UCPPS - Prostatitis, Interstitial Cystitis Forum

Prostatic Diseases and Male Voiding Dysfunction
Culture-independent Next Generation Sequencing of Urine and Expressed Prostatic Secretions in Men With Chronic Pelvic Pain Syndrome

Glenn T. Werneburg, Nicholas Farber, Paige Gotwald, Daniel A. Shoskes
Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH
Available online 21 October 2020. https://doi.org/10.1016/j.urology.2020.10.013

Objective

To compare standard cultures and next-generation sequencing (NGS) in men with chronic prostatitis/chronic pelvic pain syndrome (CPPS). CPPS shares clinical features with urinary tract infections, but bacteria are seldom found. NGS is more sensitive than standard cultures.

Materials and Methods

Men diagnosed with CPPS (National Institute of Health Category III) underwent traditional cultures and NGS of their urine and expressed prostatic secretions (EPS). Characteristics between groups were compared statistically.

Results

Thirty-one men with CPPS were included (mean age 44.5). All standard urine cultures were negative, and 3 EPS cultures were positive. Seventy-eight unique microbes were detected with NGS, including uropathogens in 10 of the men. There were no bacteria identified by NGS in EPS that were not also found in the urine. Men with positive NGS did not differ from those without in age, symptom severity or phenotype. Men with typical urinary tract infection symptoms (eg, dysuria, chills) were more likely to have uropathogens detected on NGS relative to men without such symptoms. Nine patients were prescribed antibiotics based on their NGS findings, but only 1 exhibited symptom improvement (11%).

Conclusion

NGS commonly identified bacteria in CPPS patients, but these did not localize to the prostate. NGS positivity did not correlate with symptom severity and antibiotic therapy was seldom effective. NGS detected uropathogens more frequently in those with clinical symptoms suggestive of urinary tract infection. Clinical trials are needed to examine the utility of NGS-guided antibiotics in this subpopulation.

Recently, a number of next-generation sequencing platforms have come to market −some of which engage in direct-to-consumer marketing. These assays have generated immense interest from physicians and the public for the management of CPPS. In our study, we subjected CPPS patients' urine and EPS to both standard culture and NGS, with the goal of identifying organisms and determining whether NGS-positive patients had differences in symptom severity relative to NGS-negative patients. We hypothesized that NGS would be a highly sensitive test for microbial presence in the urine and EPS, but that its specificity for identifying true uropathogens responsible for symptoms would be low. In the 31 patients tested, our NGS assay detected 78 unique microbial species. Two of the 3 bacteria in EPS (and both of the uropathogens) found by conventional culture were also found by NGS. Of note, our findings of a uropathogen localized to the prostate based on standard culture (standard urine negative and standard EPS positive for uropathogen) of 6.5% were mirrored by the findings of Schaeffer et al. who found 8% of men with CPPS had prostate localization of uropathogens based on standard culture. The wide variety of identified organisms was not unexpected. In previous studies, transperineal biopsy, next generation sequencing, and other techniques have demonstrated multiple microbes in CPPS patients. So far no unique, consistent biomarker, or therapeutic target has been identified. Indeed, this patient population is subject to repeated courses of antibiotics, and such overtreatment is likely to change the resident microflora. This phenomenon significantly confounds such results, and makes interpretation of these studies difficult, as the detected microbes may better reflect prior treatment than etiology of symptoms. NGS detected both uropathogenic and nonuropathogenic microbes. There was no difference in age or symptom severity in patients with positive NG versus negative NGS. This finding, in the context where multimodal therapy can help up to 84% of men with CPPS, suggest that the identified bacteria are not primary drivers of symptoms and argue against routine antibiotic use for the treatment of these patients.

Based on our data, we hypothesize that NGS detects a greater variety and quantity of organisms, and although it is more sensitive, is also less specific for clinically-meaningful uropathogens, and thus we further hypothesize that such information may not lead to better-tailored treatment. Interestingly, our study identified a subgroup of patients −those with CPPS and also clinical symptoms of bacterial infection, who frequently had uropathogens identified on NGS in the absence of such microbes on standard culture. Although our study was not sufficiently powered to statistically analyze NGS-guided treatment response, we note that in 9 patients (with or without clinical symptoms of bacterial infection) who were treated with antibiotics based on their NGS results, only 1 exhibited symptomatic improvement (1 was lost to follow-up). Thus, routine treatment of CPPS based on NGS is unlikely to lead to significant benefit.