UPOINT System: A Diagnostic/Therapeutic Algorithm for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

1. Urinary

The efficacy of several alpha-blockers used in mono-therapy has been assessed, but the results varied. Nickel et al. [7] conducted a randomized controlled trial (RCT) and reported that tamsulosin 0.4 mg daily significantly improved the NIH-CPSI scores across multiple domains compared to the placebo. In another study, silodosin 4 mg reduced the NIH-CPSI scores compared to the placebo [8]. Alpha-block-ers may be beneficial when used in multimodal therapy. Owing to the heterogeneity of previous studies, however, the authors of a recent study could not recommend alpha-blockers as first-line monotherapy [9].

Some studies reported that phosphodiesterase-5 inhi-bitors could improve the lower urinary tract symptoms (LUTS) by inhibiting nitric oxide synthase. Kong et al. [10] reported that the use of mirodenafil in combination with levofloxacin versus levofloxacin alone improved the NIH-CPSI score by -7.2 and -3.2 (p<0.05), respectively.

2. Psychosocial

Cannabis has been used in other chronic pain syndromes for symptom relief. Tripp et al. [11] performed a study on men with CP/CPPS who visited clinics and shared their experience with cannabis online. In total, 342 participants responded to questions regarding the baseline NIH-CPSI scores, symptom improvement with cannabis usage, and side effects. The results showed that 57% of clinics and 63% of online participants believed that cannabis was effective to some extent in treating CP/CPPS symptoms. Moreover, it may play a role in the management of CP/CPPS. On the other hand, multiple studies revealed an association between regular cannabis use and low sperm concentration and total sperm count as well as decreased sperm function [12,13]. CP/CPPS is a disease common in men younger than 50 years old. Thus, male fertility and the desire for future offspring should be considered before initiating therapy with cannabis [5].

3. Organ-Specific

Phytotherapies, such as quercetin, saw palmetto, and cernilton, have been used owing to their success in improving the symptoms of patients with CP/CPPS [14]. In another study on the effects of pollen extract, compared to patients (n=10) in the placebo group, patients in the experimental group experienced an improvement in pain and LUTS based on a symptom questionnaire survey [15].

OM-89 is a novel oral immunostimulatory agent developed from lysed pathogenic Escherichia coli bacteria. Wagenleh-ner et al. [16] conducted a randomized, double-blind placebo-controlled study on 185 patients who received either OM-89 or a placebo. The results showed that the NIH-CPSI score decreased by 40.5% and 44.0% in the treatment and placebo groups, respectively. Moreover, the positive response rates were 67% and 64.3%, respectively. On the other hand, the results did not differ significantly.

Increasing evidence suggests that low-intensity pulsed ultrasound (LIPUS) can inhibit inflammation and pain by regulating the cyclooxygenase pathway. Li et al. [17] performed a randomized study on 96 CP/CPPS patients who either received treatment with transperineal ultrasono-graphy daily for two weeks or underwent a sham treatment. The results showed that the two groups differed significantly in terms of the total NIH-CPSI and pain and urinary symptom scores after the LIPUS treatment.

4. Infection

Antibiotics are often used for patients with CP/CPPS. On the other hand, the use of antibiotics has been controversial in the absence of infection. Zhou et al. [18] reported that the mean NIH-CPSI score decreased by 18.5 points in the tetracycline group. Nevertheless, two other RCTs compared the efficacy of ciprofloxacin or levofloxacin for six weeks versus placebo in the treatment of CP/CPPS. The results did not reveal any significant difference in the changes in NIH-CPSI scores [14]. Hence, there is no sufficient evidence supporting the efficacy of antibiotics in the primary treatment of CP/CPPS [1,9].

Anti-inflammatory medications have been a therapeutic option for CPPS. On the other hand, the outcomes have varied. A previous study showed that celecoxib improves the condition of patients. On the other hand, deterioration was observed two weeks after therapy [19]. In another RCT on pentosan polysulfate sodium, there was no significant improvement in the Clinical Global Improvement and total NIH-CPSI scores [15].

New second-generation drugs, including beclomethasone dipropionate, are aimed to decrease the systemic activity while maintaining local efficacy. Hence, they have attracted increasing interest. Bozzini et al. [20] performed a study on 180 men with CP/CPPS, who received beclomethasone dipropionate suppositories. Of these patients, 136 received a Serenoa repens extract. The results showed that the men in the steroid group and those in the steroid and S. repens-combined group experienced significant decreases in voiding frequency (-3.55 vs. -3.68 voids per day, respectively) and increases in uroflowmetry (3.26 vs. 5.61 ml/s, respectively). Moreover, both groups experienced an improvement in perineal pain based on the visual analog scale. Therefore, beclomethasone dipropionate supposi-tories were considered safe and were associated with improvement in LUTS and pain.

Kotb et al. [21] examined the efficacy of antifungals and urinary alkalization with potassium citrate in 1,000 men who did not respond to four weeks of treatment with antibiotics and alpha-blockers 31. Of 1,000 men, 803 experienced at least 80% improvement in their urinary and pain symptoms. A low initial prostate-specific antigen level and age were associated with a better response to antifungals.

5. Neurological/Systemic

Neuromodulatory techniques have shown promising results in the treatment of CP/CPPS. In a randomized, placebo-controlled, double-blind trial, Kessler et al. [22] examined the effects of sono-electromagnetic (SEM) therapy in the treatment of refractory CP/CPPS. The patients had received other therapies, including antibiotics, nonsteroidal anti-inflammatory drugs, and alpha-blockers, for at least six weeks. At home, the device was placed over the perineum twice a day for 10 minutes using a portable device provided by the manufacturer. After 12 weeks, there was no significant difference in the NIH-CPSI scores between the SEM and placebo groups. On the other hand, subgroup analysis showed that the benefit of SEM was more evident than that of the placebo in patients with a symptom duration of <12 months.

Although the precise mechanism of action is not completely understood, acupuncture has been used as a complementary therapeutic option in the management of refractory CP/CPPS in Eastern countries. Several studies have reported that acupuncture may increase the endogenous release of opioids and modulate the sympathetic tone and pain pathways [14,23]. Qin et al. [24] conducted a recent systematic review of acupuncture for the treatment of CP/CPPS. They reported that it was effective in managing CP/CPPS.

6. Tenderness

The targeting of key modulators in the pain pathway and nerve growth factor (NGF) inhibition has attracted increasing interest. Both modulators have been found to reduce pain in animal models. Tanezumab, a monoclonal antibody against NGF, is an effective agent. Nickel et al. [25] performed a pooled analysis in patients with chronic pelvic pain, including women with interstitial cystitis and men with CP/CPPS. Pooled analysis showed that tanezumab improved the pain scores. On the other hand, the results were not significant in the male population with CP/CPPS. Therefore, tanezumab is considered a promising therapy. Nevertheless, further studies, particularly in the CP/CPPS population, will be needed.

Botulinum neurotoxin-A (BoNT-A) is a toxin familiar to several urologists and is used in different urologic conditions, including neurogenic detrusor overactivity. Falahatkar et al. [26] performed a randomized, double-blind study. They reported statistically significant continuous and stable improvement in the total and subscale scores of the NIH-CPSI during the final six-month evaluation in 60 patients with CP/CPPS who received a transurethral intraprostatic injection of BoNT-A or normal saline. Similar results were obtained using other instruments, such as the American Urologic Association (AUA) symptom score, visual analog scale, and quality of life scores. No significant adverse events were recorded except in two patients who developed transient gross hematuria, which was managed con-servatively.