Akbar Ashrafi Surgical Students Society of Melbourne September 2010

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

 Uncontrolled cell division  95% vs 4%  Neuroendocrine rare

 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)

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

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

 Incidental / Screening  PSA  DRE  TURP

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

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

 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

 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)

 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%

 PSA >20  PSA density = PSA value by the volume of the prostate measured by trans-rectal ultrasound  PSA density > => 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

 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

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

 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

 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

 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

 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

 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)

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

 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

 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