The effect of adrenalectomy on overall survival in metastatic adrenocortical carcinoma

Abstract

Context: Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown. Objective: This work aimed to assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting. Methods: Patients with mACC aged 18 years or older with metastatic ACC at initial presentation who were treated between 2004 and 2020 were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020), and we tested for differences according to adrenalectomy status. Intervention included primary tumor resection status (adrenalectomy vs no adrenalectomy). Kaplan-Meier plots, multivariable Cox regression models, and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs historical (2004-2011), single vs multiple metastatic sites, and assessable specific solitary metastatic sites (lung only and liver only). Results: Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; P < .001), as well as with 3 months' landmark analyses (HR: 0.57; P = .002). The same association effect with 3 months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49; P < .001), contemporary patients (HR: 0.57; P = .004), historical patients (HR: 0.42; P < .001), and in those with lung-only solitary metastasis (HR: 0.50; P = .02). In contrast, no statistically significant association was recorded in patients naive to systemic therapy (HR: 0.68; P = .3), those with multiple metastatic sites (HR: 0.55; P = .07), and those with liver-only solitary metastasis (HR: 0.98; P = .9). Conclusion: The present results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.