BACKGROUND: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.METHODS: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.RESULTS: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.CONCLUSIONS: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. Cancer 2009. © 2009 American Cancer Society.

Adrenocortical carcinoma (ACC) is a rare malignancy, and patients with ACC have a poor prognosis. Even after radical surgery, up to 85% of patients develop recurrent disease. Systemic treatment options still have limited efficacy. Because the role of radiotherapy is not defined well and because ACC often is considered radioresistant, the authors reviewed the available data on radiotherapy for ACC. Original articles and reviews were identified using a PubMed search strategy that included the period up to July 2008. Ten articles were identified that covered radiotherapy in a total of 129 patients with ACC (64 patients received postoperative irradiation, and 65 patients received palliative therapy for advanced disease). In addition, 26 patients were identified in the German ACC Registry who received palliative radiotherapy. Furthermore, patterns of failure after adjuvant radiotherapy were investigated, and the authors provided recommendations for patient selection, treatment planning, and treatment protocols. In an adjuvant setting, postoperative radiotherapy was able to prevent local recurrence in the majority of patients. In those with advanced disease, a response to radiotherapy was observed in 57% of patients who received palliative radiotherapy. Therefore, the authors concluded that radiotherapy may play an important role in the care of patients with ACC. Until better evidence is available, the authors recommended the following approach: Adjuvant radiotherapy to the tumor bed should be considered in patients at high risk for local recurrence (eg, incomplete/R1 resection); a total dose of >40 grays (Gy) with single fractions of 1.8 Gy to 2 Gy should be administered (including a boost volume to reach from 50 Gy to 60 Gy in individual patients); and radiotherapy in a palliative setting may be used for symptomatic metastases to bone, brain, or vena cava obstruction. With state-of-the-art technology, acute and long-term toxicities mostly were mild to moderate. However, the authors concluded that prospective investigations would be required to fully define the therapeutic potential of this important treatment option.

Patients who are followed up prospectively after surgery for stage II ACC and receive early specialized care have a much better prognosis than previously reported due to a major referral bias in previous series and use of adjuvant mitotane. These findings will impact on the perception of prognosis in newly diagnosed stage II ACC.