Impact of Prostate Radiotherapy on Urinary Bacterial Profiles and the Emergence of Multidrug-Resistant Organisms: A Prospective Study

preprint OA: closed
Full text JSON View at publisher
AI-generated deep summary by claude@2026-07, 2026-07-06 · read from full text

This prospective observational study evaluated 120 men with localized prostate cancer receiving 3D conformal radiotherapy (with or without androgen deprivation therapy) by performing urine cultures and antibiograms before treatment, weekly during treatment, and at 1, 3, and 6 months after. Urinary infection incidence was 24% before radiotherapy, 18% during treatment, and rose to 40% after treatment, with Escherichia coli and Enterococcus faecalis as common pre-treatment pathogens. Multidrug-resistant bacteria increased from 10% before treatment to 28% after radiotherapy, and multivariate analysis reported radiotherapy as the only independent factor associated with emergence of resistant strains (OR 3.6, 95% CI 1.8–7.2, p = 0.001). The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via keyword match in the upstream search index.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Abstract Background Radiotherapy represents a major therapeutic modality for localized prostate cancer. Despite technological advances, pelvic irradiation remains associated with urinary complications including radiation cystitis and urinary tract infections (UTIs). Emerging evidence suggests that radiation may alter urinary microbiota and promote antibiotic resistance. Objective To evaluate the impact of prostate radiotherapy on urinary bacteriological profiles and the emergence of multidrug-resistant bacteria. Methods This prospective study included 120 patients treated for prostate cancer between March 2024 and February 2026 at the Radiation Oncology Department of Hassan II University Hospital, Fez. All patients received 3D conformal radiotherapy with or without androgen deprivation therapy. Urine cultures and antibiograms were performed before radiotherapy, weekly during treatment, and during follow-up at 1, 3 and 6 months. Infection rates and antibiotic resistance profiles were analyzed. Results Urinary infection incidence was 24% before radiotherapy, 18% during treatment, and increased to 40% after treatment. Escherichia coli (48%) and Enterococcus faecalis (32%) were the most common pathogens before radiotherapy. Multidrug-resistant bacteria increased from 10% before treatment to 28% after radiotherapy. Multivariate analysis identified radiotherapy as the only independent factor significantly associated with the emergence of resistant strains (p < 0.01). Conclusion Prostate radiotherapy significantly modifies the urinary bacteriological ecosystem and promotes the emergence of multidrug-resistant organisms. Systematic microbiological monitoring is recommended during and after radiotherapy.
Full text 64,493 characters · extracted from preprint-html · click to expand
Impact of Prostate Radiotherapy on Urinary Bacterial Profiles and the Emergence of Multidrug-Resistant Organisms: A Prospective 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 Research Article Impact of Prostate Radiotherapy on Urinary Bacterial Profiles and the Emergence of Multidrug-Resistant Organisms: A Prospective Study Hassan Yamine, S. Khalfi, W. Hassani, K. Soussy, F. Farhane, Z. Alami, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9035707/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 12 You are reading this latest preprint version Abstract Background Radiotherapy represents a major therapeutic modality for localized prostate cancer. Despite technological advances, pelvic irradiation remains associated with urinary complications including radiation cystitis and urinary tract infections (UTIs). Emerging evidence suggests that radiation may alter urinary microbiota and promote antibiotic resistance. Objective To evaluate the impact of prostate radiotherapy on urinary bacteriological profiles and the emergence of multidrug-resistant bacteria. Methods This prospective study included 120 patients treated for prostate cancer between March 2024 and February 2026 at the Radiation Oncology Department of Hassan II University Hospital, Fez. All patients received 3D conformal radiotherapy with or without androgen deprivation therapy. Urine cultures and antibiograms were performed before radiotherapy, weekly during treatment, and during follow-up at 1, 3 and 6 months. Infection rates and antibiotic resistance profiles were analyzed. Results Urinary infection incidence was 24% before radiotherapy, 18% during treatment, and increased to 40% after treatment. Escherichia coli (48%) and Enterococcus faecalis (32%) were the most common pathogens before radiotherapy. Multidrug-resistant bacteria increased from 10% before treatment to 28% after radiotherapy. Multivariate analysis identified radiotherapy as the only independent factor significantly associated with the emergence of resistant strains (p < 0.01). Conclusion Prostate radiotherapy significantly modifies the urinary bacteriological ecosystem and promotes the emergence of multidrug-resistant organisms. Systematic microbiological monitoring is recommended during and after radiotherapy. Prostate cancer Radiotherapy Urinary tract infection Multidrug-resistant bacteria Urinary microbiome Radiation cystitis Figures Figure 1 Figure 2 Figure 3 Introduction Prostate cancer is the most common malignancy among men in many regions of the world and represents a major public health concern. Radiotherapy plays a central role in the management of localized and locally advanced prostate cancer, either as a primary treatment or in combination with androgen deprivation therapy. Advances in radiation techniques such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) have significantly improved tumor control while reducing treatment toxicity. Despite these improvements, pelvic irradiation remains associated with genitourinary toxicity. Among these complications, radiation cystitis and urinary tract infections are frequently observed and may significantly affect patient quality of life. The pathophysiology of radiation-induced cystitis remains incompletely understood. Access to irradiated bladder tissue is limited, which restricts histopathological studies. However, recent research suggests that alterations in the urinary microbiome may play a role in post-radiotherapy urinary complications. Ionizing radiation can disrupt microbial ecosystems, modify host immune responses, and induce genetic mutations in bacterial populations. These mechanisms may promote the emergence of multidrug-resistant organisms and increase susceptibility to urinary infections. The objective of this prospective study was to evaluate the impact of prostate radiotherapy on urinary bacteriological profiles and the development of multidrug-resistant bacteria in patients treated for prostate cancer. Materials and Methods Study Design This prospective observational study was conducted at the Department of Radiation Oncology of Hassan II University Hospital, Fez. Study Population A total of 120 patients with localized prostate cancer treated between March 2024 and February 2026 were included. Inclusion criteria histologically confirmed prostate cancer indication for curative radiotherapy availability of urine cultures before and after treatment Exclusion criteria active systemic infection at baseline incomplete microbiological data Treatment Protocol Treatment Protocol All patients received 3D conformal radiotherapy (3D-CRT) according to institutional protocols. Radiotherapy was delivered using linear accelerators with standard fractionation schedules. Androgen deprivation therapy was administered when indicated according to risk stratification. Microbiological Evaluation Urine samples were collected using midstream urine collection . The following tests were performed: urine culture (ECBU) bacterial identification antibiogram sensitivity testing Clinical Data Collection Clinical data included: age diabetes mellitus history of recurrent urinary infections urethral catheterization immunosuppression prior antibiotic exposure Patients were monitored weekly during treatment using the International Prostate Symptom Score (IPSS) . Follow-up visits occurred at: 1 month 3 months 6 months after radiotherapy Results Urinary infection incidence was 24% before radiotherapy, 18% during treatment, and increased to 40% after treatment. Escherichia coli (48%) and Enterococcus faecalis (32%) were the most common pathogens before radiotherapy. Multidrug-resistant bacteria increased from 10% before treatment to 28% after radiotherapy. Multivariate analysis identified radiotherapy as the only independent factor significantly associated with the emergence of resistant strains (p < 0.01). Patient Characteristics A total of 120 patients with localized prostate cancer were included in this prospective study. The mean age of the patients was 68.5 years (range 55–82 years). Baseline clinical characteristics are summarized in Table 1. These baseline characteristics indicate that a significant proportion of patients presented risk factors potentially associated with urinary infections, particularly diabetes mellitus and prior urinary tract infections. Incidence of Urinary Tract Infections During Radiotherapy The incidence of urinary tract infections (UTIs) varied throughout the treatment course. Before the initiation of radiotherapy, 24% of patients presented positive urine cultures. During radiotherapy, the infection rate slightly decreased to 18%, while a significant increase was observed after treatment completion, reaching 40%. These findings indicate a delayed increase in infection incidence following radiotherapy, suggesting a potential relationship between radiation-induced bladder changes and urinary infections. Bacterial Spectrum The bacterial profile identified in urine cultures before radiotherapy revealed a predominance of Gram-negative organisms. These findings are consistent with previously reported epidemiological patterns of urinary infections in prostate cancer patients. Emergence of Multidrug-Resistant Organisms A major finding of this study was the significant increase in multidrug-resistant bacteria following radiotherapy. Before treatment, only 10% of infections were caused by multidrug-resistant organisms (MDR). After radiotherapy, this proportion increased significantly to 28%. This represents a nearly threefold increase in multidrug-resistant bacterial strains following radiotherapy. Risk Factor Analysis Potential risk factors associated with urinary infection were analyzed, including: diabetes mellitus urethral catheterization recurrent urinary infections immunosuppression prior antibiotic exposure In univariate analysis, diabetes and catheterization showed a trend toward association with urinary infection. However, multivariate logistic regression analysis demonstrated that radiotherapy exposure remained the only independent statistically significant factor associated with the emergence of multidrug-resistant organisms (OR = 3.6, 95% CI 1.8–7.2, p = 0.001) (Table 3, Figure 3). These results suggest that radiotherapy plays a central role in modifying the urinary microbial ecosystem and promoting the development of antibiotic resistance. Table 3 – Risk factor analysis Factor Univariate p Multivariate p OR CI95 Diabetes 0.08 0.18 1.3 0.7–2.5 Catheterization 0.06 0.12 1.4 0.8–2.9 Age 0.12 0.25 1.02 0.98–1.06 Radiotherapy 0.004 0.001 3.6 1.8–7.2 Discussion This prospective study demonstrates that prostate radiotherapy is associated with significant alterations in the urinary bacteriological profile, with a particularly high cumulative incidence of urinary tract infections observed in our cohort and a marked increase in infections during the post-treatment period. Interestingly, although the incidence of infection remained relatively modest during radiotherapy itself, it increased substantially after treatment completion, suggesting that radiation-associated urinary infections may not be exclusively related to acute inflammatory processes but rather to progressive radiobiological changes affecting the bladder environment. Radiation-induced urothelial injury typically evolves through several pathological stages including acute epithelial inflammation, microvascular damage, submucosal fibrosis, and progressive impairment of mucosal barrier integrity [2,11]. These structural and functional alterations may create a favorable environment for bacterial colonization and persistence within the urinary tract, particularly during the early post-irradiation phase. In our study, the microbiological profile was characterized by a predominance of Gram-negative bacilli, accounting for the majority of isolated pathogens, which is consistent with the classical epidemiology of urinary tract infections [15]. However, exposure to ionizing radiation may also influence bacterial virulence and resistance patterns. Experimental studies have demonstrated that gamma radiation can induce modifications in bacterial gene expression, promote enhanced resistance phenotypes, and increase the capacity of microorganisms to form biofilms [5]. In addition, radiation-induced oxidative stress generates reactive oxygen species that can damage microbial DNA and trigger stress-response mechanisms that facilitate bacterial adaptation and survival under hostile environmental conditions. These mechanisms may contribute to the emergence of multidrug-resistant strains, as observed in our cohort, where the proportion of resistant bacteria increased significantly after radiotherapy. Moreover, radiation exposure may facilitate horizontal gene transfer between bacterial species, accelerating the dissemination of resistance determinants such as blaTEM , blaCTX-M , and blaSHV genes, which encode extended-spectrum β-lactamases [13,14]. This phenomenon has been described by El-Zawahry et al., who demonstrated that radiation exposure may induce genetic mutations and promote the expression of beta-lactamase enzymes, thereby increasing bacterial resistance to β-lactam antibiotics [5]. Beyond its direct microbiological effects, pelvic irradiation may also disrupt the urinary microbiome, a complex microbial ecosystem that plays a crucial role in maintaining urological health. Emerging evidence suggests that the urinary tract is not sterile but hosts a dynamic microbial community whose balance contributes to mucosal defense mechanisms [15]. According to Maślak et al., patients undergoing prostate radiotherapy exhibit a reduction in urinary microbial diversity, a condition that may predispose to dysbiosis and opportunistic infections [4]. Pelvic irradiation may disrupt this microbial equilibrium through multiple mechanisms including direct microbial DNA damage, alterations in urinary metabolites, modifications in local pH and oxygen tension, and changes in immune responses. Recent metabolomic studies have demonstrated persistent alterations in urinary and plasma metabolic profiles following pelvic irradiation, which may impair host–microbial homeostasis and contribute to long-term urinary complications [3]. In addition to microbiological and metabolic factors, immune modulation may also play an important role in the development of post-radiotherapy infections. Radiotherapy is known to induce both local and systemic immune alterations, including radiation-induced lymphopenia, decreased mucosal immune surveillance, and modifications in cytokine signaling pathways [6]. Lymphocyte depletion may impair bacterial clearance mechanisms and increase susceptibility to infection, particularly in elderly patients who already exhibit reduced immune reserve. Although traditional risk factors such as diabetes mellitus, smoking, catheterization, or previous urinary tract infections are well-known contributors to infection risk, our analysis did not demonstrate a statistically significant association between these comorbidities and infection incidence in our cohort, suggesting that radiation exposure itself may represent the dominant determinant of urinary microbiological changes in this specific clinical setting. From a clinical perspective, the high incidence of urinary tract infections observed after radiotherapy has several important implications. Pre-treatment screening for urinary infections should be systematically performed, as the identification and adequate treatment of pre-existing infections may reduce the risk of post-treatment recurrence. Furthermore, systematic microbiological surveillance during the early post-radiotherapy period, particularly within the first three months after treatment completion, may facilitate early detection and management of infections. Another important clinical challenge is the differentiation between radiation cystitis and infectious cystitis, as both conditions share overlapping symptoms such as dysuria, urgency, frequency, and hematuria [2,11]. In addition, recurrent infections following radiotherapy may contribute to increased antimicrobial exposure, potentially promoting further emergence of antibiotic-resistant strains, thereby emphasizing the importance of appropriate antibiotic stewardship strategies [13,14]. Our findings are consistent with several reports in the literature describing microbiome alterations following pelvic radiotherapy, increased susceptibility to infections related to radiation-induced lymphopenia, and persistent metabolic perturbations affecting host–microbial interactions after irradiation [3,6]. Nevertheless, few prospective studies have specifically investigated serial urine cultures in patients undergoing prostate radiotherapy, highlighting the relevance and originality of our work. Despite these findings, several limitations should be acknowledged. This study was conducted at a single institution and included a relatively moderate sample size, which may limit the generalizability of the results. In addition, molecular characterization of the urinary microbiome using high-throughput sequencing techniques was not performed, and the follow-up period remained relatively limited. Future research should therefore integrate advanced microbiome analyses such as 16S rRNA sequencing or metagenomic profiling , longer follow-up periods exceeding twelve months, and correlations between microbiological findings and radiation dose–volume parameters. The integration of microbiome science into radiation oncology represents an emerging and promising research field that may improve our understanding of radiation-induced toxicity and identify potential preventive or therapeutic strategies. Potential future directions include the identification of predictive microbial signatures associated with radiation cystitis, the evaluation of probiotic or microbiome-modulating interventions, and comparative analyses of different radiotherapy techniques such as IMRT, VMAT, or stereotactic radiotherapy in relation to urinary microbiota alterations [7–10]. Overall, the results of this prospective study suggest that prostate radiotherapy is associated with dynamic and clinically relevant modifications of urinary bacteriological profiles, particularly during the early post-treatment period, and support the hypothesis that radiation-induced dysbiosis may contribute to post-irradiation bladder morbidity. Conclusion Prostate radiotherapy is associated with significant alterations in urinary bacteriological profiles and a notable increase in multidrug-resistant organisms. These findings suggest that radiation-induced changes in the bladder microenvironment may contribute to post-treatment urinary infections. Systematic microbiological monitoring during and after radiotherapy may facilitate early detection and appropriate management of urinary infections in patients with prostate cancer. Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Hassan II University Hospital, Fez, Morocco. Consent for publication Written informed consent was obtained from all participants for publication of the study data. Funding This research received no external funding. Author Contribution HY designed the study, collected the clinical data and wrote the manuscript. SK, KS and WH contributed to data collection and microbiological analysis. FF and ZA performed the statistical analysis and interpretation of the results. TB supervised the research project and critically revised the manuscript. All authors read and approved the final manuscript. Data Availability The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request. References Dearnaley DP et al. Radiotherapy for prostate cancer. Lancet Oncology. Delobel JB et al. Radiation-induced cystitis. Urology. Reis Ferreira M et al. Impact of pelvic radiation therapy on metabolic profiles and microbiota. Cancer Research. Maślak E et al. Microbiome identification in prostate cancer patients undergoing radiotherapy. El-Zawahry YA et al. ESBL production after gamma radiation exposure. Mohamad O et al. Genitourinary toxicity after prostate radiotherapy. Radiotherapy and Oncology. Michalski JM et al. Toxicity after IMRT for prostate cancer. Journal of Clinical Oncology. Zelefsky MJ et al. Long-term toxicity of IMRT for prostate cancer. Int J Radiat Oncol Biol Phys. De Meerleer G et al. Radiotherapy toxicity in prostate cancer. Lancet Oncology. Fonteyne V et al. Urinary complications after prostate radiotherapy. Hamstra DA et al. Radiation cystitis: pathophysiology and treatment. Muls AC et al. Urinary complications following pelvic radiation therapy. Falagas ME et al. Multidrug-resistant Gram-negative bacteria infections. Ventola CL. Antibiotic resistance crisis. Pharmacy and Therapeutics. Flores-Mireles AL et al. Urinary tract infections: epidemiology and mechanisms. Nature Reviews Microbiology. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 29 Mar, 2026 Reviews received at journal 28 Mar, 2026 Reviews received at journal 25 Mar, 2026 Reviews received at journal 24 Mar, 2026 Reviewers agreed at journal 20 Mar, 2026 Reviewers agreed at journal 20 Mar, 2026 Reviewers agreed at journal 20 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers invited by journal 18 Mar, 2026 Editor assigned by journal 15 Mar, 2026 Submission checks completed at journal 15 Mar, 2026 First submitted to journal 04 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9035707","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":608574432,"identity":"482372c9-4a08-4b0f-b256-8dbb2cdeec2d","order_by":0,"name":"Hassan Yamine","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYDCCAwxsCM4HIGZjJ0UL4wyQFmZStDDzgEkCOvhuH2B78ONPnby5RPLTzTa/tsnzMTMwfviYg1uL5LkEdsPetsOGO2ekmd3O7btt2MbMwCw5cxtuLQZnGNgkeBsOMG64kQDU0nObEaiFjZmXgBbJP3/q7DfcSP9227Lntj1RWqR52JgTN9zIMbvN8ON2IkEtkmcY26Rl2w4nbzjzpuxmb8Pt5DZmxma8fuE7w3xM8s2fOtsNx9O33fjx57bt/Pbmgx8+4tECjL8GCC2QAGS3IYsQBPwHgMQfIhWPglEwCkbBiAIAIMNU9EX2WhsAAAAASUVORK5CYII=","orcid":"","institution":"Centre Hospitalier Universitaire Hassan II","correspondingAuthor":true,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Yamine","suffix":""},{"id":608574435,"identity":"28a7bf97-8f46-4bc8-999d-07ecd09dd4f9","order_by":1,"name":"S. Khalfi","email":"","orcid":"","institution":"Centre Hospitalier Universitaire Hassan II","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Khalfi","suffix":""},{"id":608574436,"identity":"d7873b63-1816-4070-8e48-3ed9da222c3a","order_by":2,"name":"W. Hassani","email":"","orcid":"","institution":"Centre Hospitalier Universitaire Hassan II","correspondingAuthor":false,"prefix":"","firstName":"W.","middleName":"","lastName":"Hassani","suffix":""},{"id":608574438,"identity":"03af7586-ed39-464b-a074-2dfaabc78e84","order_by":3,"name":"K. Soussy","email":"","orcid":"","institution":"Centre Hospitalier Universitaire Hassan II","correspondingAuthor":false,"prefix":"","firstName":"K.","middleName":"","lastName":"Soussy","suffix":""},{"id":608574439,"identity":"f818024d-fbb7-446d-be12-f541cd2ea3f8","order_by":4,"name":"F. Farhane","email":"","orcid":"","institution":"Centre Hospitalier Universitaire Hassan II","correspondingAuthor":false,"prefix":"","firstName":"F.","middleName":"","lastName":"Farhane","suffix":""},{"id":608574442,"identity":"2c24c794-82ef-48cf-a99e-13c69da03aab","order_by":5,"name":"Z. Alami","email":"","orcid":"","institution":"Centre Hospitalier Universitaire Hassan II","correspondingAuthor":false,"prefix":"","firstName":"Z.","middleName":"","lastName":"Alami","suffix":""},{"id":608574444,"identity":"4d43ac82-cad5-4a42-b6f6-07065021853a","order_by":6,"name":"T. Bouhafa","email":"","orcid":"","institution":"Centre Hospitalier Universitaire Hassan II","correspondingAuthor":false,"prefix":"","firstName":"T.","middleName":"","lastName":"Bouhafa","suffix":""}],"badges":[],"createdAt":"2026-03-05 04:24:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9035707/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9035707/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105149799,"identity":"f4b6e542-bdf8-4f8f-a68d-d2e2415fc114","added_by":"auto","created_at":"2026-03-22 14:58:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":54489,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIncidence of urinary tract infections during treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe figure illustrates the increase in infection rates after radiotherapy, highlighting the post-treatment vulnerability period.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9035707/v1/ddadeef026af7f63595d298b.png"},{"id":105149797,"identity":"441b7fa5-c843-4b4b-b8a9-d80cbf1ae50f","added_by":"auto","created_at":"2026-03-22 14:58:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":36072,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEvolution of multidrug-resistant bacteria before, during and after prostate radiotherapy\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9035707/v1/cc94c9ea507056355a973ce4.png"},{"id":105149798,"identity":"621b2359-6f3a-4f3b-acc9-7df67bed03df","added_by":"auto","created_at":"2026-03-22 14:58:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":27505,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plot showing multivariate logistic regression analysis of risk factors associated with multidrug-resistant bacterial emergence\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9035707/v1/f2d006883b222c0a99a8f42e.png"},{"id":105149813,"identity":"7259f3f5-0371-4ec7-8681-2439d68da723","added_by":"auto","created_at":"2026-03-22 14:58:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":973294,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9035707/v1/ed009035-685d-4a1e-89a7-865c80419cdc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Prostate Radiotherapy on Urinary Bacterial Profiles and the Emergence of Multidrug-Resistant Organisms: A Prospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProstate cancer is the most common malignancy among men in many regions of the world and represents a major public health concern. Radiotherapy plays a central role in the management of localized and locally advanced prostate cancer, either as a primary treatment or in combination with androgen deprivation therapy. Advances in radiation techniques such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) have significantly improved tumor control while reducing treatment toxicity.\u003c/p\u003e \u003cp\u003eDespite these improvements, pelvic irradiation remains associated with genitourinary toxicity. Among these complications, radiation cystitis and urinary tract infections are frequently observed and may significantly affect patient quality of life.\u003c/p\u003e \u003cp\u003eThe pathophysiology of radiation-induced cystitis remains incompletely understood. Access to irradiated bladder tissue is limited, which restricts histopathological studies. However, recent research suggests that alterations in the urinary microbiome may play a role in post-radiotherapy urinary complications.\u003c/p\u003e \u003cp\u003eIonizing radiation can disrupt microbial ecosystems, modify host immune responses, and induce genetic mutations in bacterial populations. These mechanisms may promote the emergence of multidrug-resistant organisms and increase susceptibility to urinary infections.\u003c/p\u003e \u003cp\u003eThe objective of this prospective study was to evaluate the impact of prostate radiotherapy on urinary bacteriological profiles and the development of multidrug-resistant bacteria in patients treated for prostate cancer.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis prospective observational study was conducted at the Department of Radiation Oncology of Hassan II University Hospital, Fez.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population\u003c/h3\u003e\n\u003cp\u003eA total of \u003cb\u003e120 patients\u003c/b\u003e with localized prostate cancer treated between \u003cb\u003eMarch 2024 and February 2026\u003c/b\u003e were included.\u003c/p\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ehistologically confirmed prostate cancer\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eindication for curative radiotherapy\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eavailability of urine cultures before and after treatment\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eactive systemic infection at baseline\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eincomplete microbiological data\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e\n\u003ch3\u003eTreatment Protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eTreatment Protocol\u003c/div\u003e \u003cp\u003eAll patients received \u003cb\u003e3D conformal radiotherapy (3D-CRT)\u003c/b\u003e according to institutional protocols.\u003c/p\u003e \u003cp\u003eRadiotherapy was delivered using linear accelerators with standard fractionation schedules. Androgen deprivation therapy was administered when indicated according to risk stratification.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMicrobiological Evaluation\u003c/h2\u003e \u003cp\u003eUrine samples were collected using \u003cb\u003emidstream urine collection\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eThe following tests were performed:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eurine culture (ECBU)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ebacterial identification\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eantibiogram sensitivity testing\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinical Data Collection\u003c/h3\u003e\n\u003cp\u003eClinical data included:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eage\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ediabetes mellitus\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003ehistory of recurrent urinary infections\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eurethral catheterization\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eimmunosuppression\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eprior antibiotic exposure\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003ePatients were monitored weekly during treatment using the \u003cb\u003eInternational Prostate Symptom Score (IPSS)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003eFollow-up visits occurred at:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e1 month\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e6 months after radiotherapy\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eUrinary infection incidence was 24% before radiotherapy, 18% during treatment, and increased to 40% after treatment. Escherichia coli (48%) and Enterococcus faecalis (32%) were the most common pathogens before radiotherapy. Multidrug-resistant bacteria increased from 10% before treatment to 28% after radiotherapy. Multivariate analysis identified radiotherapy as the only independent factor significantly associated with the emergence of resistant strains (p \u0026lt; 0.01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 120 patients with localized prostate cancer were included in this prospective study. The mean age of the patients was 68.5 years (range 55\u0026ndash;82 years). Baseline clinical characteristics are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/127393_c7e80a1c9bb65875/127393_custom_files/img1774019641.png\" style=\"width: 491px;\"\u003e\u003c/p\u003e\n\u003cp\u003eThese baseline characteristics indicate that a significant proportion of patients presented risk factors potentially associated with urinary infections, particularly diabetes mellitus and prior urinary tract infections.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIncidence of Urinary Tract Infections During Radiotherapy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe incidence of urinary tract infections (UTIs) varied throughout the treatment course.\u003c/p\u003e\n\u003cp\u003eBefore the initiation of radiotherapy, 24% of patients presented positive urine cultures. During radiotherapy, the infection rate slightly decreased to 18%, while a significant increase was observed after treatment completion, reaching 40%.\u003c/p\u003e\n\u003cp\u003eThese findings indicate a delayed increase in infection incidence following radiotherapy, suggesting a potential relationship between radiation-induced bladder changes and urinary infections.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBacterial Spectrum\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe bacterial profile identified in urine cultures before radiotherapy revealed a predominance of Gram-negative organisms.\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/127393_c7e80a1c9bb65875/127393_custom_files/img1774019714.png\" style=\"width: 483px;\"\u003e\u003c/p\u003e\n\u003cp\u003eThese findings are consistent with previously reported epidemiological patterns of urinary infections in prostate cancer patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEmergence of Multidrug-Resistant Organisms\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA major finding of this study was the significant increase in multidrug-resistant bacteria following radiotherapy.\u003c/p\u003e\n\u003cp\u003eBefore treatment, only 10% of infections were caused by multidrug-resistant organisms (MDR). After radiotherapy, this proportion increased significantly to 28%.\u003c/p\u003e\n\u003cp\u003eThis represents a nearly threefold increase in multidrug-resistant bacterial strains following radiotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk Factor Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePotential risk factors associated with urinary infection were analyzed, including:\u003c/p\u003e\n\u003cp\u003ediabetes mellitus\u003c/p\u003e\n\u003cp\u003eurethral catheterization\u003c/p\u003e\n\u003cp\u003erecurrent urinary infections\u003c/p\u003e\n\u003cp\u003eimmunosuppression\u003c/p\u003e\n\u003cp\u003eprior antibiotic exposure\u003c/p\u003e\n\u003cp\u003eIn univariate analysis, diabetes and catheterization showed a trend toward association with urinary infection. However, multivariate logistic regression analysis demonstrated that radiotherapy exposure remained the only independent statistically significant factor associated with the emergence of multidrug-resistant organisms (OR = 3.6, 95% CI 1.8\u0026ndash;7.2, p = 0.001) (Table 3, Figure 3).\u003c/p\u003e\n\u003cp\u003eThese results suggest that radiotherapy plays a central role in modifying the urinary microbial ecosystem and promoting the development of antibiotic resistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 \u0026ndash; Risk factor analysis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"403\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate p\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate p\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCI95\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003e0.7\u0026ndash;2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003eCatheterization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003e0.8\u0026ndash;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e1.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003e0.98\u0026ndash;1.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRadiotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.8\u0026ndash;7.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eThis prospective study demonstrates that prostate radiotherapy is associated with significant alterations in the urinary bacteriological profile, with a particularly high cumulative incidence of urinary tract infections observed in our cohort and a marked increase in infections during the post-treatment period. Interestingly, although the incidence of infection remained relatively modest during radiotherapy itself, it increased substantially after treatment completion, suggesting that radiation-associated urinary infections may not be exclusively related to acute inflammatory processes but rather to progressive radiobiological changes affecting the bladder environment. Radiation-induced urothelial injury typically evolves through several pathological stages including acute epithelial inflammation, microvascular damage, submucosal fibrosis, and progressive impairment of mucosal barrier integrity [2,11].\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eThese structural and functional alterations may create a favorable environment for bacterial colonization and persistence within the urinary tract, particularly during the early post-irradiation phase. In our study, the microbiological profile was characterized by a predominance of Gram-negative bacilli, accounting for the majority of isolated pathogens, which is consistent with the classical epidemiology of urinary tract infections [15]. However, exposure to ionizing radiation may also influence bacterial virulence and resistance patterns. Experimental studies have demonstrated that gamma radiation can induce modifications in bacterial gene expression, promote enhanced resistance phenotypes, and increase the capacity of microorganisms to form biofilms [5].\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eIn addition, radiation-induced oxidative stress generates reactive oxygen species that can damage microbial DNA and trigger stress-response mechanisms that facilitate bacterial adaptation and survival under hostile environmental conditions. These mechanisms may contribute to the emergence of multidrug-resistant strains, as observed in our cohort, where the proportion of resistant bacteria increased significantly after radiotherapy. Moreover, radiation exposure may facilitate horizontal gene transfer between bacterial species, accelerating the dissemination of resistance determinants such as\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eblaTEM\u003c/span\u003e, \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eblaCTX-M\u003c/span\u003e, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eblaSHV\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003egenes, which encode extended-spectrum β-lactamases [13,14]. This phenomenon has been described by El-Zawahry et al., who demonstrated that radiation exposure may induce genetic mutations and promote the expression of beta-lactamase enzymes, thereby increasing bacterial resistance to β-lactam antibiotics [5].\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eBeyond its direct microbiological effects, pelvic irradiation may also disrupt the urinary microbiome, a complex microbial ecosystem that plays a crucial role in maintaining urological health. Emerging evidence suggests that the urinary tract is not sterile but hosts a dynamic microbial community whose balance contributes to mucosal defense mechanisms [15]. According to Maślak et al., patients undergoing prostate radiotherapy exhibit a reduction in urinary microbial diversity, a condition that may predispose to dysbiosis and opportunistic infections [4].\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePelvic irradiation may disrupt this microbial equilibrium through multiple mechanisms including direct microbial DNA damage, alterations in urinary metabolites, modifications in local pH and oxygen tension, and changes in immune responses. Recent metabolomic studies have demonstrated persistent alterations in urinary and plasma metabolic profiles following pelvic irradiation, which may impair host\u0026ndash;microbial homeostasis and contribute to long-term urinary complications [3].\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eIn addition to microbiological and metabolic factors, immune modulation may also play an important role in the development of post-radiotherapy infections. Radiotherapy is known to induce both local and systemic immune alterations, including radiation-induced lymphopenia, decreased mucosal immune surveillance, and modifications in cytokine signaling pathways [6]. Lymphocyte depletion may impair bacterial clearance mechanisms and increase susceptibility to infection, particularly in elderly patients who already exhibit reduced immune reserve.\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eAlthough traditional risk factors such as diabetes mellitus, smoking, catheterization, or previous urinary tract infections are well-known contributors to infection risk, our analysis did not demonstrate a statistically significant association between these comorbidities and infection incidence in our cohort, suggesting that radiation exposure itself may represent the dominant determinant of urinary microbiological changes in this specific clinical setting.\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eFrom a clinical perspective, the high incidence of urinary tract infections observed after radiotherapy has several important implications. Pre-treatment screening for urinary infections should be systematically performed, as the identification and adequate treatment of pre-existing infections may reduce the risk of post-treatment recurrence. Furthermore, systematic microbiological surveillance during the early post-radiotherapy period, particularly within the first three months after treatment completion, may facilitate early detection and management of infections.\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eAnother important clinical challenge is the differentiation between radiation cystitis and infectious cystitis, as both conditions share overlapping symptoms such as dysuria, urgency, frequency, and hematuria [2,11]. In addition, recurrent infections following radiotherapy may contribute to increased antimicrobial exposure, potentially promoting further emergence of antibiotic-resistant strains, thereby emphasizing the importance of appropriate antibiotic stewardship strategies [13,14].\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eOur findings are consistent with several reports in the literature describing microbiome alterations following pelvic radiotherapy, increased susceptibility to infections related to radiation-induced lymphopenia, and persistent metabolic perturbations affecting host\u0026ndash;microbial interactions after irradiation [3,6]. Nevertheless, few prospective studies have specifically investigated serial urine cultures in patients undergoing prostate radiotherapy, highlighting the relevance and originality of our work.\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eDespite these findings, several limitations should be acknowledged. This study was conducted at a single institution and included a relatively moderate sample size, which may limit the generalizability of the results. In addition, molecular characterization of the urinary microbiome using high-throughput sequencing techniques was not performed, and the follow-up period remained relatively limited.\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eFuture research should therefore integrate advanced microbiome analyses such as\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003e16S rRNA sequencing or metagenomic profiling\u003c/span\u003e, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003elonger follow-up periods exceeding twelve months, and correlations between microbiological findings and radiation dose\u0026ndash;volume parameters. The integration of microbiome science into radiation oncology represents an emerging and promising research field that may improve our understanding of radiation-induced toxicity and identify potential preventive or therapeutic strategies.\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePotential future directions include the identification of predictive microbial signatures associated with radiation cystitis, the evaluation of probiotic or microbiome-modulating interventions, and comparative analyses of different radiotherapy techniques such as IMRT, VMAT, or stereotactic radiotherapy in relation to urinary microbiota alterations [7\u0026ndash;10].\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eOverall, the results of this prospective study suggest that prostate radiotherapy is associated with dynamic and clinically relevant modifications of urinary bacteriological profiles, particularly during the early post-treatment period, and support the hypothesis that radiation-induced dysbiosis may contribute to post-irradiation bladder morbidity.\u003c/span\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eProstate radiotherapy is associated with significant alterations in urinary bacteriological profiles and a notable increase in multidrug-resistant organisms. These findings suggest that radiation-induced changes in the bladder microenvironment may contribute to post-treatment urinary infections. Systematic microbiological monitoring during and after radiotherapy may facilitate early detection and appropriate management of urinary infections in patients with prostate cancer.\u003c/span\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Hassan II University Hospital, Fez, Morocco.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all participants for publication of the study data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eHY designed the study, collected the clinical data and wrote the manuscript. SK, KS and WH contributed to data collection and microbiological analysis. FF and ZA performed the statistical analysis and interpretation of the results. TB supervised the research project and critically revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eDearnaley DP et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eRadiotherapy for prostate cancer.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eLancet Oncology.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eDelobel JB et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eRadiation-induced cystitis.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eUrology.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eReis Ferreira M et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eImpact of pelvic radiation therapy on metabolic profiles and microbiota.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eCancer Research.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eMaślak E et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eMicrobiome identification in prostate cancer patients undergoing radiotherapy.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eEl-Zawahry YA et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eESBL production after gamma radiation exposure.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eMohamad O et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eGenitourinary toxicity after prostate radiotherapy.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eRadiotherapy and Oncology.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eMichalski JM et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eToxicity after IMRT for prostate cancer.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eJournal of Clinical Oncology.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eZelefsky MJ et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eLong-term toxicity of IMRT for prostate cancer.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eInt J Radiat Oncol Biol Phys.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eDe Meerleer G et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eRadiotherapy toxicity in prostate cancer.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eLancet Oncology.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eFonteyne V et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eUrinary complications after prostate radiotherapy.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eHamstra DA et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eRadiation cystitis: pathophysiology and treatment.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eMuls AC et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eUrinary complications following pelvic radiation therapy.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eFalagas ME et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eMultidrug-resistant Gram-negative bacteria infections.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eVentola CL.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eAntibiotic resistance crisis.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePharmacy and Therapeutics.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eFlores-Mireles AL et al.\u003c/span\u003e \u003cspan type=\"BoldSmallCaps\" class=\"BoldSmallCaps\" name=\"Emphasis\"\u003eUrinary tract infections: epidemiology and mechanisms.\u003c/span\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eNature Reviews Microbiology.\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"african-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"afju","sideBox":"Learn more about [African Journal of Urology](http://link.springer.com/journal/12293)","snPcode":"12301","submissionUrl":"https://submission.springernature.com/new-submission/12301/3","title":"African Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Prostate cancer, Radiotherapy, Urinary tract infection, Multidrug-resistant bacteria, Urinary microbiome, Radiation cystitis","lastPublishedDoi":"10.21203/rs.3.rs-9035707/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9035707/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRadiotherapy represents a major therapeutic modality for localized prostate cancer. Despite technological advances, pelvic irradiation remains associated with urinary complications including radiation cystitis and urinary tract infections (UTIs). Emerging evidence suggests that radiation may alter urinary microbiota and promote antibiotic resistance.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate the impact of prostate radiotherapy on urinary bacteriological profiles and the emergence of multidrug-resistant bacteria.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective study included 120 patients treated for prostate cancer between March 2024 and February 2026 at the Radiation Oncology Department of Hassan II University Hospital, Fez. All patients received 3D conformal radiotherapy with or without androgen deprivation therapy. Urine cultures and antibiograms were performed before radiotherapy, weekly during treatment, and during follow-up at 1, 3 and 6 months. Infection rates and antibiotic resistance profiles were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eUrinary infection incidence was 24% before radiotherapy, 18% during treatment, and increased to 40% after treatment. Escherichia coli (48%) and Enterococcus faecalis (32%) were the most common pathogens before radiotherapy. Multidrug-resistant bacteria increased from 10% before treatment to 28% after radiotherapy. Multivariate analysis identified radiotherapy as the only independent factor significantly associated with the emergence of resistant strains (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eProstate radiotherapy significantly modifies the urinary bacteriological ecosystem and promotes the emergence of multidrug-resistant organisms. Systematic microbiological monitoring is recommended during and after radiotherapy.\u003c/p\u003e","manuscriptTitle":"Impact of Prostate Radiotherapy on Urinary Bacterial Profiles and the Emergence of Multidrug-Resistant Organisms: A Prospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-22 14:57:56","doi":"10.21203/rs.3.rs-9035707/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-29T10:11:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-28T12:22:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-25T13:26:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-24T17:52:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103891307089801759690867728579482004843","date":"2026-03-20T13:13:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190495871834781682901402750452761119973","date":"2026-03-20T10:29:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"60364757353749009404856042948873784804","date":"2026-03-20T07:08:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"295025244707087884472098296117875382449","date":"2026-03-19T02:48:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-18T05:29:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-16T01:09:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-16T01:08:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"African Journal of Urology","date":"2026-03-05T04:14:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"african-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"afju","sideBox":"Learn more about [African Journal of Urology](http://link.springer.com/journal/12293)","snPcode":"12301","submissionUrl":"https://submission.springernature.com/new-submission/12301/3","title":"African Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"85f1d60c-8a33-4d3e-b012-c094399246f5","owner":[],"postedDate":"March 22nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-03-29T10:23:46+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-22 14:57:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9035707","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9035707","identity":"rs-9035707","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2026) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00