title: Prognostic significance of lymphatic, vascular and perineural invasion for bladder cancer patients treated by radical cystectomy.
abstract: 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.
authors.affiliation: Departments of Laboratory Medicine and Pathology, United States.
authors.forename: Prasuna
authors.initials: P
authors.lastname: Muppa
authors.affiliation: Departments of Laboratory Medicine and Pathology, United States.
authors.forename: Sounak
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Surgery, United States.
authors.forename: Igor
authors.initials: I
authors.lastname: Frank
authors.affiliation: Department of Surgery, United States.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.affiliation: Department of Surgery, United States.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Surgery, United States.
authors.forename: R Houston
authors.initials: RH
authors.lastname: Thompson
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States.
authors.forename: Prabin
authors.initials: P
authors.lastname: Thapa
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Tarrell
authors.affiliation: Departments of Laboratory Medicine and Pathology, United States.
authors.forename: Loren P
authors.initials: LP
authors.lastname: Herrera Hernandez
authors.affiliation: Departments of Laboratory Medicine and Pathology, United States.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Jimenez
authors.affiliation: Departments of Laboratory Medicine and Pathology, United States. Electronic address: cheville.john@mayo.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D015653:Cystectomy / Q000379:methods; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology / Q000601:surgery; D009389:Neovascularization, Pathologic; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D019043:Vascular Neoplasms / Q000175:diagnosis / Q000473:pathology*
keywords: Urothelial cancer; lymphatic invasion; perineural invasion; radical cystectomy; recurrence; survival; vascular invasion