Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma

TLDR

Adrenocortical carcinoma is a rare malignancy, and the International Union Against Cancer first defined TNM criteria and published a staging classification in 2004. The study aimed to evaluate the prognostic value of the 2004 UICC staging system for ACC and to propose a revised European Network classification with improved accuracy. Using the German ACC Registry, 416 patients were staged per UICC criteria and followed for disease‑specific survival, with analysis of risk factors and definition of a revised European Network staging system. Kaplan‑Meier analysis revealed stage‑dependent disease‑specific survival, but stage II and III had similar outcomes, and stage IV without metastases fared better than metastatic disease; key risk factors were tissue infiltration, venous tumor thrombus, and positive lymph nodes, underscoring limitations of the UICC staging and supporting the revised classification.

Abstract

Adrenocortical carcinoma (ACC) is a rare malignancy, and it was only in 2004 that the International Union Against Cancer (UICC) defined TNM criteria and published the first staging classification. However, to date, the prognostic value of the proposed classification has not been evaluated.The German ACC Registry comprising 492 patients was searched for patients who were diagnosed between 1986 and 2007 with detailed information on primary diagnosis and a minimum follow-up of 6 months. Patients were assigned to UICC tumor stage, and disease-specific survival (DSS) was assessed. In addition, the contribution of potential risk factors for DSS was evaluated.In total, 416 patients with a mean follow-up of 36 months met the inclusion criteria (stage I, n=23 patients; stage II, n=176 patients; stage III, n=67 patients; stage IV, n=150 patients). Kaplan-Meier analysis revealed a stage-dependent DSS. However, DSS in patients with stage II ACC did not differ significantly from DSS in patients with stage III ACC (hazard ratio, 1.38; 95% confidence interval, 0.89-2.16). Furthermore, patients who had stage IV ACC without distant metastases had an improved DSS compared with patients who had metastatic disease (P=.004). An analysis of different potential risk factors for defining stage III ACC revealed important roles in DSS for tumor infiltration in surrounding tissue, venous tumor thrombus (VTT), and positive lymph nodes; whereas tumor invasion in adjacent organs carried a prognosis similar to that of infiltration in surrounding tissue only.The 2004 UICC staging classification for ACC has significant limitations. On the basis of the current analysis, a revised classification with superior prognostic accuracy is proposed (the European Network for the Study of Adrenal Tumors classification). In this system, stage III ACC is defined by the presence of positive lymph nodes, infiltration of surrounding tissue, or VTT; and stage IV ACC is restricted to patients with distant metastasis.