Prognostic Values and Treatment Responses Evaluated with Lymphovascular Invasion, Perineural Permeation, and Histologic Transformation for Urothelial Cancer

Abstract

Background: To evaluate the prognostic significance of adverse pathologic characteristics including lymphovascular invasion, perineural permeation, and squamous/sarcomatoid transformation in patients with urothelial tumors, and to analyze their correlations with the treatment response to neoadjuvant chemotherapy for bladder cancers. Materials and Methods: A total of 277 consecutive patients with muscle-invasive urothelial carcinoma between 2004 and 2016 at China Medical University Hospital in Taiwan were included. Radical cystectomy with extended lymphadenectomy for bladder cancer and radical nephroureterectomy for upper urinary tract cancer were performed. Neoadjuvant chemotherapy was routinely given to patients with bladder cancer. Medical records and adverse pathologic characteristics were reviewed. Overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival were analyzed using the Kaplan–Meier method with a log-rank test. Univariate and multivariate analyses were carried out using a Cox proportional hazards regression model. The association between pathologic response after neoadjuvant chemotherapy and pathologic characteristics was evaluated using logistic regression. Results: Of the 277 patients, 56.3% had at least one adverse pathologic characteristic. Compared to those without adverse characteristics, the patients with at least one adverse pathologic characteristic had significantly worse OS (5-year OS [95% confidence interval (CI)]: 77.2% [65.7%–85.3%] vs. 39.7% [29.9%–49.4%], P < 0.01), higher occult nodal metastasis (22.3% vs. 0%), and worse DMFS (5-year DMFS [95% CI]: 88.5% [80.5%–93.4%] vs. 43.0% [33.3%–52.4%], P < 0.01). When neoadjuvant chemotherapy was applied, 4.3% of the patients with adverse characteristics achieved a optimal patholoigc response, but 58.1% achieved a pCR, if they did not have any adverse characteristics (odds ratio: 38.8, 95% CI: 6.70–225.2, P < 0.01). Conclusion: Adverse pathologic characteristics could predict poor outcomes and chemotherapy resistance independently of the clinical AJCC TNM stage in patients with muscle-invasive urothelial carcinoma. Incorporating pathologic information into decision-making for cancer management should be considered.

Keywords

• neoadjuvant therapy
• prognosis
• urothelial carcinoma