London Kidney Patient Day 2013

16th October 2013 Waltham Abbey Marriott.
Introduction and welcome –
Nick Turkentine, Chief Operating Officer, Kidney Cancer UK
Nick Turkentine opened the event by welcoming everyone to the Waltham Abbey Marriott. He went on to talk about the forthcoming merger of Kidney Cancer UK and James Whale MBE Fund for Kidney Cancer to form one kidney cancer charity in the UK called Kidney Cancer UK.
The main aims of events such as this are for the patients and their carers or families to hear directly from the experts in the treatment and management of kidney cancer, to learn about treatments and to meet and chat to other patients.
The role of the clinical nurse specialist
Laura Miles, Macmillan Uro-Oncology Clinical Nurse Specialist, Mount Vernon Cancer Centre, Northwood, Middlesex
Ms Miles opened her presentation by describing her role as a keyworker essential for the holistic care and support of urology cancer patients. In order for every cancer patient to be cared for promptly and holistically, it is vital they are assigned a keyworker. Holistic therapy is the treatment of the whole person, including spiritual, emotional, psychological and physical needs.
The aim of a clinical nurse specialist (CNS) is to provide the main point of contact in the hospital that knows the patient case, to provide expertise to the patient and their family, including their family doctor, and to reduce patient anxiety and improve continuity of care. The CNS provides patients with a contactable, knowledgeable, and accessible professional who can use their knowledge and skills to provide practical, emotional and psychological support. CNSs also monitor physical symptoms and manage drug toxicity, coordinate complex care and refer patients on to other professionals, such as other members of the multidisciplinary team (MDT) and community services, and help to resolve unsatisfactory experiences for patients and their families.
Ms Miles then gave a very concise summary of the side effects of targeted therapies and how to manage them. Most side effects are easily managed and reversible; it is very rare to have to stop treatment with a targeted therapy because of a side effect to treatment. If a side effect cannot be tolerated, then a dose reduction will be considered.
Fatigue is the most common problem for patients on cancer treatment. Fatigue is usually managed by educating the patient and is not always attributed to the drug therapy. Patients are advised to rest when tired, but to try and do some light exercise, such as walking every day. Patients are also advised to try to conserve energy for the activities they enjoy in order to maintain their quality of life. Help with chores around the house and a good sleep routine/habit will help. If fatigue is a big problem and is affecting the patient’s life, a dose reduction may be recommended.
Diarrhoea; if patients are experiencing diarrhoea they should be advised to avoid foods that are spicy or fatty, and to avoid high fibre foods, such as onions, fruit, vegetables, beans, nuts, fruit juice, dried fruit and caffeine. They should be encouraged to maintain a good fluid intake to avoid dehydration, but to avoid very hot or very cold drinks. Stool-bulking foods, such as chicken, fish, eggs, basmati rice, potatoes, bananas, white bread, crackers and cooked food are recommended. Loperamide is usually effective at managing diarrhoea.
Nausea and vomiting can be treated with anti-emetics. Avoid preparing food and eating when feeling sick and avoid fried and greasy food. Try eating small, regular meals and eating dry food or food containing ginger. Rinse the mouth out before eating and suck on ice cubes to keep water intake up. Patients should be advised to drink plenty of fluids but in small amounts so that it is absorbed in the mouth before reaching the stomach. Fresh air before eating might help and avoid restrictive clothing. Make sure you look after your mouth with good oral hygiene.
Loss of appetite is caused by changes in taste sensations. Loss of appetite can be stressful at mealtimes, since other members of the family want the patient to eat to keep up their strength. Try to make meal times relaxing to reduce any anxiety over eating. Patients should be encouraged to eat little and often and to eat meals that are high in protein and calories. Try new tastes, eating a little more on a good day and a gentle walk before meals might also help. Ask someone else to prepare food or eat ready meals. Cool or cold food may be better and have some snacks available for when you are feeling hungry.
Mucocitis/stomatitis is painful inflammation of the mucous membranes lining the mouth and gastrointestinal tract. Avoid eating hot, spicy or acidic foods, and eat soft foods, such as ice cream, rice, jelly and mashed potatoes. Patients can be prescribed non-alcohol mouthwashes or artificial saliva to ease pain and help prevent infection. Patients are advised to use a soft baby toothbrush and a mild toothpaste when cleaning their teeth, and to try to keep their mouth moist. Use of an aspirin mouthwash before eating may help, but needs to be discussed with the CNS before use.
Taste changes can lead to a loss of appetite because food tastes very bland. Patients should make the most of things that taste good and avoid eating food that doesn’t taste good. If food tastes bitter, avoid eating red meat, sour juices, tea, coffee and tomatoes. If food tastes sweet, try cooking in lemon juice, mint, herbs or vinegar. Sweet flavoured drinks, ice-lollies, and herbal teas can help to cope with taste changes. Add seasoning to meals and try to eat cold food rather than hot food. Pineapple or melon can be refreshing and clean your teeth after each meal, but avoid using alcohol-based products.
Hand-foot syndrome, or palmer-planter erythrodysesthesia (PPE) results in sores on the palms of the hands and soles of the feet. Patients may experience numbness, tingling, swelling, erythema, desquamation, blistering and pain in the hands and feet to varying degrees of severity. Treatment may require temporary suspension of the drug until the episode resolves or a permanent dose reduction. Patients are advised to wear comfortable footwear, such as cotton socks, soft shoes and padded insoles, visit their chiropodist and use moisturising cream containing urea (Udderly Smooth) on their feet and hands. Cotton gloves soaked in cream inside rubber gloves overnight can help with hand problems. Avoid hot or cold water and dry your hands properly and moisten well after getting them wet.
Liver/thyroid function needs close monitoring when starting TKI treatment. Symptoms of disturbed thyroid function include fatigue, swelling around the eyes, dry skin, shortness of breath, and feeling more sensitive to the cold. Thyroid and liver function should be closely monitored and blood tests should be performed weekly, if necessary. If this side effect cannot be controlled, the dose can be reduced or the drug changed.
A key factor in the management of side effects is good communication between patients, nurses and doctors. Patients may feel more able to talk to the nurse specialist than to the doctor about some aspects of their cancer care; it is the patient’s role to report any problems to the nurse specialist, and the specialist to interpret the problem and come up with a solution. There is no such thing as a silly question!
London Cancer Network
Claire Levermore, London Cancer
Ms Levermore presented an overview of the work of London Cancer, an organisation whose main aim is to improve the care of cancer patients in London. The work of London Cancer was triggered by a model of care report written in 2010 by about 45 clinicians, which gave some recommendations on how to improve cancer care in London. London hospitals have some of the poorest cancer outcome statistics in England. London Cancer went ‘live’ on 1 April 2012 with the vision to create a ‘virtual comprehensive cancer centre’ across North and East London. They have joint working partners with charities, such as Macmillan, London Cancer Alliance and the pharmaceutical industry. Over 1000 NHS staff are involved in the development of the cancer centre, including 200 GPs and 200 patients, and they have dialogue with the Clinical Commissioning Groups, public health and GPs. The area covered includes North East and North Central London (boroughs north of the river Thames) and West Essex, and includes some of the world’s leading specialist centres, such as Great Ormond Street Hospital, Moorfield’s Eye Hospital, the Royal Free Hospital and University College London Hospital.
The main objectives of London Cancer are:

• To increase one year survival for patients in North Central and North East London and West Essex by improving earlier diagnosis, to increase 1-year survival rates and reduce deaths by 200 per year from 2015/16. London has some of the lowest survival rates in the country.
• Improve patient experience by delivering 90% positive level of response on 10 areas most important to patients on the annual National Cancer Patient Experience Survey (NCPES) in 2015, with annual improvement. The bottom 9 hospitals in the NCPES are in London.
• Give patients access to innovation by increasing participation in clinical trials to 33% enrolment over 3 years.

London Cancer is working to improve patient experience. One thousand patients were asked what matters most to them during their treatment, and the top 10 answers were: 1.Early diagnosis, 2. Ethos, 3. Communication, 4. Choice, 5. Support, 6. Carers, 7. Holistic assessment, 8. Seamless care, 9. Transport and 10. Discharge. Clinicians use this evidence to drive change and to focus on what is most important to patients for each tumour site.
Over the past 18 months, London Cancer has accomplished the following:

• Initiated and are running a service evaluation of patients first presenting with cancer as an emergency at 11 A&E departments; over 200 primary care staff have attended educational events focused on symptoms rather than disease types
• Brought together a wide body of GPs, cancer clinicians and patients to redesign specialist cancer pathways; public consultation begins in early autumn 2013
• Attained a five-fold increase in referrals of young people with cancer to age-appropriate Multi-disciplinary Teams
• Published online interactive maps for patients to navigate care locally and find advice and support, with positive feedback from patient groups
• Supported research harmonisation, increasing clinical trial participation by 7%.

During their second year they are trying to understand the variation and quality in care for the more common cancers and learn from what the London patients have told them through the NCPES. They are in the process of moving cancer services closer to home and into community settings and redesigning cancer pathways to improve patient outcomes and experience and access to innovative treatments. In the longer term, they aim to concentrate cancer services in 2-3 specialist London hospitals and will be consulting the public on whether to proceed with this in the next 2-3 weeks.
Ms Levermore went on to describe the structure of London Cancer, including the pathway boards for various tumour types, the expert reference groups, including GP and CNS forums, and sub-groups for research implementation, education and workforce and living with and beyond cancer.
Living with and beyond cancer work stream focuses on the recovery, health and wellbeing of people living with cancer by taking a holistic approach and providing the appropriate level of support for those with active and advanced disease. This programme aims to ensure that all individuals diagnosed with cancer receive co-ordinated and personalised care and support.
Treatment summary and cancer care review aims to ensure that GPs have the information they need to best support cancer patients in the community and to provide patients with information on diagnosis, summary of treatment received and future management. This includes information on medication; possible side effects and contact details for health professionals in secondary care should concerns arise.
The urology pathway board of London Cancer is lead by Dr John Hines and has similar objectives to London Cancer overall:

1. Implement the agreed service specification for future urology cancer services
2. Diagnose urological cancers earlier and better
3. Unify diagnosis and treatment guidelines across London Cancer
4. Improve patient information and experience
5. Improve care for those living with and beyond urological cancer
6. Improve research and access to clinical trials

They have been heavily involved with the government’s national Be Clear on Cancer blood in pee awareness campaign and have linked with Spurs football club to promote awareness of all urological cancers and hope to build similar links with other London-based football clubs in the future.
Questions
Why is there no screening programme for urological cancers? Before a screening programme can be introduced, the clinicians need to prove that the screening programme saves money further down the line. Also, there is the need to balance the emotional aspects of screening with the benefits; testing could potentially scare some people. The GP could perform the tests, but not everyone wants to go to their GP. Blood in pee testing could be done at home and there will probably be a move towards more community-based testing. However, this could increase the stress and anxiety of people resulting in ‘worried well’ people. Testing could also be done at pharmacies. The vast majority of non-visible blood in pee is not cancer, however, the GP should refer these people on to the hospital for a scan. London Cancer is trying to change this system such that all positive tests are referred on to the hospital.
The public can get involved with the work of London Cancer by attending the published meetings and events in London http://www.londoncancer.org/
My kidney cancer journey – a patient story
Neil Cameron
Neil gave a very entertaining and moving presentation about his kidney cancer journey. Neil is 58 years old and has been diagnosed with metastatic renal cell carcinoma (RCC). He has been on pazopanib (Votrient) for 3 years. In September 2010 he noticed some blood in his urine so he went to his GP who confirmed that it wasn’t an infection and he was referred to the urology clinic in Epping. Two weeks later he had an ultrasound scan, but his experience of diagnosis was appalling; he would have had to wait another 3 weeks for a CT scan on the NHS. Instead he had a CT scan at a private clinic 2 days later. A friend recommended he see Professor David Nichol, a urologist, who told him he has metastatic RCC with secondary tumours on his pancreas and lungs. He took his wife and a friend who is a nurse along with him for the diagnosis, so that he didn’t miss anything that the professor told him and for moral support.
In mid October 2010, he saw Professor Tom Powles at the Barts Cancer Institute and was enrolled on the PANTHER trial, during which he took pazopanib for 3 months before have a nephrectomy to remove the tumour. After the operation he went back on pazopanib. He didn’t tolerate pazopanib very well at first; his platelet count was reduced and he had very sore feet. His dose was reduced from 800 mg to 600 mg per day and used Udderly cream on his feet. He also visited the chiropodist regularly and bought some very good insoles for his shoes, which helped to ease the soreness. He also had raised blood pressure, which was controlled with drugs and monitored regularly via self-monitoring. The pazopanib shrank the tumour before the nephrectomy.
After the nephrectomy, when he went back on pazopanib for the second time, he suffered with severe fatigue; he had no energy, but thought that the way he was feeling could be partly attributed to his state of mind. He also had diarrhoea and had to watch what he ate. The BRAT diet (bananas, rice, apples and toast or crackers) and loperamide (Imodium Instants) helped with this side effect. And avoid eating curries!
Before taking pazopanib, Neil was a type II diabetic and on metformin. When he started to take pazopanib, he moved on to insulin for his diabetes. However, gradually his blood sugar levels reduced and he no longer needed to take insulin; the pazopanib seemed to have ‘cured’ his type II diabetes!
After 2 years on pazopanib, Neil’s lung metastases have shrunk; he had radio frequency ablation (RFA) to one of the metastases in the lung, but it grew back. Pazopanib did not have any effect on the pancreatic metastasis, so he had cyberknife radiotherapy to remove it and it has not grown back. Cyberknife radiotherapy is an expensive treatment costing around £15-20,000; Neil had to make a case to the NHS Trust to get this treatment. After this, he took a short holiday from the drug, and was able to eat curries again! However, his diabetes came back and he was back on insulin.
Neil is now back on pazopanib. His metastases have unfortunately grown back in the same places as previously; he does not have any new metastases. There are a lot of options for him in terms of second line treatment, and he remains positive about his treatment. Neil closed his presentation by imparting the following thoughts:

• Being positive may not cure you, but being negative certainly doesn’t
• Support – (physical and emotional) really matters; more people helping you lightens the load
• Be a demanding patient (not rude) – you deserve the best
• Be honest with your partner – no secrets
• Be lucky!

Surgical treatment of renal cancer
Mr Stephen Connolly, Honorary Consultant Surgeon and Lecturer in Urology, Cambridge University and Addenbrooke’s Hospital, Cambridge
Twenty to thirty years ago, the diagnosis of renal cancer was a challenge; modern imaging modalities, such as CT and ultrasound have changed that. The location of the kidneys is also challenging; tucked away at the back of the abdomen. There is no single best way to approach the kidneys during surgery. About 85% of solid lumps in the kidney are cancerous. Cysts are far more common in the kidneys. Renal cell carcinoma (RCC) is the most common form of kidney cancer, accounting for 90% of cases. Some patients (around 10%) will have the less common cancer of the renal pelvis or cancer of the ureter.
Kidney cancer is a relatively common cancer (8th most common cancer in the UK) and incidence is increasing. Kidney cancer is mostly sporadic; in other words it arises for no clear reason and there is no pattern of inheritance. There is a male predominance, and smoking, obesity and high blood pressure are all risk factors for kidney cancer. Staging of kidney cancer shows the extent of the disease in the body. Originally, the Robson method from 1969 was used to stage kidney cancer as stage I, II, III and IV. This has been superseded by the TNM system which stages the disease according to the size and spread of the cancer, the number of lymph nodes involved and the number of metastases.
Most kidney tumours (about 50%) are detected incidentally when a patient is having a scan for an unrelated condition and kidney tumours are being detected much earlier than before as a result of more advanced imaging technology. The classic triad of symptoms is pain, haematuria (blood in the urine) and abdominal mass. Haematuria is the most common symptom. Thirty percent of patients present to their doctor with symptoms due to spread of the cancer (metastases).
Radical open nephrectomy is the surgical removal of the kidney containing the tumour along with a healthy margin of tissue from around the tumour. An American surgeon, Robson, originally pioneered radical open surgery in 1959. This surgery provides the best access to the kidney and still represents the best option for many patients; it is the gold standard for kidney cancer surgery. It has very favourable outcomes in hospitals that treat a high volume of RCC patients, and will be curative for many patients.
Laparoscopic nephrectomy, or key hole surgery results in lower morbidity than radical open surgery; recovery from the operation is quicker and it is cosmetically superior to open surgery, resulting in small puncture wounds rather than a large wound across the abdomen. The oncological aspects of laparoscopic surgery are identical to open surgery in that it can be curative for many patients. The first laparoscopic surgery was conducted in 1990 by a surgeon called Ralph Clayman, and the technique is constantly developing to be even less invasive. Single port laparoscopy through the umbilicus (belly button) can be used for nephrectomy, and there have also been cases of organs being removed through the vagina in women! Laparoscopic surgery is now more common than open surgery; however, it is not suitable for all patients. Robotics is the next big development for laparoscopic surgery.
Partial nephrectomy is the removal of the tumour without removal of the entire kidney. This technique helps to preserve kidney function; however, preservation of kidney function shouldn’t be allowed to compromise kidney cancer surgery. Partial nephrectomy can be carried out in open or laparoscopic surgery. However, this surgery is not suitable for everyone, and only small tumours can be removed in this way. Currently, about 25% of patients have partial nephrectomy.
Radio frequency ablation (RFA), cryotherapy and high intensity focused ultrasound (HIFU) are ablation techniques that destroy the tumour without the need for removal. They avoid surgery and preserve kidney tissue and thereby function. These techniques are suitable for patients who are not fit for surgery and for small, indolent tumours (not aggressive). For these patients, living with an indolent tumour may be preferable to living without a kidney. Doctors are getting better at predicting these cases. RFA uses heat from an electrical current to destroy the tumour. The electrical current is delivered via a needle inserted into the tumour. The electricity agitates the water molecules in the tumour causing it to heat up and kill the cancer cells. Cryotherapy involves freezing the tumours; the tumours are subjected to a number of freeze-thaw cycles that eventually kill the tumour cells. HIFU uses sound waves to destroy the tumour cells.
Some patients may be best left untreated and their disease monitored for any changes or progression. This is called watchful waiting and is suitable for patients with small indolent tumours who are not fit for surgery due to comorbidities. There remains an issue regarding identification of these patients, but doctors are getting better at this.
Surgery for metastatic disease (cancer that has spread) does result in longer survival for some patients; however, patients need to be carefully selected for this surgery. Surgery to remove the tumour (debulking surgery) followed by systemic drug treatment results in better outcomes for the patients and a better quality of life.
In conclusion, Dr Connolly finished his presentation by saying that renal cancer is very frequently curable by surgery and is only very rarely untreatable. Surgery is, therefore, an important treatment for renal cancer and developments in surgery will continue to reduce morbidity and allow earlier resumption of normal activities. The surgeon should discuss all suitable surgical options with the patient before moving on to the best option.
Questions
How is the patient’s choice of treatment managed? Should patients seek a second opinion if they are not offered the treatment they need? Mr Connolly recommended that if patients are not happy with their treatment, they should go back to their GP, who should act as an advocate for the patient and refer them to another specialist. The patient needs to be demanding, which can sometimes be difficult with the specialist, so the GP might be more willing to help.
Would the treatment pathway be different if the oncologist is seen first rather than the surgeon? Surgeons are specialists in oncology too and should really be called surgical oncologists. The multidisciplinary team (MDT) is important for bringing all the specialists together to discuss individual cases and determine treatment plans.
A patient with transitional cell carcinoma (TCC) left hospital 5 days after his operation and his stoma became infected. He could not be dealt with in the local community because his GP was not informed about what had happened to him in hospital. The surgeon should have better communication with the patient after surgery. This can sometimes be impractical; however, NHS departments need to be more joined-up.
Patient support and advocacy
Lee Marriott-Dowding, Team Leader – Patient Support, Kidney Cancer UK
Lee defined the role of a patient advocate and talked about the patient advocate’s role at the Kidney Cancer UK. She then went on to describe the help currently available to kidney cancer patients and their families from the Kidney Cancer UK and from local kidney cancer support groups. She also talked about the Fund’s involvement in various support groups, such as Patients Involved with NICE (PIN), International Kidney cancer Coalition (IKCC) and National Voices.
The definition of a patient advocate is someone who provides support to an individual or a group of people, or someone who pleads another’s case. A patient advocate cares passionately about an issue and takes action, speaks out about unjust and unfair situations and offers practical help, information, experience and personal support.
At the Kidney Cancer UK, our aim is to ensure the needs of the patient are first and foremost in everything we do. The patient support team at the Fund;

• Supports and empowers patients i.e. drugs funding/rarer cancer issues
• Raises awareness of kidney cancer
• Provides quality information and resources for patients
• Provides patient input into NICE quality standards and clinical trial design etc.
• Works with politicians, clinicians and pharmaceutical companies
• Promotes shared decision making/participatory medicine
• Supports fundraising for kidney cancer causes
• Challenges health policy that seems to fail the patient
• Wants to help improve the lives of kidney cancer patients, their families and carers.

The Fund supports patients in a number of ways, such as;

• Kidney Cancer Careline – telephone helpline
• Online patient and carer forum
• Individual advocacy and practical advice
• Kidney cancer patient days
• Local support groups
• Kidney cancer literature and facts sheets
• Online renal cancer course for healthcare professionals
• Patient grants for up to £1,000.

Another way the Fund can support kidney cancer patients is by providing help with setting-up and running local patient support groups. Local support groups provide support to patients in a number of ways, including;

• Providing a forum for meeting others who know how you feel
• Friendship – talking things over with people who are in a similar situation to you
• Provision of high quality information
• Influencing your hospital services for the better
• Learning from clinicians, nurses and healthcare professionals
• Managing side effects of treatment and drugs
• Expert advice about benefits, returning to work, finances, complimentary therapies, diet, daily living with cancer, pain management.

If you are interested in setting up such a group in your hospital, the Fund can help with the following;

• Communication – space on our online forum for group activities
• Publicity – group flyers, leaflets and posters
• Organising speakers on various subjects
• Start up grants to help with your set-up costs
• Experience – talk to existing kidney cancer groups for help and advice
• Introductions to clinicians and nurses.

Lee then gave some background information about Patients Involved with NICE (PIN), which is a coalition of over 75 patient organisations committed to enabling patient groups to engage productively with NICE. PIN is independent from NICE and the pharmaceutical industry. The group uses their combined knowledge, experience and direct contact with patients from a wide range of conditions to ensure NICE puts patients, carers and patient groups at the centre of its work.
She then went on to talk about the Fund’s work with the International Kidney Cancer Coalition (IKCC), which is an independent and democratic network of patient support and advocacy organisations established with the mission of improving the quality of life of patients and their families living with kidney cancer. The IKCC provides information, support and assistance to national kidney cancer organisations, all of which are welcome to participate.
Finally, Lee talked about the Fund’s involvement with National Voices, a national coalition of health and social care charities in England. They work together to strengthen the voice of patients, service users, carers, their families and the voluntary organisations that work for them. They have more than 150 members with 130 charity members and 20 professional and associate members. Their broad membership covers a diverse range of health conditions and communities and connects with the experiences of millions of people.
The Fund works with these organisations to try to improve the experience of kidney cancer patients. The recent National Cancer Patient Experience Survey (NCPES) reported that kidney cancer patients have a less positive experience than other cancer patients with respect to their diagnoses, receiving understandable written information and being involved with decisions about their care and treatments. Kidney cancer patients are also less likely than other cancer patients to be given information about support or self-help groups, and a written assessment and care plan. They also felt that there were a number of issues in continuity of care and information provision, probably as a result of patients starting their journeys in urological departments and being transferred to oncology departments for further treatment. Carers found it difficult to access information that had been communicated to the patient orally by the clinician, and there was a lack of clear information about the condition making active participation in decision making more difficult. The NCPES emphasised the need to prepare and enable patients to become active participants, rather than assuming they could take on this role.
Lee concluded her presentation by thanking the patients for listening. She provided them with the contact details for the patient support team and the careline at the Kidney Cancer UK.
Helping us to help others
Sharon Deveson Kell, Medical Publications Officer, Kidney Cancer UK
Sharon’s presentation focused on how patients and their families can get involved with fundraising events to help the Fund support others whose lives have been touched by kidney cancer. She outlined the Fund’s achievements to date and the ways people can donate to the fund. She mentioned the fact that the Fund did not receive government funding and was grateful for the funds received from the pharmaceutical industry and the public to enable them to carry out their work. She then went on to described the many fundraising events that the Fund organises each year, including;

• Donations such as a regular standing order, a one-off donation or text giving (text JWKC02 to 70070)
• Kidney Cancer Lottery – a monthly draw where the funds raised go towards supporting the Kidney Cancer UK patient grant
• The Kidney Cancer UK online shop
• Britain’s Biggest Curry Party – during a week in October each year supporters of the Fund can either hold their own curry party with their friends and families, or attend one of the curry parties held in a restaurant local to them
• Walk for A Cure – an annual event to raise money in memory of Adrian Cure, who sadly died from kidney cancer in 2011
• Arch to Arc cycle ride – 300 miles in 4 days from Marble Arch in London to the Arc de Triomphe in Paris.

Details of all fundraising events can be found on the Fund’s website www.kcuk.org.uk.
Systemic treatments for kidney cancer
Professor Thomas Powles, Clinical Professor of Genitourinary Oncology, Barts Cancer Institute, London
If the cancer has spread, systemic therapy, in which drugs are injected into the blood stream and distributed throughout the body to treat the spread, is required. Systemic therapy is, therefore, used for the treatment of metastatic disease. In the new Millennium, targeted treatments heralded a new era in the treatment of cancer. These drugs act through molecular targets in biochemical pathways in the tumour to stop the cancer from growing. Kidney cancers are hungry for blood; this aspect is exploited by targeted treatments that block blood supply to tumours by interfering with the growth of tumour blood vessels. However, eventually the drugs stop working and the patient develops resistance to the drug. Once this first line treatment has stopped working, patients can be administered another drug to try to overcome resistance to the first drug. This is called second line treatment.
Unfortunately, there have not been any positive pivotal ground breaking studies for the treatment of metastatic kidney cancer for about two years now, and researchers are failing to find a breakthrough target to increase life expectancy from about 30 months. There also seems to be some cross-resistance when two different classes of drug are given sequentially. For example, if an mTOR inhibitor such as everolimus is given after a VEGF TKI such as sunitinib, the mTOR inhibitor does not extend life as much as if it was given as a first line treatment. If these two classes of drug are given together, their effects are not accumulative and there is no difference in overall survival compared to one drug alone, but an increase in toxicity in the VEGF TKI plus mTOR group (RECORD 2 clinical trial results). Clinicians give drugs to cancer patients to help them live longer and feel better; combinations of drug treatments are no more active than one drug alone, but there is more toxicity.
First line treatments
The later tyrosine kinase inhibitors (TKIs), pazopanib (Votrient) and axitinib (Inlyta) are more specific with respect to the part of the biochemical pathway that they target and, therefore, have fewer off-target effects and less side effects. Currently in the UK, about 90% of patients with advanced RCC have first line treatment (sunitinib and pazopanib) and about 50% have second line treatment (sorafenib, axitinib and everolimus). Patients tend to be on first line treatment twice as long as second line treatment.
The COMPARZ trial compared the two first line treatments, sunitinib and pazopanib. The primary end point of the trial was to show that one drug is no worse than the other. There were about 1000 patients in this trial, about 500 patients on each drug. The results showed that there was no statistically significant difference between the two drugs with respect to progression free survival (PFS) and overall survival (OS). In other words, regardless of which drug you start with, the outcome will be the same. The tolerability of a drug affects compliance of the patient taking the drug. There was a difference in tolerability between pazopanib and sunitinib in the COMPARZ trial, with pazopanib being better tolerated. However, because of the cyclical nature of administering sunitinib, there were peaks and troughs of toxicity, which were not seen with pazopanib, which is taken continuously. The timing of the side effect patient questionnaires favoured pazopanib. Patients on pazopanib experienced fewer fatigue, hand and foot syndrome, stomatitis and taste, and reduced platelet count (thrombocytopenia) side effects than patients on sunitinib, while patients on sunitinib experienced fewer liver function side effects and hair/skin changes than those on pazopanib. The quality of life data showed that pazopanib outperformed sunitinib for every factor over 12 months.
Results of another clinical trial comparing sunitinib with pazopanib confirmed the results of the COMPARZ trial; patients were on either sunitinib or pazopanib for 10 weeks and then crossed over to the other drug after a 2-week wash out. Patients and doctors did not know which drug they were on (the trial was double-blind). Patients were asked to rate each drug and say which one they preferred. Seventy percent preferred pazopanib, while only 22% preferred sunitinib. Eight percent couldn’t tell the difference. The doctors also rated each drug and the results were similar. The reasons they gave for preferring pazopanib were as follows, in order of preference:

1. No reason given
2. No hand and foot syndrome on pazopanib
3. No taste changes on pazopanib
4. Less tiredness on pazopanib

The EFFECT trial compared two dosing regimes for sunitinib and looked at tolerability of each dosing regime. One group of patients took 37.5g of sunitinib continuously, while the other group took 50g intermittently. The latter group tolerated the drug slightly better than the continuous group.
Second line treatments
Currently, there are three second-line treatments available to patients in the UK (via the Cancer Drugs Fund in England, Individual Patient Treatment Requests in Scotland* and Wales or through participation in clinical trials). The AXIS trial compared axitinib with sorafenib after prior sunitinb. Axitinib was shown to increased progression free survival by about 1 month compared to sorafenib (4.8 versus 3.4 months), but there was no difference in overall survival. Axitinib is slightly more tolerated than pazopanib.
Current research into kidney cancer treatments
Clinical trials are ongoing to determine the benefit of removing the kidney from patients with metastatic renal cell carcinoma and to identify an effective third line treatment (RECORD 3). A number of new drugs are also being investigated in clinical trials:

• VEGF inhibitors – it is unlikely that researchers will be able to find a better VEGF inhibitor than is currently available (axitinib, pazopanib, sunitinib and sorafenib)
• mTOR inhibitors – there is room for improvement with this class of drug. There are two mTOR receptors, TORC1 and TORC2. Current mTOR inhibitors, everolimus and temsirolimus, only act through TORC1. Research is ongoing to identify a drug that can act through both TORC1 and TORC2 to give a more effective response
• PI3 kinase inhibitor – PI3 kinase inhibitor blocks all 3 TKI receptors and is called a multi-kinase inhibitor. A clinical trial is ongoing to compare PI3 kinase inhibitor with everolimus
• Src inhibition – the Src pathway is another biochemical pathway that controls the growth of blood vessels within a tumour. Inhibition of this pathway with saracatinib or a drug called FGF2 could help to overcome resistance to VEGF TKIs, such as sunitinib and pazopanib. Unfortunately, FGF2 failed in a recent clinical trial to prove efficacy
• PDL-1 inhibitor – this is an immunotherapy, which acts through the body’s immune system to attack the cancer cells. Cancer cells create a protein that shields the cancer from attack by the body’s T cells (part of the immune system). PDL-1 is one of these proteins. PDL-1 inhibitor removes the shield and allows the T cells to attack the cancer. This treatment has almost no toxicity. Patients may need to be preselected for this treatment. PDL-1 receptors are found on cancer cells, while PD-1 receptors are found on T cells. Clinical trials are ongoing with both PDL-1 and PD-1 inhibitors as first or second line treatment
• MET inhibition – this is a similar principle as for Src inhibition and a clinical study opens for recruitment in October 2013
• Biomarkers – the identification of biomarkers for renal cancer is proving very complicated. If or when biomarkers are found it will enable doctors to identify which treatment each individual patient will benefit the most from, resulting in more personalised treatment for kidney cancer patients. The difficulty with these studies is the collection of kidney tumour tissue; most is historical tissue collected during clinical trials that have long since been completed. Tissue collection needs to be real time.

*Axitinib received recommendation from the Scottish Medicines Consortium (SMC) on 11^th November 2013 for use within NHS Scotland for the second line treatment of adults with advanced renal cell carcinoma after failure of prior treatment with sunitinib (Sutent) or a cytokine.
Questions
How do doctors decide which first line drug to give to their patients? Do patient see the data and make their own decisions? The first line drug depends on the individual patient. For example, a patient with liver problems is likely to be administered sunitinib, while a patient with a job that requires them to be on their feet most of the day will be administered pazopanib. The care and support given to patients while on the drug is sometimes more important than which drug is prescribed. For example, access to a clinical nurse specialist and the support and advice they provide with respect to toxicity management helps patients to cope while on the drug. Doctors will prescribe the highest tolerated dose of first line treatment to get the best effect.
In what circumstances might a nephrectomy not be done for advanced kidney cancer patients? This depends on the burden of the disease and how much spread there is. If the patient’s prognostic factors (factors that predict the outcome of the patient) are good, a nephrectomy is likely to be performed, and if they are intermediate, it is possible a nephrectomy will be performed. If a patient’s prognostic factors are poor, it is likely that the kidney will not be removed and the doctor will concentrate on controlling the disease to give the patient a good quality of life. Otherwise, the patient could wait up to 4 weeks for their operation, spend 4 weeks recovering and die shortly after.
Question and Answer Session
What is the future for surgery? Robotics is the future for renal surgery; however, the cost of this treatment is prohibitive within the NHS and it is not offered at all hospitals. GP-led commissioning groups do not feel that it offers a cost-effective means of treating patients. There is currently a postcode lottery with respect to access to this treatment; the patient needs to be knowledgeable about where to go to get the best treatment and work with their GP to access this treatment.
How can patients access axitinib? Currently, axitinib is not available within the NHS and is being appraised by both the Scottish Medicines Consortium (SMC)* and the National Institute for Health and Care Excellence (NICE). In England, axitinib can be accessed through application to the Cancer Drugs Fund (CDF) and in Scotland and Wales through Individual Patient Treatment Requests (IPTR).
*Axitinib received recommendation from the Scottish Medicines Consortium (SMC) on 11^th November 2013 for use within NHS Scotland for the second line treatment of adults with advanced renal cell carcinoma after failure of prior treatment with sunitinib (Sutent) or a cytokine.
What is the best way to put pressure on GPs to commission the best treatments (i.e. robotics)? Patients can put pressure on GPs to send them to the hospitals that offer the best treatment for them. Clinical commissioning groups are now more interested in getting patients involved with commissioning and have patients on their commissioning committees or sub-committees.
 
What research and development is ongoing for new technologies? Surgical treatment has moved on in recent years with the development of keyhole surgery, robotics, cyberknife and ablative treatments. However, all these new technologies require more monitoring to see if they are effective and have not yet taken off because of this. It is very difficult to conduct a randomised clinical trial with these technologies. Professor Powles was sceptical as to whether robotics would be taken up in the UK because it has not been fully tested here and there is very little experience with this technology in the UK.