Marker Lesion Experiments in Bladder Cancer—What Have We Learned?
Received 4 July 2009 published online 17 March 2010.
Refers to article:
Are We Making Significant Progress in the Diagnosis and Management of Bladder Cancer?
, 17 March 2010
G. Joel DeCastro, Gary D. Steinberg
The Journal of Urology
May 2010 (Vol. 183, Issue 5, Pages 1667-1668) Full Text |
Full-Text PDF (107 KB)
Purpose
In marker lesion experiments a single bladder tumor is deliberately left unresected for later ablation by intravesical instillation of a novel agent. While the benefits are clear, eg the opportunity to examine the effect of therapy on measurable disease, the safety and medical ethics of these experiments are less obvious. We review the goals, inclusion criteria, definition of success, agents used, effectiveness, safety and ethics of marker lesion studies, and suggest a framework for future experiments.
Materials and Methods
Published bladder cancer studies using the marker lesion concept were identified with a MEDLINE® search through March 2009.
Results
A total of 23 well documented marker lesion studies were identified involving more than 1,200 patients. Most agents studied were cytotoxins (mitomycin-C, epirubicin, gemcitabine, valrubicin, apaziquone) or immune response modifiers (bacillus Calmette-Guerin, tumor necrosis factor-α, interferon-α, granulocyte-macrophage colony-stimulating factor). The highest complete response rate in intermediate risk patients (67%) was attained with apaziquone. Patients who achieved a complete response with this agent also had a prophylactic benefit with a 2-year recurrence-free rate of 45.2% compared to 26.7% in those who did not achieve a complete response. The complete response rate in bacillus Calmette-Guerin trials ranged from 32% to 61%. Marker lesion experiments were deemed safe with progression to T2 disease in only 7 patients (0.6%) and only when high risk patients were selected.
Conclusions
Marker lesion studies are most appropriate for the evaluation of novel anticancer therapeutics. Only patients with multiple recurrent, noninvasive, low grade tumors (intermediate risk) should be recruited. Primary end points should be complete response and recurrence rates after 2 to 3 years.
aDepartment of Urology, Hadassah Hebrew University Hospital, Jerusalem, Israel
bDepartment of Surgery, Section of Urology, University of Chicago Medical Center, Chicago, Illinois
Correspondence: Department of Urology, Hadassah University Hospital, P.O. Box 12000, Jerusalem 91120, Israel (telephone: +972-2-6776874; FAX: +972-2-6430929)
ABSTRACT