Adrenal metastasis originating from HCC is rare. In a cohort of 11770 HCC patients treated at Yonsei University Medical Center, Seoul, Korea, Park et al. observed 45 individuals with adrenal metastasis (0.4%), whereas Teegen et al. reported ten patients with HCC adrenal metastasis in a cohort of 1293 patients treated with either liver resection (990 patients) or liver transplantation (303 patients) for underlying HCC at Charité University Medical Center, Berlin, Germany (0.8%) [
11,
15]. In this sense, the seemingly small number of cases in the current cohort undergoing adrenalectomy for HCC adrenal metastasis (16 patients) represents a noteworthy collective of 25 years of surgical practice in our clinic. The prognosis of untreated HCC adrenal metastasis is poor, with overall survival described to be expectedly 6 months [
11,
20,
21]. Currently, there are no definitive guidelines of how to treat adrenal metastases originating from HCC [
11]. Potential treatment options are surgery, local ablative treatment (transcatheter arterial chemoembolization (TACE), percutaneous radiofrequency ablation, percutaneous ethanol injection therapy (PEIT) or radiotherapy) and systemic treatment (sorafenib), which should be chosen according to the overall condition of the individual patient concerned [
11,
13,
19,
20,
22‐
24]. Adrenalectomy was shown to be associated with significantly longer survival, compared to other treatment options [
11]. In the present cohort of patients with surgically treated HCC adrenal metastases, the choice of the primary therapy for HCC had an influence on the outcome. Overall survival was longer, if HCC was primarily treated with liver transplantation (median 66 months) or liver resection (median 51 months), compared to other primary therapy approaches (systemic treatment: median 35 months, local ablation: 23 months). Similarly, post-resection survival illustrated a more favorable outcome for surgically treated patients (liver resection or transplantation). Another factor which influenced overall survival was the onset of HCC adrenal metastasis: metachronous onset was associated with tendentially longer overall survival. In the present cohort, synchronous adrenal HCC metastasis was observed in three cases (all three cases received different primary HCC treatment: systemic treatment with sorafenib, local ablative treatment or liver resection with simultaneous adrenalectomy). The literature described that liver transplantation as a primary therapy for HCC was associated with later onset of metastasis to the adrenal gland, when compared to different primary treatment concepts [
15,
25]. Also, in the present cohort, the onset of adrenal metastasis was later, if the overall treatment concept included liver transplantation (median 24 months vs. 13 months). Yet, most patients of the present cohort received multimodal treatment in the course of disease (Fig.
1). Combinations of surgical treatment and local ablative treatment as well as combinations of these approaches with additional systemic treatment were common. The indication to perform surgery for adrenal metastases in the present cohort was based on interdisciplinary tumor board conference discussion and was either curative (13 of 16 cases) or to treat otherwise stable (i.e., therapeutically controlled) disease with singularly progressive adrenal metastasis (three of 16 cases). In this study, post-resection survival after adrenalectomy for adrenal HCC metastasis was 15 months in the entire group. Park et al. [
11] observed a superior post-resection survival after adrenalectomy of 21 months. In comparison, Teegen et al. [
15] reported a median post-resection survival of 69 months after adrenalectomy for metastatic HCC. Whereas the median overall survival in the present cohort of patients who underwent surgery for HCC adrenal metastasis was 35 months, Teegen et al. [
15] observed a median overall survival of 110 months. If patients had received liver transplantation, median overall survival in the cohort reported by Teegen amounted to 126 months [
15]. The inclusion of only recently operated patients with short follow-up accounts for the shorter overall survival times in our study. In addition, three cases of palliative adrenalectomy (19%) were included. Finally, changes in the surgical and oncological management over the past 25 years influenced the presently reported results, whereas the operations documented by Teegen et al. [
15] were collected from 2005 onward, resulting in a more homogeneous patient group.
Depending on tumor size and surgical expertise, minimally invasive techniques are considered suitable to resect locally confined adrenal metastases [
5,
26,
27]. In patients suffering from HCC, who in many cases harbor liver cirrhosis, portal hypertension and a potentially compromised blood coagulation, the use of minimally invasive techniques can be complicated. In the present cohort, two adrenalectomies were performed laparoscopically and one was resected via a retroperitoneoscopic approach. Minimally invasive techniques were chosen for tumors with a median diameter of 2.5 cm, whereas larger tumors (> 6 cm) prompted open adrenalectomy. Similarly, other centers reported the successful application of minimally invasive surgery for HCC adrenal metastasis [
15,
28]. Due to the extended interval of this retrospective study (25 years), changes in the surgical management and the primary choice of techniques might have influenced the observed distribution of surgical techniques: in the early study period, also for smaller tumors, open surgery was chosen for adrenalectomy. However—as a major drawback of the study—the absolute number of patients is associated with a limited statistical power, which has to be taken into account when considering the results. Furthermore, the selection of patients for adrenalectomy includes a bias with respect to tumor burden and comorbidities. Yet, a prospective randomized trial that investigates the benefits of adrenalectomy in these rare subgroups of patients will not be possible.
Therefore, adrenalectomy can be considered in selected patients with underlying metastatic HCC and should receive particular attention in patients with metachronous onset of disease and in patients with primarily performed liver transplantation or liver resection. It can be performed via minimally invasive approaches, dependent on tumor size and basic patient conditions.