Adrenocortical cancer (ACC) treatment

Your adrenal glands are located at the top of each kidney and these are responsible for the production of vital hormones such as cortisol. Like all organs, the adrenal glands can succumb to cancer. Mr Radu Mihai is a renowned general and endocrine surgeon who has performed many procedures for patients with adrenocortical cancer (ACC). In this article, he provides you with an in-depth understanding of its treatment.

What are a patient's treatment options for adrenal cancer?

Adrenocortical cancer (ACC) is a complex condition that needs individualised decisions based on:

• the extent of the cancer at the time of diagnosis
• the patient’s associated and pre-existing medical conditions

The scans performed before the operation (CT scans and/or PET scans) will determine the size of the adrenal tumour, check if the tumour has invaded nearby organs and will assess if metastases have occurred, which is when the disease spreads to distant organs via the bloodstream, such as to the liver or lung(s).

There are four methods of treating ACC:

1. Surgery is the main treatment option. For patients with localised tumours and no signs of metastases, this treatment offers the best long-term results. Metastasis is when cancer cells from the original tumour move to another part of the body (e.g. liver or lung), forming another tumour.
2. Mitotane will be recommended if surgery is not possible – this chemotherapy drug is the most commonly used chemotherapy for ACC.
3. Radiotherapy is an option although not routinely used as its benefits are still being argued.
4. Endocrine medication can control the excessive secretion of cortisol from the tumour but it is not routinely used - its effects are slow to be established and do not outweigh the risks of delaying the operation.

When is surgery an option?

Surgery is the cornerstone of treatment for all patients with ACC. In those with early disease (i.e. without metastases), radical removal of the tumour, surrounding fat and local lymph nodes lessens/mitigates the risk of recurring cancer in the same location, therefore improving long-term survival. In patients with metastatic disease, surgery still plays a role by removing a large tumour and consequently, improving the side effects of excess cortisol secretion. Then, mitotane alone or with other chemotherapy agents can be used to control the metastatic disease.

Surgery should also be considered for disease recurrence, mainly for fit patients with small-volume metastases, whose recurrence is diagnosed over 12 months after the initial operation and for whom surgery can provide complete excision of the new (recurrent) tumour(s).

Patients with tumours that are not amenable of being surgically removed should be discussed in centres with significant experience in dealing with advanced ACC. Invasion of the tumour in the surrounding blood vessels (e.g. renal veins, inferior vena cava) is not by itself a reason to not offer surgical intervention. Such patients raise significant operative challenges that can only be addressed in centres where collaboration with cardiac surgeons and liver surgeons is well versed.

What are the different types of surgery used?

1. Open adrenalectomy remains the standard of care for ACC. This is the best way of ensuring the tumour can be removed intact, without fragmenting or dividing the mass with the surrounding perirenal fat. It is also the only operation that can facilitate multiorgan resection (the process of cutting out tissue or part of an organ) for large tumours that need to be removed with the spleen and/or kidney.
2. Laparoscopic adrenal surgery is feasible for smaller tumours up to a maximum diameter of 6-8 cm, as long as the same oncological principles can be respected.
3. Minimally invasive surgery through the retroperitoneum should not be attempted as the small working space makes it very unlikely that the tumour will not be fractured during dissection.

How long does recovery take from surgery?

• Keyhole surgery (laparoscopic adrenalectomy) has undeniable benefits of shorter recovery (3-5 days).
• After open adrenalectomy, the average stay in hospital post-operation is seven days, so patients should expect to spend 5-10 days in hospital before being discharged. This is influenced by the patient’s age and ‘performance status’ before the operation, the extent of the operation, the use of epidural analgesia (pain relief) for open adrenalectomy and the need to establish a safe cortisol replacement regime.
• Because the incision interferes with core muscles, intense physical activities (swimming, tennis, gym, team sports) have to be delayed for a further 6-8 weeks.

What treatment would typically follow surgery?

If the tumour secreted too much cortisol, the remaining contralateral adrenal gland will remain ‘suppressed’ for many months and therefore patients need cortisol replacement. This is to be discussed with the endocrinology and surgical teams before the operation.

It is routine practice to offer 4-weeks course of prophylactic anticoagulation (medication to prevent blood clots) to all patients who had open resection of large tumours.

Patients with early disease who had a complete removal of the tumour are entered into a surveillance programme with repeat CT scans/PET scans at 3-6 months after the operation and every six months afterwards. Arguably, they benefit from mitotane as follow-up treatment (adjuvant medication, i.e. used to decrease the risk of the cancer recurring). This treatment is currently being assessed in a pan-European randomised trial (ADUVIO) and the results of this trial will inform future patients with ACC on whether or not to agree to have mitotane treatment in the absence of metastatic disease.

Where can I find more information about the treatment needed for ACC?

It is expected that the medical team in charge of your care (an endocrinologist and surgeon) will discuss your case in the local multidisciplinary meeting. The facts related to your condition will be explained to you before informed consent is obtained for future treatment.

There is a patient support group that can be contacted online (https://accsupport.org.uk) and they provide advice for patients with ACC. They can direct patients towards a medical centre closer to their home where expertise for the management of ACC is known to have been established

Several recent publications from the European Society of Endocrinology (ESE), European Society of Endocrine Surgeons (ESES) and European Network for the Study of Adrenal Tumours (ENSAT) have provided guidelines for the treatment of ACC - click here and here for access.

The ESES is of the opinion that surgery for ACC should be offered only in centres performing at least 12 adrenal operations per year. You are entitled to ask your local team what their personal experience with this condition is.

Mr Mihai has performed over 50 surgeries for adrenal gland cancer in the last 10 years and over 400 adrenal operations since his appointment as a Consultant Surgeon in Oxford in 2007. To learn more and to get in touch, see his profile.