title: Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition.
abstract: OBJECTIVE
  Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options.
  
  
  METHODS
  The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer.
  
  
  RESULTS
  The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade.
  
  
  CONCLUSIONS
  The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression.
authors: Department of Surgery, University of Arizona and BCG Oncology, Phoenix, Arizona. Electronic address: dlamm@bcgoncology.com.
authors: Donald
authors: D
authors: Lamm
authors: Department of Urology/Surgery, Bristol Royal Infirmary & Bristol Urological Institute, Bristol, United Kingdom.
authors: Raj
authors: R
authors: Persad
authors: Department of Urology, AUSL Modena, Modena, Italy.
authors: Maurizio
authors: M
authors: Brausi
authors: Department of Urology, North York General Hospital, Toronto, Ontario, Canada.
authors: Roger
authors: R
authors: Buckley
authors: Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors: J Alfred
authors: JA
authors: Witjes
authors: Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Joan
authors: J
authors: Palou
authors: Department of Urology, HELIOS Agnes Karll Hospital, Bad Schwartau, Germany.
authors: Andreas
authors: A
authors: Böhle
authors: Department of Urology, MD Anderson Cancer Center, Houston, Texas.
authors: Ashish M
authors: AM
authors: Kamat
authors: Department of Urology, Claude Bernard University, Hôpital Edouard Herriot, Lyon, France.
authors: Marc
authors: M
authors: Colombel
authors: Department of Urology, University of Miami School of Medicine, Miami, Florida.
authors: Mark
authors: M
authors: Soloway
mesh_terms: D018450:Disease Progression; D006801:Humans; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
keywords: BCG; BCG vaccine; CIS; MMC; NMIBC; TURBT; administration; bacillus Calmette-Guérin; carcinoma in situ; disease progression; drug therapy; intravesical; mitomycin C; nonmuscle invasive bladder cancer; transurethral resection of the bladder tumor; urinary bladder neoplasms