastasis in the current Chinese cohort. This study confirmed the prognostic value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, for Chinese patients. Histologic features, such as tumor thickness and ulceration, should be emphasized when assessing prognosis and guiding the treatment of CM.

Keywords: American Joint Committee on Cancer; Category; Conjunctival melanoma; Disease-specific survival; Metastasis.