We appreciate the letter by Grubbs and Lee regarding our article concerning the staging classification of adrenocortical carcinoma (ACC)1 and their endorsement of a revision to the International Union Against Cancer (UICC) staging system. We fully understand and support their request to acknowledge appropriately the prior contributions of other investigators. In fact, in our article, we cite all the publications they mention and refer specifically to the work by Lee et al, who already proposed in 1995 that the stage IV classification should be limited to patients with distant metastases and also introduced venous tumor thrombus as a criterion for stage III disease.2 The theoretic concept of this classification by Lee et al is related to the surgical approach to ACC and had already appealed to us in 2003 when we established the German Adrenocortical Carcinoma Registry. Therefore, we used this system as the standard staging system in our registry for the first 5 years. However, our current analysis identified a significant weakness of the classification of Lee et al2 with regard to the definition of stage III disease. According to Lee et al, tumors infiltrating surrounding tissue are classified as stage II and only those tumors invading neighboring organs are termed stage III tumors.2 However, based on our analysis, we suggest defining any locally invasive tumor as stage III, because there was no survival difference noted in our study between tumors infiltrating only surrounding tissue and tumors that invaded neighboring organs as well (see Fig. 3D of our article).1 Therefore, 45 of 416 patients (10.8%) in our published cohort who were classified as having stage III disease would have been described as having stage II disease using the classification of Lee et al.2
However, as discussed in our article,1 tumor staging classification is a dynamic process. Thus, continuous re–evaluations, revisions, and improvements also can be expected for ACC staging systems. Furthermore, the results of our study should be confirmed in an independent cohort. In fact, we are convinced that further improvement is possible only when international groups join forces and collect and analyze together large cohorts of patients with ACC.