Association between Prostatic Inflammation and Detrusor Overactivity in men with Benign Prostatic Hyperplasia and Bladder Outlet Obstruction: A prospective urodynamic and histological study

Association between Prostatic Inflammation and Detrusor Overactivity in men with Benign Prostatic Hyperplasia and Bladder Outlet Obstruction: A prospective urodynamic and histological study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Association between Prostatic Inflammation and Detrusor Overactivity in men with Benign Prostatic Hyperplasia and Bladder Outlet Obstruction: A prospective urodynamic and histological study Michael Samarinas, Evangelos Varelas, Georgios Antoniadis, Aikaterini Tsionga, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6881933/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Oct, 2025 Read the published version in Prostate Cancer and Prostatic Diseases → Version 1 posted 12 You are reading this latest preprint version Abstract Background Benign prostatic hyperplasia (BPH) frequently leads to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS) in aging men. Detrusor overactivity (DO) is a common functional consequence of BOO, often persisting even after surgical intervention. Prostatic inflammation (PI) has been implicated in BPH pathogenesis, but its relationship with DO remains unclear. This study aimed to evaluate the association between histologically confirmed PI and DO in men undergoing transurethral resection of the prostate (TURP) for BPH-related BOO. Methods We conducted a prospective, observational study involving 125 men aged ≥ 50 years with BPH, BOO confirmed by pressure-flow studies, and moderate-to-severe LUTS (IPSS ≥ 7). All patients had received standard medical therapy and were candidates for TURP. Urodynamic testing was performed before and three months after surgery. Based on baseline urodynamic findings, patients were categorized into two groups: those with DO (Group A) and those without (Group B). Resected prostate tissue was examined histologically, and PI was graded using the Irani score. Statistical analysis was performed using SPSS v26, with odds ratios (OR) and 95% confidence intervals (CI) reported. Results Prostatic inflammation was identified in 78.4% of patients overall and was significantly more prevalent in those with DO (84.9% vs. 69.2%; OR = 2.47, 95% CI: 1.11–5.49, p = 0.02). Inflammation was also more severe in Group A. DO resolved postoperatively in 75.3% of patients, while persistent DO was associated exclusively with moderate-to-severe PI. The odds of persistent DO following TURP were significantly higher in this subgroup (OR = 4.00, 95% CI: 1.33–12.05). Conclusions Prostatic inflammation is more frequent and severe in men with DO and is associated with its persistence after TURP. These findings suggest that PI contributes to both the pathogenesis and postoperative course of DO, supporting its role as a therapeutic target in BPH-related LUTS management. Health sciences/Diseases/Urogenital diseases/Prostatic diseases Health sciences/Medical research/Outcomes research Introduction Benign prostatic hyperplasia (BPH) is a highly prevalent condition among aging men, frequently associated with lower urinary tract symptoms (LUTS) such as urinary frequency, urgency, nocturia, and a diminished urinary stream, all of which can significantly impair quality of life [ 1 ][ 2 ]. One of the principal complications of BPH is bladder outlet obstruction (BOO), wherein the enlarging prostate gland impedes urinary flow, leading to progressive alterations in bladder function [ 1 ][ 3 ][ 4 ]. Among these functional changes, detrusor overactivity (DO) is commonly observed. DO is characterized by involuntary detrusor contractions during the bladder filling phase and often coexists with BOO, contributing to increased symptom severity and therapeutic complexity [ 5 ]. Recent studies have highlighted the frequent presence of prostatic inflammation (PI) in patients with BPH [ 6 ], suggesting a potential pathophysiological role for chronic inflammation in the initiation and progression of both BPH and DO [ 7 ][ 8 ]. Despite the availability of contemporary pharmacologic and surgical interventions, including transurethral resection of the prostate (TURP), a subset of patients continues to experience persistent or refractory symptoms [ 3 ][ 4 ][ 9 ]. This clinical scenario may be attributable to the interplay between mechanical obstruction, neurogenic bladder dysfunction, and inflammatory processes [ 10 ]. In this context, the present study aims to investigate the potential association between DO and PI in men with BOO secondary to BPH. Clarifying this relationship may enhance understanding of the underlying mechanisms and inform more effective strategies for the management of LUTS in this population. Materials/Subjects and Methods This prospective, observational, and comparative study was conducted at the Urodynamics Clinic of our department, collaborating with the Pathology Laboratory, following approval by the Local Ethics Committee, ensuring compliance with ethical standards for human research. Male patients aged 50 years or older who presented with lower urinary tract symptoms LUTS attributed to BPH were consecutively enrolled. All participants had been receiving standard medical therapy for BPH, either with an alpha-adrenergic antagonist alone or in combination with a 5-alpha reductase inhibitor. To be included in the study, patients were required to have an International Prostate Symptom Score (IPSS) of 7 or higher, indicating at least moderate symptom severity [ 3 ]; a prostate volume of at least 30cc 3 as measured by transrectal ultrasound; and bladder outlet obstruction confirmed by pressure-flow studies (PFS). All patients were also deemed appropriate candidates for transurethral resection of the prostate. A summary of inclusion and exclusion criteria is provided in Table 1 . Table 1 Inclusion and exclusion criteria Inclusion Criteria Exclusion Criteria Male patients with LUTS attributed to BPH Neurological disorders IPSS ≥ 7 History of lower urinary tract surgeries or interventions Prostate volume ≥ 30 ml Presence of prostate cancer in TURP specimens Documented BOO on pressure-flow studies Bladder stones Suitable for TURP Long-term catheterization > 3 months Prior use of alpha-blockers or 5-alpha-reductase inhibitors LUTS: lower urinary tract symptoms, IPSS: International Prostate Symptoms Score, TURP: transurethral prostatectomy, BOO: bladder outlet obstruction Exclusion criteria included a history of neurological disease that could affect bladder function, previous surgical or endoscopic procedures involving the prostate, urethra, or bladder, the presence of bladder calculi, prostate cancer detected in TURP specimens, or chronic indwelling urinary catheterization lasting longer than three months. All participants underwent standardized multichannel urodynamic testing, including pressure-flow studies, in accordance with the guidelines of the International Continence Society [ 11 ]. Urodynamic assessments were performed before surgery and repeated three months postoperatively. Based on the baseline urodynamic findings, patients were categorized into two groups: those with detrusor overactivity (DO) and those without. During the TURP procedure, resected prostatic tissue was collected and submitted for histological examination. The presence and severity of prostatic inflammation (PI) were assessed using the Irani scoring system, which evaluates both the extent and the aggressiveness of inflammatory infiltrates. The Irani score classifies prostatic inflammation based on the extension of inflammatory cells and their effect on prostate tissue. A four-point scale (0–3) is used for inflammation and aggressiveness [ 12 ]. The primary objective of the study was to compare the prevalence of PI between patients with and without DO. Secondary outcomes included the severity of inflammation, postoperative changes in DO status, and variations in prostate-specific antigen (PSA) levels following surgery. Statistical analysis was performed using IBM SPSS Statistics for iOS, version 26.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize baseline characteristics and clinical variables. Categorical variables were compared using the chi-square test or Fisher’s exact test as appropriate, while continuous variables were analyzed using the Mann–Whitney U test due to non-normal distribution. Statistical significance was set at p < 0.05. Relative risks were calculated to estimate the strength of association between prostatic inflammation and detrusor overactivity, as well as between inflammation severity and postoperative persistence of DO. Results Out of the total number of 127 men who met the eligibility requirements for the study, 125 participants (median age: 62yo, range: 55–77) were able to complete all the necessary tests and follow-ups. The initial median values for prostate volume were 55cc 3 (range: 35–70) and for PSA was 2.7ng/ml (range: 0.5-4) respectively. At the beginning of the study, these individuals were divided into two groups based on whether they had DO. Group A included 73 patients (58.4%) who showed signs of DO on their initial urodynamic assessment. Group B included the remaining 52 patients (41.6%). The prostate tissue samples collected during surgery were examined for signs of inflammation. Prostatic inflammation was identified in most participants, 98 out of 125 men (78.4%). Notably, PI was more common in Group A, with 62 out of 73 patients (84.9%) showing signs of inflammation. In contrast, only 36 out of 52 patients (69.2%) in Group B had inflammation. This difference was statistically significant (p = 0.02), and the presence of DO was associated with increased odds of having PI (OR = 2.47, 95% CI: 1.11–5.49). These data are summarized in Table 2 . Table 2 Baseline Group characteristics and prostatic inflammation prevalence Group Participants (n) PI Present (n, %) Odds ratio (DO + PI) Group A ( DO ) 73 62 (84.9%) 2.47, 95% CI: 1.11–5.49 Group B ( non-DO ) 52 36 (69.2%) — Total 125 98 (78.4%) — DO: detrusor overactivity, PI: prostatic inflammation The severity of inflammation was also assessed. Among the 62 patients in Group A with PI, 14 patients (22.6%) had mild inflammation, 28 patients (45.1%) had moderate inflammation, and 20 patients (32.3%) had severe inflammation. In Group B, among the 36 patients with PI, 16 (44.4%) had mild inflammation, 14 (38.9%) had moderate inflammation, and only 6 (16.7%) had severe inflammation. This suggests that not only is PI more frequent in patients with DO, but the inflammation is often more severe in this group. After the surgical treatment (TURP), a significant number of patients in Group A experienced improvement. Specifically, DO resolved in 55 out of the 73 patients (75.3%). However, 18 patients continued to show signs of DO after surgery. Importantly, all these individuals with persistent DO had moderate or severe PI in their prostate tissue; 6 patients (33.3%) had moderate inflammation and 12 patients (66.7%) had severe inflammation. The odds of persistent DO in patients with moderate-to-severe PI were significantly elevated (OR = 4.00, 95% CI: 1.33–12.05), suggesting that increased inflammation may hinder DO resolution postoperatively. These findings are detailed in Table 3 . Table 3 Severity of Prostatic Inflammation and DO resolution after TURP Group Mild PI Moderate PI Severe PI DO Resolution Persistent DO (n = 18) Group A (n = 73) 14 (22.6%) 28 (45.1%) 20 (32.3%) 55 (75.3%) 6 moderate 12 severe Group B (n = 52) 16 (44.4%) 14 ( 38.9%) 6 (16.7%) N/A N/A Odds ratio (Persistent DO with Mod/Sev PI) — — — — 4.00, 95% CI: 1.33–12.05 TURP: transurethral prostatectomy, PI: prostatic inflammation, DO: detrusor overactivity, Mod/ Sev: moderate/ severe In terms of surgical outcomes, the median amount of prostate tissue removed during TURP was 35cc 3 (range: 15–50). Additionally, a significant decrease in PSA levels was observed after the procedure, with a reduction of 65% (final median value: 1.7, range: 0.3–2.6). This confirms that the surgery was effective in reducing prostate size and improving at least some aspects of the patients’ conditions. Discussion This study demonstrated a significant association between prostatic inflammation and detrusor overactivity in men diagnosed with benign prostatic hyperplasia and bladder outlet obstruction. The primary objective was to explore whether inflammatory changes within the prostatic tissue contribute to the pathogenesis or persistence of DO, a condition that exacerbates lower urinary tract symptoms. To this end, patients were stratified based on the presence or absence of DO, and histological analysis of prostate tissue obtained during TURP) was performed using the Irani scoring system to assess inflammation. Our findings revealed that PI was significantly more prevalent among patients with DO. Moreover, the severity of inflammation was positively correlated with the grade of DO. Patients exhibiting moderate or severe PI were more likely to experience persistent DO following TURP, suggesting that inflammation may not only precipitate DO but also impede postoperative symptom resolution. These results support the hypothesis that PI plays a mechanistic role in bladder dysfunction among patients with BOO. The results are consistent with earlier, although limited, clinical investigations. Mi Oh et al. examined the relationship between BOO and DO, showing that a subset of men with BOO exhibited urodynamic evidence of DO; however, the role of inflammation was not evaluated in that study [ 13 ]. Verhovsky et al. further discussed this understanding by showing that BOO does not necessarily correlate with increased DO prevalence but does induce bladder hypersensitivity, reinforcing the complexity of bladder responses to obstruction [ 14 ]. Treatment modality also appears to influence DO outcomes. In a long-term observational study, De Nunzio et al found that DO persisted in patients managed conservatively, while significant improvement was noted in those undergoing surgical relief of obstruction [ 15 ]. Despite surgery, DO may persist in select patients, influenced by factors such as age, baseline bladder capacity, and preoperative DO amplitude. Antunes et al. identified these variables as predictors of incomplete symptom resolution after TURP [ 16 ]. However, a meta-analysis concluded that the presence of DO prior to surgery did not significantly affect objective postoperative outcomes such as flow rate or residual volume, suggesting a limited predictive role [ 17 ]. Nonetheless, bladder outlet obstruction, primarily due to BPH, remains a major etiological factor in male overactive bladder syndrome [ 18 ]. Experimental data from animal models also substantiate a role for inflammation. Ni et al. demonstrated that experimentally induced prostatitis in rats leads to bladder overactivity and increased afferent signaling, providing physiological evidence for a causative link between prostatic inflammation and DO [ 19 ]. These findings align with clinical data showing that advanced age and more severe obstruction are independent predictors of DO, with affected individuals presenting with decreased bladder compliance, reduced functional capacity, and diminished voided volumes [ 20 ]. Bellucci et al. described also histological changes, including collagen deposition in the detrusor, contributing to decreased bladder compliance and increased storage symptoms in men with BPH [ 21 ]. Recent studies have increasingly emphasized the role of chronic inflammation in the pathogenesis and progression of BPH. While the influence of androgens such as dihydrotestosterone is well established, inflammation is now recognized as a parallel pathogenic pathway and a potential therapeutic target in managing LUTS [ 22 ]. Chronic inflammation is not merely incidental but appears to actively contribute to tissue remodeling and disease progression. Infiltrates composed of T lymphocytes and macrophages release pro-inflammatory cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-γ), which stimulate stromal and epithelial proliferation, facilitating nodular growth and prostate enlargement independent of hormonal stimulation [ 23 ]. Data from the REDUCE trial also demonstrated that men with histologically confirmed PI had significantly larger prostate volumes, further strengthening the link between inflammation and glandular enlargement [ 8 ]. In this study, PI was evaluated using the Irani scoring system, which grades both the extent and aggressiveness of inflammatory infiltrates. Though initially developed for the classification of chronic prostatitis, the Irani score has proven useful in assessing inflammation associated with BPH, aiding in the differentiation between histological subtypes and potentially guiding individualized management approaches, including the use of anti-inflammatory or antibiotic therapies [ 12 ][ 22 ]. Taken together, these findings suggest that prostatic inflammation plays a meaningful role in the development and persistence of detrusor overactivity in men with BPH-related BOO, with potential implications for diagnosis, prognosis, and treatment. However, while the correlations observed are compelling and support existing experimental and clinical evidence, they must be interpreted within the context of certain methodological constraints. Several limitations should be acknowledged. As an observational study, causality between PI and DO cannot be definitively established. The histological grading, while informative, remains semi-quantitative and may be influenced by interobserver variability. Although the sample size was sufficient for exploratory analysis, it may not allow broad generalization. Additionally, the absence of extended postoperative follow-up precludes evaluation of long-term changes in DO or symptom progression beyond the three-month postoperative window. This study underscores a significant relationship between prostatic inflammation and detrusor overactivity in men with BPH-related bladder outlet obstruction. Prostatic inflammation was more frequent and severe among patients with DO and was associated with persistence of DO following TURP. These findings suggest that PI may play a pivotal role not only in the pathogenesis but also in the persistence of DO, even after surgical relief of obstruction. As such, inflammation should be considered a critical component in the management of BPH and LUTS. Future therapeutic strategies may benefit from incorporating anti-inflammatory interventions alongside standard surgical and pharmacological treatments to optimize clinical outcomes. Declarations Conflict of Interest: none for all the authors contributed Ethics Approval and Consent to Participate This study was approved by the Scientific Council of General Hospital of Larissa, Greece, and all procedures involving human participants were conducted in accordance with the ethical standards of the institutional and national research committees, as well as the 1964 Helsinki Declaration and its later amendments. Written informed consent was obtained from all participants prior to inclusion in the study. Funding: none Author Contributions Varelas Evangelos conducted data interpretation, and drafted the manuscript Acknowledgements The authors would like to thank the staff of the Urodynamics Clinic and the Pathology Laboratory for their technical assistance and support during the study. No external funding or commercial sponsorship was received for this research. All materials used in this study were available through routine clinical care and standard institutional resources. Availability of Data and Materials The datasets generated and analyzed during the current study are not publicly available due to institutional restrictions and participant confidentiality but are available from the corresponding author on reasonable request. All relevant data supporting the findings of this study are included in the main manuscript or are available upon request for academic and non-commercial purposes. References Roehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol. 2005;7(Suppl 9):S3–S14. Coyne KS, Sexton CC, Thompson CL, et al. The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int. 2009;104(3):352–360. Management of Non-neurogenic Male LUTS. EAU Guidelines. 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Eur Urol 2008 54(6):1379–1384 Sandhu JS, Bixler BR, Dahm P et al. Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia (BPH): AUA Guideline Amendment 2023. J Urol. 2024;211(1):11–19. doi: 10.1097/JU.0000000000003698 . Peyronnet B, Mironska E, Chapple C et al. A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment. Eur Urol. 2019;75(6):988–1000. doi: 10.1016/j.eururo.2019.02.038 . Rosier PFWM, Schaefer W, Lose G et al. International Continence Society Good Urodynamic Practices and Terms 2016: Urodynamics, uroflowmetry, cystometry, and pressure-flow study. Neurourol Urodyn. 2017;36(5):1243–1260. doi: 10.1002/nau.23124 . Irani J, Levillain P, Goujon JM, et al. Inflammation in benign prostatic hyperplasia: correlation with prostate specific antigen value. J Urol 1997 157(4):1301–1303. Oh MM, Choi H, Park MG, et al. 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Effect of urodynamic preoperative detrusor overactivity on the outcomes of transurethral surgery in patients with male bladder outlet obstruction: a systematic review and meta-analysis. World J Urol. 2019;37(3):529–538. doi: 10.1007/s00345-018-2402-8 . Dmochowski RR, Staskin D. Overactive bladder in men: special considerations for evaluation and management. Urology. 2002;60(5 Suppl 1):56–62; discussion 62 – 3. doi: 10.1016/s0090-4295(02)01797-1 . Ni J, Mizoguchi S, Bernardi K, et al. Long-lasting bladder overactivity and bladder afferent hyperexcitability in rats with chemically-induced prostatic inflammation. Prostate. 2019;79(8):872–879. doi: 10.1002/pros.23794 . Oelke M, Baard J, Wijkstra H, et al. Age and bladder outlet obstruction are independently associated with detrusor overactivity in patients with benign prostatic hyperplasia. Eur Urol. 2008;54(2):419–26. doi: 10.1016/j.eururo.2008.02.017 . Epub 2008 Feb 25. PMID: 18325657. Bellucci CHS, Ribeiro WO, Hemerly TS, et al. Increased detrusor collagen is associated with detrusor overactivity and decreased bladder compliance in men with benign prostatic obstruction. Prostate Int. 2017;5(2):70–74. doi: 10.1016/j.prnil.2017.01.008 . De Nunzio C, Salonia A, Gacci M, et al. Inflammation is a target of medical treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia. World J Urol. 2020;38(11):2771–2779. doi: 10.1007/s00345-020-03106-1 . Epub 2020 Feb 14. Erratum in: World J Urol. 2020;38(11):2781. doi: 10.1007/s00345-020-03290-0 Samarinas M, Gacci M, de la Taille A, et al. Prostatic inflammation: a potential treatment target for male LUTS due to benign prostatic obstruction. Prostate Cancer Prostatic Dis. 2018;21(2):161–167. doi: 10.1038/s41391-018-0039-8 . Epub 2018 Apr 24. PMID: 29686417. Additional Declarations There is NO conflict of interest to disclose. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6881933","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":472168363,"identity":"7f76e527-373a-4b47-bae3-925e45acf7c3","order_by":0,"name":"Michael Samarinas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYDACZjYwxWPA3gNh8BGvhecMA8MBIIONsDVQJQYSOWAtDAS16LazJT78UbNNxlzy7cHHH3PsZNgYmB8+uoFHi9lhtsPGPMdu81jOzks2OLgtGegwNmPjHLxa2NukGdhu8xjczjGTOLiNGaiFh02agJb2nz/+AbXcPAPSUk+MFrZjDLxtQC03eEBaDhOlJVmatw+o5UyOscHZbcd52JgJ+eX8McOPP77dtjc4fsbwQeW2ant+9uaHj/FpwQKYSVM+CkbBKBgFowALAACMFEXFrVp7KQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-9424-795X","institution":"Aristotle University of Thessaloniki","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"","lastName":"Samarinas","suffix":""},{"id":472168364,"identity":"aa03c982-0607-44c8-9550-5d563f56308a","order_by":1,"name":"Evangelos Varelas","email":"","orcid":"","institution":"Aristotle University of Thessaloniki, 2nd Urology Department","correspondingAuthor":false,"prefix":"","firstName":"Evangelos","middleName":"","lastName":"Varelas","suffix":""},{"id":472168365,"identity":"fae85ac5-5fb0-43f9-ac32-da32cf61bda0","order_by":2,"name":"Georgios Antoniadis","email":"","orcid":"","institution":"General Hospital of Larissa, Urology Department","correspondingAuthor":false,"prefix":"","firstName":"Georgios","middleName":"","lastName":"Antoniadis","suffix":""},{"id":472168366,"identity":"484d9886-3627-4d78-8f30-bf74ae1f1d53","order_by":3,"name":"Aikaterini Tsionga","email":"","orcid":"","institution":"Private Practice","correspondingAuthor":false,"prefix":"","firstName":"Aikaterini","middleName":"","lastName":"Tsionga","suffix":""},{"id":472168367,"identity":"7a0b676e-2543-47e7-af48-25ea1ca45d41","order_by":4,"name":"Merkourios Kolvatzis","email":"","orcid":"","institution":"Aristotle University of Thessaloniki, 2nd Urology Department","correspondingAuthor":false,"prefix":"","firstName":"Merkourios","middleName":"","lastName":"Kolvatzis","suffix":""},{"id":472168368,"identity":"ddf1df35-86ce-4f3b-9725-832834b77571","order_by":5,"name":"Stavros Gravas","email":"","orcid":"https://orcid.org/0000-0001-7805-6651","institution":"University of Cyprus","correspondingAuthor":false,"prefix":"","firstName":"Stavros","middleName":"","lastName":"Gravas","suffix":""},{"id":472168369,"identity":"1790b0e9-b291-476b-acc8-cdb8ed453765","order_by":6,"name":"Konstantina Zacharouli","email":"","orcid":"","institution":"Private Practice","correspondingAuthor":false,"prefix":"","firstName":"Konstantina","middleName":"","lastName":"Zacharouli","suffix":""}],"badges":[],"createdAt":"2025-06-12 15:51:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6881933/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6881933/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41391-025-01039-7","type":"published","date":"2025-10-29T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":94651764,"identity":"526277a5-bb44-47b9-96e1-69e136118bce","added_by":"auto","created_at":"2025-10-29 09:50:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":558481,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6881933/v1/553ae8e5-ed0b-47a5-8c64-cbbc9f67410d.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Association between Prostatic Inflammation and Detrusor Overactivity in men with Benign Prostatic Hyperplasia and Bladder Outlet Obstruction: A prospective urodynamic and histological study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBenign prostatic hyperplasia (BPH) is a highly prevalent condition among aging men, frequently associated with lower urinary tract symptoms (LUTS) such as urinary frequency, urgency, nocturia, and a diminished urinary stream, all of which can significantly impair quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. One of the principal complications of BPH is bladder outlet obstruction (BOO), wherein the enlarging prostate gland impedes urinary flow, leading to progressive alterations in bladder function [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e][\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong these functional changes, detrusor overactivity (DO) is commonly observed. DO is characterized by involuntary detrusor contractions during the bladder filling phase and often coexists with BOO, contributing to increased symptom severity and therapeutic complexity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Recent studies have highlighted the frequent presence of prostatic inflammation (PI) in patients with BPH [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], suggesting a potential pathophysiological role for chronic inflammation in the initiation and progression of both BPH and DO [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e][\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the availability of contemporary pharmacologic and surgical interventions, including transurethral resection of the prostate (TURP), a subset of patients continues to experience persistent or refractory symptoms [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e][\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e][\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This clinical scenario may be attributable to the interplay between mechanical obstruction, neurogenic bladder dysfunction, and inflammatory processes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this context, the present study aims to investigate the potential association between DO and PI in men with BOO secondary to BPH. Clarifying this relationship may enhance understanding of the underlying mechanisms and inform more effective strategies for the management of LUTS in this population.\u003c/p\u003e"},{"header":"Materials/Subjects and Methods","content":"\u003cp\u003e This prospective, observational, and comparative study was conducted at the Urodynamics Clinic of our department, collaborating with the Pathology Laboratory, following approval by the Local Ethics Committee, ensuring compliance with ethical standards for human research. Male patients aged 50 years or older who presented with lower urinary tract symptoms LUTS attributed to BPH were consecutively enrolled. All participants had been receiving standard medical therapy for BPH, either with an alpha-adrenergic antagonist alone or in combination with a 5-alpha reductase inhibitor. To be included in the study, patients were required to have an International Prostate Symptom Score (IPSS) of 7 or higher, indicating at least moderate symptom severity [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]; a prostate volume of at least 30cc\u003csup\u003e3\u003c/sup\u003e as measured by transrectal ultrasound; and bladder outlet obstruction confirmed by pressure-flow studies (PFS). All patients were also deemed appropriate candidates for transurethral resection of the prostate. A summary of inclusion and exclusion criteria is provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInclusion and exclusion criteria\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInclusion Criteria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExclusion Criteria\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale patients with LUTS attributed to BPH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeurological disorders\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPSS\u0026thinsp;\u0026ge;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHistory of lower urinary tract surgeries or interventions\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate volume\u0026thinsp;\u0026ge;\u0026thinsp;30 ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresence of prostate cancer in TURP specimens\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDocumented BOO on pressure-flow studies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBladder stones\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuitable for TURP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLong-term catheterization\u0026thinsp;\u0026gt;\u0026thinsp;3 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior use of alpha-blockers or 5-alpha-reductase inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cem\u003eLUTS: lower urinary tract symptoms, IPSS: International Prostate Symptoms Score, TURP: transurethral prostatectomy, BOO: bladder outlet obstruction\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eExclusion criteria included a history of neurological disease that could affect bladder function, previous surgical or endoscopic procedures involving the prostate, urethra, or bladder, the presence of bladder calculi, prostate cancer detected in TURP specimens, or chronic indwelling urinary catheterization lasting longer than three months. All participants underwent standardized multichannel urodynamic testing, including pressure-flow studies, in accordance with the guidelines of the International Continence Society [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Urodynamic assessments were performed before surgery and repeated three months postoperatively. Based on the baseline urodynamic findings, patients were categorized into two groups: those with detrusor overactivity (DO) and those without.\u003c/p\u003e \u003cp\u003eDuring the TURP procedure, resected prostatic tissue was collected and submitted for histological examination. The presence and severity of prostatic inflammation (PI) were assessed using the Irani scoring system, which evaluates both the extent and the aggressiveness of inflammatory infiltrates. The Irani score classifies prostatic inflammation based on the extension of inflammatory cells and their effect on prostate tissue. A four-point scale (0\u0026ndash;3) is used for inflammation and aggressiveness [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The primary objective of the study was to compare the prevalence of PI between patients with and without DO. Secondary outcomes included the severity of inflammation, postoperative changes in DO status, and variations in prostate-specific antigen (PSA) levels following surgery.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using IBM SPSS Statistics for iOS, version 26.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were used to summarize baseline characteristics and clinical variables. Categorical variables were compared using the chi-square test or Fisher\u0026rsquo;s exact test as appropriate, while continuous variables were analyzed using the Mann\u0026ndash;Whitney U test due to non-normal distribution. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Relative risks were calculated to estimate the strength of association between prostatic inflammation and detrusor overactivity, as well as between inflammation severity and postoperative persistence of DO.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOut of the total number of 127 men who met the eligibility requirements for the study, 125 participants (median age: 62yo, range: 55\u0026ndash;77) were able to complete all the necessary tests and follow-ups. The initial median values for prostate volume were 55cc\u003csup\u003e3\u003c/sup\u003e (range: 35\u0026ndash;70) and for PSA was 2.7ng/ml (range: 0.5-4) respectively.\u003c/p\u003e \u003cp\u003eAt the beginning of the study, these individuals were divided into two groups based on whether they had DO. Group A included 73 patients (58.4%) who showed signs of DO on their initial urodynamic assessment. Group B included the remaining 52 patients (41.6%).\u003c/p\u003e \u003cp\u003eThe prostate tissue samples collected during surgery were examined for signs of inflammation. Prostatic inflammation was identified in most participants, 98 out of 125 men (78.4%). Notably, PI was more common in Group A, with 62 out of 73 patients (84.9%) showing signs of inflammation. In contrast, only 36 out of 52 patients (69.2%) in Group B had inflammation. This difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.02), and the presence of DO was associated with increased odds of having PI (OR\u0026thinsp;=\u0026thinsp;2.47, 95% CI: 1.11\u0026ndash;5.49). These data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Group characteristics and prostatic inflammation prevalence\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParticipants (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePI Present (n, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOdds ratio (DO\u0026thinsp;+\u0026thinsp;PI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup A (\u003cem\u003eDO\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62 (84.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.47, 95% CI: 1.11\u0026ndash;5.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup B (\u003cem\u003enon-DO\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36 (69.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e98 (78.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eDO: detrusor overactivity, PI: prostatic inflammation\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe severity of inflammation was also assessed. Among the 62 patients in Group A with PI, 14 patients (22.6%) had mild inflammation, 28 patients (45.1%) had moderate inflammation, and 20 patients (32.3%) had severe inflammation. In Group B, among the 36 patients with PI, 16 (44.4%) had mild inflammation, 14 (38.9%) had moderate inflammation, and only 6 (16.7%) had severe inflammation. This suggests that not only is PI more frequent in patients with DO, but the inflammation is often more severe in this group.\u003c/p\u003e \u003cp\u003eAfter the surgical treatment (TURP), a significant number of patients in Group A experienced improvement. Specifically, DO resolved in 55 out of the 73 patients (75.3%). However, 18 patients continued to show signs of DO after surgery. Importantly, all these individuals with persistent DO had moderate or severe PI in their prostate tissue; 6 patients (33.3%) had moderate inflammation and 12 patients (66.7%) had severe inflammation. The odds of persistent DO in patients with moderate-to-severe PI were significantly elevated (OR\u0026thinsp;=\u0026thinsp;4.00, 95% CI: 1.33\u0026ndash;12.05), suggesting that increased inflammation may hinder DO resolution postoperatively. These findings are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSeverity of Prostatic Inflammation and DO resolution after TURP\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMild PI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerate PI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere PI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDO Resolution\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePersistent DO (n\u0026thinsp;=\u0026thinsp;18)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup A (n\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003cp\u003e(45.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55\u003c/p\u003e \u003cp\u003e(75.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 moderate\u003c/p\u003e \u003cp\u003e12 severe\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup B (n\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (\u003c/p\u003e \u003cp\u003e38.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOdds ratio\u003c/b\u003e \u003cem\u003e(Persistent DO with Mod/Sev PI)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.00, 95% CI: 1.33\u0026ndash;12.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eTURP: transurethral prostatectomy, PI: prostatic inflammation, DO: detrusor overactivity, Mod/ Sev: moderate/ severe\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn terms of surgical outcomes, the median amount of prostate tissue removed during TURP was 35cc\u003csup\u003e3\u003c/sup\u003e (range: 15\u0026ndash;50). Additionally, a significant decrease in PSA levels was observed after the procedure, with a reduction of 65% (final median value: 1.7, range: 0.3\u0026ndash;2.6). This confirms that the surgery was effective in reducing prostate size and improving at least some aspects of the patients\u0026rsquo; conditions.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated a significant association between prostatic inflammation and detrusor overactivity in men diagnosed with benign prostatic hyperplasia and bladder outlet obstruction. The primary objective was to explore whether inflammatory changes within the prostatic tissue contribute to the pathogenesis or persistence of DO, a condition that exacerbates lower urinary tract symptoms. To this end, patients were stratified based on the presence or absence of DO, and histological analysis of prostate tissue obtained during TURP) was performed using the Irani scoring system to assess inflammation.\u003c/p\u003e \u003cp\u003eOur findings revealed that PI was significantly more prevalent among patients with DO. Moreover, the severity of inflammation was positively correlated with the grade of DO. Patients exhibiting moderate or severe PI were more likely to experience persistent DO following TURP, suggesting that inflammation may not only precipitate DO but also impede postoperative symptom resolution. These results support the hypothesis that PI plays a mechanistic role in bladder dysfunction among patients with BOO.\u003c/p\u003e \u003cp\u003eThe results are consistent with earlier, although limited, clinical investigations. Mi Oh et al. examined the relationship between BOO and DO, showing that a subset of men with BOO exhibited urodynamic evidence of DO; however, the role of inflammation was not evaluated in that study [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Verhovsky et al. further discussed this understanding by showing that BOO does not necessarily correlate with increased DO prevalence but does induce bladder hypersensitivity, reinforcing the complexity of bladder responses to obstruction [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment modality also appears to influence DO outcomes. In a long-term observational study, De Nunzio et al found that DO persisted in patients managed conservatively, while significant improvement was noted in those undergoing surgical relief of obstruction [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Despite surgery, DO may persist in select patients, influenced by factors such as age, baseline bladder capacity, and preoperative DO amplitude. Antunes et al. identified these variables as predictors of incomplete symptom resolution after TURP [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, a meta-analysis concluded that the presence of DO prior to surgery did not significantly affect objective postoperative outcomes such as flow rate or residual volume, suggesting a limited predictive role [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Nonetheless, bladder outlet obstruction, primarily due to BPH, remains a major etiological factor in male overactive bladder syndrome [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExperimental data from animal models also substantiate a role for inflammation. Ni et al. demonstrated that experimentally induced prostatitis in rats leads to bladder overactivity and increased afferent signaling, providing physiological evidence for a causative link between prostatic inflammation and DO [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. These findings align with clinical data showing that advanced age and more severe obstruction are independent predictors of DO, with affected individuals presenting with decreased bladder compliance, reduced functional capacity, and diminished voided volumes [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Bellucci et al. described also histological changes, including collagen deposition in the detrusor, contributing to decreased bladder compliance and increased storage symptoms in men with BPH [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecent studies have increasingly emphasized the role of chronic inflammation in the pathogenesis and progression of BPH. While the influence of androgens such as dihydrotestosterone is well established, inflammation is now recognized as a parallel pathogenic pathway and a potential therapeutic target in managing LUTS [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Chronic inflammation is not merely incidental but appears to actively contribute to tissue remodeling and disease progression. Infiltrates composed of T lymphocytes and macrophages release pro-inflammatory cytokines such as interleukin-2 (IL-2) and interferon-gamma (IFN-γ), which stimulate stromal and epithelial proliferation, facilitating nodular growth and prostate enlargement independent of hormonal stimulation [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Data from the REDUCE trial also demonstrated that men with histologically confirmed PI had significantly larger prostate volumes, further strengthening the link between inflammation and glandular enlargement [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, PI was evaluated using the Irani scoring system, which grades both the extent and aggressiveness of inflammatory infiltrates. Though initially developed for the classification of chronic prostatitis, the Irani score has proven useful in assessing inflammation associated with BPH, aiding in the differentiation between histological subtypes and potentially guiding individualized management approaches, including the use of anti-inflammatory or antibiotic therapies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e][\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTaken together, these findings suggest that prostatic inflammation plays a meaningful role in the development and persistence of detrusor overactivity in men with BPH-related BOO, with potential implications for diagnosis, prognosis, and treatment. However, while the correlations observed are compelling and support existing experimental and clinical evidence, they must be interpreted within the context of certain methodological constraints.\u003c/p\u003e \u003cp\u003eSeveral limitations should be acknowledged. As an observational study, causality between PI and DO cannot be definitively established. The histological grading, while informative, remains semi-quantitative and may be influenced by interobserver variability. Although the sample size was sufficient for exploratory analysis, it may not allow broad generalization. Additionally, the absence of extended postoperative follow-up precludes evaluation of long-term changes in DO or symptom progression beyond the three-month postoperative window.\u003c/p\u003e \u003cp\u003eThis study underscores a significant relationship between prostatic inflammation and detrusor overactivity in men with BPH-related bladder outlet obstruction. Prostatic inflammation was more frequent and severe among patients with DO and was associated with persistence of DO following TURP. These findings suggest that PI may play a pivotal role not only in the pathogenesis but also in the persistence of DO, even after surgical relief of obstruction. As such, inflammation should be considered a critical component in the management of BPH and LUTS. Future therapeutic strategies may benefit from incorporating anti-inflammatory interventions alongside standard surgical and pharmacological treatments to optimize clinical outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of Interest:\u003c/h2\u003e \u003cp\u003enone for all the authors contributed\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e \u003cp\u003e This study was approved by the Scientific Council of General Hospital of Larissa, Greece, and all procedures involving human participants were conducted in accordance with the ethical standards of the institutional and national research committees, as well as the 1964 Helsinki Declaration and its later amendments. Written informed consent was obtained from all participants prior to inclusion in the study.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003enone\u003c/p\u003e\u003ch2\u003eAuthor Contributions\u003c/h2\u003e \u003cp\u003eVarelas Evangelos conducted data interpretation, and drafted the manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThe authors would like to thank the staff of the Urodynamics Clinic and the Pathology Laboratory for their technical assistance and support during the study. No external funding or commercial sponsorship was received for this research. All materials used in this study were available through routine clinical care and standard institutional resources.\u003c/p\u003e\u003ch2\u003eAvailability of Data and Materials\u003c/h2\u003e \u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to institutional restrictions and participant confidentiality but are available from the corresponding author on reasonable request. All relevant data supporting the findings of this study are included in the main manuscript or are available upon request for academic and non-commercial purposes.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRoehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol. 2005;7(Suppl 9):S3\u0026ndash;S14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoyne KS, Sexton CC, Thompson CL, et al. 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PMID: 29686417.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"prostate-cancer-and-prostatic-diseases","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"pcan","sideBox":"Learn more about [Prostate Cancer and Prostatic Diseases](http://www.nature.com/pcan/)","snPcode":"41391","submissionUrl":"https://mts-pcan.nature.com/cgi-bin/main.plex","title":"Prostate Cancer and Prostatic Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6881933/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6881933/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBenign prostatic hyperplasia (BPH) frequently leads to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS) in aging men. Detrusor overactivity (DO) is a common functional consequence of BOO, often persisting even after surgical intervention. Prostatic inflammation (PI) has been implicated in BPH pathogenesis, but its relationship with DO remains unclear. This study aimed to evaluate the association between histologically confirmed PI and DO in men undergoing transurethral resection of the prostate (TURP) for BPH-related BOO.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a prospective, observational study involving 125 men aged\u0026thinsp;\u0026ge;\u0026thinsp;50 years with BPH, BOO confirmed by pressure-flow studies, and moderate-to-severe LUTS (IPSS\u0026thinsp;\u0026ge;\u0026thinsp;7). All patients had received standard medical therapy and were candidates for TURP. Urodynamic testing was performed before and three months after surgery. Based on baseline urodynamic findings, patients were categorized into two groups: those with DO (Group A) and those without (Group B). Resected prostate tissue was examined histologically, and PI was graded using the Irani score. Statistical analysis was performed using SPSS v26, with odds ratios (OR) and 95% confidence intervals (CI) reported.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eProstatic inflammation was identified in 78.4% of patients overall and was significantly more prevalent in those with DO (84.9% vs. 69.2%; OR\u0026thinsp;=\u0026thinsp;2.47, 95% CI: 1.11\u0026ndash;5.49, p\u0026thinsp;=\u0026thinsp;0.02). Inflammation was also more severe in Group A. DO resolved postoperatively in 75.3% of patients, while persistent DO was associated exclusively with moderate-to-severe PI. The odds of persistent DO following TURP were significantly higher in this subgroup (OR\u0026thinsp;=\u0026thinsp;4.00, 95% CI: 1.33\u0026ndash;12.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eProstatic inflammation is more frequent and severe in men with DO and is associated with its persistence after TURP. These findings suggest that PI contributes to both the pathogenesis and postoperative course of DO, supporting its role as a therapeutic target in BPH-related LUTS management.\u003c/p\u003e","manuscriptTitle":"Association between Prostatic Inflammation and Detrusor Overactivity in men with Benign Prostatic Hyperplasia and Bladder Outlet Obstruction: A prospective urodynamic and histological study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-18 06:59:23","doi":"10.21203/rs.3.rs-6881933/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-07-17T14:30:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-07-11T08:28:40+00:00","index":3,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-07-01T19:39:21+00:00","index":3,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-29T17:35:26+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-06-29T16:40:38+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-06-26T13:49:43+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-06-26T13:35:02+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-06-26T10:37:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-26T10:27:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-25T15:46:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Prostate Cancer and Prostatic Diseases","date":"2025-06-23T18:23:32+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2025-06-16T16:33:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"prostate-cancer-and-prostatic-diseases","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"pcan","sideBox":"Learn more about [Prostate Cancer and Prostatic Diseases](http://www.nature.com/pcan/)","snPcode":"41391","submissionUrl":"https://mts-pcan.nature.com/cgi-bin/main.plex","title":"Prostate Cancer and Prostatic Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"24d96924-83cc-4680-aecf-c3e799089bf5","owner":[],"postedDate":"June 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":50143592,"name":"Health sciences/Diseases/Urogenital diseases/Prostatic diseases"},{"id":50143593,"name":"Health sciences/Medical research/Outcomes research"}],"tags":[],"updatedAt":"2025-10-29T09:50:34+00:00","versionOfRecord":{"articleIdentity":"rs-6881933","link":"https://doi.org/10.1038/s41391-025-01039-7","journal":{"identity":"prostate-cancer-and-prostatic-diseases","isVorOnly":false,"title":"Prostate Cancer and Prostatic Diseases"},"publishedOn":"2025-10-29 04:00:00","publishedOnDateReadable":"October 29th, 2025"},"versionCreatedAt":"2025-06-18 06:59:23","video":"","vorDoi":"10.1038/s41391-025-01039-7","vorDoiUrl":"https://doi.org/10.1038/s41391-025-01039-7","workflowStages":[]},"version":"v1","identity":"rs-6881933","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6881933","identity":"rs-6881933","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}