Introduction to Prostate Cancer

1. Akbar Ashrafi Surgical Students Society of Melbourne September 2010 Introduction to Prostate Cancer

2. Background • Most common solid tumour in males • Second highest cause of cancer death in men • Affects men > 50 years • Global increase in prostate cancer deaths since 1985 • Unusual malignancy

3. Pathophysiology • Uncontrolled cell division • 95% vs 4% • Neuroendocrine rare

4. Aetiology • Genetics - chromosome 1, 17, and the X chromosome • Diet • Increased – high fat diet • Decreased – selenium, vitamin E • Hormones • 5-alpha-reductase inhibitor -  CaP, but histologically more aggressive (Prostate cancer prevention trial)

5. Anatomy

6. Anatomy

7. Symptoms • Largely asymptomatic • Poor symptom-disease correlation • Local disease: • Weak stream, hesitancy, sensation of incomplete emptying, urinary frequency, urgency, urge incontinence • Same symptoms as BPH

8. Symptoms • Metastatic disease • Bone pain or sciatica • Paraplegia secondary to spinal cord compression • Lymph node enlargement • Loin pain or anuria due to ureteric obstruction by lymph nodes • Lethargy (anaemia, uraemia) • Weight loss, cachexia

9. Presentation • Incidental / Screening • PSA • DRE • TURP

10. Signs • Rectal exam • Irregular, hard prostate • Nodules, asymmetry, immobile, palpable seminal vesicles, induration of prostate • Systemic • Cachectic, bone pain, anorexia, weight loss • Obstructive • Palpable bladder • Renal angle tenderness

11. Investigations • PSA • Urine microscopy + culture • UEC • Transrectal USS and biopsy • 20% false negative rate • Uroflow measurement, post void residual urine, cystoscopy • MRI, CT, Bone scan

12. TRUS

13. Staging • Non-metastatic prostate cancer • clinically localised or locally advanced disease • Metastatic disease • Spread beyond the prostate to lymph nodes, or to other organs • Bone metastases are particularly common • TNM classification

15. Gleason score • Gleason score estimates the grade of prostate cancer according to its differentiation • Gleason grade 1 to 5 • Gleason score is the sum of the two most prominent grades • Gleason grades • ranges from 2 (well-differentiated) to 10 (poorly differentiated)

16. Prognostic value • The Gleason score is the best prognostic indicator for prostate cancer • <4: well differentiated; ten-year risk of local progression 25% • 5-7: moderately differentiated; 50% • > 7: poorly differentiated; 75%

17. Other Prognostic factors • PSA >20 • PSA density = PSA value by the volume of the prostate measured by trans-rectal ultrasound • PSA density > 0.304 => increased prostate cancer detection • at 2 and 5 years • PSA velocity = PSA velocity > 0.35ng/ml/yr has greater risk of dying from CaP • Stage

18. Active Surveillance • Preferred option for low-risk cancers • Serial PSA assessment and repeat prostate biopsy every 1-2 years • Any evidence of disease progression => offer radical treatment • 1/3 will need treatment • Carefully selected patients will not miss a window for cure with this approach • Avoid risks of radical treatment

19. Watchful waiting • Watchful waiting • small tumour • well differentiated (Gleason score of 6 or lower), watchful waiting • older patients with significant other diseases

20. Radical prostatectomy • Radical prostatectomy • extra-prostatic extension but no evidence of distant metastases • Early stage high risk cancer or patient who has failed to respond to radiotherapy • Laparoscopic vs open vs robotic • Complications • erectile dysfunction (up to 80%) • incontinence (up to 20% ) • 40% have positive surgical margins

21. Radiotherapy • Radiotherapy using external beam radiation • preferred option if there are distant metastases • erectile dysfunction (up to 60%) • incontinence (5%) • Long term bowel problems (10%) • Brachytherapy • transperineal implantation of radioactive seeds into the prostate (rare) • alone or in combination with external beam radiotherapy

22. High Intensity Focussed Ultrasound • ablate/destroy the tissue of the prostate • high success rate with a reduced risk of side effects in preliminary studies • dubious studies - 94% of patients with a pretreatment PSA) of less than 10 ng/mL were cancer-free after three years

23. Metastatic Prostate Ca • Androgen suppression • Monthly or three-monthly depot injections of Goserelin (Zoladex) • Increased cardiovascular risk 30% • Bilateral orchidectomy as an alternative to continuous LHRHa therapy • Bicalutamide (Cosudex 50 mg) , a non-steroidal anti-androgen • In combination with LHRHa or surgical castration • Monotherapy

24. Screening • American Cancer Society • Annual PSA + DRE • age > 50 + >10-year life expectancy • high-risk younger men • +: screening will identify early prostate cancer and reduce likelihood of CaP mortality • -: screening will detect cancers that are not biologically significant (ie those that die with prostate cancer rather than from it)

25. PSA • Single-chain glycoprotein • Hydrolyzes peptide bonds, liquidifying semen • Upper limit of normal for PSA is 4 ng/m • Diagnostic • Prognostic • Monitoring

26. Literature on screening • Canadian and Austrian studies suggest that mortality rates are lower with PSA screening • US data:  1% per year since 1990 • Scandinavian study in 2002 => reduced disease-specific mortality with radical prostatectomy compared to watchful waiting

27. Summary • Prostate cancer is common • Prostate cancer is generally asymptomatic • PSA is a useful screening tool in selected patients • Management depends on patient preference, grade and stage of cancer • Active surveillance is a recognised management option