Current Treatment Options for Benign Prostatic Hyperplasia

Written by Charles O’Connor, Patrick Collins and Gregory Nason

Introduction

Benign prostatic hyperplasia (BPH) is a histologic diagnosis of prostatic enlargement from benign proliferation of epithelial prostate cells as well as smooth muscle. BPH prevalence increases with age with rates ranging from 50% to 75% for men older than 50 years of age to 80% in men 70 years of age and older. 1 The average prostate volume is 20-30cc, patients with BPH will typically have a larger prostate volume than 30cc. BPH is often diagnosed with patients experiencing lower urinary tract symptoms (LUTS). These can be broadly categorised in to storage and voiding LUTS. Storage LUTS include frequency, urgency, nocturia and occasional incontinence. Voiding LUTS include hesitancy to start flow, straining, intermittent ‘or stopstart’ flow and a sensation of incomplete emptying. An objective measure of LUTS severity is the use of the international prostate symptoms score (IPSS). This score is the same as the validated American urological associate symptom index (AUASI) score but it asks one more key question- “If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about this?”. The IPSS is shown in figure 1. 2

Risk factors for Benign Prostatic Hyperplasia

Risk factors that are associated with BPH include age, lack of exercise, smoking, excessive alcohol consumption, obesity, hypertension, diabetes, hyperlipidaemia and a genetic disposition. Factors that tend to decrease the risk of BPH include increased physical activity, moderate or decreased alcohol intake and increased vegetable consumption. 3 Thus, like with many conditions, the first steps to manage BPH should be in terms of lifestyle modification. Other methods of lifestyle modification to deal with LUTS secondary to BPH include cutting out factors that cause increased frequency or nocturia. This can include cutting out or limiting caffeine or medications that increase frequency e.g., diuretics. For patients who experience nocturia a practical first step to manage this is to limit fluid intake in the hours prior to sleeping.

Medical management of Benign Prostatic Hyperplasia

Medical management of LUTS generally starts with a patient’s primary care physician. As a recent increase in LUTS can be associated with prostate cancer, consideration can be given to performing a prostate specific antigen (PSA) test to screen for prostate cancer. Guidelines suggest that PSA should only be checked in a patient with a life expectancy of 10 years or more and after discussion of the risks and benefits of screening. A digital rectal examination (DRE) should be carried to assess the prostate size and the presence of masses or nodules, although this examination tends to under-estimate prostate volume. 4 Urinalysis can be performed to out rule the presence of a urinary tract infection (UTI). The use of the IPSS score can assess severity of symptoms. If bladder outflow obstruction (BOO) is suspected, laboratory tests including creatinine should be checked and an ultrasound performed of a patient’s bladder post-void to ensure sufficient emptying- generally termed PVR (post void residual). A uroflowmetry test can also be carried out which measures a patient’s maximum flow rate (Qmax), average flow rate and voided volume. The pattern of flow can give an insight into the aetiology of the symptoms.

Medical management for Benign Prostatic Hyperplasia can be initiated if a patients LUTS fall in to the moderate or severe class as per their IPSS score or if their mild LUTS are bothersome to them. The two main classes of medication for Benign Prostatic Hyperplasia are alpha-adrenergic blockers including tamsulosin, alfuzosin and doxazosin and 5-alpha reductase inhibitors (5-ARIs) including dutasteride and finasteride, combination therapy is also common in the form of tamsulosin/ dutasteride or “Combodart”.

Alpha blockers work by blocking sympathetic nerve fibres which decreases contraction of smooth muscle at the bladder neck and improves emptying. Symptomatic relief is generally noted after 1 week of use but may take up to 4 weeks. IPSS scores improve by 5-8 points by taking an alpha blocker. As alpha blockers were initially developed as antihypertensive agents, one of their main side effects is orthostatic hypotension. Other side effects of alpha blockers include headache, retrograde ejaculation and with tamsulosin especially a condition called ‘floppy iris syndrome’ after ophthalmic surgeons noted iris flopping or prolapsing during cataract surgery. Men should not be started on an alpha blocker if planning this surgery. Notably, in contrast to tamsulosin, alfuzosin does not cause retrograde ejaculation and one recent systematic review confirmed that it may even improve ejaculatory function. 5

Antimuscarinic medications work by blocking muscarinic receptors from the action of acetylcholine which mediates parasympathetic nerves. Alpha blockers can be combined with antimuscarinic mediations like solifenacin in men with Benign Prostatic Hyperplasia who have predominantly bladder storage systems. The EAU strongly recommends their use in this subset of patients and the risk of acute urinary retention is rare with these provided a patients’ PVR is less than 150mls. 6 Beta-3 agonists like Betmiga similarly improve these storage symptoms and can be used in combination with alpha-blockers.

Both testosterone and DHT are implicated in the stimulation of prostatic tissue. The second class of BPH medication- (5- ARIs) work by inhibiting the enzyme 5-alpha reductase which metabolises testosterone to dihydro testosterone (DHT). Less DHT means less prostate tissue stimulation and resulting atrophy and apoptosis. 5-ARIs should only be started in men with prostate volumes over 30cc or glands enlarged on clinical examination.

These medications reduce the prostate size by up to 25% and decrease the vascularity of the prostate. For this reason, they can be beneficial for patients prior to prostate surgery or who are experiencing bleeding from the prostate. In contrast to alpha blockers, 5-ARIs can take 2-6 months to take full effect. IPSS scores improve by 3-5 points by taking a 5-ARI. The risk of urinary retention is decreased more significantly by taking a 5-ARI than an alpha blocker, and is decreased even more with combination therapy. After 6 months these medications should reduce a patient’s PSA by 50%. It is important that every clinician knows this to prevent abnormal PSA readings not being detected.

Side effects of 5-ARIs with prolonged use include erectile dysfunction, decreased libido, and gynecomastia.

Surgical management of Benign Prostatic Hyperplasia who should it be offered to?

Surgical management of BPH should be offered to patients who fail medical management, have refractory urinary retention, recurrent UTIs, persistent haematuria, bladder stones or renal insufficiency. This article aims to provide the reader with an outline of the various different surgical managements of BPH, outlining the pros and cons of each procedure. In recent years, minimally invasive technologies have emerged which may be an alternative to the traditional TURP for some patients.

Prior to proceeding with surgery

Prior to proceeding with a surgical procedure, the AUA advocates estimation of prostate volume and shape delineation (presence or absence of median lobe). Another consideration prior to proceeding with surgery is to perform urodynamics (or bladder pressures reading tests) in patients where there is diagnostic uncertainty, to identify if the symptoms are in fact due to BPH or perhaps due to conditions like detrusor underactivity or detrusor sphincter dyssynergia where there is a lack of co-ordination between bladder and sphincter stimulation. However, it has been shown that routinely investigating patients with urodynamics does not reduce surgical rates and therefore this should be reserved for cases of diagnostic uncertainty. 7

Minimally invasive techniques

Minimally invasive techniques used in Ireland include Rezum and Urolift. These procedures are particularly attractive to patients who wish to avoid the sexual dysfunction that can come with medical therapy and more definitive surgery. While these procedures are often compared to other surgical techniques, as more data becomes available these may be more commonly compared to medical therapy. These procedures offer a better maximum flow rate improvement and IPSS score decrease compared to medication and could be a cost-effective option, possibly rendering them a future first line option. The longer efficacy and durability of Urolift and Rezum are unknown.

Rezum

Rezum is the brand name for convective water vapour energy (WAVE) ablation. This system uses radiofrequency power on a few drops of sterile water to create thermal energy in the form of water vapour. This steam causes prostate tissue necrosis. This procedure can be used for men with prostate volumes from 30-80ccs, with or without a median lobe. This procedure can be performed under local anaesthesia but currently is only performed under general anaesthesia in Ireland. A catheter is usually placed for a number of days post procedure. The 5 years follow up data comparing Rezum to sham was published in September 2021. This shows durable results with the improvement in LUTS being sustained since the <3month follow up. IPSS scores reduced by 48%, Maxium flow rates improved by 44%. Surgical re-treatment remains quite low at 4.4%, while 11.1% resumed on BPH medications. There are no reports of sexual dysfunction in patients treated with Rezum. 8 BAUS published an information leaflet on Rezum in June 2021. 9

Urolift

Urolift is the brand name for prostatic urethral lift. This procedure involves inserting an implant which looks like a treasury tag into the prostatic capsule via a cystoscope to compress the lateral lobes of the prostate therefore dilating the prostatic channel. This procedure can be used for men with prostate volumes from 30-80ccs, without a median lobe. This procedure can be performed under local anaesthesia or general anaesthesia. Around 20% of patients will require catheter insertion usually for 1 day. 5 years follow up for Urolift published in June 2017, reported an IPSS score reduction of 36% and a maximum flow rate improvement of 44%. Surgical retreatment was 13.6% over 5 years, while 10.7% of patients resumed on BPH medications. Sexual function was not affected in these patients over 5 years of follow up. 10 A consideration with the use of Urolift is the 15mm artefact extension noted on MRI from the implant. The impact of this artefact on prostate cancer detection by MRI is not well studied, however, reports suggest that MRI protocol can be adjusted to minimise this. The British Association of Urological Surgeons (BAUS) published an information leaflet on Urolift in December 2021. 11

Definitive Benign Prostatic Hyperplasia surgery

Definitive BPH surgical procedures can be classed into a number of categories. Those for 1. Small prostates <30ccs, 2. Average sized prostates 30-80ccs, 3. Large and very large prostates and 4. Any sized prostates. TURP (Transurethral resection of prostate) is the standard and most common procedure for BPH to which these treatments are usually compared. Transurethral incision of the prostate (TUIP) also known as bladder neck incision or (BNI) is reserved for prostates less than 30ccs. Procedures like TURP and PVP (Photoselective vaporisation of the prostate- or “Greenlight laser”) are used most commonly for prostates between 30-80ccs, but can also be used for smaller prostates. Enucleation of the prostate with Holmium or Thulium lasers can be used on prostates of any size. Open and robotic simple prostatectomy is reserved for large prostates (80-150cc) or very large prostates (>150cc)

1. Small prostatesTUIP/BNI

This procedure uses an electrocautery knife to make an incision from the bladder neck towards the verumontanum in men without a median lobe and a prostate size less than 30ccs. This acts to dilate the prostatic urethra and improve LUTs. This procedure shows similar efficacy to TURP in men with prostates less than 30ccs. This procedure is usually performed under general anaesthesia. A meta-analysis comparing TUIP to TURP demonstrated a lower rate of retrograde ejaculation (18.2% vs 65.4%) and need for blood transfusion (0.4% vs 8.6%) as the main advantages of TUIP over TURP. 12 A drawback of TUIP is the higher rate of re-operation vs TURP (18.4% vs 7.2%). 13 A patient information leaflet on BNI can be found on the BAUS website. 14

2. “Average” sized prostatesTURP

The initial TURP was a monopolar TURP traditionally performed in glycine. The standard TURP procedure is now the bipolar TURP which can be performed in saline. This has led to a greater side effect profile and has rendered TUR-syndrome (acute dilutional hyponatremia) an historic event. Patients require a catheter for 2-3 days post procedure until haematuria has settled. TURP results in an average 14-point improvement in IPSS score at 1 year with a Qmax improvement of 13.7 mL/s. 15,16 While retrograde ejaculation/ejaculatory dysfunction is common after TURP (65-75%), erectile dysfunction is uncommon (3.5-8.5%). 17,18 Similar to previous, a patient information leaflet on the procedure is available on the BAUS website. 19 This is the most commonly performed BPH procedure.

“Greenlight laser”- Photoselective vaporisation of the prostate

The greenlight laser works by ablation or vaporisation of the prostate adenoma from the urethra towards the prostate capsule. This procedure provides good haemostasis and is performed with saline irrigation. Meta-analyses comparing greenlight to TURP show similar outcomes. Greenlight takes significantly longer to perform but results in decreased length of stay, catheterisation times and bleeding. 20 The EAU gives a strong recommendation to offer this procedure as an alternative to TURP. 6 A reference to this procedure is found on the BAUS website. 21

3. Large & very large prostates

Open simple prostatectomyThis is the oldest procedure described to treat moderate to severe LUTs due to bladder outlet obstruction (BOO). Open prostatectomy was initially described by two Irish surgeons (Terence Millin described the simple retropubic prostatectomy while Peter Freyer described the simple transvesical prostatectomy). This procedure is associated with high blood loss and a transfusion rate of between 7-14%. Open prostatectomy provides very durable and quick results with a decrease in IPSS points between 12.5-23.3, a significant increase in maximum flow (16.5-20.2 mL/s), and a large reduction in PVR between 86-98%. Efficacy is maintained for up to six years. 22,23 Metaanalyses evaluating the efficacy of this procedure show comparable outcomes to those achieved with HoLEP, and in centres with an absence of HoLEP, open prostatectomy is a reasonable treatment choice for men with prostates >80mls. 24 The frequency of this procedure in Ireland is dwindling. A patient information leaflet for this procedure is also available from the BAUS website. 25

Robotic simple prostatectomy

Performing a simple prostatectomy robotically results in decreased length of stay, less blood loss and equivalent functional outcomes for patients. 26 Most studies to date on this procedure are retrospective and there is need for high quality randomised controlled trials (RCTs). Results from our centre on 5 patients over a 12-month period show excellent results with a median (IQR) length of stay of 3(1) days. No patient required a blood transfusion. 27 This is a challenging procedure and carries a significant learning curve. As experience from robotic prostatectomy grows, we anticipate this procedure to become more common.

4. Any sized prostates

Holmium laser enucleation of the prostate (HoLEP)

HoLEP is an endoscopic enucleation of the prostate using a laser commonly used to treat kidney stones. Three meta-analyses evaluating HoLEP vs bipolar TURP showed no difference in short term efficacy in terms of IPSS improvement, quality of life and maximum flow. 28-30 A retrospective comparison of 2,869 HoLEP procedures vs 37,577 TURP procedures demonstrated longer operation times with HoLEP.

However, there were shorter hospitalisation times and less infectious complications. Overall complication rates were similar. 31 One meta-analysis of 7 RCTs showed similar short and midterm erectile function scores between HoLEP and TURP, however long-term scores were significantly better in HoLEP patients. 32 This procedure can be offered as an alternative to TURP or Millin prostatectomy. The learning curve with this procedure is said to be steep with 50 procedures being quoted as the number required to become proficient. A patient information leaflet on HoLEP is similarly available on the BAUS website. 33

Thulium:yttrium-aluminiumgarnet laser (Tm:YAG) enucleation of the prostate (ThuLEP)

The Thulium laser is another laser which is used for treating kidney stones, with recent research and clinical experience demonstrating it to be significantly faster than the standard holmium (Ho:YAG) laser. ThuLEP is performed in exactly the same way as HoLEP. A key visual difference in the procedure vs HoLEP is the carbonisation of prostate tissue during the procedure giving it a brown or burnt look. Current data shows similar efficacy between ThuLEP, HoLEP and TURP. ThuLEP seems to be faster to perform than HoLEP, although it is associated with a larger haemoglobin drop. 34,35

Prostate artery embolization (PAE)

PAE is a procedure which uses digital subtraction angiography to identify suitable prostatic arterial supply to embolize. This procedure can be performed as a day case under local anaesthesia with access via femoral or radial arteries. This procedure can be particularly useful in co-morbid patients who may be more suited to minimally invasive treatment. This procedure seems to be less effective than TURP for objective improvement in functional outcomes. However, blood loss as well as catheterisation and hospitalisation time all favour PAE. This procedure is still under investigation and it is advised that it only be performed in centres where urologists work with trained interventional radiologists to select appropriate candidates. 36

Summary

Benign prostatic hyperplasia is a condition characterised by a prostate volume over 30mls. This is predominantly a condition of older men. Patients with suspected BPH should be worked up by their physician with a history including LUTs (IPSS) and DRE. Patients should be first advised on lifestyle modifications to improve their condition. Reasonable first line investigations for LUTs include laboratory investigations including PSA, creatinine and urine for microscopy or culture and sensitivity. Common BPH medications to treat obstructive urinary symptoms include alpha blockers and 5-ARIs. Common BPH medications to treat storage urinary symptoms include antimuscarinics and beta-3 agonists. Uroflowmetry, urodynamics, ultrasound, flexible cystoscopy, and CT/MRI are all useful investigations for BPH.

Shared decision making is important between clinician and patient when deciding on the necessity for, and the type of BPH procedure to be carried out. This decision should be guided by a patient’s co-morbidities, functional status, prostate size and shape as well as most importantly the patient’s treatment goals.

References available on request

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