“Rare diseases need to be focussed into specialist centres so that patient outcomes can improve”: Meet Professor Michael Seckl

Rare cancers affect less than 6 in 100,000 people a year or 1 in 5 new patients diagnosed with cancer. Professor Michael Seckl is a consultant oncologist at the Trust, director of our national Gestational Trophoblastic Disease Service, and the lead for our germ cell tumour service. He is also a Professor of Molecular Cancer Medicine at Imperial College London. Here, he discusses research into rare cancers and how we care for patients with rare cancers at our hospitals.

What inspired you to pursue this career path?

When I was a medical student the first patient that I saw had breast cancer and passed away the very next day. This shocked me. I saw research as the key to changing cancer from an incurable disease to a curable one. My interest in rare cancers evolved during my training as a junior doctor. I was placed in the first ever Department of Medical Oncology in the country, run by Professor Ken Bagshawe who had started to develop treatments for rare cancers that occur during or after pregnancy. I also have a specialist interest in lung cancer.

Tell us a bit about rare cancers. Are there disparities around who they affect?

Each year, about 21,000 women in the European Union (EU) of childbearing age will develop gestational trophoblastic disease (GTD), which are diseases that occur during or following pregnancy. People often assume that molar pregnancies are not that uncommon because they affect between one and three of every 1,000 pregnancies. But the cancers associated with these pregnancies are rare and terribly important to identify because, if caught early, we can achieve a 100 per cent cure rate in the UK. Ovarian germ cell tumours – my other specialty – are extremely rare. They affect about one in 500,000 women, whereas testicular germ cell tumours are the most common cancer in young men, affecting one in 100 in their lifetime.

Some research suggests that ethnicity dictates certain pre-dispositions to rare cancers. Within the context of GTD, there is evidence to suggest that it is more common in Southeast Asian populations. Some of this may relate to diet. However, all sorts of factors are involved, including genetic factors.

Tell us more about the Gestational Trophoblastic Disease Service.

Based at Charing Cross Hospital, it is a highly specialist service providing comprehensive registration, screening and clinical management for all forms of GTD. We recently marked the service’s 50th anniversary; it is still one of only two hospitals in the UK designated to treat GTD, and our internationally renowned team are world leaders in the investigation and treatment of these rare conditions. Our service also has the largest database of GTD patients in the world, holding records of over 70,000 women. This secure database provides excellent data for research and audit, leading to improved treatment and outcomes for patients.

Patients most commonly present with bleeding during early pregnancy because they've had a molar pregnancy. Their doctor will typically refer them for an early ultrasound which may show that it isn’t a normal pregnancy and lead to the pregnancy being terminated. Following surgery to remove the tumour from the womb, the material is then studied under a microscope so an official diagnosis can be made. Patients are then put on a screening programme with us for human chorionic gonadotropin (hCG) monitoring to detect whether they are going to run into further problems which may require more aggressive treatment.

What impact has the service had to date?

When I joined as a consultant in 1995, we were still experiencing a considerable number of deaths in advanced disease cases– some early deaths within the first four weeks of admission to hospital and late deaths from multidrug resistant disease. We have since eliminated the early deaths by modifying the initial treatment making it more gentle and we’re close to eliminating the late deaths. The latter is largely due to the development of immunotherapies which are highly effective, saving 75 per cent of patients otherwise expected to die from their cancer, and fortunately much less toxic than some of our other treatments. Today, our survival figures for patients with advanced gestational trophoblastic cancers are now close to 100 per cent, having previously been 85 per cent in 1995. We are also looking to see if we can maintain our 100 per cent cure rate in lower risk patients, whilst sparing them combination agent chemotherapy.

Getting the diagnosis right ensures patients get the best treatment but taking tissue samples from these cancers can be very dangerous so we have developed technology to diagnose the disease on a blood sample.

We have further shown that women who have twin pregnancies – where one baby is healthy and the other is a molar pregnancy – can be allowed to progress with careful monitoring. About 51 per cent now result in healthy babies.

I have also established a national service for ovarian germ cell tumours. Previously we were seeing about five new cases a year at Charing Cross, but due to this centralised approach we now see about 50 – 55 cases. Survival rates for women with advanced, stage four ovarian germ cell cancer have increased from 65 per cent to 80 per cent at five and ten years which is really positive.

How long are patients seen for within these services?

Recent analysis has revealed that we can safely stop monitoring most women who come to our Gestational Trophoblastic Disease Service after 10 years – whereas previously we had to monitor them for life. Patients with ovarian germ cell tumours are being followed for life until there is sufficient data to relax this. However, all our patients know that if they develop symptoms or are worried, they can come back straight away.

Throughout your career, what have been some of the advances in treating rare cancers?

One of the biggest steps forward was when the EU recognised that rare cancers need to be focused into dedicated centres. Britain was still a member at the time, so we played a large role in helping the EU do this. The European Rare Adult Cancer Network has also enabled specialists to set up pan European multidisciplinary team meetings where experts across Europe can discuss complex cases and share best practice. This has enabled patients across Europe to access treatments that would have previously been out of bounds.

What research is your team currently focussing on?

In terms of GTD, there are two rare forms of the disease that contribute to the main deaths: placental site trophoblastic tumours and epithelioid trophoblastic tumours. A paper we published based on data up to 2007 showed a 100 per cent death rate in women who had a tiny bit of the disease in the womb more than four years after the end of the causative pregnancy. Using immunotherapy, we have since reduced the death rate for these women to just 20 per cent which is a big improvement. Now we are trying to understand the molecular changes that have taken place inside the cancer that makes it behave so badly after four years. We are also looking for other genes that might cause the disease and to see whether we can introduce immunotherapy as a treatment earlier on in the patient pathway.

Are there any patient stories that have had a real impact on you?

A patient came to us after being managed remotely by another hospital. Without physical review and examination, signs of the cancer were missed and the patient had skin, brain and lung growths. Luckily, we were able to get her back into remission with intensive treatment including high dose chemotherapy and she’s now a long-term survivor. This reaffirmed to me how important it is for patients to have face-to-face appointments with their doctors.

What have been some of your career highlights?

Right now, we are running a trial in lung cancer where we are reducing the frequency of giving immunotherapy. If this works, it will make our patients’ quality of life better because they won’t have to come to hospital as often and they will experience less toxicity. Just by running this trial we are saving the NHS £30 million in drug costs. If it is successful, we'll save the NHS hundreds of millions of pounds every year, and that's just for lung cancer. If you spread it into the other cancers, we are talking billions of pounds a year which could be used for other new treatments.

Underlying all of this is having a supportive wife and family – I couldn’t have got this far without them.

What is your takeaway message this Rare Diseases Day (29 February)?

Our Gestational Trophoblastic Disease Service is a poster child of what can be achieved, but other rare diseases need to be focussed into specialist centres so that patient outcomes can improve.