Predictive model for systemic recurrence following cisplatin-based neoadjuvant chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma

Rashed A Ghandour; Yuval Freifeld; Joseph Cheaib; Nirmish Singla; Xiaosong Meng; Alexander Kenigsberg; Aditya Bagrodia; Solomon Woldu; Jean Hoffman-Censits; Dmitry Enikeev; Leonid Rapoport; Firas G Petros; Jay D Raman; Philip M Pierorazio; Surena F Matin; Vitaly Margulis

doi:10.1016/j.urolonc.2021.05.037

Predictive model for systemic recurrence following cisplatin-based neoadjuvant chemotherapy and radical nephroureterectomy for high risk upper tract urothelial carcinoma

Urol Oncol. 2021 Nov;39(11):788.e15-788.e21. doi: 10.1016/j.urolonc.2021.05.037. Epub 2021 Jul 28.

Authors

Rashed A Ghandour¹, Yuval Freifeld², Joseph Cheaib³, Nirmish Singla⁴, Xiaosong Meng², Alexander Kenigsberg², Aditya Bagrodia², Solomon Woldu², Jean Hoffman-Censits⁵, Dmitry Enikeev⁶, Leonid Rapoport⁶, Firas G Petros⁷, Jay D Raman⁸, Philip M Pierorazio³, Surena F Matin⁷, Vitaly Margulis⁹

Affiliations

¹ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH. Electronic address: vitaly.margulis@utsouthwestern.edu.
² Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
³ The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
⁴ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.
⁵ The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD.
⁶ Institute for Urology and Reproductive Health, Sechenov University, Moscow.
⁷ Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX.
⁸ Division of Urology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA.
⁹ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Institute for Urology and Reproductive Health, Sechenov University, Moscow.

PMID: 34330655
DOI: 10.1016/j.urolonc.2021.05.037

Abstract

Introduction: Neoadjuvant chemotherapy (NAC) is increasingly used prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Systemic recurrence (SR) carries a dismal prognosis. We sought to determine risk factors associated with SR in this setting.

Methods: We evaluated a multi-center database of patients with UTUC who received cisplatin-based NAC before RNU. Final pathology at RNU was dichotomized into ypT<2 vs ypT≥2. Univariable and multivariable analyses were performed to identify risk factors associated with SR. Three groups were defined based on the number of significant risk factors (groups 1, 2, 3 for 0-1, 2, 3 risk factors, respectively) and evaluated for recurrence-free survival (RFS) using the Kaplan-Meier method.

Results: 106 patients were identified between 2004 and 2018. Median age was 67.0 years [IQR = 61-73.3]; 57 (54%) and 49 (46 %) patients received MVAC and GC, respectively. Final pathological stage was ypT<2 in 57 (54%); 23% (24/106) had SR. On univariable analysis, pathological variables on final specimen including ypT≥2, lymphovascular invasion (ypLVI), and nodal involvement were associated with SR. On multivariable analysis, ypLVI OR = 4.1 (95% CI 1.2-13.6; P = 0.024) and pathological nodal involvement OR = 4.5 (95% CI 1.3-15.7; P = 0.017) were predictive of recurrence. Stratifying by the number of risk factors, the 2-year RFS was 95%, 55%, and 18% for groups 1, 2, and 3 respectively (log-rank <0.001).

Conclusion: This model evaluates the risk of SR following NAC and RNU to guide counseling and decision-making after surgery. Adverse pathological variable including ypLVI and nodal involvement, in combination with ypT-stage, are strongly associated with SR.

Keywords: Neoadjuvant chemotherapy; Radical nephroureterectomy; Risk factors; Systemic recurrence; Upper tract urothelial carcinoma.

Publication types

Multicenter Study

MeSH terms

Aged
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Cisplatin / pharmacology
Cisplatin / therapeutic use*
Humans
Male
Middle Aged
Neoadjuvant Therapy / methods*
Neoplasm Recurrence, Local
Nephroureterectomy / methods*
Risk Factors
Urinary Bladder Neoplasms / drug therapy*
Urinary Bladder Neoplasms / surgery*

Substances

Antineoplastic Agents
Cisplatin