JALYN for Benign Prostatic Hyperplasia (BPH) and Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS)

Benign Prostatic Hyperplasia (BPH) describes a common medical condition in men over 45 associated with voiding (obstructive) and storage (irritative) lower urinary tract symptoms and is in part related to prostate enlargement and obstruction [1]. The standard medical therapy for this condition includes 5-alpha reductase inhibitors -5ARI (eg dutasteride) or alpha blocker therapy (eg tamsulosin), while the most effective medical therapy for BPH is the combination of these two medications [2]. Approximately 10 to 20% of patients diagnosed with BPH also have either a diagnosis of or symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with typical genito-urinary pain and discomfort [3,4,5]. This particular subset of patients of BPH patients with prostatitis symptoms pose a therapeutic dilemma [6].

CP/CPPS (organ specific phenotype) is the third most prevalent prostate disease after prostate cancer and BPH. CP/CPPS is very prevalent (3-9% of men) [7,8] and represents a significant percentage of urology outpatients (3-8% of male outpatient visits) [9,10] resulting in a major impact on quality of life of patients [11] and economic costs to society [12].

There are no good evidence based therapies for CP/CPPS [13,14], although there is some evidence available to consider 5 alpha reductase inhibitor and alpha blocker therapies [22]. There is an enormous unmet need to evaluate potential therapies for this condition.

Our current understanding of CP/CPPS patients are that they are a heterogeneous group of unique patients (the "snow flake" hypothesis) presenting with different clinical phenotypes [15]. We have proposed [16,17], validated [18] and recently proved that clinical phenotyping (using our UPOINT classification system) is possible and provides more effective treatment strategies [19].

There are studies that suggest that the same medical therapy that has proven effective for the treatment of BPH would also be beneficial for prostatitis like symptoms as well. A number of small pilot studies with finasteride [20], including a contemporary 6 month RCT [21], have strongly suggested that 5 ARI therapy may be effective in patients with CP/CPPS, but these studies were limited by study design including inclusion of all patients with the diagnosis of CP/CPPS (ages and clinical phenotypes that we now know could not possibly benefit from a 5ARI). REDUCE and many other epidemiology studies, have documented that men over 45 years old suffer from prostatitis and prostatitis symptoms [23]. REDUCE also clearly shows that dutasteride favorably impacts on prostatitis-like symptoms and men with prostatitis-like syndrome enrolled in that study [24]. In fact, the potential benefits suggested by extrapolating REDUCE results far outweigh any other intervention we have evaluated in any of the large North American NIH sponsored RCTs in the last decade [25,26,27]. A further sub-analyses of REDUCE shows that men with IPSS ≥ 8 and enlarged prostates (eg BPH) have a significant symptom benefit with dutasteride, irregardless of prostate size [28].These initial findings in REDUCE in patients not specifically diagnosed with CP/CPPS should be expanded to examine the benefits in a CP/CPPS population.

There are more clinical trials evaluating alpha blockers than any other therapy in CP/CPPS [22, 29]. While two North American RCTs [25,26] did not show benefit, 6 other alpha blocker randomized placebo controlled trials using validated contemporary outcomes were positive in terms of measureable benefits [30-35]. The latest clinical trial confirming the benefits of alpha blocker therapy in selected CP/CPPS patients (approximately 50 patients per arm in 12 week study) was recently published [35] and showed benefit, primarily in the LUTS symptom domain.

Clinical phenotyping allows for prediction of the patients with CP/CPPS most likely to respond to dutasteride and tamsulosin (age, Lower Urinary Tract Symptoms [LUTS] and prostate related phenotypes [BPH]). It can be estimated that up to 30% of men currently diagnosed with CP/CPPS will include men with co-existing Benign Prostatic Hyperplasia (BPH)