Abstract
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.