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

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.

• Authors: 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
• Journal: Urologic oncology (Urol Oncol) Vol. 39 Issue 11 Pg. 788.e15-788.e21 (11 2021) ISSN: 1873-2496 [Electronic] United States
• PMID: 34330655 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cisplatin

Topics

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