UK Genetic Prostate Cancer Study (UKGPCS) Newsletter

Newsletter Issue 9 AN UPDATE FOR PATIENTS, THEIR FAMILIES, DOCTORS AND NURSES

An update from Professor Ros Eeles

2012-2013 was another productive year for UKGPCS. We have found more genetic variants that predispose to prostate cancer, which we will be able to use in the development of a genetic risk profile. These findings were highlighted on BBC, ITV and Sky News.

Our current studies are: (1) To try to determine the overall spectrum of genetic variants that predispose to prostate cancer. (2) To try to identify if genetic variants interact with environmental factors that contribute to increased prostate cancer risk. (3) To use the information from our genetic and environmental studies to develop targeted prostate screening programmes. (4) To investigate how genetic variants might impact on cancer care.

UKGPCS Research Sister, Audrey Ardern-Jones is awarded an OBE!

In January 2013 our very own Audrey Ardern-Jones was named in the New Years Honours list for services to cancer genetics nursing care.

Audrey joined the Royal Marsden as a research sister in 1993 and set up the UK Genetic Prostate Cancer Study (formally the UK Prostate Familial Study) with Professor Ros Eeles. Some of our patients and families know Audrey very well, so we thought you would like to join us in congratulating Audrey on this fantastic achievement.

Audrey has kindly written about her experience at the Royal Marsden for us.

“It really seems only yesterday that, in 1993 when I started work at The Royal Marsden Hospital as a research sister, setting up the UK Prostate Familial Study. It was an exciting time as very little work had been done on the genetics of this disease. I loved every minute of the project and now feel so proud of the many important discoveries that have been made following the initial collection of data from men in this country and the wider world.

During this time I studied Genetics at the Open University followed by a Masters at London University. Later I worked with Professor Eeles in the setting up of the Cancer Genetics Clinic in the Chelsea branch of the Royal Marsden Hospital and was appointed the first Clinical Nurse Specialist in Cancer Genetics. I developed a support group for gene mutation carriers and education days and published many papers with other authors on the psycho social impact of genetic testing and risk.

Throughout my career I have taught cancer genetics to nurses and other health professionals world wide. I have sat on various Department of Health committees and also helped cancer charities with their literature and support.

Although I am retired from a full time job, I remain involved in teaching and continue to work part-time in the research onco-genetics clinic with Professor Eeles.

I am truly honoured to receive the OBE for my work in cancer genetic nursing care.”

Audrey Ardern-Jones Page 2

Prostate Cancer from a Wife's Perspective

My husband John’s diagnosis of prostate cancer over five years ago was a shock to say the least. Outwardly he appeared to be very healthy. There had been none of the classic symptoms of prostate cancer – no problems whatsoever in passing water, no blood in the urine ... nothing. Earlier that year he’d been treated successfully for emboli on the lungs, an illness which in itself had been a shock to us as he was generally never ill. Even colds or flu had never been bad enough to stop him going in to work. It was during a routine follow-up CT scan for the emboli that the cancer was picked up. To make matters worse we were told that the cancer was advanced, had spread to the bones and his PSA was sky-high. The prognosis was not great – 2 to 3 years. In hind- sight the only symptom had been fatigue, but we had put this down to the greater work- load and associated stress in the office – we never dreamt that this could be a sign of a serious health problem.

Since then a rollercoaster of treatment has been part of our lives. Treatment is determined on and given; things are fine for a time; then the treatment stops working and we’re betwixt and between while options are considered; and then we start all over again. We started with Zoladex (which still continues), this worked for 7 months on its own – things were looking great and then the PSA started to rise again. We had ascertained from various sources including the internet that on average hormone treatment alone was effective at keeping the cancer stable for 2-3 years, but some men were successfully treated for 5, 10 and even in some exceptional cases 20 years. But there we were after just 7 months looking at the next option. We were then referred onto a Clinical Trial for the chemotherapy drug Docetaxel plus an antibody and have been on one or other Clinical Trial drug ever since.

We’ve learnt a number of things along the way. You may have already noticed my use of the royal “we” - “we started with Zoladex”; “we had chemotherapy”. I have caught myself so often at this, but in a way it’s true. Although it is John who has the therapy, I’m there by his side going through it in my own way with him. John generally doesn’t want to know the details of any treatment especially not the side effects or the odds of it being successful. When a new treatment is proposed I read the documentation, find out more information, and relay it in a more palatable format to John. Although we’ll have discussed things at home and know what questions we want to ask of the doctors before a new therapy starts – I generally do the asking as John says “I hear things that he doesn’t” at our medical consultations and can then explain things when we get home. I know that I’m not unique in this as I have found that a lot of Prostate Cancer wives also use the royal “we”! But then cancer doesn’t just affect the husband – it affects the wife and the whole family.

Another thing we’ve learnt is that we never ask for a prognosis. Thankfully, our initial prognosis is already wrong, but also we’ve come to understand that none of our specialists can give a realistic answer. Statistics can be misleading. As I’ve already said some patients can have their cancer controlled with hormone therapy alone for many years. We never did ask whether John’s prognosis of 2-3 years was with or without treatment, but whichever the hormone therapy alone worked for just a short time. Every patient responds differently to the same treatment – some do not respond at all to one treatment, but do so spectacularly to another. We have met patients who have been successfully treated with Abiraterone for 5-6 years whilst John’s treatment lasted just over 8 months. The response to a drug is so variable that it is almost pointless asking the question. In the future DNA testing may indicate which patient is likely to respond to which drug, but that is still some way in the future and for the time-being no-one really knows.

It is as a direct result of our involvement in Clinical Trials that I started keeping a diary. We were being asked questions about when this or that symptom started or the extent of the pain, so I started to note things down as neither John nor I could ever remember exactly. My diary has been a feature of our lives ever since. I record symptoms and side effects, the highs and the lows of treatments and for us it’s been a great help. I like to think that it has also helped the Clinical Teams by giving them more accurate feedback as to the effectiveness of a particular treatment.

The last five years have not been easy - the rollercoaster of different therapies has been the most difficult to cope with. Whilst things are good we can live almost normal lives and forget that John is ill, but when we’re “betwixt and between” therapies it is sometimes difficult to see the way through. It is at these times particularly that John and I have appreciated the support not just of our friends and family, but of the superb medical teams that we have come into contact with. Firstly at our local hospital, then at the Royal Surrey County Hospital (where we attended for our first Clinical Trial), but especially Professor De Bono’s team in the Prostate Targeted Therapy Group at the Royal Marsden. We’ve learnt to live with the disease (which is not easy at all) and we take each day as it comes. We plan holidays and meetings with friends. If those plans come to fruition that’s great. If not, well, there will be a next time. We try not to let the cancer dominate our decision making, but sometimes the symptoms (especially pain) are such that we have no alternative. However, we do what we can, when we can and make the most of every day that we have together. Page 3

Prostate Cancer from a Wife's Perspective cont…..

Last year was probably the most difficult for us as both the second course of chemotherapy and then another drug trial last autumn barely held the cancer in check. John’s symptoms got worse and he was in considerable pain. But already this year things look more hopeful. John started on a double-blind phase 3 trial of a drug called Cabozantinib at the end of January. It’s early days yet, but there has been an improvement particularly where the pain is concerned – at the moment he is virtually pain free. If things continue this well then I’ve a number of jobs around the house that are just waiting for John to do!

I’m full of admiration not just for the Medical Team for the way they look after John and do everything to ensure he has the best and most appropriate treatment that they or other specialist teams can provide, but also for the Research Team in devising so many new ways to treat this disease. They try to understand why certain treatments stop working and then find ways to circumvent this. I know that there are many new treatments in development. When we started out on the road of Clinical Trials we were told by one Consultant that there was an alphabet worth of therapies being developed. We were on therapy A and it was a long way to go to therapy Z. Well 4.5 years down the road we’re now on therapy F. It’s still a long way to therapy Z, but from what I hear of the research that’s going on there may be more than an alphabet worth of therapies available now. It’s certainly an exciting time for Prostate Cancer Research and it’s thanks to that research and the dedication of everyone involved, the doctors, nurses, researchers, support staff etc, that my John is doing as well as he is and that I’m planning his DIY jobs around the house and then a well-deserved holiday this summer.

Mrs Alina Matuszewska

News for our Collaborators

The UK Genetic Prostate Cancer Study (UKGPCS) was first established in 1993 and is the largest prostate cancer study of its kind in the UK, involving nearly 189 hospitals.

Our target is to recruit 26,000 gentlemen into the UKGPCS by 2017. Men are eligible to take part if they fit into at least one of the following groups:

 They have been diagnosed with prostate cancer at 60 years of age or under (up to their 61st birthday)  They and a first, second or third degree relative have had a diagnosis of prostate cancer where at least one of them was diagnosed with prostate cancer at 65 years of age or under  They are affected and have 3 or more cases of prostate cancer on one side of their family  They are a prostate cancer patient at the Royal Marsden NHS Foundation Trust

The study has recently undergone a major protocol change. Amendment 9 was approved on 9th April 2013.

The reason for the change is in response to requests from collaborators and to aid both better recruitment and more complete data collection.

Changing the way patients are recruited will:

 Give local sites control over the collection of consents, study forms and blood samples which will ensure that a full set of data for all new patients entering the study is received  Potentially improve the current consent rate  Allow the UKGPCS office to concentrate on collecting any missing patient data for older samples  And to follow up and recruit members of families with more incidence of prostate cancer thus collecting a larger number of samples from these families.

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Hot off the press! None of the 23 genetic changes on its own Over 40,000 men are diagnosed with

Your UKGPCS samples really are helping to raises a man’s risk of prostate cancer by prostate cancer in the UK each year, with change the way that prostate cancer more than a slight amount. But when a man almost 11,000 men dying from the disease. screening could be carried out in the not so has a number of the genetic changes these If it is caught early treatments are more distant future. 50,000 samples (25,000 can combine to raise his risk significantly. effective, which is why identifying those most prostate cancer cases and 25,000 controls) at risk, particularly from aggressive forms of were used in this latest research, with the With the genetic changes discovered, the disease, is so important. largest set of case samples, 4,100, coming scientists can for the first time identify men from UKGPCS. Other samples were who have inherited just over a 50% lifetime The team, from the ICR and the University of provided by our collaborators in 10 risk of developing prostate cancer. Cambridge, analysed 211,000 genetic different countries. Our latest press release variants from blood samples from 25,000 below, was covered by BBC News, Sky Following these discoveries scientists now prostate cancer patients and compared them News, The Guardian and The Telegraph on think they can identify the top 1% of men with those of a similar number of healthy the 27th March 2013: with the highest risk of developing prostate men. The gene variants were analysed as cancer who have 4.7 times the risk of the part of the COGS (Collaborative Huge study could lead to genetic population average. It is these men who, it is Oncological Gene-environment Study) hoped, will be identified by screening. They project, which publishes a series of research screening for prostate cancer: would then receive close monitoring in order papers simultaneously today about the that, if they do develop the disease, it is causes of prostate, breast and ovarian Genetic screening for prostate cancer is now caught early when it is easier to treat. The cancer. a real possibility following results from the way in which that screening would be largest-ever study into inherited risk factors conducted – for example, through blood Professor Alan Ashworth, Chief Executive of for the disease. We are applying for tests or biopsies – will be indicated by the The Institute of Cancer Research, said: “Up approval for a clinical trial to start this year results of future clinical studies. until now, our management of prostate as a result of the ground-breaking findings cancer risk has been a fairly crude process from an international group led by The Study leader Professor Ros Eeles, Professor involving the evaluation of just a handful of Institute of Cancer Research, London, and the major risk genes. But our new research really University of Cambridge, funded by Cancer of Oncogenetics at The Institute of Cancer Research (ICR) and Honorary Clinical changes the game for use of genetics in Research UK and the European Commission. Consultant at The Royal Marsden NHS prostate cancer, by identifying so many new Foundation Trust, said: “These results are the prostate cancer variants that screening for The three-year study of 50,000 men single biggest leap forward in finding the different levels of risk now becomes a real (prostate cancer patients and controls genetic causes of prostate cancer yet made. possibility. Today’s studies, across prostate, without cancer), published today in Nature They allow us, for the first time, to identify breast and ovarian cancer, provide a vivid Genetics, identified 23 new genetic men who have a very high risk of illustration of just how powerful genetic variations associated with an increased risk developing prostate cancer during their research can be in uncovering the causes of of the disease. This raises the total lifetime through inheritance of multiple risk cancer and opening up new avenues for discovered so far to 78. Significantly, 16 of genetic variants. If we can show from further prevention and treatment.” the 23 newly discovered genetic changes studies that such men benefit from regular are associated with the disease at its most screening, we could have a big impact on aggressive and life-threatening. the number of people dying from the disease, which is still far too high.”

We would like to thank the organisations supporting our work:

And many thanks to our generous donors The Annabel Evans Memorial Fund Chris Jones in memory of his father Tony Jones, Anne and Stuart Cliff, Mr Tony Maxse, The Ronald and Mr Hugh Knowles, Liz, Chris, Tim and Sarah Powell, Mrs Rogers, Mr J and Mrs F A Lavington and Rita McAulay Richard and Debbi Burston Foundation

UKGPCS CONTACT DETAILS: TELEPHONE NO: 020 8722 4162 / 4395 FAX NO: 020 8722 4110 WEBSITE: WWW.ICR.AC.UK/UKGPCS EMAIL: [email protected]