Adrenocortical Cancer: Use of New ENSAT Staging System and Re-Evaluation of Old and New Markers of Prognosis

A modification of the TNM classification (WHO-UICC 2004) for adrenocortical cancer (ACC) has been recently proposed in order to improve the prognostic value as to the disease-free and disease-specific survival.(1) So far an increasing number of molecular markers has been proposed for early detection, confirmation of malignancy and/or outcome prediction, but none of them is considered as reliable as the Weiss score morphological system.(2,3) Aim: to compare the prognostic value of WHO-UICC 2004 and new ENSAT TNM staging classification in a single Institution ACC series as to the disease-free and disease-specific survival and to compare these findings with tumor Weiss score and ki67 expression. Methods: Clinical and pathological data of 26 pts (19F, 7M, median age 52 yrs, range 25-78) surgically treated for ACC, were retrospectively reviewed; the follow up period was 26 months (median, range 6-192). ACC staging was performed according to both WHO-UICC 2004 and ENSAT classification, tumor malignancy was assessed according to Weiss system. A multivariate analysis of disease-free and overall survival in ACC according to Weiss score and ki67 (IHC, monoclonal Mib1 Ab) was performed. Results: 70% of tumors were hypersecreting ; mean size was 10,7cm (range 50-2500), mean weight was 512g (range 50-2500). WHO-UICC identified 2 stage I, 11 stage II, 4 stage III and 9 stage IV disease (Kaplan-Meyer, log-rank test: p=0,0004). Two pts with stage IV WHO-UICC and good prognosis switched to stage III ENSAT (Kaplan-Meyer, log-rank test: p=0,0002). In our series ki67>7% (sensitivity 85,7%, specificity 62,5%, ROC analysis) and Weiss score>4 (sensitivity 100%, specificity 50%) were the best cut-off values suggestive for a poor prognosis (Kaplan-Meyer, p=0,06 and p=0,04 respectively); taken together the two risk factors showed a significant effect on survival probability (Cox-regression, p= 0,04). Ki67>7% and Weiss score>4 showed a slight correlation also with disease-free survival (Kaplan-Meyer, p=0,06 and p=0,04 respectively); when both risk factors were concomitantly present, the correlation with probability of disease recurrence was higher (Cox-regression, p=0,02). Conclusions: The outcome of pts with ACC is strictly related to the stage of the disease, being new ENSAT proposal a valuable tool to improve the power of the stage-related prognostic value. Ki67 expression and Weiss score combined may play a role of interest, but more reliable molecular markers are needed.