Multimodal therapy for category III chronic prostatitis/chronic pelvic pain syndrome in UPOINTS phenotyped patients

The complex network of etiological factors, signals and tissue responses involved in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) cannot be successfully targeted by a single therapeutic agent. Multimodal approaches to the therapy of CP/CPPS have been and are currently being tested, as in the frame of complex diagnostic-therapeutic phenotypic approaches such as the urinary, psychosocial, organ-specific, infection, neurological and muscle tenderness (UPOINTS) system. In this study, the effect of combination therapy on 914 patients diagnosed, phenotyped and treated in a single specialized prostatitis clinic was analyzed. Patients received α-blockers, Serenoa repens (S. repens) extracts combined or not with supplements (lycopene and selenium) and, in the presence of documented or highly suspected infection, antibacterial agents. Combination treatment induced marked and significant improvements of National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) prostatitis symptom scores, International Index of Erectile Function (IIEF) sexual dysfunction scores, urinary peak flow rates and bladder voiding efficiency. These improvements, assessed after a 6-month course of therapy, were sustained throughout a follow-up period of 18 months. A clinically appreciable reduction of ≥6 points of the total NIH-CPSI score was achieved in 77.5% of patients subjected to combination therapy for a period of 6 months. When the patients were divided in two cohorts, depending on the diagnosis of CP/CPPS [inflammatory (IIIa) vs. non-inflammatory (IIIb) subtypes], significant improvements of all signs and symptoms of the syndrome were observed in both cohorts at the end of therapy. Intergroup comparison showed that patients affected by the IIIa sub-category of CP/CPPS showed more severe signs and symptoms (NIH-CPSI total, pain and quality of life impact scores, and Qmax) at baseline when compared with IIIb patients. However, the improvement of symptoms after therapy was significantly more pronounced in IIIa patients when compared with IIIb patients. In contrast to current opinion, the evidence emerging from the present investigation suggests that the inflammatory and non-inflammatory sub-categories of CP/CPPS may represent two distinct pathological conditions or, alternatively, two different stages of the same condition. In conclusion, a simple protocol based on α-blockers, S. repens extracts and supplements and antibacterial agents, targeting the urinary, organ specific and infection domains of UPOINTS, may induce a clinically appreciable improvement of the signs and symptoms of CP/CPPS in a considerable percentage of patients. In patients not responding sufficiently to such therapy, second-line agents (antidepressants, anxiolytics, muscle relaxants, 5-phosphodiesterase inhibitors and others) may be administered in order to achieve a satisfactory therapeutic response.