II. Basic Principles: Benign Prostatic Hyperplasia (BPH) and Its Treatment

 Benign Prostatic Hyperplasia (BPH) and Its Treatment

Pathophysiology

Evaluation

Treatment

Watchful waiting

Medical Therapy

Surgical Therapy  (Thermal therapy, Laser prostatectomy , TURP , Open Prostatectomy)

 

Pathophysiology:

• Pathogenesis of BPH is more complex than the simplistic notation of "large prostate = obstruction"
  • Complex interaction of anatomic and physiologic processes result in increased resistance of prostatic urethra.
    • Glandular enlargment
      • Hyperplastic process in the glandular tissues of the transitional zone and periurethral tissues (Figure 1 and 2, see prostate anatomy page for full description of prostate anatomy).
      • Presence of prostatic capsule results in compressive forces on prostatic urethra (BPH in dogs, for example, does not cause bladder outlet obstruction, since there is no prostatic capsule).
    • Increased prostatic smooth muscle tone - mediated by the alpha-1a receptors.
    • Decreased prostatic compliance.
    • Changes in prostatic urethral geometry.
  • Important to note that pathology unrelated to the prostate can result in identical lower urinary tract symptoms (LUTS) -- e.g.: urethral stricture disease, bladder neck dysfunction, bladder pathology.

  	Figure 1: Cystoscopic view of lateral lobes.  Edge of the verumontanum is seen at 6 o'clock. Rollover image with mouse to see position of scope in in prostatic urethra.
  	Figure 2: Cystoscopic view of a large median lobe. The ball-valve obstruction created by a median lobe in some men is clearly appreciated from this image. Rollover image with mouse to see position of scope in prostatic urethra.

Evaluation of a Man with Lower Urinary Tract Symptoms indicative of BPH:

• History
  • Be sure to elicit history of conditions that contribute to bladder dysfunction and polyuria
  • Include family history of BPH and prostate cancer
  • Assess symptoms with Americal Urologic Association Symptom Index (AUA-SI) -- identical to International Prostate Symptom Score

• Physical examination should include digital rectal exam (DRE) t
  • Assess prostate size -- DRE shown to underestimate prostate size, but glands that feel large on exam usually are indeed hyperplastic.
  • Assess presence of localized prostate cancer -- a possible cause of LUTS in elderly men.
• Urinalysis -- to screen for bladder calculi, UTIs, and bladder cancer as cause of LUTS.
  • Consider voided urine cytology for those men with predominantly irritative symptoms or a significant history of smoking.
• Discussion of PSA screening is appropriate in men with LUTS.
• Other tests at initial visit for LUTS include:
  • Flow/PVR -- but be aware that there are no established guidelines for acceptable Qmax or PVR in men with LUTS.
  • Creatinine -- shown to be unnecessary as men with BPH have same rate of renal insufficiency (<1%) as general population.

Treatment:

• Watchful waiting
  • Men with AUA-SI equal or <7.
  • Men with AUA-SI >7 and are:
    • reluctant to undergo invasive treatments or are unwilling to initiate life-long medical therapy
    • do not have BPH complications such as UTIs, retention, bladder stones, or renal insufficiency
  • Reevaluate patients at least annually.
• Medical therapy
  • alpha-Adrenergic blockade
    • reduces AUA-SI by an average of 4-6 points within weeks of therapy initiation
    • alfuzosin, doxazosin, tamsulosin and terazosin are therapeutically equivalent
      • costs and side-effects differ
      • overall side effects are mild and include dizziness, headache, fatigue, postural hypotension, nasal congestion, edema, and retrograde ejaculation
    • first-line agents for LUTS treatment
  • 5-alpha-reductase inhibitors
    • block production of dihydrotestosterone (DHT) in the prostate, while serum testosterone levels remain within normal limits
    • AUA-SI reduced by 3 points (less than alpha-blockers) and are ineffective in men with normal-sized prostates
    • 5-alpha-reductase enzyme
      • Type I - liver, sebaceous glands, skin, and most hair follicles
      • Type II - face/scalp/gentialia hair follicles, prostate
    • Finasteride
      • competitive inhibitor of Type II isoenzyme
      • 60-70% reduction in serum and 85%-90% reduction in prostatic DHT levels
      • prostatic glandular epithelium atrophies; prostate size decreases by 15-30% within several months
    • Dutasteride
      • competitive inhibition of both Type I and Type II isoenzymes
      • more global suppression of DHT than finasteride
      • no head to head trial of finasteride to dutasteride, but the two drugs appear clinically to be simial (dutasteride may have quicker onset of action)
    • Well-tolerated -- small risk of libido reduction and erectile dysfunction.
  • Combination therapy
    • Based on assumption that drugs that work by different mechanisms will have synergistic or at least additive action
    • Initial trials that enrolled men with small glands showed no benefit to adding 5-alpha reductase inhibitors.
    • MTOPS trial
      • randomized, double-blind, placebo-controlled trial: 3047 men randomized to placebo, doxazosin, finasteride, or combination with mean follow up of 4.5 years
      • mean prostate volume 35.3 cm^3 and AUA-SI 8 to 30 (mean 16.9).
      • disease progression defined as at least 4 point rise in AUA-SI, acute urinary retention, urinary incontinence, renal insufficiency, recurrent UTIs
      • placebo group - 17% progression; doxazosin group - 10% progression (39% reduction); finasteride group - 34% reduction; combination therapy only 5% progression (66% reduction, p<0.001).
    • Combination therapy currently used in men with LUTS and documented prostatic enlargement (if gland is small use alpha blockade monotherapy)
    • Recently some have advocated addition of anticholinergic agents and even PDE-5 inhibitors to alpha blockade in treating men with LUTS.
• Surgical therapy
  • Thermal therapy
    • RF Therapy
      • Employs heat to produce coagulation necrosis in the lateral lobes of the prostate
      • Heating is achieved with two radiofrequency energy-emitting needles
  •  
    • Transurethral microwave thermotherapy (TUMT)
      • Produces coagulation necrosis of prostatic tissues through heat produced by a microwave-emitting coil.
      • Several companies produce devices that work in similar fashion and most employ a water-cooling balloon coupled with a high-energy source.
      • Complications include prolonged urinary retention and prolonged irritative voiding symptoms.s, Urology
  • Laser prostatectomy -- offers decreased blood loss and shorter catheterization as compared to TURP
    • HoLEP
      • Enucleation of tissue using front-firing laser fiber of a HYAG laser (2097 nm)
      • Prostatic tissue is pushed into bladder and extracted using an evacuator or morcillator
    • HoLAP
      • Side-firing HYAG laser (2097 nm) used for tissue vaporization
    • Photoselective Vaporization of the Prostate (PVP)
      • Side-firing KTP laser (532 nm)
  • Transurethral Resection of the Prostate (TURP)
    • Said to be the hallmark of the urologist and is the "Gold Standard" BPH treatment
    • Prostatic adenoma resected transurethrally using electrocautery loop (Figure 4)
    • Spinal anesthesia is preferred to monitor patient's mental status in face of potential hyponatremia (TURP syndrome)
    • Up to 90% of patient see improvement in symptoms -- upto 9.6 AUA-SI points and in some studies up to 80% reduction in AUA-SI score.
    • Complications
      • TURP syndrome
        • 2% of patients
        • Vision disturbances, changes in mental status, wide complex tachycardia
        • Glycine is used as irrigation -- does NOT prevent hyponatremia but limits hemolysis
      • Incontinence -- patients should be warned regarding this rare yet devastating side-effect
      • Erectile dysfunction -- prospective data does not support retrospective reports suggesting that men following TURP are at risk for new erectile dysfunction.
  
  
  

  Figure 4: Resection with electrocautery loop during TURP

   .

  • Open prostatectomy
    • Enucleation of periurethral prostatic tissues, leaving prostatic capsule intact
    • Retropubic - make lower abdominal incision, gain access to adenoma through incision in anterior prostate (Figure 3).
    • Suprapubic (aka transvesical) - access to adenoma through incision in anterior bladder wall; better for patients with large median lobes and large bladder calculi.
    • Procedure currently reserved for patients with glans greater than 100 grams and is performed in <1% of patients with BPH, but must keep in mind that reoperation rate is very low and morbidity is comparable to TURP.

    Figure 3: Delivery of enucleated lateral and median lobes during an open prostatectomy in a patient with a ~250 g gland. Another lateral lobe is yet to be enucleated.