Abstract
BACKGROUND: Reports of long-survival patients (>10 years) with metastatic adrenocortical carcinoma (ACC) and prolonged treatment with mitotane alone (>5 years) are rare. We present four patients treated for low tumour burden (LTB) metastatic ACC using multidisciplinary approaches, including long-term mitotane, who maintained a relatively good life quality for over 10-year survival. CASE SERIES PRESENTATION: Four patients (one female) aged 34-52 years underwent adrenalectomy for ACC between 2004 and 2013. Two patients presented only with flank pain, while two presented with overt Cushing's Syndrome. Ki-67 index ranged from <1% to 37%, and European Network for Study of Adrenal Tumour (ENSAT) tumour stage ranged from 2 to 3. Time to first recurrence ranged from 8 to 48 months. Overtime, all patients experienced recurrent metastatic disease, mostly in lungs or liver. From 2008 to 2024, we recorded a total of two stereotactic ablative radiotherapies, one microwave and eight radiofrequencies ablations, 10 liver and eight lung resections and three selective excisions for other abdominal metastases. Mitotane treatment lasted from 7.7 to 12.9 years, with mitotane average dose and plasma levels equal to 2.6 ± 0.9 g/day (±standard deviation) and 20.4 ± 5.3 mg/L, respectively. Our patients developed different degrees of mitotane-induced hypothyroidism, hypogonadism, hypercholesterolaemia and mineralocorticoid insufficiency as well as episodes of neurologic and gastrointestinal side effects, which were countered with continuous dose adjustments, hormonal replacement therapies and specific treatments. Specialist nurses provided continuous support for mitotane dose titration and management of mitotane-induced adverse effects. All the patients were still taking mitotane at last available follow-up visit without radiological evidence of tumour manifestations, with a follow up duration ranging from 11.5 to 20 years from initial surgery. CONCLUSION: Metastatic ACC should be managed by multidisciplinary tailored approaches, including close surveillance and local therapies (LT). In patients with LTB, prolonged mitotane therapy can represent a safe option to slow down disease progression and contribute to prolonging survival.