Treatment and Prognosis of Primary Adrenalcortical Adenocarcinoma—Report of 21 Cases

DISCUSSION

Adrenocortical adenocarcinomas are rare malignant neoplasms of the adrenal cortex. The annual incidence of these tumors has been reported to be approximately between 0.5 and 2 per 1 × 10⁶ population, accounting for 0.2% of all malignant tumors. Adrenocortical adenocarcinoma can develop at any age from early infancy to the seventh and eighth decades of life with most presenting at ages 40 to 50 years.^[1-4] Most of these cancers are unilateral, and on the left side.

Based on endocrine manifestations and hormonal activity, tumors have been classified as functional or nonfunctional, having a different distribution in many studies.^[5] Most of our patients with functional tumors were adults, and those with nonfunctional tumors were children. Most adults presented with Cushing’s syndrome, whereas abnormal sexual characteristics were seen in children. Patients with nonfunctioning tumors or no recognizable endocrine symptoms presented with clinical manifestation related to the growth of the tumor itself. The most common complaint was abdominal pain and/or a palpable tumor. Other clinical features included weight loss, weakness, fever, anorexia and nausea.^[5,6] Some patients presented with symptoms of metastatic disease before a primary diagnosis was established. Most common sites of metastases included the liver, lung, and bones. Based on symptoms and signs, laboratory findings and imaging, patients with a functional tumor were easily diagnosed. But patients with nonfunctional tumors were difficult to diagnose in an early stage, because of an absence of special symptoms and signs. Patients with a nonfunctional tumor mostly were diagnosed at an advanced stage. Staging at diagnosis was based on the results of radiological and pathological studies. Stage I disease was defined as a primary adrenal tumor less than 5 cm in diameter and as Stage II if it was a primary tumor greater than 5 cm in diameter. Tumors of both stages showed no local or distant extension. In contrast, Stage III disease was defined as a primary tumor of any size with limited extension into the peri-adrenal fat or to regional lymph nodes. Stage IV disease was defined as a primary tumor of any size invading adjacent organs or with spread to distant sites.

Imaging is the key to diagnosing adrenocortical adenocarcinoma. Modem day imaging, including ultrasound, computerized tomography (CT) and magnetic resonance imaging, have greatly improved the diagnosis and staging of adrenal carcinoma. Most studies indicate that malignant adrenal lesions tend to be 5 cm or greater, present with blurred margins, an irregular shape, heterogeneity, and calcification, as well as any associated necrosis and invasion (extracapsular invasion, vascular invasion and venous thrombosis). ^[7,8] Magnetic resonance imaging (MRI) is superior to CT in some aspects. MRI is more sensitive for evaluating adrenal tumors for thrombosis in blood vessels, particularly in the vena cava, adrenal and renal vein extensions, and to distinguish benign from malignant tumors.

Curative surgery is the most effective treatment of all primary and recurrent tumors, even with local invasion and distant spread. Resection in the operation includes the ipsilateral adrenal, peri-adrenal fat and local-region of possible invasion. But for patients with no adjacent invasion, extensive radical adrenalectomy and retroperitoneum lymph nodes dissection are not conducive to improve the survival rate.^[5] The prognoses of inoperable adrenal cortical carcinoma and incomplete operation of patients are poorer due to lack of effective treatment modalities. The tumors usually present with adhesions and fixation, which are difficult to separate. Subcostal incisions provide a comparatively ideal surgical approach. Because of a comparatively large exposure, it is easy to completely resect the tumor and handle blood vessel bleeding due to trauma, that may occur in the vena cava, arteriae aorta or the blood vessels of the kidney pedicle. ^[9] Adrenal cortical carcinomas appear to have a tendency to invade adjacent organs, so it is of the utmost importance to prepare to resect adjacent organs such as the kidney, spleen and partial lobes of the liver. In our study of 21 adrenocortical adenocarcinomas, 2 cases received adrenalectomy plus nephrectomy and one received adrenalectomy plus partial hepatectomy.

Adrenocortical adenocarcinomas often recur after an operation. Many studies show that medical therapy with mitotane and its successors appear to be of little benefit for decreasing the recurrence rate and improving survival.^[1,5,10] Reoperation for a solitary local recurrent tumor should be attempted whenever possible,^[11] as surgery was followed by longer survival than simple medical therapy, and both relieved the symptoms of excessive steroid secretion.

The prognosis of patients with adrenocortical adenocarcinoma is generally poor. Factors associated with an unfavorable prognosis were tumor stage^{[1,2,5,6,10-14]} and size,^[15,16] vascular invasion, positive surgical margins and histopathology after operation.^[17,18] The prognosis for adrenocortical adenocarcinoma is generally better for low stage and small size tumors in contrast to high stage and a large size. For tumors in Stages I to IV, approximate 5-year survival was 30% to 45%, 12.5% to 57%, 5% to 18% and 0%, respectively.^[19] Over-all 3 and 5-year patient survival rates of the patients were 37.5% and 25.1%, respectively. Patient 3 and 5-year survival rates with localized disease were 51.0% and 43.9%, respectively, in contrast to 3 and 5-year survival rates of the patients with local invasion and distant spread which were 12.5% and 5.5%, respectively. ^[2] Our study of 21 adrenocortical adenocarcinoma patients indicate that the over-all 2 and 5-year survival rates were 52.4% (11/21) and 23.8% (5/21), respectively.

In conclusion, the prognosis for adrenocortical adenocarcinoma patients is generally poor. Early diagnosis and curative surgery were the most effective treatments.