NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Bladder Cancer Version 4.2019 — July 10, 2019 For important information regarding the BCG shortage NCCN.org see MS-11. Also see the AUA BCG Shortage Notice. Continue Version 4.2019, 07/10/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Bladder Cancer Discussion *Thomas W. Flaig, MD †/Chair Christopher Hoimes, MD † Anthony Patterson, MD ϖ University of Colorado Cancer Center Case Comprehensive Cancer Center/ St. Jude Children’s Research Hospital/ University Hospitals Seidman Cancer Center The University of Tennessee *Philippe E. Spiess, MD, MS ϖ/Vice Chair and Cleveland Clinic Taussig Cancer Institute Health Science Center Moffitt Cancer Center *Brant A. Inman, MD, MSc ϖ Elizabeth R. Plimack, MD, MS † Neeraj Agarwal, MD ‡ † Duke Cancer Institute Fox Chase Cancer Center Huntsman Cancer Institute at the University of Utah Masahito Jimbo, MD, PhD, MPH Þ Kamal S. Pohar, MD ϖ University of Michigan Rogel Cancer Center The Ohio State University Comprehensive Rick Bangs, MBA Cancer Center - James Cancer Hospital Patient Advocate ϖ A. Karim Kader, MD, PhD and Solove Research Institute UC San Diego Moores Cancer Center Stephen A. Boorjian, MD ϖ Michael Porter, MD, MS ϖ Mayo Clinic Cancer Center Subodh M. Lele, MD ≠ Fred Hutchinson Cancer Research Center/ Fred & Pamela Buffett Cancer Center Mark K. Buyyounouski, MD, MS § Seattle Cancer Care Alliance Stanford Cancer Institute ϖ Joshua J. Meeks, MD, PhD Mark A. Preston, MD, MPH ϖ Robert H. Lurie Comprehensive Cancer *Sam Chang, MD, MBA ¶ Dana-Farber/Brigham and Women’s Center of Northwestern University Vanderbilt-Ingram Cancer Center Cancer Center Jeff Michalski, MD, MBA § Tracy M. Downs, MD ϖ Wade J. Sexton, MD ϖ Siteman Cancer Center at Barnes- University of Wisconsin Moffitt Cancer Center Jewish Hospital and Washington Carbone Cancer Center University School of Medicine Arlene O. Siefker-Radtke, MD † Jason A. Efstathiou, MD, DPhil § The University of Texas Jeffrey S. Montgomery, MD, MHSA ϖ Massachusetts General Hospital MD Anderson Cancer Center University of Michigan Rogel Cancer Center Cancer Center Jonathan Tward, MD, PhD § Lakshminarayanan Nandagopal, MD † Terence Friedlander, MD † Huntsman Cancer Institute University of Alabama at Birmingham UCSF Helen Diller Family at the University of Utah Comprehensive Cancer Center Comprehensive Cancer Center Jonathan Wright, MD ϖ Lance C. Pagliaro, MD † *Richard E. Greenberg, MD ϖ Fred Hutchinson Cancer Research Center/ Mayo Clinic Cancer Center Fox Chase Cancer Center Seattle Cancer Care Alliance Sumanta K. Pal, MD † Khurshid A. Guru, MD ϖ NCCN City of Hope National Medical Center Roswell Park Comprehensive Cancer Center Lisa Gurski, PhD Alyse Johnson-Chilla, MS Harry W. Herr, MD ϖ Memorial Sloan Kettering Cancer Center ‡ Hematology/Hematology § Radiotherapy/Radiation Continue oncology oncology NCCN Guidelines Panel Disclosures Þ Internal medicine ¶ Surgery/Surgical Oncology † Medical oncology ϖ Urology ≠ Pathology * Discussion writing committee member Version 4.2019, 07/10/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Bladder Cancer Discussion NCCN Bladder Cancer Panel Members Summary of the Guidelines Updates Clinical Trials: NCCN believes that the best management for any patient Introduction with cancer is in a clinical trial. Bladder Cancer Participation in clinical trials is • Clinical Presentation and Initial Evaluation (BL-1) especially encouraged. • Noninvasive or Tis, Primary Evaluation/Surgical Treatment (BL-1) To find clinical trials online at NCCN Secondary Surgical Treatment, Adjuvant Intravesical Treatment, Follow-up (BL-2) Member Institutions, click here: Posttreatment cTa, cT1, Tis Recurrent or Persistent Cancer (BL-3) nccn.org/clinical_trials/clinicians.aspx. • Muscle Invasive or Metastatic, Primary Evaluation/Surgical Treatment, Additional Workup (BL-1) Stage II (cT2, N0) Primary and Adjuvant Treatment (BL-4) NCCN Categories of Evidence and All recommendations Stage IIIA (cT3, N0; cT4a, N0; cT1-cT4a, N1) Primary and Adjuvant Treatment (BL-6) Consensus: are category 2A unless otherwise Stage IIIB (cT1-cT4a, N2,3) Primary and Subsequent Treatment (BL-7) indicated. Stage IVA (cT4b, Any N, M0; Any T, Any N, M1a) Primary and Subsequent Treatment (BL-8) Metastatic Disease, Additional Workup, Primary Treatment (BL-9) See NCCN Categories of Evidence Follow-up, Recurrent or Persistent Disease (BL-10) and Consensus. • Principles of Imaging for Bladder/Urothelial Cancer (BL-A) NCCN Categories of Preference: • Principles of Surgical Management (BL-B) All recommendations are considered • Principles of Pathology Management (BL-C) appropriate. • Bladder Cancer: Non-Urothelial and Urothelial with Variant Histology (BL-D) • Follow-up (BL-E) See NCCN Categories of Preference. • Principles of Intravesical Treatment (BL-F) • Principles of Systemic Therapy (BL-G) • Principles of Radiation Management of Invasive Disease (BL-H) Upper GU Tract Tumors: • Renal Pelvis (UTT-1) • Urothelial Carcinoma of the Ureter (UTT-2) • Urothelial Carcinoma of the Prostate (UCP-1) • Primary Carcinoma of the Urethra (PCU-1) Staging (ST-1) The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2019. Version 4.2019, 07/10/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Bladder Cancer Discussion Updates in Version 4.2019 of the NCCN Guidelines for Bladder Cancer from Version 3.2019 include: MS-1 • The discussion section was updated to reflect the changes in the algorithm. Updates in Version 3.2019 of the NCCN Guidelines for Bladder Cancer from Version 2.2019 include: BL-7 • Additional Workup, Molecular/genomic testing, footnote w is new: "Including FGFR RGQ RT-PCR for FGFR3 or FGFR2 genetic alterations." Also for BL-8. BL-9 • "including FGFR RGQ RT-PCR for FGFR3 or FGFR2 genetic alterations." was added to footnote bb. BL-G (3 of 5) • Subsequent systemic therapy for locally advanced or metastatic disease: Erdafitinib was added as an alternative preferred regimen for patients with FGFR3 or FGFR2 genetic alterations with appropriate reference. Updates in Version 2.2019 of the NCCN Guidelines for Bladder Cancer from Version 1.2019 include: Global • Note added directing user to the discussion section and a link to the AUA notice for more information regarding the BCG shortage. BL-F (1 of 3) • Induction (Adjuvant) Intravesical Chemotherapy or BCG: The third bullet and sub bullets are new. • Maintenance Intravesical BCG: The second bullet and sub bullet are new. MS-11 • A section with additional information on the BCG shortage was added. Updates in Version 1.2019 of the NCCN Guidelines for Bladder Cancer from Version 4.2018 include: Bladder Cancer INTRO BL-2 • This is a new page. • Footnote j was updated: "The most commonly used options for intravesical chemotherapy are gemcitabine (preferred) and BL-1 mitomycin." • Primary Evaluation/Surgical Treatment: "Preferred" added to BL-3 gemcitabine. • "Cystoscopy positive" and "cystoscopy suspicious for recurrence • Footnote c was updated: "Immediate intravesical chemotherapy post-intravesical therapy; no more than 2 consecutive cycles," reduces the recurrence rate by 35%. not immunotherapy, has been evaluation: "Preferred" added to gemcitabine. shown to decrease recurrence for patients with suspected non- • Top pathway, treatment updated: "Based on tumor stage and grade: muscle invasive bladder cancer based on cystoscopic appearance. Adjuvant intravesical therapy or Cystectomy based on tumor stage See Principles of Intravesical Treatment (BL-F)." (Also for BL-3) and grade." Continued Version 4.2019, 07/10/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. UPDATES NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Bladder Cancer Discussion Updates in Version 1.2019 of the NCCN Guidelines for Bladder Cancer from Version 4.2018 include: BL-3 (continued) Principles of Imaging for Bladder/Urothelial Cancer • Bottom pathway, Tis or cTa: "(preferred for cT1, high grade)" was BL-A (2 of 5) added to cystectomy.