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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.


    turp
    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.