Comparing surgical and conservative treatment of keratinizing squamous metaplasia (leukoplakia) of the bladder: a systematic review

BACKGROUND: Leukoplakia is a condition requiring histological confirmation and is associated with persistent symptoms of recurrent cystitis. No universal treatment standards are currently available.

AIM: This study aimed to compare surgical and conservative treatment approaches for keratinizing squamous metaplasia (leukoplakia) of the bladder in adults.

METHODS: A scientific data search was conducted in MEDLINE/PubMed, Scopus, Web of Science, the Russian Science Citation Index, and other databases (last search: September 2025). Comparative studies and surgical case series following drug therapy failure were included; single case reports, pediatric cases, and schistosomiasis-associated cases were excluded. The primary outcome was clinical and endoscopic resolution, i.e. symptom disappearance and complete epithelialization on follow-up cystoscopy. Secondary outcomes included recurrence, adverse events, cancer occurrence, and quality-of-life measures. Risk of bias was assessed using ROBINS-I and RoB 2.0 tools (ROBINS-I prioritized), and overall certainty of evidence was evaluated using the GRADE approach. A random-effects meta-analysis (DerSimonian–Laird method with Hartung–Knapp adjustment) with heterogeneity assessment (I², Cochran χ²) was pre-specified but was limited by small sample sizes and substantial heterogeneity.

RESULTS: Seven studies were included (0 randomized controlled trials), comprising a total of 826 patients. Conservative strategies (antibacterial and anti-inflammatory therapy, intravesical instillations) rarely resulted in lesion regression and provided mainly short-term symptom relief. Endoscopic removal or ablation of lesions (laser ablation, argon plasma coagulation, mono- or bipolar transurethral resection) demonstrated high rates of clinical and morphological resolution (80%–97%) and meaningful improvements in quality of life. In the largest series, the 5-year recurrence risk after complete endoscopic removal was 13.9%, with no cases of cancer reported over a median follow-up of 49 months. Laser ablation was associated with fewer coarse scars in the surgical treatment area and greater reduction in pain symptoms compared with transurethral resection; serious complications were rare. Overall certainty of evidence was low to very low (due to retrospective study designs, confounding, and selective reporting), although effect directions were consistent.

CONCLUSION: In symptomatic keratinizing squamous metaplasia of the urothelium, an active management approach is justified, comprising biopsy-based diagnosis verification, elimination of inflammatory triggers, and organ-sparing endoscopic removal of lesions (preferably using laser techniques), followed by scheduled follow-up cystoscopy. Conservative therapy plays an adjunctive role and rarely provides durable resolution. The quality of available evidence remains low to very low, underscoring the need for prospective comparative studies.