The impact of lymphovascular invasion in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma: An extensive updated systematic review and meta-analysis

Patients with upper tract urothelial carcinoma (UTUC) often have a delayed diagnosis and by then, present with advanced disease which has been shown to be associated with lymphovascular invasion (LVI). It has been suggested to be involved in the metastatic cascade of the disease. In this review, we provide an extensive up-to-date summary of the current knowledge about the prognostic impact of LVI in patients undergoing radical nephroureterectomy (RNU). A systematic search of PubMed/MEDLINE, Scopus, EMBASE, and Web of Science for all reports published from 2010 through 2021 was performed. We performed pooled analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of series that evaluated LVI as a prognostic factor in adults with UTUC who underwent RNU. The assessed oncological outcomes were disease recurrence, cancer-specific and overall survival. A meta-regression analysis was used to explore potential heterogeneity. A total of 58 series met the eligibility criteria for qualitative and quantitative synthesis. We included 29,829 patients, ranging from 101 to 2492 per study. All series were retrospective. LVI was present in 7,818 patients (26.2%). The median age of the patients was 69 years and the median follow-up was 40 months. In 40 of 58 studies (68.9%), adjuvant chemotherapy was given. The pooled HRs show that LVI predicts a greater risk of recurrence of the disease (pooled HR 1.43, 95% CI: 1.31–1.55, P = 0.000; I2 = 76.3%), and decreases cancer-specific survival (pooled HR 1.53, 95% CI: 1.41–1.66, P = 0.000; I2 = 72.3%) and overall survival (HR 1.56, 95% CI 1.45–1.69, P = 0.000; I2 = 62.9%). It can be concluded that LVI is a common histologic pattern in surgical specimen in patients undergoing RNU for UTUC. LVI predicts a greater risk of recurrence and mortality, thus it should be carefully assessed in clinical practice to determine prognosis, and for optimal decision-making within the concept of personalized therapies.