A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy

Purpose: Pelvic lymph node metastases (ypN+) after multiagent neoadjuvant chemotherapy (NAC) is a poor prognostic sign in nonmetastatic muscle-invasive bladder cancer (nmMIBC). We sought to create a nomogram predicting probability of ypN+ after NAC for cN0 nmMIBC and determine association with overa...

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Main Authors: Garrett K. Harada, MD, Steven N. Seyedin, MD, Olivia Heutlinger, BS, Armon Azizi, BS, Audree Hsu, BS, Arash Rezazadeh, MD, Michael Daneshvar, MD, MS, Greg E. Gin, MD, Edward M. Uchio, MD, Giovanna A. Giannico, MD, Jeremy P. Harris, MD, Aaron B. Simon, MD, PhD, Jeffrey V. Kuo, MD, Nataliya Mar, MD
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Advances in Radiation Oncology
Online Access:http://www.sciencedirect.com/science/article/pii/S2452109424002343
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author Garrett K. Harada, MD
Steven N. Seyedin, MD
Olivia Heutlinger, BS
Armon Azizi, BS
Audree Hsu, BS
Arash Rezazadeh, MD
Michael Daneshvar, MD, MS
Greg E. Gin, MD
Edward M. Uchio, MD
Giovanna A. Giannico, MD
Jeremy P. Harris, MD
Aaron B. Simon, MD, PhD
Jeffrey V. Kuo, MD
Nataliya Mar, MD
author_facet Garrett K. Harada, MD
Steven N. Seyedin, MD
Olivia Heutlinger, BS
Armon Azizi, BS
Audree Hsu, BS
Arash Rezazadeh, MD
Michael Daneshvar, MD, MS
Greg E. Gin, MD
Edward M. Uchio, MD
Giovanna A. Giannico, MD
Jeremy P. Harris, MD
Aaron B. Simon, MD, PhD
Jeffrey V. Kuo, MD
Nataliya Mar, MD
author_sort Garrett K. Harada, MD
collection DOAJ
description Purpose: Pelvic lymph node metastases (ypN+) after multiagent neoadjuvant chemotherapy (NAC) is a poor prognostic sign in nonmetastatic muscle-invasive bladder cancer (nmMIBC). We sought to create a nomogram predicting probability of ypN+ after NAC for cN0 nmMIBC and determine association with overall survival (OS). Methods and Materials: We reviewed the National Cancer Database for patients with cT2-4N0M0 urothelial carcinoma of the bladder receiving multiagent NAC and surgery from 2004 to 2020. Following a data split, univariate logistic regression identified variables associated with ypN+ at P < .05. Eligible variables were used for multivariate logistic regression and nomogram generation. A threshold for 95% sensitivity defined high- and low-risk groups for ypN+. Fine–Gray models assessed ypN+ risk group and OS, accounting for competing risks of surgical mortality. Results: A total of 6194 patients were identified with a median follow-up of 39.5 months (interquartile range [IQR], 20.5-67.2 months). Most patients had high-grade (97.7%) cT2 disease (70.8%) with nonpapillary urothelial histology (67.3%) and initiated NAC at a median of 41.0 days after diagnosis (IQR, 28.0-59.0 days).The nomogram included age in decades (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.87–1.03; P = .172), weeks from diagnosis to NAC (OR, 1.02; 95% CI, 1.01-1.04; P = .004), nonpapillary histology (OR, 1.17; 95% CI, 0.99-1.39; P = .068), and clinical T-stage. Within the testing cohort, ypN+ was found in 392 (22.8%) high-risk and 12 (8.0%) low-risk patients (P < .001), with median OS of 36.1 and 74.0 months, respectively (P < .001). High-risk patients had worse OS despite competing risks of 30-day (subdistribution hazard ratio [SHR], 1.80; 95% CI, 1.49-2.18; P < .001) and 90-day surgical mortality (SHR, 1.68; 95% CI, 1.39-2.04; P < .001). Conclusions: This is the first study to provide a tool for predicting ypN+ and prognosticate worse OS in primarily high-grade nmMIBC and could select patients for alternative neoadjuvant therapy and facilitate future study.
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spelling doaj-art-295ff701639d49f28808b65fd9f8b31b2025-08-20T02:05:31ZengElsevierAdvances in Radiation Oncology2452-10942025-01-0110110167110.1016/j.adro.2024.101671A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant TherapyGarrett K. Harada, MD0Steven N. Seyedin, MD1Olivia Heutlinger, BS2Armon Azizi, BS3Audree Hsu, BS4Arash Rezazadeh, MD5Michael Daneshvar, MD, MS6Greg E. Gin, MD7Edward M. Uchio, MD8Giovanna A. Giannico, MD9Jeremy P. Harris, MD10Aaron B. Simon, MD, PhD11Jeffrey V. Kuo, MD12Nataliya Mar, MD13Department of Radiation Oncology, Chao Family Cancer Center, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Radiation Oncology, Chao Family Cancer Center, University of California, Irvine Medical Center, Orange, California; Corresponding author: Steven N. Seyedin, MDSchool of Medicine, University of California, Irvine, Irvine, CaliforniaSchool of Medicine, University of California, Irvine, Irvine, CaliforniaCalifornia University of Science and Medicine, Colton, CaliforniaDivision of Hematology and Oncology, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Urology, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Urology, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Urology, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Pathology and Laboratory Medicine, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Radiation Oncology, Chao Family Cancer Center, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Radiation Oncology, Chao Family Cancer Center, University of California, Irvine Medical Center, Orange, CaliforniaDepartment of Radiation Oncology, Chao Family Cancer Center, University of California, Irvine Medical Center, Orange, CaliforniaDivision of Hematology and Oncology, University of California, Irvine Medical Center, Orange, CaliforniaPurpose: Pelvic lymph node metastases (ypN+) after multiagent neoadjuvant chemotherapy (NAC) is a poor prognostic sign in nonmetastatic muscle-invasive bladder cancer (nmMIBC). We sought to create a nomogram predicting probability of ypN+ after NAC for cN0 nmMIBC and determine association with overall survival (OS). Methods and Materials: We reviewed the National Cancer Database for patients with cT2-4N0M0 urothelial carcinoma of the bladder receiving multiagent NAC and surgery from 2004 to 2020. Following a data split, univariate logistic regression identified variables associated with ypN+ at P < .05. Eligible variables were used for multivariate logistic regression and nomogram generation. A threshold for 95% sensitivity defined high- and low-risk groups for ypN+. Fine–Gray models assessed ypN+ risk group and OS, accounting for competing risks of surgical mortality. Results: A total of 6194 patients were identified with a median follow-up of 39.5 months (interquartile range [IQR], 20.5-67.2 months). Most patients had high-grade (97.7%) cT2 disease (70.8%) with nonpapillary urothelial histology (67.3%) and initiated NAC at a median of 41.0 days after diagnosis (IQR, 28.0-59.0 days).The nomogram included age in decades (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.87–1.03; P = .172), weeks from diagnosis to NAC (OR, 1.02; 95% CI, 1.01-1.04; P = .004), nonpapillary histology (OR, 1.17; 95% CI, 0.99-1.39; P = .068), and clinical T-stage. Within the testing cohort, ypN+ was found in 392 (22.8%) high-risk and 12 (8.0%) low-risk patients (P < .001), with median OS of 36.1 and 74.0 months, respectively (P < .001). High-risk patients had worse OS despite competing risks of 30-day (subdistribution hazard ratio [SHR], 1.80; 95% CI, 1.49-2.18; P < .001) and 90-day surgical mortality (SHR, 1.68; 95% CI, 1.39-2.04; P < .001). Conclusions: This is the first study to provide a tool for predicting ypN+ and prognosticate worse OS in primarily high-grade nmMIBC and could select patients for alternative neoadjuvant therapy and facilitate future study.http://www.sciencedirect.com/science/article/pii/S2452109424002343
spellingShingle Garrett K. Harada, MD
Steven N. Seyedin, MD
Olivia Heutlinger, BS
Armon Azizi, BS
Audree Hsu, BS
Arash Rezazadeh, MD
Michael Daneshvar, MD, MS
Greg E. Gin, MD
Edward M. Uchio, MD
Giovanna A. Giannico, MD
Jeremy P. Harris, MD
Aaron B. Simon, MD, PhD
Jeffrey V. Kuo, MD
Nataliya Mar, MD
A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy
Advances in Radiation Oncology
title A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy
title_full A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy
title_fullStr A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy
title_full_unstemmed A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy
title_short A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy
title_sort predictive nomogram for development of lymph node metastasis in muscle invasive bladder cancer following neoadjuvant therapy
url http://www.sciencedirect.com/science/article/pii/S2452109424002343
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