Prevalence of Risk Factors for Potential Peripheral Neuropathy in Patients with Locally Advanced/Metastatic Urothelial Carcinoma: A Systematic Literature Review and Meta-Analysis

Introduction: Despite advances in treatment options for locally advanced/metastatic urothelial carcinoma (la/mUC), concerns remain about the occurrence of peripheral neuropathy (PN), a disabling and difficult-to-treat condition. This study aimed to analyze the prevalence of potential risk factors for PN in patients with la/mUC. Methods: A systematic literature review (SLR) was conducted to identify observational studies published from 1 January 2014 to 10 July 2024 (search date) that reported on the prevalence of risk factors for PN in patients with la/mUC. Risk factors of interest were identified from a previous SLR and supported by multivariable/univariable analyses. Pooled prevalence was determined via meta-analysis using fixed-effects and random-effects models. Sensitivity analyses were performed for the following subgroups: studies with ≥100 patients and studies with cisplatin-eligible populations. Results: The following risk factors were feasible for meta-analysis based on data availability across 109 included studies: age ≥ 65 years, anemia, body mass index (BMI) < 18.5 kg/m2, BMI ≥ 30 kg/m2, Charlson Comorbidity Index > 2, cardiovascular disease, diabetes, Eastern Cooperative Oncology Group performance status score ≥ 2, estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2, and hypertension. Using the random-effects model, the baseline prevalence of relevant risk factors ranged from 4.12% for BMI < 18.5 to 66.10% for age ≥ 65 years. Impaired kidney function (51.84%), cardiovascular disease (44.19%), and hypertension (37.78%) were also observed to be potentially important risk factors. Conclusions: Older age and specific comorbidities (e.g., impaired kidney function, cardiovascular disease, and hypertension) were the most prevalent potential risk factors for PN in patients with la/mUC based on meta-analysis. Given the varying risk of developing PN as an adverse event with different therapeutic options for la/mUC, tailored treatment should be considered in populations with these risk factors.