ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P312

Prognostic factors in localized adrenocortical carcinoma (ACC) after complete resection

Jens Obracay1, Martin Fassnacht1, Wolfgang Saeger2, Sarah Johanssen1, Quinkler Marcus3, Tobias Linden4, Koschker Ann-Kathrin1, Wortmann Sebastian1, Michael Morcos5, Holger Willenberg6, Peter Langer7, Matthias Behrend8, Silke Klose9, Nicole Reisch10, Michael Brauckhoff11, Stephan Petersenn12, Peter Bucsky4, Wolfgang Oelkers3, Uwe Maeder13, Stefanie Hahner1 & Bruno Allolio14

1Department of Medicine I, University Hospital, Wuerzburg, Germany; 2Marienkrankenhaus, Hamburg, Germany; 3Charite, Berlin, Germany; 4Coordinating Center for the GPOH-MET 97 Study, Lübeck, Germany; 5University Hospital, Heidelberg, Germany; 6University Hospital, Duesseldorf, Germany; 7University Hospital, Marburg, Germany; 8Hospital, Deggendorf, Germany; 9University Hospital, Magdeburg, Germany; 10University Hospital, Muenchen, Germany; 11University Hospital, Halle, Germany; 12University Hospital, Essen, Germany; 13University Hospital, Tumor Center, Wuerzburg, Germany; 14University Hospital Wuerzburg, on Behalf of the German Adrenal Network GANIMED, Wuerzburg, Germany.

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: 59–78%) vs 36% (13–58); P<0.01) or with uncertain resection status (Rx; n=72)(51% (37–65%); 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: 0.27–0.55)), atypical mitosis (HR 0.43 (0.31–0.59)), mitoses >5/50HPF (HR 2.3 (1.6–3.2)), advanced age (HR 1.02 (1.01–1.02)), positive lymph nodes (HR 3.2 (1.9–5.1)), and vascular invasion (HR 1.8 (1.3–2.4)). Furthermore, spongiocytic tumor cells <25% (HR 6.9 (2.6–18.1)), tumor (thrombus) in the v.cava (HR 2.8 (1.9–4.0)), and positive lymph nodes (HR 3.5 (2.3–5.3)) 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.

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