Adrenal Cortical Cancer

Background

Adrenocortical cancer (ACC) is a very rare, but very deadly cancer of the adrenal glands. It arises from the outer layer of the adrenal gland called the cortex. There are only about 600 new cases diagnosed every year (about 1 case in one million people). It is most common either before the age of 10 or between 50 and 60 years of age. Fortunately, adrenocortical cancer in children is often diagnosed and treated at an early stage. For this reason, the prognosis for children is much better than for adults. Adults rarely have obvious symptoms, so they often are not diagnosed until the cancer is large and has spread to other parts of the body. Although adrenal cancer can be treated in adults, it usually comes back. Once it comes back, it is almost always fatal.

Signs and Symptoms

There is usually no obvious sign or symptom that an adult has an ACC. This fact makes it very hard to diagnose ACC at an early stage. These are typically aggressive tumors which grow quickly and spread rapidly. Occasionally, patients may feel pain in the back or sides because the tumor is growing so quickly or is very large. ACC can make too much of any of the hormones that the adrenal cortex makes (i.e. aldosterone, cortisol, sex hormones). The most common symptoms of this hormone overproduction are high blood pressure, weight gain, and diabetes. Since these are widespread conditions in middle-aged adults, the possible connection with an adrenal tumor is often overlooked until the disease is very far along. One key warning sign is if these symptoms develop rapidly.

If the adrenal tumor is slow-growing and non-functional – meaning it does not affect hormone production – there are no symptoms in the early stages of the disease. This type of tumor is sometimes diagnosed “by accident” if the patient has a CT scan for some other reason. (See Adrenal Incidentaloma)

Treatment

Complete surgical removal of the tumor is the only known way to cure adrenal cancer. The best opportunity for complete removal is at the first operation. Although laparoscopic removal is preferable for most small benign tumors, laparoscopic removal of ACC is very controversial with several noted endocrine surgeons being strongly opposed to this approach due to the risk of spreading cancer cells throughout the abdominal cavity at the time of surgery. These surgeons believe that all ACC should be removed with an open operation if it is known pre-operatively that the tumor is cancer. These surgeons have published data suggesting that patients undergoing laparoscopic resection of their ACC have a higher and earlier rate of tumor recurrence. A recent study from Europe, however, suggests that for tumors smaller than 10 cm, the results of laparoscopic surgery are equivalent to open. Regardless, an expert opinion should be obtained for surgical management decisions when dealing with adrenocortical carcinoma.

After surgery to remove the adrenal gland and surrounding tissue, patients may receive radiation or chemotherapy to reduce the risk of tumor recurrence. Mitotane, a drug that is a chemical relative of the pesticide DDT, has been shown to reduce the risk of tumor recurrence.

For advanced or metastatic ACC, the current standard chemotherapy regimen is a combination of drugs including doxorubicin, cisplatin, etoposide and mitotane. The most recent clinical trial comparing this combination to streptozotocin and mitotane (FIRM-ACT study) has been completed and results are pending. Results from a previous smaller study showed a response rate of 48%. For patients whose tumors progress despite standard chemotherapy, there are no proven second-line options. A multi-site phase III clinical trial using OSI-906, a blocker of insulin growth factor receptor type 1 has been completed and the results are pending.

Prognosis

Adult adrenocortical carcinoma are aggressive tumors with a very poor prognosis. The prognosis depends on the stage. Unfortunately, 60 to 70% of patients have stage III or IV disease at the time of diagnosis. The 5-year survival refers to the percent of patients on average who are alive 5 years after their diagnosis.

 Stage      Description                      5 year survival          Recurrence

    
I< 5 cm, contained in adrenal       65%         40%
II> 5 cm, contained in adrenal       65%         60%
IIICancer spread to areas near adrenal       40%    70 to 80%
IVMetastatic disease       10%      > 90%

Adrenal cancer often recurs, even after complete removal of the tumor. Treatment options for recurrent tumor include re-operation if all of the tumor can be removed. If local treatment of recurrent tumor and any metastatic disease cannot be offered, systemic therapy using mitotane and  platinum-based chemotherapy regimens may be the best option.