The diagnosis of prostate cancer comes with challenges.

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2 The diagnosis of prostate cancer comes with challenges. The PSA test lacks the specificity to reliably detect prostate cancer and under our current guidance 1 requires asymptomatic men aged 50 and over to often proactively reach an informed choice about whether or not to have a test. Once tested, those men with a raised PSA often have to endure an invasive biopsy, which for up to 3 in 50 men (6%) can cause a serious infection that can on occasion lead to hospitalisation 2. There is also the need for men to wait post biopsy for damaged tissue to heal before having a magnetic resonance imaging (MRI) scan, which can cause many men to miss the 62 day standard to commence first definitive treatment from the point of referral by their GP. Biopsy is also currently insufficiently sophisticated in the detection of all prostate cancers, as this is often carried out without image guidance which carries the potential to miss significant cancer or to find insignificant low grade cancer. This means that some men choose treatment for a type of prostate cancer that would not have caused them any problems or shortened their life and can be left with often life-changing side effects, such as urinary and bowel problems and problems getting or keeping an erection. The aim of this pathway is to transform men s experiences from the pre-diagnostic phase and beyond, using clinical consensus on ways to improve the use of the PSA test for men without symptoms and newly published clinical research that offers the potential to reduce unnecessary biopsies. 2

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4 Not all men are at the same risk of developing prostate cancer, there are some specific factors that put men at higher than average risk of developing prostate cancer include age, a family history of the disease and obesity (specifically in relation to advanced disease). Prostate cancer is the most prevalent cancer in men in the UK; approximately 1 in 8 men living in the UK will get prostate cancer at some point in their life. Our research shows that in men of black* ethnicity, the risk of getting prostate cancer is doubled to 1 in 4. Asian men have a much lower risk with 1 in 13 men developing prostate cancer 3. It is not understood why there is a difference in risk amongst different ethnic groups but it could be linked to genetics. Prostate cancer mostly affects men over 50 and the risk of developing prostate cancer increases with age with a 75% incidence rate in men over Men under 50 can develop prostate cancer but it less common. Black men and men with a family history of prostate cancer are more likely to be diagnosed at a younger age 5,6. Men with a family history of prostate cancer are 2.5 times more likely to develop prostate cancer if their father or brother has been diagnosed compared to men with no relatives that have had the disease. Men are twice as likely to develop prostate cancer if they have a second-degree relative (grandfather, uncle or nephew) who has been diagnosed 7. There is also an increased risk of developing prostate cancer if a man s mother or sister have been diagnosed with breast cancer and had faults in the BRCA1 or BRCA2 gene. These inherited genetic faults have been found to be linked with an increased risk of developing a more aggressive prostate cancer 8. Being overweight or obese increases a man s risk of developing aggressive or advanced prostate cancer 9. Obesity is linked to lower levels of testosterone. Testosterone controls how the prostate gland grows and develops. *The 1 in 4 lifetime risk was worked out using information about men self-reporting as Black African, Black Caribbean or Black other. Men presenting with the following symptoms should go on to have a PSA test and digital rectal examination (DRE) as per the NICE suspected cancer pathway for referral 11 : lower urinary tract symptoms (difficulty passing urine or a frequent need to pass urine), visible haematuria or erectile 4

5 dysfunction; and for a small percentage other symptoms may include weight loss, back and/or bone pain 11. Most early prostate cancers have no symptoms; general practitioners (GPs) and practice nurses should be aware of the factors that put men at higher than average risk. The Prostate Cancer Risk Management programme (PCRMP) 12 (see Appendix 1), which is produced by Public Health England, has recently been updated to support primary care professionals in their use of the PSA test with asymptomatic men. Unlike its previous version, it now recommends one referral threshold for PSA value of 3ng/ml for men between the ages of 50 to 69. Due to different methodologies and accepted levels of evidence, Prostate Cancer UK s PSA consensus 1 (see Appendix 2) covers aspects of PSA testing not included in the PCRMP, where robust published evidence is lacking. Prostate Cancer UK s PSA consensus recommends for GPs to have proactive conversations about prostate cancer risk and the PSA test with men at higher than average risk, especially if they don t often visit their GP 1. These men may not know they re at higher risk. Men without symptoms who have a life expectancy of clearly less than 10 years are unlikely to benefit from a PSA test. Prior to going ahead with a PSA test the following should be covered: Exclusion of urinary tract infection (UTI) or sexually transmitted infection (STI) Ensure patient is fully counselled about the pros and cons of the PSA test and next steps if the PSA is elevated. Before actually having the test: Advice about refraining from vigorous exercise or sexual activity (including masturbation) 48 hours ahead of a PSA test. A digital rectal examination (DRE) should also be performed prior to referral to feel for malignancy. Indicators of a clinically malignant cancer will be a firm, hard or craggy feeling prostate on DRE 11. Depending on presenting symptoms, GPs may consider performing a DRE prior to a PSA test. It is not necessary to delay giving a PSA test due to a DRE having been performed first as the rise in PSA is minimal following DRE 13. A delay in performing the PSA could have a detrimental effect on the speed at which a prostate cancer is detected. 5

6 A raised PSA alone should not be an indicator for referral to a urologist and other risk factors that should be considered are as follows 12 : DRE findings and prostate size Age (see 1.1) Ethnicity (see 1.1) Family history (see 1.1) Comorbidities BMI (see 1.1) Any previous PSA or prostate biopsy history Referral values for PSA dependant on age ranges are: In men between 45 and 50 a PSA of 2.5ng/ml is reported 1 In men between 50 and 69 a PSA of 3.0ng/ml is reported 12 In men 70 and over a PSA of 3.0ng/ml is reported 14 At the point of referral patients should be counselled and informed that they are being referred to a cancer service 15. They should be given the reasons for the referral decision and provided with reassurance that most people referred will not have a diagnosis of cancer. Those with a very high PSA should be counselled appropriately about the likelihood of a prostate cancer being detected. Other possible outcomes such as benign prostate hyperplasia should also be discussed. Information should be presented both orally and in an accessible written format in order to promote their active participation in care and self-management 16. Information to be given to the patient should include details about 15 : Where they have been referred to and the type of specialist they will see When to expect to be contacted with an appointment and how long they should have to wait before seeing a specialist What types of tests they may undergo and how long it may take before they should expect to receive the results Other sources of information about prostate cancer that can be accessed prior to their appointment with the specialist unit NICE recommends in its latest Quality Standards that patients are provided with written information encouraging them to attend their appointment with a specialist. This is to avoid missed appointments and ensure an earlier diagnosis 17. The NHS England cancer strategy published in May sets out an expectation that by 2020 cancer will be diagnosed or excluded within 28 days of a GP referral to secondary care. Whilst it would appear that the 2 week wait will remain a reportable standard for England, currently this standard is not reported against in Wales, who usually follow NICE Guidelines. There are no similar targets in Scotland and Northern Ireland 19. 6

7 In a move to support earlier diagnosis we recommend that men should be seen between days 0 10 from the point of referral by their GP. We believe that by expediting the first appointment this timeframe enables all diagnostic tests for prostate cancer to be undertaken within waiting time targets. To improve the overall patient experience, reduce anxiety and the number of hospital attendances, the initial outpatient appointment should take place in a one stop setting. A one stop clinic allows the patient to be reviewed by the specialist team and undergo their investigations on the same day. This appointment may take several hours but it negates the need for the patient to attend on two to three separate occasions for investigative tests. One stop clinics have been well documented as a mechanism to achieve earlier diagnosis and improve the overall patient experience through the reduction of hospital attendance 20,21. If a one-stop facility is not available, men should be sent for an multi-parametric MRI (mpmri) scan before biopsy, if clinically appropriate. Appropriate triage should be put in place to ensure that only clinically suitable patients are sent straight to MRI to ensure that resources are maximised. Patients not suited to MRI include those with pacemakers or metallic implants. Further details can be found in Section 1.7. Patients will also need to be assessed for any comorbidities that would contra-indicate undergoing a biopsy without prior work-up. This will review the patient s fitness to undergo a surgical procedure and assess if there are any medications that would need to be stopped prior to undergoing a biopsy e.g. anticoagulants. We believe that mpmri before biopsy offers the potential for a step-change in prostate cancer prediagnosis. Results from the PROMIS trial 22 show that this pre-diagnostic technique can reduce immediate biopsies by 27%. There is also the potential for the scan image to guide biopsies, which can result in fewer cores being taken, and for men to experience a faster and less invasive procedure. To ensure that mpmri before biopsy delivers strong outcomes for men it is important that it is rolled out with some or all of the following mechanisms in place: A training programme for Radiologists and potentially Radiographers A quality assurance programme that audits Radiologists and Urologists to make sure they are taking / interpreting the scans correctly A Clinical Consensus that guides on the number of men a Radiologist should scan before proficient, how much training they should have and the regularity of their audit Having enough of the right scanners in place with the capacity for prostate MRI before biopsy A timely diagnosis can be achieved when a biopsy should is performed within a week of an mpmri being undertaken if a one stop facility is not available or clinically appropriate. According to the outcome of the mpmri, results should be discussed with the patient to determine the most appropriate method of biopsy. As with any surgical procedure, informed consent should be sought from the patient prior to the biopsy being performed. Patients should be provided with written information clearly explaining the 7

8 purpose and the nature of the procedure. The patient should also be informed of the risks of expected complications including 23 : Haematuria Haematospermia Bleeding from the rectum Serious infection that may result in re-hospitalisation Urinary tract infection Lower urinary tract symptoms (LUTS) Unsuitability for MRI can be for a variety of reasons such as pacemakers, metallic implants, and claustrophobia. For this group of patients, we recommend that they are sent straight to biopsy for confirmation or exclusion of prostate cancer. This group of patients have other comorbidities or age related quality of life indicators that mean they would not benefit from radical treatment. A bone scan or other cross sectional imaging should be considered for this group of patients to confirm or rule out advanced disease. Should metastases be confirmed then treatment via the advanced disease pathway could be commenced. This group of men will present with a very high PSA and other symptoms suggestive of advanced disease such as weight loss and bone pain. For this group of patients, a bone scan or other cross sectional imaging would confirm metastatic spread before they commence non-curative treatment. For patients who may be suitable for or wish to participate in clinical trials or some forms of treatment a biopsy may be required. In this case their age and ECOG performance status 24 or Karnofsky performance status 26 should be considered. Unless there is a very high PSA result and significant symptoms, hormone therapy should be delayed until all relevant investigations have been completed, as commencing hormone therapy early can impact eligibility for clinical trials and other forms of treatment. An effective multi-disciplinary team (MDT) is essential for achieving the coordinated care of patients throughout their cancer journey and is the means to ensure that all relevant healthcare professionals are involved in and contribute to the decision-making process for the clinical management of patients. Members of the MDT should include, but are not limited to: Urological Surgeons, Clinical and Medical Oncologists, Radiologists, Histopathologists, Clinical Nurse Specialists, MDT coordinator and administrative support 27. 8

9 Following the MDT meeting patients should be given an urgent follow-up in the outpatient clinic so that the MDT discussion can be shared and the management plan agreed. Patients with a benign condition may be given treatment to alleviate symptoms. This may be commenced in secondary care and followed up by the patient s GP in the form of monitoring in the primary care setting. Dependent on the stage and grade of the cancer, some patients may need a consultation with a Urologist and an Oncologist. If this is the case, patients then should be seen in a joint Uro-Oncology clinic thus preventing the need for two separate appointments. It is recommended that the Clinical Nurse Specialist is present for this consultation to ensure continuing support and advocacy. At this stage, patients should be given written information in relation to the options available to them in terms of treatment or monitoring. Some patients will require further investigations prior to commencing treatment. It is imperative that men are given enough time to consider all options available to them including potential side effects of any treatments in order to make a fully informed choice. We would recommend a minimum of a week is given to consider treatment options. All men should have access to a Clinical Nurse Specialist following a diagnosis of prostate cancer. The Clinical Nurse Specialist should be introduced at the stage a cancer diagnosis is confirmed. Nurse specialists are key points of contact for men with prostate cancer. They provide information about treatment options, answer questions or concerns and support men to make decisions about their care. This is particularly important immediately after diagnosis and when difficult choices about treatment need to be made 28. The Clinical Nurse Specialist should be present through all aspects of the treatment and follow-up pathways thereafter for consistency, support and advocacy. Nurse specialists also provide personalised care plans and information about support services 28. Once a patient is discussed at the MDT meeting some patients may need further imaging such as a bone scan, PET-CT scan or whole body MRI scan. 9

10 1. Prostate Cancer UK. Consensus statements on PSA testing in asymptomatic men in the UK - Information for HCPs [Internet] Available from: 2. Loeb S, Vellekoop A, Ahmed HU, Catto J, Emberton M, Nam R, et al. Systematic review of complications of prostate biopsy. Eur Urol [Internet] Dec;64(6): Available from: 3. Lloyd T, Hounsome L, Mehay A, Mee S, Verne J, Cooper A. Lifetime risk of being diagnosed with, or dying from, prostate cancer by major ethnic group in England BMC Med [Internet] Jul 30 [cited 2015 Jul 30];13(1):171. Available from: 4. Cancer Research UK. Prostate cancer incidence statistics: By Age ( ) [Internet] [cited 2016 Feb 26]. Available from: professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer/incidence#heading- One 5. Lange EM, Salinas CA, Zuhlke KA, Ray AM, Wang Y, Lu Y, et al. Early onset prostate cancer has a significant genetic component. The Prostate [Internet] Feb 1;72(2): Available from: 6. Metcalfe C, Evans S, Ibrahim F, Patel B, Anson K, Chinegwundoh F, et al. Pathways to diagnosis for Black men and White men found to have prostate cancer: the PROCESS cohort study. Br J Cancer [Internet] Oct 7;99(7): Available from: 7. Johns L, Houlston R. A systematic review and meta-analysis of familial prostate cancer risk. BJU Int [Internet] [cited 2013 May 23];91(9): Available from: 8. Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. N Engl J Med [Internet] Aug 4;375(5): Available from: 9. World Cancer Research Fund International. Continuous Update Project Report: Diet, Nutrition, Physical Activity, and Prostate Cancer [Internet] [cited 2014 Nov 18]. Available from: San Francisco IF, Rojas PA, DeWolf WC, Morgentaler A. Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int [Internet] Aug;114(2): Available from: National Institute for Health and Care Excellence. Suspected cancer: recognition and referral Recommendations organised by site of cancer: Urological cancers. NICE guideline 12 [Internet] [cited 2016 Aug 11]. Available from: 10

11 12. Public Health England. Prostate cancer risk management programme (PCRMP): benefits and risks of PSA testing [Internet] [cited 2016 Jul 11]. Available from: Chybowski FM, Bergstralh EJ, Oesterling JE. The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study. J Urol [Internet] Jul;148(1):83 6. Available from: Public Health England. What PSA referral value should be used for men aged 70+? Information provided via personal correspondence with Janet Rimmer from Public Health England National Institute for Health and Care Excellence. Suspected cancer: recognition and referral. Recommendations on patient support safety netting and the diagnostic process. NICE Guideline 12 [Internet] [cited 2016 Aug 11]. Available from: National Institute for Health and Care Excellence. Patient experience in adult NHS services: improving the experience of care for people using adult NHS services (CG138) [Internet] [cited 2016 Oct 10]. Available from: Guidance 17. National Institute for Health and Care Excellence. NICE quality standard [QS124]. Quality statement 4: Encouraging attendance at cancer services [Internet] [cited 2016 Jul 11]. Available from: encouraging-attendance-at-cancer-services). 18. NHS England. Achieving world-class cancer outcomes: Taking the strategy forward [Internet] [cited 2016 Aug 11]. Available from: Cancer Research UK. Cancer waiting times definitions by country [Internet] [cited 2016 Aug 11]. Available from: Coull N, Rottenberg G, Rankin S, Pardos-Martinez M, Coker B, Jenkins E, et al. Assessing the Feasibility of a One-Stop Approach to Diagnosis for Urological Patients. Ann R Coll Surg Engl [Internet] May [cited 2016 Jul 13];91(4): Available from: Shah J. Assessment of activity and outcome from a one-stop clinic for men with suspected prostate cancer: Five years experience. J Clin Urol [Internet] Jun 26 [cited 2016 Jul 13]; Available from: 11

12 22. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet [Internet] Feb 25;389(10071): Available from: British Association of Urological Surgeons & British Association of Urological Nurses. TRANSRECTAL ULTRASOUND AND PROSTATIC BIOPSY: GUIDELINES & RECOMMENDATIONS FOR TRAINING [Internet] Available from: 0Prostatic%20Biopsy%20FINAL.pdf 24. ECOG-ACRIN. ECOG Performance Status [Internet]. [cited 2016 Aug 11]. Available from: Zubrod CG, Schneiderman M, Frei E, Brindley C, Lennard Gold G, Shnider B, et al. Appraisal of methods for the study of chemotherapy of cancer in man: Comparative therapeutic trial of nitrogen mustard and triethylene thiophosphoramide. J Chronic Dis [Internet] Jan 1 [cited 2017 Apr 6];11(1):7 33. Available from: Karnofsky D & Burchenal J. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C, ed. Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press; p. 27. British Uro-oncology Group and British Association of Urological Surgeons Section of Oncology. Multi-disciplinary Team (MDT) Guidance for Managing Prostate Cancer [Internet] Available from: E%20CANCER%20ALGORITHMS%20SEPT% pdf 28. National Institute for Health and Care Excellence. Prostate cancer- Quality Standard (QS91) [Internet] [cited 2016 Oct 7]. Available from: 12

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16 Consensus statements on PSA testing in asymptomatic men in the UK [HP version] March The consensus statements We've produced a set of statements, representing the consensus view of hundreds of health professionals, to support primary health care professionals to use the PSA test more effectively for men without symptoms of prostate cancer. The set of thirteen consensus statements, providing additional guidance to Public Health England's Prostate Cancer Risk Management Programme (PCRMP), will drive improvements in the early detection of prostate cancer in men without symptoms whilst aiming to avoid over treatment and reduce variation in practice. You can read more about the evidence behind the statements and the methods used to develop the consensus on the 'How the consensus was developed' tab above. Statement 1: A man s PSA level should be built into a validated risk assessment tool, when available, alongside other known risk factors to better assess a man s risk of prostate cancer and aid in the decision-making process. We're working with experts from around the world to change the way prostate cancer is diagnosed across the UK by developing a risk prediction tool for primary care practice. Statement 2: Primary healthcare professionals need to be aware of the factors that put men at higher than average risk of prostate cancer. Increasing age, Black ethnicity and a family history of prostate cancer put men at higher than average risk of prostate cancer. Statement 3: Primary healthcare professionals need to be prepared to have proactive conversations with men at higher than average risk of prostate cancer about prostate cancer risk and the PSA test. Statement 4: Governments and public health agencies have primary responsibility for raising awareness of prostate health and prostate cancer risk factors amongst men in the UK, with relevant contribution from healthcare professionals and charities. Statement 5: All men should be able to access PSA testing from the age of 50, but men at higher than average risk of prostate cancer should be able to access the PSA test from the age of

17 The PCRMP guidance states that "The PSA test is available free to any man aged 50 or over who requests it, after careful consideration of the implications". Statement 6: When a PSA test is being considered, primary healthcare professionals should provide balanced information on the pros and cons of the PSA test in order to allow the man to make up his own mind on whether to have the test. Information on the pros and cons of the PSA test can be found in the PCRMP guidance and on our information page on the PSA test. Statement 7: Asymptomatic men with a life expectancy clearly less than 10 years should be recommended against an initial or repeat PSA test as they are unlikely to benefit. We acknowledge that further work is required to better estimate an individual s life expectancy. Statement 8: GPs should offer a digital rectal examination (DRE) to all asymptomatic men who have decided to have a PSA test. Statement 9: Asymptomatic men at higher than average risk of prostate cancer who have a PSA test between the ages of 45 and 49 should be referred for further investigations if their PSA level is higher than 2.5ng/ml. This recommendation is based on the limited evidence currently available, and may need to be reviewed if further information becomes available. Statement 10: PSA history and a rising PSA (whilst still under the referral threshold) should be taken into consideration when deciding whether to refer to secondary care. The PCRMP states the new recommended prostate biopsy referral value for men aged years is 3ng/ml. Statement 11: Asymptomatic men who have a PSA level below the threshold referral value should not be denied a repeat PSA test. Re-testing intervals should be individualized following a discussion incorporating prostate cancer risk factors. Statement 12: Asymptomatic men over 40 should consider a single baseline PSA test to help predict their future prostate cancer risk. If the PSA level is above the age-specific median value, they should be considered at higher than average risk of prostate cancer and should be encouraged to be re-tested in the future. The age-specific median value for men aged years is 0.7ng/ml. Statement 13: The PSA test, even when combined with the DRE, should not be used in a UK population-wide screening programme for asymptomatic men. 17

18 Read our policy position on the PSA test, which includes more information on why there is no national screening programme using the PSA test in the UK. 18