Association of Lymphovascular Invasion with Biochemical Recurrence and Adverse Pathological Characteristics of Prostate Cancer: A Systematic Review and Meta-analysis

Abstract

Background and objective: Lymphovascular invasion (LVI) is a significant histopathological feature in prostate cancer (PCa) associated with higher risk of biochemical recurrence (BCR) and other adverse outcomes. Our aim was to assess the association of LVI found in radical prostatectomy (RP) specimens with BCR and adverse clinicopathological findings.

Methods: A systematic literature search was conducted using the PubMed, Embase, and Web of Science databases in July 2023, with an additional search in May 2024. We included 94 prospective and retrospective studies reporting on LVI in RP specimens and its association with the specified outcomes.

Key findings and limitations: Meta-analyses revealed that LVI is significantly associated with higher BCR risk (hazard ratio 1.96, 95% confidence interval [CI] 1.73-2.21), higher pathological tumour stage (odds ratio [OR] 5.77; 95% CI 3.96-8.40), higher Gleason score (OR 5.19, 95% CI 4.12-6.54), lymph node metastasis (OR 11.52, 95% CI 7.65-17.34), distant metastasis (OR 9.10, 95% CI 5.46-15.17), positive surgical margins (OR 2.38, 95% CI 1.83-3.09), extraprostatic extension (OR 5.01, 95% CI 3.11-8.06), seminal vesicle invasion (OR 7.50, 95% CI 3.47-16.23), and perineural invasion (OR 133.71, 95% CI 65.93-271.15). Major limitations of this study include high heterogeneity of the data and the reliance on nonrandomised studies.

Conclusions and clinical implications: Our findings reveal that LVI is associated with nearly twofold higher risk of BCR, highlighting its potential role as a critical prognostic marker.

Patient summary: We analysed data from multiple studies to understand the impact of the spread of prostate cancer into the lymph or blood vessels, called lymphovascular invasion (LVI). We found that LVI is linked to a higher risk of cancer recurrence after surgery and other negative outcomes. Our findings highlight the importance of considering LVI in treatment decisions for better management of prostate cancer.

Keywords: Biochemical recurrence; Histopathological examination; Lymphovascular invasion; Prognostic factors; Prostate cancer; Radical prostatectomy; Risk assessment.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. LVI = lymphovascular invasion; RP = radical prostatectomy.

Fig. 2

Forest plot and meta-analysis of studies evaluating the association between LVI and the risk of biochemical recurrence for men who underwent radical prostatectomy. HR = hazard ratio; SE = standard error; IV = inverse variance; CI = confidence interval; df = degrees of freedom; LVI = lymphovascular invasion.

Fig. 3

Funnel plot for evaluation of potential publication bias in 51 studies included in the main meta-analysis of biochemical recurrence. SE = standard error; HR = hazard ratio.