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

Overview

Journal Adv Radiat Oncol

Specialty Oncology

Date 2024 Dec 10

PMID 39655154

Authors

Garrett K Harada

Steven N Seyedin

Olivia Heutlinger

Armon Azizi

Audree Hsu

Arash Rezazadeh

Michael Daneshvar

Greg E Gin

Edward M Uchio

Giovanna A Giannico

Jeremy P Harris

Aaron B Simon

Jeffrey V Kuo

Nataliya Mar

Affiliations

Soon will be listed here.

Abstract

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 < .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; = .172), weeks from diagnosis to NAC (OR, 1.02; 95% CI, 1.01-1.04; = .004), nonpapillary histology (OR, 1.17; 95% CI, 0.99-1.39; = .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 ( < .001), with median OS of 36.1 and 74.0 months, respectively ( < .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; < .001) and 90-day surgical mortality (SHR, 1.68; 95% CI, 1.39-2.04; < .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.

References

Zhu S, Yu W, Yang X, Wu C, Cheng F . Traditional Classification and Novel Subtyping Systems for Bladder Cancer. Front Oncol. 2020; 10:102. PMC: 7025453. DOI: 10.3389/fonc.2020.00102. View

Collins G, Reitsma J, Altman D, Moons K . Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD Statement. BMC Med. 2015; 13:1. PMC: 4284921. DOI: 10.1186/s12916-014-0241-z. View

Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb S, van der Heijden M . Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019; 25(11):1706-1714. DOI: 10.1038/s41591-019-0628-7. View

Charlson M, Pompei P, Ales K, MacKenzie C . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987; 40(5):373-83. DOI: 10.1016/0021-9681(87)90171-8. View

Leow J, Martin-Doyle W, Rajagopal P, Patel C, Anderson E, Rothman A . Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol. 2013; 66(1):42-54. DOI: 10.1016/j.eururo.2013.08.033. View

Powles T, Bellmunt J, Comperat E, De Santis M, Huddart R, Loriot Y . Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2021; 33(3):244-258. DOI: 10.1016/j.annonc.2021.11.012. View

Audenet F, Sfakianos J, Waingankar N, Ruel N, Galsky M, Yuh B . A delay ≥8 weeks to neoadjuvant chemotherapy before radical cystectomy increases the risk of upstaging. Urol Oncol. 2018; 37(2):116-122. DOI: 10.1016/j.urolonc.2018.11.011. View

Necchi A, Anichini A, Raggi D, Briganti A, Massa S, Luciano R . Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2018; 36(34):3353-3360. DOI: 10.1200/JCO.18.01148. View

Sui W, Lim E, DeCastro G, McKiernan J, Anderson C . Use of Adjuvant Chemotherapy in Patients with Advanced Bladder Cancer after Neoadjuvant Chemotherapy. Bladder Cancer. 2017; 3(3):181-189. PMC: 5545911. DOI: 10.3233/BLC-170107. View

10.

Wu S, Zheng J, Li Y, Yu H, Shi S, Xie W . A Radiomics Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer. Clin Cancer Res. 2017; 23(22):6904-6911. DOI: 10.1158/1078-0432.CCR-17-1510. View

11.

Fonteyne V, Dirix P, Van Praet C, Berghen C, Albersen M, Junius S . Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial. Eur Urol Focus. 2021; 8(5):1238-1245. DOI: 10.1016/j.euf.2021.11.004. View

12.

Wu S, Huang J, Liu Z, Chen H, Guo P, Cai Q . A Genomic-clinicopathologic Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Bladder Cancer. EBioMedicine. 2018; 31:54-65. PMC: 6014062. DOI: 10.1016/j.ebiom.2018.03.034. View

13.

Diaz D, Pollack A, Reis I, Mahmoud O, Gonzalgo M, Ishkanian A . Neoadjuvant Radiotherapy Improves Survival in Patients With T2b/T3 Bladder Cancer: A Population-Based Analysis. Clin Genitourin Cancer. 2015; 13(4):378-384.e1. DOI: 10.1016/j.clgc.2015.02.014. View

14.

Deyo R, Cherkin D, Ciol M . Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992; 45(6):613-9. DOI: 10.1016/0895-4356(92)90133-8. View

15.

Seisen T, Jamzadeh A, Leow J, Roupret M, Cole A, Lipsitz S . Adjuvant Chemotherapy vs Observation for Patients With Adverse Pathologic Features at Radical Cystectomy Previously Treated With Neoadjuvant Chemotherapy. JAMA Oncol. 2017; 4(2):225-229. PMC: 5838707. DOI: 10.1001/jamaoncol.2017.2374. View

16.

Saginala K, Barsouk A, Aluru J, Rawla P, Padala S, Barsouk A . Epidemiology of Bladder Cancer. Med Sci (Basel). 2020; 8(1). PMC: 7151633. DOI: 10.3390/medsci8010015. View

17.

Vickers A, Elkin E . Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making. 2006; 26(6):565-74. PMC: 2577036. DOI: 10.1177/0272989X06295361. View

18.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

19.

Bhindi B, Frank I, Mason R, Tarrell R, Thapa P, Cheville J . Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy: A Pathologic Stage-matched Analysis. Eur Urol. 2017; 72(5):660-664. DOI: 10.1016/j.eururo.2017.05.016. View

20.

Tian Z, Meng L, Wang X, Diao T, Hu M, Wang M . Predictive Nomogram and Risk Factors for Lymph Node Metastasis in Bladder Cancer. Front Oncol. 2021; 11:690324. PMC: 8242250. DOI: 10.3389/fonc.2021.690324. View