From the Guidelines
Post-operative management of adrenocortical carcinoma (ACC) should prioritize complete en bloc resection of all adrenal tumors suspected to be ACC by a surgeon experienced in adrenal and oncological surgery, followed by adjuvant mitotane in patients at high risk of recurrence. The management of ACC post-operatively involves a multidisciplinary approach focusing on hormonal control, adjuvant therapy, and surveillance 1.
Key Considerations
- Complete en bloc resection is the mainstay of a potentially curative approach, with open surgery being the standard treatment, but laparoscopic adrenalectomy is reasonable for tumors <6 cm without evidence of local invasion, if the surgeon has sufficient experience 1.
- A locoregional lymphadenectomy is suggested, and perioperative hydrocortisone replacement is required in all patients with autonomous cortisol secretion 1.
- Adjuvant mitotane is recommended in patients at high risk of recurrence, including those with stage III, or R1-RX resection, and/or Ki-67 index >10% 1.
Adjuvant Therapy
- The use of adjuvant mitotane has been shown to delay and possibly prevent recurrence of disease, with a suggested dosing regimen guided by plasma measurements, aiming at a concentration between 14 and 20 mg/ml 1.
- Glucocorticoid replacement is necessary to cover adrenal insufficiency, and mineralocorticoid supplementation may be required in some patients 1.
Surveillance
- Regular surveillance includes clinical assessment, hormonal evaluations, and imaging (CT or MRI) every 3 months for the first 2 years, then every 3-6 months for at least another 3 years 1.
- Functional tumors require monitoring of relevant hormones to detect recurrence early, and management of complications like venous thromboembolism and metabolic disturbances is essential. The goal of post-operative management is to reduce recurrence risk, manage hormone excess, and improve long-term survival in this aggressive malignancy, with a comprehensive approach that prioritizes morbidity, mortality, and quality of life as the outcome.
From the Research
Post-Operative Management of Adrenocortical Carcinoma
- The management of adrenocortical carcinoma (ACC) post-operatively involves a multidisciplinary approach, including clinicians with expertise in adrenal tumors, such as endocrinologists, oncologists, surgeons, radiation oncologists, pathologists, geneticists, and radiologists 2, 3.
- Adjuvant mitotane treatment is suggested in patients after radical surgery who have a perceived high risk of recurrence, such as those with ENSAT stage III, R1 resection, or Ki67 >10% 2, 4.
- For patients with advanced ACC not amenable to complete surgical resection, local therapeutic measures such as radiation therapy, radiofrequency ablation, or chemoembolization may be of value 2, 5.
- Systemic therapy with mitotane and/or cytotoxic chemotherapy, such as etoposide, doxorubicin, and cisplatin (EDP), may also be considered for patients with advanced or recurrent disease 4, 5.
Role of Mitotane in Post-Operative Management
- Mitotane remains the only approved drug for adjuvant and palliative care in ACC 6.
- The time in target range (14-20 mg/l) is related to low risk of relapse both in adjuvant and in palliative setting 4.
- Adjuvant mitotane has been shown to significantly increase recurrence-free and overall survival in patients with ACC 5.
Emerging Therapies and Future Directions
- Targeted therapies, such as tyrosine kinase inhibitors and antibodies, and immunotherapy with checkpoint inhibitors are being explored as potential treatment options for ACC 6, 5.
- Individualized treatment concepts based on molecular characterization by next-generation sequencing methods may also be considered in the future 6.
- Ongoing clinical trials are investigating the efficacy of these emerging therapies, although only a small proportion of patients may be able to access these trials 5.