Prognostic Value of Abnormal p53 Expression in Locally Advanced Prostate Cancer Treated With Androgen Deprivation and Radiotherapy: A Study Based on RTOG 9202

• Published in: International journal of radiation oncology, biology, physics Vol. 69; no. 4; pp. 1117 - 1123
• Main Authors: Che, Mingxin, M.D., Ph.D, DeSilvio, Michelle, Ph.D, Pollack, Alan, M.D., Ph.D, Grignon, David J., M.D, Venkatesan, Varagur Mohan, M.D, Hanks, Gerald E., M.D, Sandler, Howard M., M.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2007
• Subjects: Aged; Analysis of Variance; Androgen Antagonists - therapeutic use; Androgen deprivation and radiotherapy; ANDROGENS; Biomarkers, Tumor - metabolism; CARCINOMAS; Cause of Death; Combined Modality Therapy - methods; HEALTH HAZARDS; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Locally advanced prostate cancer; Male; METASTASES; MORTALITY; p53; PATIENTS; Prognosis; Prognostic factor; PROSTATE; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; RTOG 9202; Survival Analysis; TUMOR CELLS; Tumor Suppressor Protein p53 - metabolism; Immunohistochemistry; Prognostic factor; RTOG 9202; Locally advanced prostate cancer; Androgen deprivation and radiotherapy; p53
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2007.04.070

Purpose The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca). Methods and Materials Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes. Results Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 – 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13–2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32–4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40–10.37; p = 0.0087). Conclusions Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.