Impact of High-Intensity Local Treatment on Overall Survival in Stage IV Upper Tract Urothelial Carcinoma - Beyond the Abstract

Recent studies in metastatic bladder cancer suggest an overall survival benefit from treating the primary tumor.1 Upper tract urothelial cancer has similar biology to bladder cancer and nephroureterectomy has a lower complication rate; we, therefore, hypothesized that high-intensity local treatment for metastatic upper tract urothelial carcinoma (UTUC) would also be associated with improved overall survival.  In our recently published analysis, we used the National Cancer Database (NCDB) to investigate the impact of high-intensity local treatment on overall survival in patients with stage IV UTUC.2


Within the NCDB, we identified 7,357 men and women diagnosed with stage IV UTUC from 2004 to 2015. Patients who underwent high-intensity local treatment, defined as radical surgery of the primary tumor, were compared with those who did not. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics and simulate random allocation as would be the case in a prospective trial. Weighted survival analyses were used to test the association between high-intensity LT and overall survival.

On IPTW-adjusted survival analysis, high-intensity LT was associated with a significantly longer median survival (11.17 months [IQR, 5.19 to 24.28] months vs. 6.18 months [IQR, 2.27 to 14.49], p=<0.001). A similar benefit was seen on adjusted survival analyses in each stage IV subgroup (T4, N+, and M+) and among both patients who received chemotherapy first (“consolidative strategy”) and those who received no systemic therapy prior (“cytoreductive strategy”).

Our findings suggest that high-intensity therapy for men and women with stage IV UTUC is be associated with prolonged overall survival. Coming on the heels of the UK-based POUT trial, this work underscores the role of multimodality treatment for men with advanced UTUC.3   Although our study is limited by its retrospective design, in the absence of prospective randomized data, these results may inform decision-making regarding whether or not to incorporate radical treatment of the primary lesion in the management of advanced and metastatic UTUC.

Written by: Marco Paciotti, MD, @Marco_Paciotti & Alexander P. Cole, MD, @Putnam_Cole, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

  1. Seisen T, Sun M, Leow JJ, et al. Efficacy of High-Intensity Local Treatment for Metastatic Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Analysis From the National Cancer Data Base. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016;34(29):3529-3536.
  2. Paciotti M, Nguyen DD, Modonutti D, et al. Impact of high-intensity local treatment on overall survival in stage IV upper tract urothelial carcinoma. Urologic oncology. 2021.
  3. Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. The Lancet. 2020;395(10232):1268-1277.

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