Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Quebec Canada

Collegium Medicum Faculty of Medicine WSB University Dąbrowa Górnicza Poland

Department of Biomedical Sciences Humanitas University Pieve Emanuele Italy

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Jikei University School of Medicine Tokyo Japan

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology Semmelweis University Budapest Hungary

Department of Urology Shariati Hospital Tehran University of Medical Sciences Tehran Iran

Department of Urology Shimane University Faculty of Medicine Shimane Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX

Department of Urology Weill Cornell Medical College New York NY

Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Research center of Evidence Medicine Urology department Tabriz University of Medical Sciences Tabriz Iran

Unit of Oncologic Minimally Invasive Urology and Andrology Department of Experimental and Clinical Medicine Careggi Hospital University of Florence Florence Italy

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