Prognostic significance of lymphatic, vascular and perineural invasion for bladder cancer patients treated by radical cystectomy

Summary

In radical cystectomy specimens with bladder cancer, lymphatic and vascular invasion are often reported as ‘angiolymphatic’ or ‘lymphovascular’ invasion, terms that combine the findings of tumour within simple endothelial-lined lymphatic spaces and tumour within muscle-lined blood vessels. It is unclear if these patterns of invasion have different prognostic significance. In addition, there are conflicting data regarding the significance of lymphatic, vascular and perineural invasion in patients with bladder cancer. Herein, we studied 1504 patients treated by radical cystectomy for bladder cancer at our institution and followed for a mean of 10.6 years. Cases were re-reviewed by a urological pathologist for lymphatic invasion defined as tumour within a non-muscle-lined endothelial-lined lymphatic space, vascular invasion defined as tumour in a muscle-lined blood vessel, and perineural invasion defined as tumour within the perineural sheath. Associations of clinical and pathological features with bladder cancer death were evaluated using Cox proportional hazards regression models and summarised with hazard ratios and 95% confidence intervals. Survival was estimated by the Kaplan–Meier method. Multivariate analysis showed that lymphatic and vascular invasion but not perineural invasion were significantly associated with cancer specific survival (p < 0.0001 and p = 0.02, respectively). There was a significant association of lymphatic and vascular invasion but not perineural invasion with involved regional lymph nodes (p < 0.0001 and p = 0.004, respectively). In patients with metastasis to regional lymph nodes, lymphatic invasion remained significantly associated with outcome (p = 0.02). The frequency of lymphatic and vascular invasion varied amongst histological subtypes of bladder cancer. Vascular and lymphatic invasion should be clearly defined and reported for radical cystectomy specimens containing bladder cancer.

Introduction

There is conflicting evidence for the prognostic significance of lymphatic invasion, vascular invasion, and perineural invasion in patients with bladder cancer treated by cystectomy.1, 2, 3 In addition, many studies have combined invasion within lymphatics (non-muscle-lined endothelial-lined space) and muscle-lined blood vessels as ‘angiolymphatic’ or ‘lymphovascular’ invasion in their analyses.4, 5, 6, 7, 8, 9, 10 However, it is unknown if the prognostic significance of lymphatic invasion differs from vascular invasion. In addition, there is a paucity of data regarding the importance of perineural invasion in radical cystectomy specimens. Finally, nearly all previously published studies lack central pathological re-review, and none have considered the variant histologies of bladder cancer in their analyses.

The objective of this study was to examine a large cohort of surgically treated bladder cancer patients to determine the significance of lymphatic, vascular, and perineural invasion in predicting bladder cancer specific survival. The study included review of all cases by a urological pathologist and variant histologies.