The Role of Adjuvant Radiotherapy in Non-Metastatic Adrenocortical Carcinoma: Analysis of a National Hospital-Based Registry

Abstract

Adrenocortical carcinoma (ACC) is a rare tumor, and the treatment paradigm has been largely based on small retrospective studies. The use of post-operative radiation therapy (PORT) is controversial. Using a national hospital-based registry, this study aims to further characterize the patient population who may benefit from PORT.The National Cancer Database was queried for ACC by site and histology as specified by the ICD-O-3. Only patients with histologic confirmation were included. Patients with metastatic disease, non-oncologic surgical procedures, or death within 30 days of surgery were excluded. Patients were stratified by receipt of PORT. Those who received radiation to other sites, presumably for metastatic disease, were excluded. Analysis between groups was done by chi-square test, Fisher's exact test, and student's t-test. Optimal-full propensity score matching for the receipt of PORT was performed. Survival analysis was done using the Kaplan-Meier method with differences compared by the log-rank test. Cox-proportional hazards models were generated to determine significant predictors of survival.A total of 1557 patients were diagnosed with ACC from 2004-2017. The mean age was 61.1 (40-90), 59% were female, the median follow up was 11.1 months, and 24.5% had distant metastasis. 755 patients with histologically confirmed non-metastatic ACC underwent oncologic surgery, with 95 (12.6%) receiving PORT. Compared to those who underwent surgery alone, patients who received PORT were more likely to have a diagnosis in 2009 or later (75.8 vs 46.4%; P < 0.0001), a Charlson Deyo comorbidity score (CDCC) of 0 (82.1 vs 67.7%; P = 0.004), a higher clinical T stage (20.0 vs 11.5%; P = 0.0004), a higher pathologic T stage (39.0 vs 18.6%; P < 0.0001), lymphovascular invasion (34.6 vs 15.0%; P < 0.0001), positive resection margins (37.9 vs 18.2%; P < 0.0001), and chemotherapy (51.6 vs 27.0%; P < 0.0001). On propensity matched analysis, patients who received PORT had worse median survival compared to those who underwent surgery alone (19.5 vs 22.8 months; P = 0.042). On multivariate analysis, factors associated with survival included clinical T4 stage (HR 2.06, 95% CI 1.01-4.19), CDCC > 0 (HR 1.28, 95% CI 1.02-1.60), and negative resection margins (HR 0.66, 95% CI 0.54-0.79); PORT was not significantly associated with survival (P = 0.65). There was no difference in survival between PORT and surgery alone even for patients with positive resection margins (HR 0.77 95% CI 0.52-1.15).Use of PORT in treating ACC has significantly increased in recent years, especially for disease with high-risk features; however, results of our analysis suggest radiation therapy does not confer a survival benefit in the adjuvant setting. Given the rarity of the disease and lack of prospective randomized data, the decision for PORT should be individualized.