Even after complete resection, patients with ACC have a high risk of relapse, and adjuvant treatment with mitotane is frequently recommended. Although mitotane has significant efficacy in this setting, it is associated with a wide range of side effects. As survival is highly variable, prognostic factors are of great interest to better guide adjuvant therapy after radical resection.
We analyzed clinical and histopathological data of patients without distant metastases registered with the German ACC registry (n=291). As patients with histologically confirmed complete resection (R0; n=162) have a significant better 5-year survival than patients with R1 resection (n=14)(68% (95%-CI: 5978%) vs 36% (1358); P<0.01) or with uncertain resection status (Rx; n=72)(51% (3765%); P=0.06), we only included patients with R0 resection in the detailed analysis.
In univariate analysis, the following factors were indicators of poor prognosis for disease-free and overall survival (DFS/OS): tumor size >8 cm, positive lymph nodes, tumor(thrombus) in v.cava, Ki67 >10%, absence of atypical nuclei or atypical mitoses, mitoses >5/50 HPF, spongiocytic tumor cells <25%, vascular invasion. Multivariate analysis demonstrated improved or impaired DFS (P<0.05) for the following factors: atypical nuclei (hazard ratio 0.39 (95% CI: 0.270.55)), atypical mitosis (HR 0.43 (0.310.59)), mitoses >5/50HPF (HR 2.3 (1.63.2)), advanced age (HR 1.02 (1.011.02)), positive lymph nodes (HR 3.2 (1.95.1)), and vascular invasion (HR 1.8 (1.32.4)). Furthermore, spongiocytic tumor cells <25% (HR 6.9 (2.618.1)), tumor (thrombus) in the v.cava (HR 2.8 (1.94.0)), and positive lymph nodes (HR 3.5 (2.35.3)) were associated with decreased overall survival. Using these factors, it is possible to calculate prognostic indices. A patient without any of these adverse risk factors has a 5-year disease-free survival rate of >90%.
In conclusion, we have identified important prognostic factors in ACC patients with R0 resection based on clinical and histological parameters. These factors may help to guide adjuvant therapy in ACC.
03 - 07 May 2008
European Society of Endocrinology