Prostate disease

• Background

  Benign prostatic enlargement (BPE)

  • Musculofibrous and glandular proliferation, leading to inner ('transitional') zone enlargement.
  • Common cause of bladder outlet obstruction.
  • Aka benign prostatic hypertrophy.

  Prostate cancer (PCa)

  • Adenocarcinoma leading to peripheral enlargement.
  • 1 in 8 lifetime risk.
  • Can metastasize via lymphatics to seminal vesicles, bladder, and rectum, and via bloodstream to bone.

• Signs and symptoms

  Symptoms of prostate enlargement:

  • Irritative (storage) bladder symptoms: frequency, urgency and incontinence, nocturia, dysuria.
  • Obstructive (voiding) bladder symptoms: ↓stream (size and force), hesitancy and interruption, terminal dribbling, retention, overflow incontinence, bladder pain. Can lead to UTI, kidney impairment, or stones.
  • These two symptom groups are collectively known as lower urinary tract symptoms (LUTS).

  Symptoms suggesting PCa as opposed to BPE:

  • Haematuria, hematospermia.
  • Perineal and suprapubic pain.
  • Tenesmus
  • Loin pain from ureteric obstruction.
  • Metastases: bone pain, spinal cord compression.
  • Paraneoplastic: weight loss, DVT.

  Digital rectal exam (DRE):

  • BPE: smooth, palpable, rubbery prostate, with sulcus felt.
  • PCa: hard, irregular prostate.

• Risk factors

  Prostate cancer:

  • Demographic: age, black.
  • Family history.

• Investigations

  Initial tests

  International prostate screening score (IPSS) to rate symptom severity.

  Screening for PCa:

  • Prostate-specific antigen (PSA) plus DRE.
  • PSA is not very specific, but very elevated levels (>10) are.
  • NICE recommend PSA plus DRE for those with suggestive symptoms, after appropriate counselling.
  • Exclude UTI before PSA, and postpone PSA for 1 month if present.

  Other initial tests:

  • Urinalysis
  • FBC (anaemia), U+E (renal impairment), and LFT (baseline pre androgen therapy).
  • Patient voiding diary to quantify problem.

  Investigating urinary function:

  • Measure post-void residual volume with bladder US; catheterisation can also do this, but is more invasive.
  • Kidney US to look for hydronephrosis if large post-void residual volume present or there is renal impairment.
  • Urine flow test – measuring rate in ml/s – and urodynamic studies – measuring bladder and voiding pressure – are optional. Useful as a baseline before surgery or invasive procedures.
  • Consider cystoscopy if other causes of obstruction are suspected e.g. stricture, stones, bladder cancer.

  Diagnosis of PCa

  MRI and/or biopsy should only be offered to those eligible for radical treatment, and decision to proceed should take into account PSA, DRE findings, and other risk factors.

  Multiparametric MRI:

  • Includes spectroscopy, dynamic contrast enhancement, and diffusion weighting.
  • Provides probability of PCa rated on 5 point Likert scale (1 low to 5 high)
  • Results used to direct biopsy location, stage cancer, and in those with score 1-2, can consider avoiding biopsy (accepting some risk of false negatives).

  Transrectal US (TRUS)-guided prostate biopsy:

  • In PCa, TRUS may show hypoechoic area in peripheral zone.
  • Gleason histological grade used to score severity of samples from 1 to 5, with the two most prominent patterns summed to give an overall score from 2 to 10.
  • Biopsy can also be done via transperineal route.

  Further staging of PCa

  Technetium-99 bone scan only in those with suggestive symptoms or in those at high risk of bone metastases.

• Management

  Obstructive symptoms

  • Self-help: avoid caffeine, alcohol, practice holding, double voiding.
  • Catheterise if: pain, UTI, kidney failure.

  BPE

  Medical:

  • α-blockers (e.g. tamsulosin) relax smooth muscle, reducing symptoms.
  • 5-α reductase inhibitors (e.g. finasteride) shrink prostate, but take 1 year for effect. Prevents conversion of testosterone to more potent dihydrotestosterone (DHT).

  Interventional:

  • Offered in refractory disease.
  • Options: prostate artery embolisation, transurethral resection of the prostate (TURP), transurethral laser-induced prostatectomy, or retropubic prostatectomy.

  TURP complications:

  • Transurethral syndrome (TUR) (early). TUR is a fluid and electrolyte imbalance that occurs due to excess hypotonic irrigation fluid during prolonged surgery entering the systemic circulation.
  • Urethral stricture.
  • Retrograde ejaculation leading to infertility (70%).
  • Perforation of prostate (early).
  • Also bleeding and sepsis.

  Prostate cancer

  Risk stratify:

  • Low: PSA <10 and Gleason ≤6 and ≤T2a (less than half of one lobe).
  • Intermediate: PSA 10-20 or Gleason 7 or T2b (more than half of one lobe).
  • High: PSA >20 or Gleason ≥8 or ≥T2c (both lobes).

  Conservative treatment:

  • Watchful waiting if asymptomatic and unsuitable for treatment. Annual PSA in primary care and manage urinary symptoms.
  • Active surveillance if low risk localised cancer but would be candidate for surgery if disease progressed. 6-monthly PSA, 12-monthly DRE, and repeat multiparametric MRI at 1 year.

  Radical treatment for localised disease:

  • Indications: low risk localised cancer (alternative to active surveillance, based on shared decision making) or intermediate to high risk disease.
  • Radical prostatectomy with removal of seminal vesicles. Retropubic (commoner) or perineal approach.
  • Radical radiotherapy is an alternative. External-beam ± brachytherapy, with adjunctive androgen deprivation therapy. Add pelvic radiotherapy if lymph node involvement suspected.
  • Side effects: erectile dysfunction (50% surgery, 35% radiotherapy), urinary incontinence (70% surgery, 50% radiotherapy). Offer PDE5 inhibitors for ED.

  Androgen deprivation (aka hormonal) therapy for metastases:

  • Castration: chemical (GnRH analogues) or surgical (bilateral orchiectomy).
  • Bicalutamide is an alternative for men who whish to retain sexual function and accept a higher risk of death and gynaecomastia.
  • Chemotherapy with docetaxel ± prednisolone is an adjunct for those without significant comorbidities.
  • Abiraterone or enzalutamide if resistant to castration and docetaxel.

  Palliation:

  • Radiotherapy
  • Bisphosphonates if analgesia and radiotherapy ineffective.

• Prognosis

  PCa 5 year survival: 85%.

• Hormonoal treatment of prostate cancer

  GnRH analogues

  • Mechanism: continuous GnRH analogues (as opposed to physiological pulsed release) prevent luteinizing hormone formation and thus suppress testosterone levels.
  • Aka GnRH agonists, luteinizing hormone releasing hormone (LHRH) agonists.
  • Drugs: goserelin, leuprorelin.
  • Side effects: hot flushes (treat with medroxyprogesterone), sexual dysfunction (↓libido and ED), osteoporosis, fatigue.

  Bicalutamide and enzalutamide

  • Androgen receptor blockers.
  • Side effects: gynaecomastia, sexual dysfunction (but less than GnRH analogues).

  Abiraterone

  • 17 α-hydroxylase inhibitor.
  • Side effects: peripheral oedema, ↓K+, HTN, UTI.