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Authors: Stadler WM et al, ASCO 2009. Reviewed by: Dr. Lori Wood Abstract: 5017

Randomized Trial of p53 Targeted Adjuvant Therapy for Patients (pts) With Organ-Confined Node-Negative Urothelial Bladder Cancer (UBC). Authors: Stadler WM et al, ASCO 2009. Reviewed by: Dr. Lori Wood Abstract: 5017 Date posted: June 12, 2009. Treatment A: Adjuvant MVAC x 3. R.

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Authors: Stadler WM et al, ASCO 2009. Reviewed by: Dr. Lori Wood Abstract: 5017

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  1. Randomized Trial of p53 Targeted Adjuvant Therapy for Patients (pts) With Organ-Confined Node-Negative Urothelial Bladder Cancer (UBC) Authors: Stadler WM et al, ASCO 2009. Reviewed by: Dr. Lori Wood Abstract: 5017 Date posted: June 12, 2009

  2. Treatment A: Adjuvant MVAC x 3 R Treatment B: Observation pT1-T2 N0M0 urothelial cancer, post cystectomy and PLND p53 positive n = 272 (p53 positive) n = 114 randomized primary endpoint = time to recurrence (goal: improvement by 20% at 3 years)

  3. STUDY RATIONALE • Previous small studies showed that p53 positive tumors had  probability of recurrence post resection in organ confined bladder cancer. • Prior USC randomized trial of adjuvant chemotherapy versus observation showed improved outcome in p53 positive tumors. • p53 positive cells may be more susceptible to chemotherapy agents that damage DNA. • Hypothesis: • p53 IHC is a valid biomarker • p53 IHC is prognostic • p53 IHC is predictive for benefit from DNA damaging chemotherapy Cole et al, Nature 1997; 385:123

  4. RESULTS • 521 patients registered • 499 had successful p53 assessment • 272 p53 positive ( 10% nuclear reactivity) • 158 refused randomization • 114 randomized (only 42% of p53 positive) • 56 observation • 46 MVAC • 12 refused

  5. RESULTS (CONTINUED) • n = 499; 5-year relapse-free survival = 80%. • no difference if p53 positive or negative • n = 114; 5-year relapse-free survival = 83%. • no difference if MVAC or observation • Therefore, p53 positivity was not of prognostic or predictive value.

  6. STUDY COMMENTARY • Study was halted early by DSMB after review of futility analysis. • Only 42% of p53 positive patients were randomized. • Lower than expected event rate and failure (i.e.: 15% recurrence rate at 3 years) and the a priori hypothesis was  50%; therefore, study very underpowered. • Lower event rate probably because only pT1-T2 N0 disease and excluded pT3-T4 or N+ disease. • p53 positivity not predictive or prognostic.

  7. BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS • p53 as assessed by IHC will not help guide therapeutic decisions in resected bladder cancer at this point in time. • The role of adjuvant chemotherapy in all stages of (pT1-T4 N0 or N+) resected bladder cancer is still very controversial and understudied.

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