DEFINING PROGRESSION IN NONMUSCLE INVASIVE BLADDER CANCER: IT IS TIME FOR A NEW, STANDARD DEFINITION

Donald Lamm,*, Raj Persad, Maurizio Brausi, Roger Buckley, J. Alfred Witjes, Joan Palou, Andreas Bohle, Ashish M. Kamat,jj Marc Colombel and Mark Soloway

The most important clinical outcomes in nonmuscle invasive bladder cancer There is currently no standard definition of disease progression. New defination prognosis and comparing treatment option

MATERIALS AND METHODS IBCG : analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012 critically review the literature and form consensus The members of the IBCG (the authors) met on 2 occasions (June 23, 2012 and April 6, 2013)

RESULTS

Current Definitions of Progression : definitions of progression in NMIBC is an increase in stage from nonmuscle invasive disease, stage Ta, T1 or CIS to muscle invasive disease stage T2 or > stage T3, T4, lymph node positive (N+) or metastatic (M+) because of the major difference in prognosis and treatment between nonmuscle invasive and muscle invasive disease

Limitations of Current Definitions : Given the discrepancies in progression outcomes in therapeutic trials, a standard definition of progression is required to improve the consistency of these reports and help better select appropriate interventions for patients with NMIBC Ideal criteria : as were other parameters of advancing disease beyond local stage progression.

Increase from stage Ta to T1 disease (lamina propria invasion): IBCG agreed that

progression to lamina propria invasion (Ta to T1) included in the definition of NMIBC progression
Increase in stage from CIS to T1 (lamina propria

Invasion) Anatomically an increase in stage from CIS (urothelium) to T1 (lamina propria invasion) is clear evidence of disease progression, IBCG recommends : included in the definition of stage progression

Increase from nonmuscle invasive to muscle invasivebladder cancer or metastatic disease

the IBCG agreed that an increase fromnonmuscle invasive to muscle invasive bladdercancer or metastatic disease should be included in a standard definition of disease progression

Grade :

Grade is a better prognostic indicator of progression and mortality than recurrence Based on this evidence the IBCG agreed that increase in grade is evidence of advancing disease that has prognostic importance, and recommends that grade progression be included in a standard definition of NMIBC

CONCLUSIONS
The group proposes that this new definition encompass grade and stage progression, progression from low to high grade disease (including CIS), and from stage Ta or CIS to lamina propria invasion (Appendix 3) The IBCG investigators examining disease progression in NMIBC consider the use of this new definition in future trials or, at a minimum, ensure that progression is clearly defined in publications and protocols.

CONT

the proposed definition as shown in Appendix 3 has yet to be validated and anticipates that use of this definition in upcoming NMIBC studies will help provide the data required for its validation. The IBCG further acknowledges that tumors are often under staged on initial resection due to incomplete resection and, therefore, emphasizes the importance of thorough TURBT with adequate deep and lateral margins, as well as repeat resectionfor high grade, T1 tumors

APPENDIX 2

Lay and general medical definitions of progression

Merriam-Webster16 The action or process of progressing: advance MedlinePlus17 Progressive: increasing in extent or severity; a progressive disease Tabers Online18 An advancing or moving forward (Latin: progressus) National Cancer Institute19 In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body

Appendix 3

IBCG consensus definition for progression in NMIBC

Presence or development of any of the following: Stage progression: Development of or increase in stage to: Lamina propria invasion: - eg increase from Ta to T1, or CIS to T1 Muscle invasive disease (stage T2 or greater) Lymph node (N) or distant metastasis (M1) disease (patient must have previously been diagnosed with N0 and/or M0 disease) Grade progression: Increase in grade from low to high (including CIS)

Terima Kasih