Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation
Journal Article
·
· International Journal of Radiation Oncology, Biology and Physics
- Academic Urology Unit, Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)
- Department of Cellular Pathology, St. George's Hospital, Tooting (United Kingdom)
- Statistics, Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)
Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation. Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome. Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression. Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.
- OSTI ID:
- 21436138
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 78; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
Similar Records
Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy
Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?
Percentage of Biopsy Cores Positive for Malignancy and Biochemical Failure Following Prostate Cancer Radiotherapy in 3,264 Men: Statistical Significance Without Predictive Performance
Journal Article
·
Sat May 01 00:00:00 EDT 2010
· International Journal of Radiation Oncology, Biology and Physics
·
OSTI ID:21372250
Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable Is High-Risk Disease?
Journal Article
·
Wed Nov 30 23:00:00 EST 2011
· International Journal of Radiation Oncology, Biology and Physics
·
OSTI ID:22054471
Percentage of Biopsy Cores Positive for Malignancy and Biochemical Failure Following Prostate Cancer Radiotherapy in 3,264 Men: Statistical Significance Without Predictive Performance
Journal Article
·
Sat Mar 15 00:00:00 EDT 2008
· International Journal of Radiation Oncology, Biology and Physics
·
OSTI ID:21039840