PSA is elevated in other prostate diseases. PSA velocity is the rate of change of PSA over time. A PSA > 100 ng/mL is usually seen with Bony involvement. Rectal examination is not now believed to raise the PSA. PSA is a 34 KDa glycoprotein protease secreted from epithelial cells that line the acini of the prostate and is responsible for liquefying semen. PSA rises with Prostate carcinoma, BPH, Age, post ejaculation, prostate calculi.
- A cancer commonly found at post mortem in the over 70s
- The issue is when to screen and treat disease
- Screening has not been shown to improve survival
- Testosterone dependent
- in UK 41,700 new diagnoses per year
- 1% of diagnoses in under 50s
- Commoner in patients of black African or Caribbean ethnic origin
- Family history 1st degree relative X 3.5 risk
- Smoking is a risk for fatal disease
- Obesity is also a risk factor
- 95% are acinar adenocarcinomas arising from glandular epithelial cells
- 5% are squamous and transitional + other
- Most cancers originate in the periphery of the gland
- A transition state exists - Prostate Intraepithelial neoplasia
- Epithelial cells produce prostate-specific antigen (PSA) and acid phosphatase
- Lower urinary tract symptoms (LUTS) e.g. increased urinary frequency, nocturia, poor stream and terminal dribbling
- Bone pain or fractures in metastatic disease
- Elevated Screening PSA or histology of benign prostate post-TURP
- Hard craggy prostate with loss of midline sulcus on DRE (digital rectal exam)
- Bladder outflow obstruction - poor stream and nocturia
- Secondary renal problems
- Late with bony pain and metastases are osteosclerotic and show up on plain X-Ray and bone scan
- Very late disease - haematospermia, outflow obstruction, haematuria
Prostate specific antigen
- Normal PSA <3ng/mL in patients aged under 50
- Normal PSA<4ng/mL for men aged 60-69 is normal
- Normal PSA > 5ng/mL normal over 70
- A PSA <10ng/mL is commonly associated with BPH and/or chronic prostatic inflammation, with only 20% of men testing positive for cancer histologically.
- Likelihood of malignancy increases up to 50% in men with a PSA >10ng/mL.
- U&E - renal function , ↑ ALP suggests boney metastases
- FBC - leukoerythroblastic anaemia
- PSA > 4 ng/ml suggests malignancy in 40% of biopsies
- PSA > 10 ng/ml suggests malignancy in 60% of biopsies
- Transrectal USS guided prostate biopsy
- Bone scan if PSA > 20 ng/ml or those with bone pain to look for metastases. False-positive bone scan - Paget's disease, healing fractures and arthritis. Bone metastases are common and tend to involve the axial spine and ribs.
- Many urologists now recommend imaging with multi-parametric MRI (MP-MRI) of the prostate, prior to consideration of prostate biopsy.
- The Gleason system is used to grade the tumour
|Risk stratification, localised prostate cancer|
|Level of risk|| PSA ||Gleason score ||Clinical stage|
|Low|| <10ng/mL and ||=6 ||and T1-T2a|
|Intermediate||10-20ng/mL or||7 ||or T2b|
|High||>20ng/mL or ||8-10 ||or =T2c|
Management of local disease
- Radical retropubic prostatectomy - aims to remove all disease and preserve continence by avoiding external sphincter and avoid impotence by avoiding neurovascular bundle containing autonomic nerves. Suggested in those with > 10 years life expectancy.
- Radiation therapy - external or implantation of radioactive source. Main complication is diarrhoea due to anterior rectal wall proximity. Urinary frequency and even urethral strictures
- Watchful waiting is reasonable waiting until there is tumour progression. Usually in older men with well differentiated tumours. Remember that most will die of unrelated disease
- Side effects of treatment: Impotence, Incontinence, Bowel dysfunction
Management of Metastatic disease
- Block androgen action or decrease androgen production by medical or surgical means
- Ketoconazole blocks androgen production
- GnRH analogues - give early rise in FSH and LSH with testosterone rise before it falls due to downregulation of receptors. This gives an initial flare so best avoid where spinal cord or obstructive lesions or painful lesions.
- Anti androgens e.g. flutamide are given initially to block the effects of the flare along with GnRH analogues
- Surgical orchidectomy: Side effects are Hot flushes, Fatigue, weakness, Impotence, Loss of muscle mass, Changed personality