Dr Liau Kui Hin, general surgeon at Mount Elizabeth Hospitals specialising in liver, gall bladder, and pancreatic cancers and disorders, explains pancreatic neuroendocrine tumours (PNETs) and the evolving treatments for this uncommon cancer.
What are PNETs?
Pancreatic neuroendocrine tumours, or PNETs, are cancers that arise from the endocrine cells in the pancreas. PNETs gained a lot of attention after the late Apple co-founder, Steve Jobs, was diagnosed with the condition. Before that, not many people knew about them. Unlike the common type of pancreatic cancer known as adenocarcinoma, PNETs are rare. They account for less than 3% of all pancreatic tumours.
Arising from the endocrine cells in the pancreas, these cancers can be hormone secreting or non-hormone secreting. Some of these hormones are active or functional and they cause hormone-related symptoms while others are inactive or non-functional. The majority of PNETs are nonfunctional tumours. Non-functional PNETs generally show no symptoms in the early stage and by the time they are diagnosed, they are often in the advanced stage.
Due to the rarity of PNETs and the scarcity of reliable medical evidence in the treatment, managing patients with this condition can be very challenging. Specialists have to rely on their clinical experience and judgment.
A silent killer
It does not help that PNETs may not have signs or symptoms. This means the cancer could be diagnosed late, at which point surgery may no longer be an option. PNETs are also complex. They can appear in various guises and differ greatly in the speed of growth. Their speed of growth can switch from slow to fast or from fast to slow.
This is why some patients may live for years, even after the tumour has spread to the liver or other parts of the body. Others may not, if their slow-growing PNETs suddenly turn aggressive. This observation, known medically as the flip-flop phenomenon, describes the unpredictability and interchangeability of cancer biology. Predicting the speed of growth of these tumours remains an inexact science at best.
What are the symptoms?
As mentioned, majority of patients with PNETs often experience no symptoms, especially the non-functional PNETs. When PNET-related symptoms do occur, they are often non-specific. It is therefore not surprising that proper diagnosis is frequently delayed for a long time.
On the other hand, functional PNETs may have symptoms that related to the hormones that are secreted by the tumour. They may feel tired, dizzy or lightheaded, nervous or anxious, abdominal pain, nausea, watery diarrhoea, increased thirst, etc., depending on the type of hormone the tumour makes.
Non-functioning tumours do not produce any hormones so they do not cause any hormone-related symptoms. As a result, these tumours are typically diagnosed once the tumour is advanced and is causing mass effect related symptoms such as pain or jaundice or gastric outlet obstruction.
Treatment options for PNETs
Surgery is not a straightforward medical decision. It is generally not recommended if the cancer has spread. It is not surprising to receive mixed opinions from other oncologists and surgeons.
From cumulative experience worldwide, we know that extensive surgery can prolong the survival of patients, provided it can be performed safely. However, surgery is risky and also comes with a high risk of tumour recurrence.
Newer and effective drugs and therapy for PNETs
Hormonal therapy using a somatostatin analogue mimics the body's natural hormone somatostatin and blocks its activity. The treatment ameliorates the symptoms caused by excessive hormones released from the tumour cells, as well as control the growth of PNETs.
Studies have shown that the use of a somastostatin analogue called lanreotide (Somatuline) in the treatment of advanced PNETs can delay tumour growth and reduced the chance of the tumour growing again by half, when compared with a placebo treatment. It does not require preparation and the patient can self-administer it once a month. They simply inject it into the fat tissue under the skin.
Apart from lanreotide, many new drugs and new therapy, from molecular medicine and hormonal therapy to targeted therapy, have emerged to treat PNETs in recent years. One new therapy is peptide radionuclide receptor therapy (PRRT), which involves the administering of a radioactive protein that can target and kill cancer cells. Phase III clinical data, which is required for regulatory approval, will be available only a few years later.
Good news for local patients
Singapore has had the foresight to invest in the therapy as well as the training of related professionals. This means that patients who need it – those who have not responded to other treatments for PNETs – can now get PRRT locally.
Before 2013, patients here had to travel overseas for the therapy. Hopefully, newer agents in immunotherapy will also have a definitive role in the treatment of PNETs in the near future.
But the jury is still out on whether surgery should apply to all advanced PNETs cases. Sometimes, despite the option of a technically feasible and safe operation, surgery is not recommended, especially when we know that the chances of prolonging life are slim. Using drugs to tame the tumour may be a better option.
New drugs, innovative drug formulation and novel medical technology mean better responses, fewer side effects and better treatment outcomes for PNETs patients. While waiting for more medical evidence to guide treatment options for this rare cancer, the medical team must put their heads, hearts and hands together to deliver the best outcome possible for each patient.