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Radiation cystitis (RC) is a clinically challenging and often progressive complication of pelvic radiotherapy, marked by urothelial injury, vascular dysfunction, chronic inflammation, and fibrotic remodeling. Early diagnosis remains elusive due to nonspecific symptoms and the absence of validated molecular tools. As a biofluid in direct contact with the irradiated bladder, urine offers a unique molecular window into RC pathogenesis. In this review, we synthesize the current landscape of urinary biomarkers associated with the acute, latent, and chronic phases of RC, including inflammatory cytokines, oxidative stress products, epithelial injury markers, extracellular vesicles, microRNAs, proteomic signatures, and metabolomic alterations. We also integrate emerging mechanistic insights such as DNA damage responses, ROS generation, mitochondrial dysfunction, urothelial barrier disruption, senescence-associated secretory phenotypes, hypoxia-driven vascular injury, and profibrotic TGF-β signaling, all of which contribute to the release of urinary analytes. By linking phase-specific molecular pathways with corresponding urinary signatures, we highlight opportunities to leverage urine-based measurements for early detection, risk stratification, severity assessment, and therapeutic monitoring. A deeper understanding of the molecular mechanisms shaping urinary biomarker profiles will be essential for advancing precision diagnostics and improving long-term outcomes for patients with radiation cystitis.

The underlying mechanism of radiation cystitis remains unknown, however, angiogenesis induced by hypoxia seems to be important because hyperbaric oxygen therapy which suppresses HIF-1 is clinically effective and significantly associated with androgen receptor signaling. We herein assessed the impact of androgen deprivation therapy on radiotherapy-induced bladder hemorrhage in men with prostate cancer and that of androgen receptor signaling on angiogenesis in irradiated bladder cell lines and a mouse model of radiation cystitis. In 507 patients with prostate cancer undergoing external beam radiation therapy, univariate (hazard ratio 0.61, p  = 0.039) and multivariate (hazard ratio 0.50, p  = 0.006) analyses revealed that the use of androgen deprivation therapy was associated with a significantly lower risk of gross hematuria. In irradiated bladder cells, the levels of FLT1 and KDR expression were significantly elevated when pretreated with dihydrotestosterone, which was abolished by an anti-androgen hydroxyflutamide. In male mice with radiation cystitis, castration significantly reduced the incidence of hematuria. Correspondingly, microvessel density and VEGFR expression in the bladders in the castration group were significantly lower than those in the sham surgery group. Our results suggest that androgen receptor activation contributes to inducing angiogenesis in irradiated bladder cells. Androgen deprivation therapy thus has a potential for preventing radiation cystitis.

The use of radiotherapy has increased in recent years, especially for pelvic neoplasms, and this can result in long-term complications such as recurrent haemorrhagic radiation cystitis (RHC). A 73-year-old male patient presented to a hospital emergency department multiple times with visible haematuria and clots leading to urinary clot retention; he was finally diagnosed with RHC. During the last presentation, the bladder was irrigated continuously with saline using a three-way catheter. During hospitalisation, a cystourethroscopy was performed for bladder evaluation and clot evacuation. Multiple bleeding ulcers were recognised on the bladder wall, biopsies were taken for histopathology, and the ulcers cauterised. Packed red blood cell transfusions were required, and sodium hyaluronate (CystiStat ® ) bladder instillations were tried. There was no clinical improvement following any of these interventions. In light of the patient’s deteriorating condition, cystoscopic application of PuraStat ® 3ml was administered, which led to remission of the urinary bleeding in the short term. We continue to monitor the effects in the medium and long term. Based on current data, PuraStat ® haemostatic agent therapy may be considered for RHC, when traditional treatments are ineffective or infeasible, potentially eliminating the need for more aggressive therapy such as cystectomy.

Chronic radiation cystitis (CRC) is a consequence of pelvic radiotherapy and affects 5–10% of patients. The pathology of CRC is without curative treatment and is characterized by incontinence, pelvic pain and hematuria, which severely degrades patients’ quality of life. Current management strategies rely primarily on symptomatic measures and have certain limitations. Thanks to a better understanding of the pathophysiology of radiation cystitis, studies targeting key manifestations such as inflammation, neovascularization and cell atrophy have emerged and are promising avenues for future treatment. However, the mechanisms of CRC are still better described in animal models than in human models. Preclinical studies conducted to elucidate the pathophysiology of CRC use distinct models and are most often limited to specific processes, such as fibrosis, vascular damage and inflammation. This review presents a synthesis of experimental studies aimed at improving our understanding of the molecular mechanisms at play and identifying key processes in CRC.

Although radiation therapy plays a crucial role in cancer treatment, and techniques have improved continuously, irradiation induces side effects in healthy tissue. Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers and negatively impacts patients’ quality of life (QoL). To date, no effective treatment is available, and this toxicity remains a therapeutic challenge. In recent times, stem cell-based therapy, particularly the use of mesenchymal stem cells (MSC), has gained attention in tissue repair and regeneration due to their easy accessibility and their ability to differentiate into several tissue types, modulate the immune system and secrete substances that help nearby cells grow and heal. In this review, we will summarize the pathophysiological mechanisms of radiation-induced injury to normal tissues, including radiation cystitis (RC). We will then discuss the therapeutic potential and limitations of MSCs and their derivatives, including packaged conditioned media and extracellular vesicles, in the management of radiotoxicity and RC.

PurposeGiven that more cancers are being diagnosed earlier and that treatment of cancer is improving, health issues of cancer survivors are becoming more common and apparent. Pelvic radiation therapy for the treatment of gynecological cancers can lead to long-term collateral damage to the bladder, a condition termed radiation cystitis (RC). Late sequelae may take many years to develop and include incontinence and pain as well as hematuria. RC is a rare but potentially life-threatening condition for which there are few management and treatment options.MethodsThere are limited data in the literature regarding the effects of radiation on the bladder after gynecological cancer therapy and we hereby review the literature on cancer survivorship issues of pelvic radiation for gynecology literature.ResultsTreatment options are available for patients with radiation-induced hemorrhagic cystitis. However, most treatments are risky or only effective for a short timeframe and no therapy is currently available to reverse the disease progress. Furthermore, no standardized guidelines exist describing preferred management options. Common therapies include hyperbaric oxygen therapy, clot evacuation, fulguration, intravesical instillation of astringent agents, and surgery. Novel developing strategies include Botulinum Toxin injections and liposomal-tacrolimus instillations. These treatments and strategies are discussed.ConclusionsIn this review, we will present current and advanced therapeutic strategies for RC to help cancer survivors deal with long-term bladder health issues.

Background Radiation cystitis (RC) is a major complication of pelvic radiotherapy, leading to inflammation, vascular damage, and fibrosis. While mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show promise in regenerative medicine, their therapeutic effects on RC remain unclear. This study evaluates the efficacy of human umbilical cord MSC-EVs (huMSC-EVs) in mitigating Radiation-induced bladder damage. Methods Animal models of RC were established using 20 Gy pelvic irradiation. Forty-four female Sprague-Dawley rats were divided into four groups: negative control (NC, no radiation), positive control (PC, radiation only), local treatment (LT, huMSC-EVs injected into the bladder wall), and systemic treatment (ST, intravenous huMSC-EVs). Bladder function and compliance were assessed via metabolic cage and urodynamic studies (UDS) at 6 and 24 weeks. Histopathological changes and inflammatory cytokine levels were evaluated at multiple time points. Results Administration of huMSC-EVs significantly improved urinary frequency and hematuria. Histological analysis showed reduced urothelial disintegration and edema in the early phase, and improved urothelial integrity, reduced hyperplasia and vascular lesions, and restored bladder architecture in the late phase, in the treated groups. UDS demonstrated preserved bladder compliance and voiding efficiency in LT rats, with significantly higher voided volume ( p  < 0.01) and lower post-voiding residue ( p  < 0.05) compared to the PC group 24 weeks post-irradiation. Pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were markedly lowered and their levels were similar to the non-radiated NC group in LT-treated rats ( p  = 1.00, p  = 0.22, p  = 0.16), 24 weeks post-irradiation. Conclusions Local huMSC-EVs therapy effectively reduces RC-related bladder injury and preserves function, likely by modulating inflammatory response and epithelial regeneration. These findings highlight huMSC-EVs as a promising strategy to prevent chronic RC, warranting further clinical exploration.

Purpose of Review This manuscript aims to provide a comprehensive overview of the pathophysiology, risk factors, prevention strategies, and management options for radiation cystitis. Recent Findings Recent studies have shed light on the pathophysiology of radiation cystitis, highlighting the role of inflammation, fibrosis, and vascular damage. Emerging preventive measures like stem cell therapy offer promise, alongside novel treatments such as amniotic bladder therapy and hyperbaric oxygen therapy. Summary This review outlines the latest research on radiation cystitis, covering its pathophysiology, risk factors, prevention, and management. Major findings include insights into the mechanisms of RC development, promising preventive and therapeutic approaches, and the importance of standardized treatment pathways. Future research should focus on identifying genetic risk factors, improving treatment efficacy, and enhancing patient outcomes. This review offers valuable insights for clinicians and researchers, guiding future investigations into radiation cystitis management.

Backgrounds Platelet‐to‐albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. Methods A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms‐one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. Results Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune‐Inflammation Index (SII), platelet‐to‐lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five‐cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. Conclusions PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life.

Objective: To assess the effectiveness of Platelet Concentrates (PCs) in the contest of Hemorrhagic, Actinic, and Radiation Cystitis, plus Urethral Obstruction or Stenosis. Eligibility criteria: Open article in English or Italian regarding in situ applications of PCs for the selected pathologies. Information sources: MEDLINE, Cochrane Library, and ELSEVIER. Risk of bias: High (and discussed). Methods for synthesis of results: Selection of relevant contents, resumed by digital tools, checked by authors and used throughout the manuscript. Included studies: 13 screened articles + 7 personal sources + 37 “extra” articles. Synthesis of results: Pre-clinical and clinical studies demonstrated substantial symptom relief, mucosal restoration, and improved growth factor levels, reducing recurrence rates and complications. However, preparation protocols and results varied among studies. Limitations of evidence: Frequent low-quality studies with mall sample size, plus heterogeneous experimental setups and nomenclature/preparations. Interpretation: PCs demonstrate promise due to their bioactive components, enhancing tissue repair and reducing inflammation with no significant adverse events. Despite positive outcomes in pre-clinical and clinical studies, variability in preparation protocols and small sample sizes, together with inconsistent results, highlight the need for high-quality research to validate PCs’ clinical efficacy and cost-effectiveness.