House of Commons - Science and Technology

Select Committee on Science and Technology Sixth Report

APPROACHES TO CANCER DETECTION AND TREATMENT

19. Early diagnosis of cancer is important. If a cancer can be diagnosed early then treatment can often be more effective.

DIAGNOSIS IN PRIMARY CARE

20. The general practitioner (GP) is usually, but not always, the first health professional to see the symptoms of cancer. Despite the fact that cancer is one of the commonest diseases in the UK, the wide range of types of cancer and the relatively small number of individuals on each GP's list mean that it is a challenge for GPs to make an accurate and speedy diagnosis. This is particularly true in the case of the rarer forms of cancer which GPs might be expected to see only once or twice during a career. Even for the most common cancers, on average a GP will expect to see no more than one or two new patients each year. Moreover, common presenting symptoms of cancer mimic those of many diseases and conditions. For example, a headache is a primary symptom of a brain tumour but most headaches are innocent or have less sinister causes: a GP could not, and should not, refer all patients with a headache to a brain cancer specialist. To improve discrimination between cancer and more common complaints with similar symptoms, GPs need stronger evidence on which to base a diagnosis of suspected cancer before referral to a specialist. Dr Nicholas Summerton of Hull University, drew our attention to published evidence of a need for more research in general practice to inform diagnosis decision-making.[21] Professor Lister, Chairman of the Association of Cancer Physicians, believes that there is "ignorance in primary health care about what's important to investigate in cancer and what is not".[22] The Government has recently introduced new cancer referral guidelines to help GPs identify patients who might have cancer, stating that "an average GP will see eight or nine new patients with cancer each year but will see many times that number of patients with possible cancer. These referral guidelines are there to help GPs; it is about recognising the difficulties involved and making sure the right patients are seen".[23] We welcome the new cancer referral guidelines for the primary care sector. The Government must monitor the implementation of the guidelines and their effectiveness in supporting diagnosis of cancer in the primary care sector and referral to cancer specialists.

DIAGNOSIS IN SECONDARY CARE

21. When a GP suspects that a patient may have cancer, the patient is normally referred to a local hospital for diagnostic tests using both radiology and pathology. Delays in diagnosis can occur at this point. Obtaining a tumour sample requires a tissue biopsy which is performed by a surgeon or a radiologist. Histopathology of the suspect tumour tissue is used to determine whether a tumour is malignant.[24] Cytology (cell characterisation) to identify cancerous or pre-cancerous cells is also useful in the detection of some tumours, particularly cancer of the cervix or cancers associated with abnormal collections of fluid. Routine x-rays, ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and other types of imaging scans may all be used to produce images of a tumour inside the body without surgery. Serology (blood testing) is performed in hospital laboratories to look for cancer markers. All these diagnostic techniques require specialised, often expensive, equipment and the availability of specialised healthcare professionals such as pathologists, radiologists, clinical radiographers and medical laboratory scientific officers. Shortages of either healthcare professionals or specialist equipment may delay or compromise diagnosis. It is common for patients to have an extended wait for an appointment for these tests and, as in all specialised and complex areas, mistakes can be made, particularly when there are shortages in specialist staff. Moreover, problems can arise from both false positive and false negative results.

22. The relationship between the patient and their GP or consultant is not always as straightforward as this description of the diagnostic process might suggest. There are many anecdotal examples of patients having to make repeated visits or requests to their GPs before a referral to a specialist is made. The relationship may be further altered by a relatively recent development which enhances the patient's position in this respect — the rapid spread of the world wide web. The web can provide access to a considerable volume of information and patients may acquire a more detailed knowledge of their cancer than their GP and may even have made their own 'diagnosis'. Care is required however as the information which the web provides is not subject to any quality assurance and may provide misleading as well as useful advice. Several of our witnesses also drew attention to a culture gap between consultants and their patients.[25]

23. The Government has introduced a much-publicised "two week standard". The purpose is to improve access to prompt diagnosis and treatment with a programme of targets to ensure that by the end of the year 2000, all patients with a suspected cancer who are referred as urgent by their GP are seen by a specialist within two weeks.[26] In the first quarter of 2000, 96.1 per cent of women with suspected breast cancer had their first outpatient appointment within two weeks of their GP deciding they should be urgently referred.[27] Waiting time, however, to the first specialist appointment is not the most significant performance measure in terms of obtaining prompt and effective treatment. The first appointment may only put the patient on a waiting list for treatment or a scan. For instance, we heard on one of our visits that while most suspected cancer patients were seen within two weeks of referral to Hull Royal Infirmary, many received neither diagnostic or therapeutic attention at their first appointment and were then required to wait up to 43 weeks for their next appointment. While we recognise that the introduction of the two-week standard is an important step towards improving prompt access to diagnosis and treatment, and will help to reduce patients' anxiety, the time to provision of treatment would be a more relevant standard. We recommend the introduction of challenging targets to reduce the time between GP referral and commencement of treatment.

24. The introduction of a recommended maximum two week wait for those with a suspected cancer will have other effects. As we found during our visits, provision of the diagnostic radiology and pathology services required both to make a diagnosis of cancer and to monitor a patient during treatment is inadequate. The introduction of a fast-track system for people suspected of having cancer will increase the demand on an already over-stretched service. Thus it must be matched by the provision of a greater capacity in radiology and pathology if the management of cancer patients is to improve.

Screening

25. Some cancers show no early symptoms. Screening programmes are designed to detect early disease in people who do not know they have a disease, because they have no symptoms, at a stage when treatment is likely to be more effective than if the disease were diagnosed after the occurrence of symptoms. If the early signs of cancer or a pre-cancerous condition can be detected, treatment can begin while there is still a good chance of a cure. In some cases, cancer can be prevented altogether. Screening for cervical cancer, for example, can achieve this. Cervical smears can show when a woman has pre-cancerous cells in her cervix and these can often be removed by minor surgery or laser therapy before an invasive cancer develops.

26. National screening programmes are expensive. They can only be justified if they enable sufficient numbers of people who have cancer but no symptoms to be diagnosed early enough to make a significant difference to outcome. Population screening is currently used in the UK for breast cancer and cervical cancer. In 1988, a national screening programme was introduced to offer a mammogram every three years to all women aged 50 to 64 years. Women aged 20 to 64 years are offered a smear test every three to five years for cervical cancer. The Government plans to test an alternative technique for cervical cancer screening using a DNA test for the human papilloma virus (HPV), which is found in nearly all women with cervical cancer.[28] A population screening programme for ovarian cancer, using blood tests and ultrasound scans, is currently being investigated by a large multi-centre randomised trial.[29] The National Screening Committee is currently considering the possibility of a trial to look at population screening for prostate cancer using the blood test for prostate-specific antigen.[30] Strong research programmes are needed to identify and develop cost-effective screening techniques for the more common cancers.

27. We saw an impressive demonstration of new screening technology on our visit to St Mary's Hospital. This applied the latest CT scanning equipment to the early detection of lung and bowel cancer. We recognise fully the potential health and economic benefits available if such new techniques were to be introduced across the UK for appropriate high-risk individuals. We recommend that the Government and the National Screening Committee evaluate high speed and precise techniques with a view to commencing large-scale trials for CT cancer screening. This would require the NHS to purchase state-of-the-art diagnostic equipment.

Genetic Testing

28. A small number of cancer patients have a recognised genetic predisposition to certain types of cancer. For example, in familial breast cancer the BRCA1 and BRCA2 genes are associated with a strong likelihood of developing breast and ovarian cancer. Advances in genetics have made it possible to do a genetic test to detect whether an individual carries such a gene but genetic testing can only indicate a predisposition to certain types of cancer. For example, the presence of the BRCA1 or BRCA2 genes is linked to such a high probability of developing breast cancer that some women with either of these genes elect to have a preventive double mastectomy. In the case of hereditary colon cancer, the presence of the relevant gene indicates that the individual should be examined at regular intervals and colonic polyps (pre-cancerous growths) removed as they arise. Family members who do not carry the gene, on the other hand, do not require regular screening. Thus the use of genetics not only allows affected individuals to be treated early but also removes the need for costly examinations in those individuals who are not at risk. With the development of research into the genetics of cancer, such tests are likely to become more widely available for a broader range of cancers. Thus it is important that the UK is in a position to harness them effectively for the prevention and control of cancer.

29. Gene chip technology is likely to become an important diagnostic tool but it will be expensive. Essentially the gene chip, or other forms of DNA microarray, are small squares of glass in which relatively short nucleotide sequences from specific genes are attached in an ordered grid pattern. The chip will in effect resemble a brush in which the sequences are the bristles. Gene chips are capable of carrying tens of thousands of such nucleotide sequences on a square centimetre of glass. A DNA sample from a patient is amplified, labelled with a fluorescent marker and then exposed to the nucleotide array on a gene chip. If the gene DNA recognises complementary nucleotide sequences on the chip it will attach to that sequence; non-attached DNA is removed by washing. When the chip is then examined in an appropriate light the attached DNA will fluoresce and light up that position on the grid. In this way the presence of specific genes in a patient's DNA can be detected. Similarly gene chips may be loaded with nucleotide sequences from pathogenic viruses or bacteria to detect gene mutations and indicate their resistance to antiviral or antibiotic medicines, and so can aid the selection of effective treatments. Although gene chips are capable of detecting many genes in a sample — from a human subject or pathogenic organisms — and offer a powerful yet simple diagnostic technology, they are unlikely to gain widespread utility in healthcare until the cost of production of chips and the associated equipment is significantly reduced.

Treatment of Cancer

SURGERY

30. Once a patient has been diagnosed with cancer there is a range of possible courses of treatment. For solid tumours, surgery is often the first line of treatment. It can be curative if the tumour is removed early enough and especially if the operation is performed by a specialist cancer surgeon. The Society of Academic Surgeons and the Surgical Research Society argue that "the majority of patients who are cured of cancer are cured by surgery alone".[31] Indeed, in most cancers, surgery is necessary to reduce the tumour burden and other forms of adjunctive treatment usually follow.[32] Most cancer surgery is not conducted by specialist cancer surgeons despite the fact that there is published evidence suggesting that surgery conducted by a specialist will on average result in a better outcome.[33] As the Pelican Centre told us, in respect of bowel cancer, "the largest variable in outcome is the surgeon undertaking the surgery".[34] It also drew our attention to a study by McArdle and Hole which revealed that "There were significant variations in patient outcome among surgeons after surgery for colorectal cancer; such differences compromise survival. A considerable improvement in overall survival might be achieved if such surgery was undertaken by surgeons with a special interest in colorectal surgery or surgical oncology".[35] This was recognised in the Calman-Hine report. In the UK there is little investment in surgical research or in developing surgical approaches and techniques specific to cancer, despite indications that improvements in oncological surgery can have a major impact on patient outcome.[36] We recommend that the Government increases the number of specialist surgeons for each type of cancer to a level where most cancer surgery is performed by appropriate specialists. We also recommend that it supports surgical oncological research.

RADIOTHERAPY

31. Radiotherapy has long been used as an effective treatment against cancer. Bombarding the tumour with large amounts of high-energy (ionising) radiation kills any dividing cells. Ionising radiation however is itself toxic and liable to harm healthy tissues so the radiation must be focussed towards the tumour to reduce dose and damage to normal tissue. In recent years, research has led to the development of new approaches with the aim of improving the outcomes from radiotherapy. Three-dimensional conformal radiotherapy (3D-CRT) allows the operator to shape the zone of the radiation dose to the shape of the tumour, with surrounding tissues receiving a much smaller dose. Intensity-modulated radiotherapy (IMRT), which can be used in conjunction with 3D-CRT, allows the operator to vary the intensity of the radiation. Another approach to radiotherapy is implanting a radioactive source, in the form of a wire or pellet, directly into or near the tumour. Sometimes, after a tumour has been removed by surgery, radioactive wires are put into the tumour bed to kill any cancer cells that remain.

32. The equipment required for radiotherapy is expensive, in short supply and requires specialist operators. We learnt about 3D-CRT at the Royal Marsden Hospital and about IMRT in Finland.[37] Neither 3D-CRT or IMRT are commonly available in the UK, although they are available in some other countries.[38] Even when the equipment is available, the optimum use of these techniques requires specialist practitioners who will in turn require an extensive training programme. The personnel infrastructure required to deliver radiotherapy in a timely and accurate way is considerable, with radiographers, clinical oncologists, physicists and computer experts all involved. Within the NHS there is a well-publicised crisis with severe shortages of up-to-date radiotherapy equipment and inadequate numbers of trained personnel in all disciplines.[39] We have heard of little radiotherapies research being conducted in the UK. New IMRT equipment has been ordered for the NHS with funding from the New Opportunities Fund (established with proceeds from the National Lottery) but will take some time to be delivered and commissioned for patient care.[40] We recommend that the Government address the service problems in the delivery of radiotherapy and actively encourage research into radiotherapy. We recommend that IMRT and 3D-CRT equipment should be made available in all cancer centres together with trained personnel.

CHEMOTHERAPY

33. The chemotherapy of cancer involves the use of drugs to kill cancer cells anywhere in the body. Like radiotherapy, these drugs are mainly targeted at dividing cells. Unlike radiotherapy, chemotherapy is delivered systemically and the drug is distributed throughout the body and so will affect all tissues. Thus normal cells that are dividing, such as those in bone marrow, blood, hair follicles, bowel and ovaries or testicles may also be damaged by chemotherapy. This accounts for some of the side-effects of chemotherapy. The side-effects limit the dose that it is possible to administer. There are over 90 chemotherapeutic drugs in use today, many of which are based on chemicals first used up to 30 years ago.[41] Developing new chemotherapeutic drugs is the main thrust of cancer research today; there are currently 322 new compounds in clinical trials for cancer.[42]

Access to Cancer Drugs

34. A key concern for cancer physicians and patients is the availability of some anti-cancer drugs through the NHS. The latest drugs are often the most effective and also the most expensive, and may cost thousands of pounds per treatment. Some expensive drugs are available only to patients living in areas where the local NHS Health Authority has agreed to purchase them.[43] Moreover prescribing patterns are not uniform across the UK. It is unacceptable in a National Health Service founded on the principles of equity that drugs which can improve the length and quality of cancer patients' lives are only available to some of those who could benefit.

35. The National Institute for Clinical Excellence (NICE) has been given the task of determining which treatments are cost-effective for the NHS. One example of NICE's work is the recent approval of the use of taxanes, a group of chemotherapeutic drugs, in the treatment of ovarian and breast cancer. Despite the fact that there was good clinical evidence of the effectiveness of these drugs and they were already licensed for use, some Health Authorities were refusing to provide them for patients on the grounds of cost. NICE eventually recommended their use, first paclitaxel (Taxol) for ovarian cancer, and later, but only after appeal, paclitaxel and docetaxel (Taxotere) for breast cancer.[44] NICE estimates that these treatments will cost the NHS an extra £16 million per annum for breast cancer[45] and £7 million per annum for ovarian cancer.[46] There is no guarantee however that the guidance from NICE on these treatments will ensure their availability on a truly national basis. Yvette Cooper, the Minister for Public Health, told us that some of the new resources made available this year for the NHS were "to fund new treatments as they came through NICE" and that "for NICE to do all of its work and then not to be implemented in practice is not what we expect to happen".[47] She also told us that there was "a follow-up procedure in terms of clinical governance and the CHI [Commission for Health Improvement] arrangements to make sure that it happens in practice".[48] Nevertheless, we remain unconvinced that guidance from NICE alone will ensure national availability of recommended treatments. We recommend that the Government ensures that its follow-up procedures require all Health Authorities to provide anti-cancer treatments which are approved by NICE where the patient's consultant regards them as clinically appropriate and prescription is within the guidelines set by NICE.

36. The basis on which the Government plans to allocate the additional funds to make NICE-approved treatments available remains unclear. The additional costs to the NHS calculated by NICE only include the costs of treatments for those patients whose Health Authorities were not funding paclitaxel and docetaxel. Should the additional NHS funds for NICE-approved treatments be provided only to those Health Authorities where the treatment was not previously available, there will be a considerable disincentive for any Health Authority to fund expensive, new treatments in advance of NICE approval in the future. We recommend that full additional funding of NICE-approved treatments be provided to all Health Authorities, regardless of whether an authority was already providing the treatment prior to its approval by NICE.

37. The Government has announced that it will refer a number of other anti-cancer treatments to NICE for assessment. The treatments proposed for referral are: irinotecan, oxaliplatin and raltitrexed for bowel cancer; paclitaxel, vinorelbine and gemcitabine for lung cancer; fludarabine, rituximab and interferon for haematological malignancies such as leukaemia and lymphomas; temozolamide for brain tumours; and gemcitabine for pancreatic cancer. NICE does not expect to deliver a verdict on these treatments until 2001.[49] These delays can undermine optimal patient outcome. In the USA the Food and Drug Administration (FDA) licenses drugs. Part of the FDA licensing process includes an assessment of cost-effectiveness. We see no reason why guidance from NICE on cost-effectiveness of treatments cannot be delivered at the same time as marketing approval is given. We recommend that the Government find better ways of operating NICE so that guidance on drug treatment can be issued by NICE at the same time as the granting of marketing approval.

38. By the standards of other European countries and the USA, the UK spends very little on anti-cancer drugs. The Association of the British Pharmaceutical Industry (ABPI) told us that "compared to France, Germany and the USA, the UK has the highest death rate from cancer per 100,000 of the population (236, 206, 194 and 275 respectively) and the lowest Government spend on anti-cancer medicines per 100 of the population (£279, £205, £1,705 and £95 respectively)".[50] We do not accept that there is a direct connection between these sets of figures; it should also be noted that the death rates given by the ABPI are not comparable with those given in table 2 (the ABPI's figures are not standardised for age). Witnesses suggested that inexperience in the use of modern chemotherapy creates a more risky environment in which to conduct cancer clinical trials.[51] The ABPI told us that the level of investment by the pharmaceutical industry in research in a country is related to the size of a market and that the small size of the UK market is therefore a disincentive to investment in research in the UK.[52] CancerBACUP said that the lengthy time taken to provide taxanes for breast and ovarian cancer in the UK, despite evidence of their effectiveness, "demonstrates that investment in cancer research must be matched by the political will to fund new treatment, otherwise research will be of little tangible benefit to patients".[53] Dr Cullen, a consultant medical oncologist, told us that "it is quite embarrassing at international meetings... finding out that there is exciting experience with new products in various diseases that I treat and I have no access to these simply because the resources available to us for cancer treatment are inadequate".[54] The low level of use of the latest anti-cancer drugs in the UK compared to other European Countries disadvantages cancer patients in the NHS and discourages pharmaceutical industry investment in clinical trials. We recommend that the Government reviews the arrangements for the provision of anti-cancer drugs to NHS patients to ensure that the best drugs are available, to all those patients who may benefit, as quickly as possible.

IMMUNOTHERAPY

39. Immunotherapy is treatment that uses the body's own immune system or antibodies produced in animals or in tissue culture to kill cancer cells. To date, this technique has been most successful against haematological malignancies (lymphomas and leukaemias). The immune system is designed to fight foreign material — whether invading organisms or tissue grafts. Although cancer cells are for the most part the same as normal cells, some may have tumour-specific surface antigens which the immune system can recognise as foreign and attack. Another approach to immunotherapy is the use of tumour-specific antibodies as a means of delivering toxins or anti-cancer drug molecules to cancer cells to obtain a selective anti-tumour effect. Cancer-specific vaccines are also being developed against certain tumour types for both preventive and therapeutic use. Most immunotherapeutic approaches to cancer treatment are still in the experimental stage, although a number are now in clinical trials.

COMPLEMENTARY THERAPIES

40. For many cancer patients, complementary therapies provide an important element of their overall treatment. Complementary therapies are mostly used to alleviate cancer symptoms or the unpleasant side-effects of conventional therapy, thus improving the quality of life of the patient. There is a broad range of complementary therapies which are supported by varying degrees of evidence of effectiveness, but little research is being carried out to validate them. In a recent report commissioned by Macmillan Cancer Relief, a number of complementary therapies were identified which are commonly used by cancer patients and are sometimes made available in the NHS.[55] These were:

Acupuncture, to control pain and reduce the nausea induced by chemotherapy and radiotherapy;

Aromatherapy (massage with essential oils), to bring relief of stress;

Healing or "therapeutic touch" is claimed to channel spiritual forces to stimulate self-healing mechanisms in the patient;

Homœopathy, which uses chemicals diluted in water to virtually zero concentrations as medicines to treat a range of conditions including cancer;

Massage therapy, used to alleviate the pain and the anxiety associated with cancer;

Naturopathy (diets and herbals) are used as 'natural cures' to give the body the maximum opportunity to heal itself;

Psychological interventions such as relaxation and meditation techniques which are said to help with anxiety and fatigue; and

Reflexology, the application of pressure to the feet, is said to restore energy levels and promote emotional well-being.

41. Despite the very limited amount of scientific evidence for their effectiveness, complementary therapies are available in the NHS in some areas. There is however no national policy for their procurement or for clinical research programmes to test their efficacy. Despite this, many cancer patients are convinced of their effectiveness. We have received extensive evidence from patients and patients' groups recognising the value of these therapies, especially in terms of improvements in quality of life.[56] Cancerlink, for instance, told us "the public is voting with its feet on complementary therapies, it is opting into complementary therapies in increasing numbers, whether there is evidence that it is effective or not".[57]

42. It is axiomatic that the NHS should not be providing ineffective services, but there is much anecdotal evidence which indicates that many patients derive significant benefit from complementary therapies. Like more conventional treatments, those complementary therapies should be provided by the NHS to all patients who may benefit, but only if there is good evidence of efficacy. More clinical research is needed to determine the benefits that patients derive from complementary therapies. We recommend that the Government seeks guidance from NICE on the cost-effectiveness of complementary therapies for cancer care to ensure consistency of provision across the NHS.

21 Ev. p. 249. Back

22 Q. 375. Back

23 Department of Health press notice 2000/0200, 31^st March 2000. Back

24 Histopathology is the examination of suspect tissue under a microscope. Back

25 See, for example, Q. 585. Back

26 The New NHS, modern, dependable, Department of Health,1997, Cm 3807. Back

27 Department of Health, press notice, 19 June 2000. Back

28 Ev. p. 269. Back

29 Ev. p. 26. Back

30 Department of Health, press notice 2000/0333, 7 June 2000. Back

31 Ev. p. 241. See also Ev. p. 246. Back

32 Ev. p. 241. Back