Junrong Zou

Urological cancers exhibit significant sex differences in incidence, treatment response, and prognosis, with males generally showing higher morbidity and mortality. This review systematically summarizes the underlying molecular and clinical mechanisms of these disparities, focusing on sex hormones, chromosome biology, tumor immune microenvironment, and microbiota. Sex hormones modulate key tumor processes including proliferation, apoptosis, non-apoptotic cell death, and DNA repair. Genetic factors such as X chromosome inactivation escape genes and Y chromosome loss also contribute to sex-biased cancer susceptibility. Furthermore, sex-specific differences in the urinary system and gut microbiota influence local immunity and inflammation, thereby affecting tumor progression and therapeutic response. Lifestyle and environmental factors, including smoking, alcohol consumption, and occupational exposures, further exacerbate these disparities. Clinically, sex differences impact the efficacy of immunotherapy and targeted therapies, underscoring the need for sex-informed treatment strategies. Integrating sex as a biological variable in research, clinical practice, and public health policies is essential for advancing precision oncology in urologic cancers.

With increasing incidence and clinical heterogeneity, prostate cancer (PCa) treatment remains challenging. Cathepsins (CTSs) contribute to PCa progression by remodeling the tumor microenvironment (TME). Their elevated expression is linked to poor outcomes. This review outlines the roles of CTSs in PCa pathogenesis, metastasis, and therapy resistance, and evaluates their biomarker and therapeutic potential. A narrative review of the PubMed, Embase, and Web of Science databases was conducted from 2000 to 2025. Keywords such as “prostate”, “cathepsin”, “cancer”, “angiogenesis”, “immune”, “EMT”, and “therapy” were used to find relevant studies. The review includes randomized controlled trials, meta-analyses, animal studies, and reviews. The final search was conducted on October 19, 2025. The role of CTSs in PCa: (I) cell survival. CTSs are crucial for PCa cell survival, influencing proliferation, migration, and invasion. Knockdown of specific CTSs significantly reduces these behaviors. CTSs also regulate cell death pathways such as apoptosis and autophagy, contributing to tumor progression. (II) TME regulation. CTSs degrade extracellular matrix (ECM) components, enhancing tumor invasion and metastasis. They also promote angiogenesis by upregulating VEGF and MMPs, and influence immune evasion, contributing to therapy resistance. (III) Bone metastasis: bone is a common site of PCa metastasis. CTSs contribute to the epithelial-mesenchymal transition (EMT), a process through which tumor cells adopt a mesenchymal phenotype, thereby enhancing metastatic potential and therapy resistance. Specifically, CTSs, including cathepsin K (CTSK) and cathepsin Z (CTSZ), play a key role in the bone microenvironment, facilitating tumor colonization and osteoclast-mediated bone resorption. (IV) Therapy resistance: CTSs contribute to resistance against chemotherapy, immunotherapy, and radiotherapy by modulating EMT, angiogenesis, and immune escape mechanisms. (V) Clinical application of CTSs: CTSs are potential biomarkers for early PCa detection and monitoring metastasis. CTS inhibitors have shown promise in preclinical models for inhibiting tumor invasion, angiogenesis, and bone resorption, suggesting therapeutic potential. CTSs are critical players in PCa progression and therapy resistance. Targeting CTSs may improve therapeutic outcomes, though further research is needed to better understand their mechanisms and clinical applicability.

Background and Objective: Urethral stenosis is a prevalent urological disorder characterized by the fibrotic narrowing of the urethral lumen, leading to symptoms of lower urinary tract obstruction and significantly impacting patients’ quality of life. Despite substantial advancements in surgical interventions, postoperative recurrence continues to pose a significant clinical challenge. In recent years, adjunctive pharmacologic therapies aimed at reducing fibrosis and preventing restenosis have garnered increasing attention. This narrative review summarizes the current evidence on postoperative pharmacological adjuvant therapies and emerging drug-delivery systems designed to reduce recurrence following urethral stricture surgery. Methods: For the period from 2004 to 2025, we searched the terms “urethral stricture”, “postoperative recurrence”, “mitomycin C”, “paclitaxel”, “steroids”, “pirfenidone”, “hydrogel”, and “biodegradable stents” in the PubMed, Embase, and Web of Science databases and conducted a narrative review. Relevant English-language literature, including randomized controlled trials (RCTs), meta-analyses, and animal studies, was included. The final search was conducted on March 19, 2025. Key Content and Findings: Surgical outcomes vary significantly depending on the technique used. Direct vision internal urethrotomy (DVIU) and dilation exhibit long-term recurrence rates of up to approximately 30–60% at two years and 90% at five years following a single procedure. Repeated endoscopic interventions further increase failure rates. In contrast, urethroplasty achieves long-term success rates of approximately 75–100%, with recurrence rates around 10–20% at ten years, although failure rates may be higher in complex cases. Among pharmacologic approaches, mitomycin C (MMC) reduces recurrence after DVIU, as demonstrated in meta-analyses (e.g., pooled odds ratio ~0.27, 95% confidence interval: 0.16–0.45). Paclitaxel (PTX) drug-coated balloons (DCB) improve freedom from reintervention in RCTs, with approximately 78% success at two years, and have received a conditional guideline recommendation for short, recurrent anterior strictures. Steroids, particularly triamcinolone acetonide (TA), decrease recurrence when used postoperatively, including via steroid-coated or ointment-coated clean intermittent catheterization (CIC). Pirfenidone (PFD) demonstrates antifibrotic efficacy in preclinical urethral models but lacks robust clinical data in humans. Emerging hydrogel and biodegradable stent platforms facilitate sustained, localized drug delivery, showing promising results in preclinical studies. Conclusions: Evidence supports a clear distinction between outcomes of DVIU/dilation and reconstructive urethroplasty. Postoperative adjuvant strategies—particularly PTX DCB and TA-based steroid-coated CIC—can further reduce recurrence in selected scenarios. Translation of MMC and TA into standardized, postoperative regimens and rigorously designed trials for PFD and smart delivery systems are priorities.

Background and Objective: Among the complications of ureteroscopic lithotripsy, withdrawal difficulties due to ureteroscopic impaction have not been well studied. Most of the existing literature is limited to single-center retrospective analysis or small-sample case reports. The purpose of this article is to elucidate the causes of intraoperative ureteroscopic impaction, summarize relevant research evidence, and propose effective prevention and management strategies. Methods: Through a systematic search of PubMed and Web of Science spanning from 1999 to 2024, English and Chinese literature containing keywords such as “ureteroscopy”, “difficult ureteroscope withdrawal”, “ureteroscopic impaction”, and “ureteral injury” were included. The search covered retrospective studies, case reports, and experimental studies. Key Content and Findings: This review identified that the primary causes of ureteroscopic impaction encompass operator-related factors, instrumental characteristics, ureteral anatomical strictures, pathological strictures, and ureteral spasms. Preventive strategies involve comprehensive preoperative assessment, appropriate ureteroscopy selection, and meticulous procedural technique. Regarding management, mild cases may resolve spontaneously with observation, whereas severe impaction necessitates employment of specialized exit techniques. Conclusions: This review offers clinicians comprehensive strategies for preventing and managing ureteroscopic impaction, which can help reduce surgical risks and improve patient outcomes. Further multicenter, prospective studies are necessary to optimize relevant technologies and methods in the future.

He H, et al. World J Mens Health. 2023 Apr;41:e45. https://doi.org/10.5534/wjmh.220248