Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder Cancer

No AccessJournal of UrologyAdult Urology1 Oct 2021Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder CancerThis article is commented on by the following:Editorial Comment Nicholas H. Chakiryan, Da David Jiang, Kyle A. Gillis, Elizabeth Green, Ali Hajiran, Lee Hugar, Logan Zemp, Jingsong Zhang, Rohit Jain, Jad Chahoud, Michael Poch, Brandon J. Manley, Roger Li, Wade Sexton, and Scott M. Gilbert Nicholas H. ChakiryanNicholas H. Chakiryan *Correspondence: Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, Florida 33612 telephone: 813-745-3208; FAX: 813-745-8494; E-mail Address: [email protected] http://orcid.org/0000-0001-9263-8957 Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Da David JiangDa David Jiang Department of Urology, Beth Israel Deaconess Medical Center, Boston, Massachusetts , Kyle A. GillisKyle A. Gillis Department of Urology, University of Iowa Hospitals & Clinics, Iowa City, Iowa , Elizabeth GreenElizabeth Green Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Ali HajiranAli Hajiran Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Lee HugarLee Hugar Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Logan ZempLogan Zemp Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Jingsong ZhangJingsong Zhang Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Rohit JainRohit Jain Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Jad ChahoudJad Chahoud Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Michael PochMichael Poch Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Brandon J. ManleyBrandon J. Manley Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Roger LiRoger Li Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , Wade SextonWade Sexton Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida , and Scott M. GilbertScott M. Gilbert Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida View All Author Informationhttps://doi.org/10.1097/JU.0000000000001855AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC. Materials and Methods: Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS. Results: A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6–5.6]; sarcomatoid UC: OR 13.8 [5.5–39.0]; micropapillary UC: OR 9.7 [2.8–46.8]; squamous cell carcinoma: OR 7.4 [2.1–24.5]; neuroendocrine: OR 4.7 [2.6–9.2]; adenocarcinoma: OR 23.3 [8.0–74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77–0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43–0.70]). Conclusions: Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma. REFERENCES 1. : Cancer statistics, 2021. CA Cancer J Clin 2021; 71: 7. Google Scholar 2. : Oncological outcome of primary and secondary muscle-invasive bladder cancer: a systematic review and meta-analysis. Sci Rep 2018; 8: 7543. Google Scholar 3. : Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2020; 18: 329. Google Scholar 4. : Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO Guideline. J Urol 2017; 198: 552. Link, Google Scholar 5. : Updated 2016 EAU guidelines on muscle-invasive and metastatic bladder cancer. Eur Urol 2017; 71: 462. Google Scholar 6. : Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003; 349: 859. Google Scholar 7. Advanced Bladder Cancer Meta-analysis Collaboration: Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005; 48: 202. Google Scholar 8. : Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist 2016; 21: 708. Google Scholar 9. : Characteristics and clinical significance of histological variants of bladder cancer. Nat Rev Urol 2017; 14: 651. Google Scholar 10. : What is the prognostic and clinical importance of urothelial and nonurothelial histological variants of bladder cancer in predicting oncological outcomes in patients with muscle-invasive and metastatic bladder cancer? A European association of urology muscle invasive and metastatic bladder cancer guidelines panel systematic review. Eur Urol Oncol 2019; 2: 625. Google Scholar 11. : Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). BJU Int 2011; 108: 693. Google Scholar 12. : Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology. Cancer 2017; 123: 4346. Google Scholar 13. : Pathological and survival outcomes associated with variant histology bladder cancers managed by cystectomy with or without neoadjuvant chemotherapy. J Urol 2021; 205: 100. Link, Google Scholar 14. : Molecular predictors of complete response following neoadjuvant chemotherapy in urothelial carcinoma of the bladder and upper tracts. Int J Mol Sci 2019; 20: 793. Google Scholar 15. : Genomic differences between “primary” and “secondary” muscle-invasive bladder cancer as a basis for disparate outcomes to cisplatin-based neoadjuvant chemotherapy. Eur Urol 2019; 75: 231. Google Scholar 16. Commission on Cancer:Facility Oncology Registry Data Standards. 2016. Chicago, Illinois: American College Of Surgeons 2016. Available at https://www.facs.org/-/media/files/quality-programs/cancer/ncdb/fords-2016.ashx. Accessed December 14, 2020. Google Scholar 17. National Cancer Institute Surveillance, Epidemiology, and End Results Program:ICD-O-3 Coding Materials. 2020. Available at https://seer.cancer.gov/icd-o-3/. Accessed December 12, 2021. Google Scholar 18. : Optimizing the sequence of chemotherapy for upper tract urothelial carcinoma with clinically positive regional lymph nodes. J Urol 2019; 202: 76. Link, Google Scholar 19. : Trends in the utilization of neoadjuvant chemotherapy in muscle-invasive bladder cancer: results from the National Cancer Database. Urology 2014; 83: 75. Google Scholar 20. : Effectiveness of neoadjuvant chemotherapy for muscle-invasive bladder cancer in the current real world setting in the USA. Eur Urol Oncol 2018; 1: 83. Google Scholar 21. : Unconventional bladder preservation: factors predicting failure to receive definitive surgery following chemotherapy for nonmetastatic muscle invasive bladder cancer in the National Cancer Database. J Urol 2018; 200: 535. Link, Google Scholar 22. National Cancer Institute Surveillance, Epidemiology, and End Results Program:SEER*Rx Interactive Antineoplastic Drugs Database. 2020. Available at https://seer.cancer.gov/seertools/seerrx/. Accessed December 14, 2020. Google Scholar 23. : A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373. Google Scholar 24. : Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992; 45: 613. Google Scholar Editor's Note: This article is the second of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1074 and 1075. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited BySmith J (2021) This Month in Adult UrologyJournal of Urology, VOL. 206, NO. 4, (799-800), Online publication date: 1-Oct-2021.Related articlesJournal of UrologyJun 13, 2021, 12:00:00 AMEditorial Comment Volume 206Issue 4October 2021Page: 924-932Supplementary Materials Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Keywordsneoadjuvant therapydrug therapycystectomyurinary bladder neoplasmsMetricsAuthor Information Nicholas H. Chakiryan Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida *Correspondence: Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Tampa, Florida 33612 telephone: 813-745-3208; FAX: 813-745-8494; E-mail Address: [email protected] More articles by this author Da David Jiang Department of Urology, Beth Israel Deaconess Medical Center, Boston, Massachusetts More articles by this author Kyle A. Gillis Department of Urology, University of Iowa Hospitals & Clinics, Iowa City, Iowa More articles by this author Elizabeth Green Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Ali Hajiran Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Lee Hugar Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Logan Zemp Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Jingsong Zhang Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida Financial interest and/or other relationship with AstraZeneca, Bayer, Seagen, Clovis Oncology, Dendreon, Merck and Sanofi. More articles by this author Rohit Jain Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Jad Chahoud Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida Financial interest and/or other relationship with Seattle Genetics, Gilead and EMD Soreno. More articles by this author Michael Poch Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Brandon J. Manley Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida Financial interest and/or other relationship with Merck, Department of Defense and University of South Florida Office of Continuing Medical Education, and NCCN speaker and panel member, GU ASCO speaker, AUA Urology Care Scholar Award recipient, expert witness and recipient of Kidney Cancer Association Young Investigator Award. More articles by this author Roger Li Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Wade Sexton Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Scott M. Gilbert Department of Genitourinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida More articles by this author Expand All Editor's Note: This article is the second of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 1074 and 1075. Advertisement PDF DownloadLoading ...