Adrenocortical cancer

Introduction to adrenocortical cancer
Malignant tumors arising from the adrenal cortex are usually highly malignant. The management of these patients should be centralized.

Diagnosis and treatment of adrenocortical cancer
Adrenocortical cancer is a rare disease, with a reported incidence of about 1-2 per million. Signs of hormone excess, most commonly cortisol (but sometimes also sex hormones or aldosterone), is present in about 60% of patients. The diagnosis may be clear in metastatic disease after needle biopsy, or after surgery of a large adrenal mass. It is not recommended to biopsy an adrenal tumor for diagnosis since rupture of the tumor capsule may induce local spread of disease. Imaging may demonstrate a tumor thrombus in the left renal or caval veins also being indicative of malignancy. The use of 11C-metomidate PET (a tracer highly specific for adrenocortical tissue) may also discover unknown metastases.

Surgery is the only method with the potential to cure adrenocortical cancer. However, even when the tumor seems to have been radically removed, there is a risk of recurrence. In fact, the majority of patients (60-80%) who have undergone ”radical” surgery will eventually have recurrent disease. Adjuvant treatment is therefore offered. Some centers give external radiotherapy to the operated area. This is reported to decrease the risk of local recurrence, but no benefit in survival has ever been demonstrated.

Mitotane (Lysodren®) is a substance that inhibits steroid hormone synthesis, and is toxic to adrenocortical cells. It is commonly used as an adjuvant treatment, and as a component of chemotherapy regimens used to treat metastatic disease. There are two chemotherapy regimens commonly used to treat disseminated adrenocortical cancer: 1. Streptozotocin + Mitotane or 2. Etoposide, doxorubicin, cisplatin and Mitotane. None of these regimens are sufficient for many patients, but a phase III study (in fact, the first randomised study in adrenocortical cancer) is currently underway to compare the two regimens. More research in this area is needed.

First international randomized trial on locally advanced and metastatic adrenocortical carcinoma treatment (FIRM-act).
Adrenocortical carcinoma (ACC) is a rare disease with poor prognosis. Treatment of ACC has never been subjected to randomized GCP trials. Uppsala initiated a collaboration between ACC specialist in Europe, USA and Australia in order to reach an agreement on a protocol for an un-sponsored academic phase III survival study.

The study is registered and listed by NIH for ongoing clinical trials.

www.clinicaltrials.gov

The Endocrine Tumorbiology group with Prof. Britt Skogseid and system developer Mikael Björk has designed an electronic CRF, and the data collection is entirely internet based.

www.firm-act.org