Rethinking the definition of stage IV disease in adrenocortical carcinoma: Assessing the impact of clinical lymph node positive disease.

Background: Stage III (pT3N0M0 or pT1-3N1M0) adrenocortical carcinoma (ACC) encompasses both lymph node positive (LN+) and lymph node negative (LN-) disease. However, in other malignancies, prior data demonstrates that LN+ disease portends outcomes similar to metastatic, stage IV disease. We similarly wanted to examine the impact of clinical LN+ disease on oncologic outcomes in ACC. Methods: Patients with clinical stage III and stage IV (M1) disease were identified using the National Cancer Database (NCDB). Stage III patients were stratified as having either LN+ or LN- disease. Kaplan-Meier curves illustrated overall survival of the three groups – stage III LN-, stage III LN+, and stage IV. Further analysis stratified stage III LN+ and stage IV patients by whether or not patients received treatment (systemic therapy, surgery, or both). Results: A total of 917 patients were included in the analysis – 322 stage III LN-, 67 stage III LN+, and 528 stage IV. 3-year OS for patients with stage IV, stage III LN+, and stage III LN – was 15.6% (95% CI, 12.5%-19.4%), 29.4% (95% CI, 19.8%-43.6%), and 48.6% (95% CI, 43.2%-54.6%), respectively. Within the stage III LN+ group 3-year OS was 33.0% (95% CI, 18.5%-58.8%) for those who received treatment and was 27.4% (95% CI, 16.1% - 46.6%) for those who did not. Within the stage IV group 3-year OS was 29.8% (95% CI, 22.7%-39.3%) for those who received treatment and was 10.2% (95% CI, 7.4% - 14.2%) for those who did not. Conclusions: The current staging paradigm of ACC includes LN+ disease as part of the stage III classification. Herein, we see that clinical stage III LN+ disease had a 3-year OS that was more similar to clinical stage IV disease than clinical stage III LN- disease. While the survival curves appear distinct, due to the rarity of the disease and therefore small sample size there was overlapping confidence intervals. In stage IV patients there was a significant difference in OS at 3 years between those who did and did not receive treatment. This same finding was not found in stage III LN + patients.