Current Treatment Options For Benign Prostatic Hyperplasia

Benign prostatic hyperplasia is one of the common urological disorders with at least 50% incident rate amongst men aged 50 years and above. The pathological condition is linked to poor quality of life and leads to urinary problems and urinary tract infection if left untreated. This article discusses the existing treatment modalities for benign prostatic hyperplasia. Benign prostatic hyperplasia (BPH) or non-malignant enlargement of the prostate gland is characterized by the proliferation of stromal and epithelial cells. The pathological condition involving the enlarged prostate constricts the urethra that results in lower urinary tract symptoms (LUTS) such as hesitancy, frequent urination, feeling of incomplete urination, weak urinary stream, nocturia and acute urinary retention etc.  BPH is typically diagnosed after a series of clinical test that may include digital rectal examination, serum prostate-specific antigen, ultrasonography, and urinalysis. PSA, Biopsy, and radiological investigation e.g PET scan are required to distinguish BPH from prostate CA.

CURRENT TREATMENT OPTIONS .

BPH cannot be cured as of now, hence, the treatment modalities focus on relief from symptoms and improvement in the quality of life. Currently, BPH is treated surgically and/or pharmacologically. The choice between monotherapy or combination therapy is based on the severity of the symptoms. 1. Pharmacological therapies Alpha-1 Adrenergic Receptor Blockers Noradrenaline works on alpha-1 adrenergic receptors (alpha-1AR) in the prostate and the neck and sphincter of the urinary bladder. This results in vascular smooth muscle contraction and urinary retention thereby increases the symptomatic severity of BPH. To manage this, alpha-1 AR antagonists are used as the first line therapeutic agents. Selective alpha-1AR antagonists block alpha-1AR and thereby relax the smooth muscles in and around prostate and neck of the bladder to relieve the bladder outlet obstruction and hence relieve LUTS associated with BPH.  There are three subtypes of alpha-1AR: alpha-1A, alpha-1B, and alpha-1D. Alpha-1A is specific and abundant in the prostate. Hence, the drugs selective for alpha-1A subtype are more useful for the management of BPH symptoms. The first alpha-1AR selective blockers were prazosin, followed by terazosin, doxazosin, and alfuzosin. However, these agents are not alpha-1A specific. Tamsulosin is an alpha-1A and alpha-1D specific antagonist. Similarly, silodosin is a highly selective alpha-1A antagonist, with a small advantage on voiding symptoms. The high uro-selectivity of tamsulosin and silodosin thus make them more preferred therapeutic agents for BPH management.  5-Alpha-Reductase Inhibitors Dihydrotestosterone (DHT) is required for normal as well as abnormal prostate growth. DHT is synthesized from testosterone, and 5-alpha-reductase catalyze the process. 5-alpha-reductase inhibitors are thus useful to decrease the production of DHT within the prostate and hence decreased prostate volume. This improves the peak urinary flow rate, decreases urinary retention and other symptoms. Clinically approved 5-alpha-reductase inhibitors for BPH management are finasteride and dutasteride. Finasteride is a competitive inhibitor of 5-alpha-reductase type II with 10-fold higher affinity than type I. It decreases DHT level by 70-90% thus reduce prostate size and decrease BPH symptoms. Whereas, dutasteride is a non-selective completive inhibitor of both type-I and type-II 5-alpha-reductase and reduces DHT level by 90-95%. Epristeride is a novel 5-alpha-reductase inhibitor that specifically inhibits the type-II isoenzyme. Adverse effects of 5-alpha-reductase inhibitors treatments are decreased libido, erectile dysfunction, and decreased ejaculation. However, the prevalence of these adverse effects is significantly low (4-6%). Other androgen deprivation therapy Since DHT is synthesized from testosterone, several therapies indirectly reduce DHT by reducing testosterone. Progestational agents like megesterone and hydroxyprogesterone acetate reduce testosterone by inhibiting the release of luteinizing hormone. Anti-androgens like cyproterone acetate and flutamide are also useful for BPH management since they competitively inhibit the binding of DHT to the androgen receptor. Phosphodiesterase-5 inhibitors Phosphodiesterase-5 (PDE-5) inhibitors are typically used for the treatment of erectile dysfunction (ED). However, ED and BPH often co-occur. PDE-5 inhibitors can alter NO/cGMP signaling and thereby relax the prostatic smooth muscles that is beneficial for BPH management. Tadalafil, which was earlier approved for the treatment of ED, has also been approved for the treatment of BPH. Since other BPH drugs such as 5-alpha-reductase inhibitors and alpha-1AR antagonists can have ED as an adverse effect in some patients, drugs like tadalafil become a good choice as it can manage both the symptoms. Combination therapy Combination therapy becomes essential when either of the alpha-1AR inhibitor or 5-alpha-reductase inhibitor therapies fail to significantly improve the symptoms associated with BPH. The combination therapy manages the static and dynamic component in patients with enlarged prostate with symptomatic LUTS. The combination of dutasteride and tamsulosin is useful in the management of BPH. 2. Minimally invasive and surgical therapies: Minimally invasive and surgical procedures are required when the patient has moderate to severe symptoms, complications like renal problems, blood in urine or when pharmacological therapies do not significantly improve the condition of BPH.

Transurethral resection of the prostate (TURP) TURP is a gold standard approach for surgical management of BPH. It offers quicker symptomatic relief with stronger urine outflow. The total procedure takes 60-90 min which includes the resection of parts of the enlarged prostate. Transurethral incision of the prostate (TUIP) TUIP involves insertion of a lighted scope into the urethra. One or multiple incisions are done in the mild or moderately enlarged prostate gland which in turn eases urine flow through the urethra. This procedure is also useful when complications make other surgical techniques riskier. Transurethral electrovaporization (TUVP) The TUVP procedure applies the high electrical current in order to vaporize and coagulate the part of the prostatic tissue that causes urethral obstruction. It also offers less bleeding complications and has comparable long-term efficacy (compared to TURP). Transurethral microwave thermotherapy (TUMT) TUMT procedure employs microwaves to enable the destruction of tissues in the sites of the prostate. The procedure is performed by increasing the temperature to 46-60oC (thermotherapy). TUMT involves insertion of the special electrode through the urethra into the prostate area followed by the destruction of the inner portion of the prostate gland with microwave heat that makes urination easier. Further, TUMT procedure has been reported to be safe and effective with minimal impairment of sexual function. Transurethral needle ablation (TUNA) TUNA is an uncomplicated and relatively cost-effective procedure which employs twin needles to provide high-frequency radio waves to destroy the enlarged prostatic tissue. TUNA is an effective management option for small-sized prostate gland and it results in a low or no risk for impotence. Laser ablation Laser ablation is becoming a widespread form of minimally invasive therapy for BPH. This safe and effective technique utilizes a high-energy laser to remove or destroy overgrown prostate tissue at specific sites. Moreover, the procedure is associated with less operative time, rapid relief from the symptoms, and significantly lower side effects. High-intensity focused ultrasound (HIFU) HIFU of 4 MHz can relieve the BPH symptoms by effectively denaturing & coagulating proteins and necrotizing prostate tissues at specific areas. During HIFU, ultrasound waves are delivered rectally or extracorporeally. This procedure increases the urinary outflow and is usually considered safe. However, the cost is higher as compared to TURP. Water-induced thermotherapy This procedure delivers hot water (60-70oC) to a treatment balloon through a catheter in order achieve heat induced even coagulation necrosis in the defined areas of the prostate without affecting other parts. The necrotized tissue is either excreted in the urine or reabsorbed in the body. Current treatment options focus on the symptomatic relief of BPH with or without reduction of the size of the enlarged prostate. However, the treatment modalities and their combinations are chosen on the basis of the disease complexity, the benefit to risk ratios of the therapies, and patient factors such as age, comorbidities, etc.

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