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The Efficacy of Adjuvant Mitotane Therapy and Radiotherapy Following Adrenalectomy in Patients With Adrenocortical Carcinoma: A Systematic Review and Meta-Analysis Publisher Pubmed



Tsuboi I1, 2, 3 ; Kardoust Parizi M1, 4 ; Matsukawa A1, 5 ; Mancon S1, 6 ; Miszczyk M1, 7 ; Schulz RJ1, 8 ; Fazekas T1, 9 ; Cadenar A1, 10 ; Laukhtina E1, 11 ; Kawada T1, 3 ; Katayama S1, 3 ; Iwata T1, 3 ; Bekku K1, 3 ; Wada K1, 2 Show All Authors
Authors
  1. Tsuboi I1, 2, 3
  2. Kardoust Parizi M1, 4
  3. Matsukawa A1, 5
  4. Mancon S1, 6
  5. Miszczyk M1, 7
  6. Schulz RJ1, 8
  7. Fazekas T1, 9
  8. Cadenar A1, 10
  9. Laukhtina E1, 11
  10. Kawada T1, 3
  11. Katayama S1, 3
  12. Iwata T1, 3
  13. Bekku K1, 3
  14. Wada K1, 2
  15. Remzi M1
  16. Karakiewicz PI12
  17. Araki M3
  18. Shariat SF1, 9, 11, 13, 14, 15, 16, 17, 18
Show Affiliations
Authors Affiliations
  1. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  2. 2. Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan
  3. 3. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  4. 4. Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Urology, Jikei University School of Medicine, Tokyo, Japan
  6. 6. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
  7. 7. Collegium Medicum - Faculty of Medicine, WSB University, Dabrowa Gornicza, Poland
  8. 8. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  9. 9. Department of Urology, Semmelweis University, Budapest, Hungary
  10. 10. Unit of Oncologic Minimally Invasive Urology and Andrology, Department of Experimental and Clinical Medicine, Careggi Hospital, University of Florence, Florence, Italy
  11. 11. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russian Federation
  12. 12. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, QC, Canada
  13. 13. Department of Urology, University of Texas Southwestern, Dallas, TX, United States
  14. 14. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
  15. 15. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan
  16. 16. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria
  17. 17. Research center of Evidence Medicine, Urology department Tabriz University of Medical Sciences, Tabriz, Iran
  18. 18. Department of Urology, Weill Cornell Medical College, New York, NY, United States

Source: Urologic Oncology: Seminars and Original Investigations Published:2025


Abstract

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. © 2024 The Author(s)