Adrenocortical carcinoma is a rare, highly malignant neoplasm that accounts for about 0.2% of cancer deaths. Long-term survival is poor overall; the survival rate is 23% at 5 years and 10% at 10 years.
The etiology of adrenocortical cancer is unknown, but some cases have occurred in families with a hereditary cancer syndrome (eg, multiple neoplasia type I, Li-Fraumeni syndrome, or Beckwith-Wiedemann syndrome).
Approximately half of adrenocortical neoplasms produce hormonal and metabolic syndromes of hormone hypersecretion (such as Cushing's syndrome, virilizing or feminizing syndromes, and hyperaldosteronism). In children, Cushing's syndrome is rare but is often due to adrenal carcinoma. Mixed syndromes, such as Cushing's syndrome and virilization, strongly suggest adrenal carcinoma. The combination of hirsutism, acne, amenorrhea, and rapidly progressing Cushing's syndrome in a young female is a typical presentation. In men, estrogen-secreting tumors are associated with gynecomastia, breast tenderness, testicular atrophy, impotence, and decreased libido.
Often, the diagnosis of adrenocortical carcinoma is not evident until the discovery of metastases or until the primary tumor becomes large enough to produce abdominal symptoms. Smaller tumors may be discovered incidentally, when unrelated abdominal complaints are investigated radiographically.
Adrenal gland tumors are staged according to local spread of disease, nodal status, and distant metastatic involvement, using the AJCC TNM system (Table 4).
Complete surgical resection is the treatment of choice in patients with localized disease, because it offers the best chance of extending the disease-free interval and survival.
Although laparoscopic adrenalectomy is often utilized for adenomas, its role in the management of adrenocortical cancer is controversial. Recent data have shown worse outcomes following laparoscopic resections, compared with open resections. Any disruption of the tumor capsule can lead to peritoneal dissemination; therefore, the open technique is often used.
Following resection, the role of adjuvant therapy is unknown, with no prospective data available. A retrospective study suggests that adjuvant treatment with mitotane (Lysodren) improves recurrence-free survival. Owing to the study methodology, however, the conclusions are not universally accepted.
Mitotane. This drug is one of only a few effective agents; it exerts a specific cytolytic effect on adrenocortical cells and has been used to treat unresectable or metastatic adrenocortical carcinoma. Only 15% to 30% of patients experience objective tumor regression, with a median duration of about 7 months. Mitotane is given at a dose of 4 to 8 g/day as tolerated, although the dosage is variable.
Chemotherapy. Limited studies of combination chemotherapy regimens, including cisplatin(Drug information on cisplatin)/etoposide/mitotane, cisplatin/etoposide/doxorubicin/mitotane, and streptozocin/mitotane, have demonstrated responses of between 35% and 50%. A recent randomized trial of 304 patients with advanced adrenocorical carcinoma compared mitotane with etoposide, doxorubicin(Drug information on doxorubicin) and cisplatin vs mitotane and streptozocin. There was no difference in survival; however, the three-drug combination produced superior response (23.2% vs 9.2%, P < .001) and progression-free survival (5 months vs 2.1 months, P < .001). The preferred treatment approach remains participation in a clinical trial, when available.
Controlling hormone hypersecretion. Hormone hypersecretion can be controlled medically, in most cases. Agents that are effective in reducing steroid production and in palliating associated clinical syndromes include the antifungal drug ketoconazole, 800 mg/day; aminoglutethimide (Cytadren), 1 to 2 g/day; and metyrapone (Metopirone), 1 to 4 g/day or higher as needed to control cortisol levels. These agents may be used alone or with mitotane.