Paraneoplastic syndromes in palliative care

A paraneoplastic syndrome is a set of symptoms and signs (which are often quite unusual) caused by cancer that are not directly attributable to the presence of the tumour, metastases or the consequences of its treatment. These syndromes are caused by uncontrolled secretion of hormones by tumours (eg growth factors, analogues of parathyroid hormone, analogues of arginine vasopressin [AVP] [also known as antidiuretic hormone]), inflammatory mediators (eg cytokines, interleukins, antibodies), or other cell products (eg mucin) that react with normal tissues to cause changes in tissue function. There is a wide range of paraneoplastic syndromes; some are very rare, and others are common well-recognised complications of cancer. Paraneoplastic syndromes can occur at any time during the course of cancer; a syndrome may present at the time of diagnosis (eg digital clubbing, hypercalcaemia associated with cancer) or develop during their illness (eg cachexia–anorexia syndrome, syndrome of inappropriate antidiuretic hormone secretion [SIADH]).

Clinical manifestations occur at sites remote from the primary cancer or its metastases. Carcinoid syndrome is a paraneoplastic syndrome most commonly occurring in patients with liver metastases from carcinoid-type tumours of the gut, pancreas or lungs, and is due to excess histamine or serotonin secretion. It presents with wheezing, flushing and diarrhoea.

In advanced cancer, paraneoplastic syndromes do not necessarily reflect the extent or burden of the cancer, but if they are untreated or unresponsive to treatment, the consequences may herald death.

Diagnosing and treating paraneoplastic syndromes is challenging; most patients are managed by specialist services, although care may be shared with the general practitioner. The decision and approach to paraneoplastic syndrome management must take into consideration the potential benefits and burdens of therapy, and the patient’s overall condition, prognosis, preferences and goals of care—see Principles of symptom management in palliative care. The most effective treatment for paraneoplastic syndromes is usually treatment of the cancer. Treatments that target paraneoplastic syndromes only provide temporary reversal or relief of symptoms.

In addition to the above principles, general advice is available in these guidelines on managing hypercalcaemia associated with cancer and sweating associated with a paraneoplastic syndrome (including cancer-related fever).