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

Benign Prostatic Hyperplasia (BPH) and Its Treatment

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.