p21 and p53 as prognostic factors for bladder preservation and survival in patients with bladder cancer treated with neoadjuvant chemotherapy

Reviewer: Ryan Smith, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 20 de mayo del 2002

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Presenter: Garcia Del Muro
Presenter's Affiliation: Institut Catala d'Oncologia-Ciutat Sanitaria de Bellvitge
Type of Session: Scientific

Background

    Muscle invasive cancer has traditionally been treated with cystectomy. However, more recently, combined chemoradiation has been used as a bladder sparing regimen in selected patients. This study investigates the presence of p53 and p21 mutations as prognostic factors in this group of patients.

Materials and Methods

  • Tumor samples from 82 consecutive patients with muscle invading (T2-4a) TCC were analyzed
  • A positive phenotype was denoted to be >20% (+) staining for p53 and p21
  • These patients were all treated with TUR followed by chemotherapy and rebiopsy. If CR was obtained, they received 64 Gy of radiation to complete bladder sparing treatment. If CR was not obtained, cystectomy was performed.
  • 3 different chemotherapy regimens were used (MVAC, accelerated CMV, or carboplatin, vinblastine, and methotrexate)
  • Median FU was 55 months

Results

  • Median age was 61
  • 71 patients had T2 tumors, with the remaining 11 having T3-4a tumors
  • 47% were positive for p53
  • 52% were positive for p21
  • 5 yr OS for the entire group was 54% 5 yr DFS for the entire group was 47.5%
  • 5yr bladder preservation survival (BPS) for the entire group was 40%
  • p53 (p=.02) and p21 (p=.02) immunoreactivity together was an independent predictor of decreased survival
  • p53 and p21 were predictors of poor DFS (p<.01)
  • p53 was a predictor of decreased OS (p=.01)
  • Though exact numbers for BPS, DFS, and OS were not presented, the combination of p53 and p21 immunoreactivity carried a hazard rate for DFS of 5.47 and a hazard rate for OS of 4.12

Author's Conclusions

  • Lack of p53 and p21 expression has prognostic value for long term bladder preservation and survival in bladder cancer
  • This could be useful in selecting therapy

Clinical/Scientific Implications

    Selective bladder preservation with TUR followed by chemoradiation is an alternative to cystectomy. It is known that advanced T stage tumors and bulky tumors do poorly with bladder preservation. However, further prognostic factors are needed to select who should be eligible for this therapy. In addition, with conflicting results of adjuvant chemotherapy in patients who receive cystectomy, more prognostic factors are needed to attempt to determine who could benefit from this chemotherapy. Prior studies have shown p53 is associated with poor survival and that p21 expression is associated with chemoresistance. This study continues to support this, as the differences in outcome presented in the data are likely due to the tumors' responses to chemotherapy. For further investigation, screening and stratification for p53 and p21 reactivity should be done to determine if it is these patients that benefit from chemotherapy. Therefore, the population of patients with muscle invasive bladder cancer who should be offered chemotherapy can be better defined, with the now cloudy results with adjuvant chemotherapy hopefully made clearer.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.



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