Lymphadenectomy for Adrenocortical Carcinoma: Is There a Therapeutic Benefit?

Abstract

Background Lymph node metastasis is an established predictor of poor outcome for adrenocortical carcinoma (ACC); however, routine lymphadenectomy during surgical resection of ACC is not widely performed and its therapeutic role remains unclear. Methods Patients undergoing margin-negative resection for localized ACC were identified from a multi-institutional database. Patients were stratified into 2 groups based on the surgeon’s effort or not to perform a lymphadenectomy as documented in the operative note. Clinical, pathologic, and outcome data were compared between the 2 groups. Results Of 120 patients who met inclusion criteria from 1993 to 2014, 32 (27 %) underwent lymphadenectomy. Factors associated with lymphadenectomy were tumor size (12 vs. 9.5 cm; p = .007), palpable mass at presentation (26 vs. 12 %; p = .07), suspicious lymph nodes on preoperative imaging (44 vs. 7 %; p < .001), and need for multivisceral resection (78 vs. 36 %; p <.001). Median number of lymph nodes harvested was higher in the lymphadenectomy group (5.5 vs. 0; p < .001). In-hospital mortality (0 vs. 1.3 %; p =.72) and grade 3/4 complication rates (0 vs. 12 %; p = .061) were not significantly different. Patients who underwent lymphadenectomy had improved overall survival (5-year 76 vs. 59 %; p = .041). The benefit of lymphadenectomy on overall survival persisted on multivariate analysis (HR = 0.17; p = .006) controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging, and multivisceral resection. Conclusions In this multicenter study of adrenocortical carcinoma patients undergoing R0 resection, the surgeon’s effort to dissect peritumoral lymph nodes was independently associated with improved overall survival.

Role of Additional Organ Resection in Adrenocortical Carcinoma: Analysis of 167 Patients from the U.S. Adrenocortical Carcinoma Database

“…Intraoperative factors were obtained from the surgeon’s operative report (e.g., if a surgeon dictated that a LND was performed, this was recorded as such regardless of anatomic landmarks used as limits of dissection or number of lymph nodes removed). 23 The pathologic variables included tumor size, tumor weight, tumor-node-metastasis (TNM) stage, tumor grade, number of lymph nodes in the specimen, vein involvement, and margin status.…”

“…11,20–22 Performance of lymph node dissection (LND) also may be associated with improved survival. 23–25 …”

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors

“…According to large American and French series, approximately 10-30% of patients with ACC had formal lymphadenectomy as part of the tumor resection, reflecting the heterogeneity of operative management (25,198). A minimum of four lymph nodes should be retrieved in order to declare lymph node-negative cases (201) Furthermore, in an analysis of 120 cases identified from a multi-institutional database, the benefit of lymphadenectomy on overall survival persisted on multivariable analysis controlling for adverse preoperative and intraoperative factors associated with lymphadenectomy, such as tumor size, palpable mass, irregular tumor edges, suspicious nodes on imaging and multivisceral resection (202). The largest series so far included 283 patients and the resection of more than five lymph nodes reduced also the risk of local recurrence and disease-related death in a multivariate analysis (203).…”

Critical analysis of lymph node examination in patients undergoing curative‐intent resection for adrenocortical carcinoma

“…This is highlighted by the variety of definitions used to describe regional lymphadenectomy for ACC in studies evaluating its impact on prognosis and survival. 5,[12][13][14][15] Among these studies, reported rates of lymphadenectomy range from only 6% to 33%. 3,5,[12][13][14][15][16][17] Moreover, examination of any lymph nodes has been alarmingly low, with reported rates less than 35%.…”

“…5,[12][13][14][15] Among these studies, reported rates of lymphadenectomy range from only 6% to 33%. 3,5,[12][13][14][15][16][17] Moreover, examination of any lymph nodes has been alarmingly low, with reported rates less than 35%. 3,5,[12][13][14][15][16][17] Despite the low frequency of lymph node examination, nodal metastasis has been identified as an independent negative predictor of survival.…”