Alfredo Berruti1, Salvatore Grisanti1, Alina Pulzer2, Mélanie Claps1, Fulvia Daffara3, Paola Loli4, Massimo Mannelli5, Marco Boscaro6, Emanuela Arvat7, Guido Tiberio8, Stefanie Hahner9, Barbara Zaggia3, Francesco Porpiglia10, Marco Volante11, Martin Fassnacht2,9, Massimo Terzolo3. 1. Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, and. 2. Comprehensive Cancer Center Mainfranken, and. 3. Internal Medicine 1, Department of Clinical and Biological Sciences, San Luigi Hospital. 4. Endocrine Unit, Department of Medical Specialties, Ospedale Niguarda Cà Granda, 20162 Milano, Italy. 5. Department of Experimental and Clinical Biomedical Sciences "Mario Serio," University of Florence, 50121 Florence, Italy. 6. Endocrinology Unit, Department of Medicine, Padova University Hospital, 35122 Padova, Italy. 7. Oncological Endocrinology Unit, Department of Medical Sciences, and. 8. Surgical Clinic, Department of Medical and Surgical Sciences, University of Brescia, 25123 Brescia, Italy. 9. Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital, University of Würzburg, 97070 Würzburg, Germany. 10. Urology and. 11. Pathology Units, Department of Oncology, University of Turin, 10129 Torino, Italy.
Abstract
CONTEXT: In 2007, a retrospective case-control study provided evidence that adjuvant mitotane prolongs recurrence-free survival (RFS) in patients with radically resected adrenocortical carcinoma (ACC). OBJECTIVE AND DESIGN: We aimed to confirm the prognostic role of adjuvant mitotane in the same series after 9 additional years of follow-up. SETTING, PATIENTS, AND INTERVENTIONS: One hundred sixty-two ACC patients who did not recur or die after a landmark period of 3 months were considered. Forty-seven patients were enrolled in four Italian centers where adjuvant mitotane was routinely recommended (mitotane group), 45 patients in four Italian centers where no adjuvant strategy was undertaken (control group 1), and 70 German patients left untreated after surgery (control group 2). MAIN OUTCOME MEASURES: The primary aim was RFS, the secondary was overall survival. RESULTS: An increased risk of recurrence was found in both control cohorts [group 1: hazard ratio (HR) = 2.98; 95% confidence interval (CI), 1.75 to 5.09; P < 0.0001; group 2: HR = 2.61; 95% CI, 1.56 to 4.36; P < 0.0001] compared with the mitotane group. The risk of death was higher in control group 1 (HR = 2.03; 95% CI, 1.17 to 3.51; P = 0.011) but not in control group 2 (HR = 1.60; 95% CI, 0.94 to 2.74; P = 0.083), which had better prognostic factors and more aggressive treatment of recurrences than control group 1. The benefit of adjuvant mitotane on RFS was observed regardless of the hormone secretory status. CONCLUSIONS: Adjuvant mitotane is associated with prolonged RFS, without any apparent influence by the tumor secretory status. The retrospective nature of the study is a major limitation.
CONTEXT: In 2007, a retrospective case-control study provided evidence that adjuvant mitotane prolongs recurrence-free survival (RFS) in patients with radically resected adrenocortical carcinoma (ACC). OBJECTIVE AND DESIGN: We aimed to confirm the prognostic role of adjuvant mitotane in the same series after 9 additional years of follow-up. SETTING, PATIENTS, AND INTERVENTIONS: One hundred sixty-two ACC patients who did not recur or die after a landmark period of 3 months were considered. Forty-seven patients were enrolled in four Italian centers where adjuvant mitotane was routinely recommended (mitotane group), 45 patients in four Italian centers where no adjuvant strategy was undertaken (control group 1), and 70 German patients left untreated after surgery (control group 2). MAIN OUTCOME MEASURES: The primary aim was RFS, the secondary was overall survival. RESULTS: An increased risk of recurrence was found in both control cohorts [group 1: hazard ratio (HR) = 2.98; 95% confidence interval (CI), 1.75 to 5.09; P < 0.0001; group 2: HR = 2.61; 95% CI, 1.56 to 4.36; P < 0.0001] compared with the mitotane group. The risk of death was higher in control group 1 (HR = 2.03; 95% CI, 1.17 to 3.51; P = 0.011) but not in control group 2 (HR = 1.60; 95% CI, 0.94 to 2.74; P = 0.083), which had better prognostic factors and more aggressive treatment of recurrences than control group 1. The benefit of adjuvant mitotane on RFS was observed regardless of the hormone secretory status. CONCLUSIONS: Adjuvant mitotane is associated with prolonged RFS, without any apparent influence by the tumor secretory status. The retrospective nature of the study is a major limitation.
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