Prostate cancer

1. Prostate cancer

2. Why is there currently a problem? Prostate Cancer Advisory Group April 2007

3. ‘Prostate cancer patients in the NHS have historically reported a worse experience than patients with other cancers. The gap in reported experience between prostate cancer and other cancers has actually widened between 1999 and 2004. Not all men currently get access to high standards of advice and support on treatment options’

4. Background

5. What does the prostate gland do? • What diseases affect the prostate? • What is the incidence and prevalence of prostate cancer? • What is the workload? • How do we grade prostate cancers? • What disease scoring systems are used? • What are the clinical features of prostate cancers? • Are they all the same? • What are the known risk factors? • Are there any preventive treatments?

6. What does the prostate gland do?

7. Makes, stores and secretes an enzyme-rich fluid that makes up about 1/3 of the ejaculate volume (the rest is produced by the seminal glands) • The main role is to liquefy semen and protect sperm during fertilisation • Smooth muscle around the prostate helps to expel semen during ejaculation • The function of the prostate is regulated by androgens(mainly testosterone)

8. What diseases affect the prostate?

9. Diseases of the prostatewww.cancerscreening.nhs.uk/prostate • Prostate cancer • Malignant growth of prostate cells, localised and may spread • Nearly all prostate cancers are adenocarcinomas, mainly occurring in the peripheral zone of the prostate gland • Rare in men < 50, and is more common with increasing age • Benign prostatic hyperplasia • Non-malignant increase in size of the prostate with age • Rare in men under 50 • Prostatitis • Inflammation of the prostate • Can occur in men of any age The early symptoms of prostate diseases are very similar

10. What is the incidence and prevalence of prostate cancer?

11. Prostate cancer: Incidence and prevalencewww.info.cancerresearchuk.org • Most common cancer in men in UK • In 2005 >34000 men in the UK were newly diagnosed • ¼ of all newly diagnosed cancers in men • Accounts for 12% of male deaths from cancer in the UK and is the 2nd most common cause of cancer death in men after lung cancer • Lifetime risk is 1 in 14 • ½ of men in their 50’s have histological evidence of prostate cancer, which rises to 80% by 80 years, but only 1 in 26 men (3.8%) die from the disease • Men are more likely to die with it than from it

12. What is the workload?

13. What is the workload?NICE 2002 • A GP with a list size of 2000 is likely to see 1-2 new patients with urological cancer each year • A DHG serving 200000 people deals with 70 men with prostate cancer each year out of 150 urological cancers

14. How do we grade prostate cancers?

15. TNM stages of prostate cancerwww.cancerhelp.org.uk • Tumour • T1 – Tumour too small to be seen on scans or be felt on examination • T2 – Tumour completely inside the prostate gland (palpable) • T3– Tumour has broken through the capsule of the prostate gland • T4 – Tumour has spread to other body organs nearby such as rectum or bladder

16. TNM stages of prostate cancerwww.cancerhelp.org.uk • Lymph nodes • N0 – No cancer cells found in any lymph nodes • N1 – one +ve lymph node smaller than 2cm across • N2 – more than one +ve lymph node. Or one that is between 2-5cm across • N3 – Any +ve lymph node that is >5cm across • Metastases • M0 – No cancer spread outside the pelvis • M1 – Cancer has spread outside the pelvis

17. What disease scoring systems are used?

18. Gleason scoreEUA guidelines 2007 • Most commonly used system • Total score ranges from 2 (least aggressive) to 10 (most aggressive) • The sum of the 2 most common patterns (grades 1-5) of tumour growth found in the biopsy specimen • The Gleason histological score correlates well with prognosis in localised prostate cancer, but there is considerable observer variation

19. What are the clinical features of prostate cancers?

20. Clinical features of prostate cancerwww.cancerscreening.nhs.uk/prostate/prostate-booklet-text.pdf • Prostate cancers (unlike BPH) tend to develop in the outer part of the prostate gland • Unusual for early cancers to cause any symptoms • Locally advanced prostate cancers that have extended outside the capsule are also frequently without symptoms • If the tumour is large enough, it can cause lower urinary tract symptoms(LUTS) eg frequency, urgency, hesitancy, leaking, but by the time this happens the cancer will usually have reached an advanced stage • LUTS are similar to those of BPH. Most men with LUTS will not have prostate cancer • Often the first sign of prostate cancer is evidence of metastases(frequently in bone, causing bone pain) • About 20–30% of patients in the UK present with metastatic disease

21. Are they all the same?

22. Prostate cancers vary in their natural histories • Prostate cancer is biologically heterogeneous • Some grow very slowly and never cause symptoms, others grow fast and metastasise quickly, other types grow at a modest pace

23. What are the known risk factors?

24. Risk factors for prostate cancerwww.info.cancerresearchuk.org • Age • Increases with age • Ethnicity • Highest rates in African-American men • Lowest rates in Asians • Family history • 2-3x higher for men with FH in 1st degree relative, particularly is a brother, or were affected when young • Diet • Associated with Western diet

25. Are there any preventive treatments?

26. Finasteride: Preventative therapy?Thompson IM, et al. N Engl J Med 2003; 349: 215-24 • Increases sexual side effects but decreases urinary symptoms • May prevent or delays the appearance of prostate cancer but this possible benefit and reduced risk of urinary problems must be weighed against sexual side effects • There is no evidence that preventative therapy increases survival • Not licensed in the UK for the prevention or treatment of prostate cancer

27. Screening and diagnosis

28. How do you detect prostate cancer? • What is the role of PSA detection? • Can we use digital rectal examination to improve prostate cancer detection? • What are the referral guidelines for specialist investigations?

29. How do you detect prostate cancer?

30. Detection of prostate cancerNICE 2002 • Prostate cancer can be detected by: • Digital rectal examination (DRE) • Prostate specific antigen (PSA) testing • Trans-rectal ultrasound (TRUS) guided biopsy • Pathological examination of tissue samples removed following TURP • CT/MRI scans provide information on staging and spread • Before referral men should be offered DRE and PSA testing as set out in ‘Referral guidelines for suspected cancer’ CG27 - NICE CG 58, 2008

31. What is the role of PSA detection?

32. Prostate specific antigen (PSA) • PSA is produced by prostatic epithelium and is present in seminal fluid, urine and serum. It is involved in the liquefaction of seminal coagulum formed at ejaculation • With cancer the epithelial cells are disorganised and the barrier between the prostate and blood vessels is disrupted. More PSA leaks into the blood vessels as a result

33. Prostate specific antigen (PSA)NICE 2002. Improving outcomes in urological cancers • Men with cancer tend to have higher levels in their blood (up to 30% have normal levels) • There is no level below which a man does not have prostate cancer, nor is there a level that is agreed as diagnostic • Levels tend to increase naturally with age • Levels tend to increase with other conditions eg BPH, urinary infection • Different assay systems can produce different results and levels can vary in response to • Exercise • Sexual activity • Clinical investigation • Other forms of treatment

34. Can we use digital rectal examination to improve prostate cancer detection?

35. Digital rectal examinationNICE 2002. Improving outcomes in urological cancers. The Manual. 2002. www.NICE.org.uk • The cancer may not produce symptoms until it is at an advanced stage, but early cancer can be detected by DRE, which is used to investigate LUTS • A positive test cannot be used for diagnosis but does indicate a need for further investigations &/or referral

36. What are the referral guidelines for specialist investigations?

37. Referral guidelines for suspected cancer: Prostate cancerNICE CG 27. June 2005 • A DRE and PSA (after counselling) are recommended for a patient with any of the following symptoms: • Inflammatory or obstructive urinary tract symptoms • Erectile dysfunction • Haematuria • Lower back pain • Bone pain • Weight loss, especially in the elderly • Exclude UTI before PSA testing. Postpone a PSA for at least 1 month after treatment for a proven UTI

38. Referral guidelines for suspected cancer NICE CG 27. June 2005 • In an asymptomatic male with a borderline PSA, repeat test after 1-3 months. If PSA is rising, refer patient urgently • Refer a patient with symptoms and signs or a urological cancer to a specialist team • Urgent referral: • Patient with a hard irregular prostate. Measure PSA and send with referral (not urgent if prostate is simply enlarged and PSA is in the age-referenced range) • Patients with a normal prostate but rising / raised age-specific PSA with or without LUTS • Patients with symptoms and high PSA levels

39. What are the age specific cut offs for PSA measurements and referral?

40. Age-specific cut offs for PSA measurements and referralNICE CG 27, June 2005

41. What ten principles should govern a screening programme?

42. Ten principles which should govern a national screening programmewww.cancerscreening.nhs.uk/prostate/index.htlm • The condition is an important health problem • Its natural history is well understood • It is recognisable at an early stage • Treatment is better at an early stage • A suitable test exists • An acceptable test exists • Adequate facilities exist to cope with abnormalities detected • Screening is done at repeated intervals when the onset in insidious • The chance of harm is less than the chance of benefit • The cost is balanced against benefit

43. The Department of Health view • There is often increased anxiety amongst men with risk factors. If these men present in primary care it is important that they receive the best available information to assist them in deciding whether or not to have a PSA test • Until more evidence is available about screening active case finding of men with risk factors is not recommended

44. Prostate cancer risk management • Although evidence does not yet support population screening there is considerable demand for the PSA test amongst men worried about the disease • In response the Government has introduced a PSA Informed Choice Programme – Prostate Cancer Risk Management • Key elements: • Provision of high quality information for those requesting testing • Enables them to decide whether to have the test based on available evidence about risks and benefits

45. Should you take the test?

46. Should you take the test?www.cancerscreening.nhs.uk/prostate/prostate-summary-sheet.pdf Benefits Risks It can miss cancer and provide false reassurance It may lead to unnecessary anxiety and medical tests when no cancer is present It might detect slow growing cancer that may never cause any symptoms or shorten life span The main treatments have significant side effects and there is no certainty that Rx will be successful • May provide reassurance if normal • May find cancer before symptoms develop • May detect cancer at an early stage when treatments could be beneficial • If treatment is successful the consequences of more advanced cancer is avoided

47. What would happen to 1000 men aged 50-70 years having a PSA test?

48. 900 are –ve and 7 later develop prostate cancer • 100 are +ve • 100 undergo biopsy • 74 are –ve and 7 later develop prostate cancer • 26 are +ve • It is not known how many of these would have suffered any morbidity or mortality are a result of their cancer if it have been detected earlier

49. Detecting prostate cancer: BiopsyNICE CG58 2008 • Provide • Information • Support • Time to make decisions • Discuss • Risks and benefits of biopsy • Individual risk factors • Estimated prostate size • DRE finding and PSA level • Comorbidities

50. Treatment and service issues