ASCO GU 2020: Sequencing Chemotherapy and Surgery in Upper Tract Urothelial Cancers

San Francisco, California ( Upper tract urothelial carcinoma is rare and accounts for 5-10% of all urothelial cancers. Unfortunately, the prognosis for high-grade, non-metastatic upper tract urothelial carcinoma (renal pelvis or ureter) has not improved in the past two decades. Given improvements in disease-free survival in the Phase III POUT study with adjuvant chemotherapy (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.30-0.74; p = 0.001), adjuvant chemotherapy has become the preferred approach. However, neoadjuvant chemotherapy is favored based on a median survival (OS) benefit seen in urothelial bladder cancer and the utility of having two kidneys in situ during chemotherapy. Presenting during the Urothelial Carcinoma Session at the 2020 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Saurabh Parasramka and colleagues from the University of Kentucky assessed the impact of timing of chemotherapy among patients with upper tract urothelial carcinoma.

This study utilized the National Cancer Data Base (NCDB; 2010-2015) to identify adults > 18 years with non-metastatic, high grade, upper tract urothelial carcinoma. All patients received surgery of the primary site and chemotherapy in the neoadjuvant or adjuvant setting. Patients receiving radiation therapy or who died within 90 days of surgery were not included. Descriptive statistics, log-rank tests, and cox-regression tests were performed. Patients achieving complete pathological response defined as pTis, pT0, pTa, and N0 were assessed for OS.

There were 1,191 patients with complete data that were identified: 225 (19%) received neoadjuvant chemotherapy and 966 (81%) received adjuvant chemotherapy. Among those included, 60% were males, the median age was 68 years, and 73% had a Charlson comorbidity index score of zero. The median follow-up time for alive patients was 30.4 months in the neoadjuvant chemotherapy group and 36.7 months in the adjuvant chemotherapy group. The renal pelvis was the primary disease site in 760 cases (63%) and ureter in 441 (37%). On univariate analysis, receiving neoadjuvant chemotherapy, age < 75 years, and Charlson comorbidity score of zero were associated with a significant survival benefit (p < 0.05).

The Kaplan Meier curve for survival is as follows:

product limit survival estimates

On multivariate analysis, receiving neoadjuvant chemotherapy (HR 0.75, 95% CI 0.58-0.96) and having a Charlson comorbidity score of zero (HR 0.80, 95% CI 0.65-0.96) had significantly better survival. In this model, age > 75 years had worse survival HR 1.34 (95% CI 1.08-1.66). Thirty-seven patients (17%) in the neoadjuvant chemotherapy group achieved a pathologic complete response with a median OS of > 71.6 months, which was significantly better than the adjuvant chemotherapy group and non-responders in the neoadjuvant chemotherapy group (p < 0.05):

product limit survival 2

The main limitation of this study is the retrospective design and the lack of cancer-specific mortality outcomes in the NCDB. However, within the limitations of the database, there is a trend that patients receiving neoadjuvant chemotherapy vs adjuvant chemotherapy have a better clinical outcome in the terms of OS, especially in the subset with pathological complete response.

Presented by: Saurabh Parasramka, MD, Department of Hematology and Oncology, Kentucky University, Lexington, Kentucky

Co-Authors: Alex Cook, Zin Myint, Ding Xue, Jianrong Wu, Peng Wang; University of Kentucky, Lexington, KY

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California 

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