Current evidence across the treatment spectrum of adrenocortical carcinoma: a comprehensive scoping review.

Abstract

Adrenocortical carcinoma is a rare and aggressive malignancy for which high-quality evidence to guide clinical decision-making remains limited. This scoping review aimed to map and synthesize the extent, nature, and direction of evidence across five therapeutic domains in the management of adrenocortical carcinoma. Following the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidance, MEDLINE, Embase, and the Cochrane Library were searched without date restrictions. Eligible sources included clinical trials, observational studies, systematic reviews, and clinical guidelines addressing any treatment modality for adrenocortical carcinoma. Data were extracted using a standardized form and synthesized narratively across domains. Evidence visualizations and an intervention-by-domain matrix were developed to identify areas of consistency, uncertainty, and research gaps. Forty-nine studies met the inclusion criteria. Complete tumor resection with negative margins consistently emerged as the strongest prognostic factor. Minimally invasive adrenalectomy showed comparable outcomes only in carefully selected low-risk patients. Adjuvant mitotane demonstrated potential benefit in high-risk disease but not in low- to intermediate-risk patients. In metastatic disease, multimodal management incorporating etoposide, doxorubicin, cisplatin, and mitotane, together with metastasectomy and local therapies, was associated with improved outcomes in selected cases. Recurrence was frequent and often occurred early, particularly in large or invasive tumors. Cortisol-secreting tumors were associated with higher postoperative morbidity and earlier recurrence. Although the available evidence is predominantly retrospective and heterogeneous, consistent patterns emerge that can inform clinical management. This review provides a structured evidence base for future consensus development and highlights priorities for further research.