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Authors Ritter MA, Gilchrist KW, Jarrard DF, Verhoven BM
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Journal J. Clin. Oncol. Volume: 22 Issue: 14_suppl Pages: 9604
Publish Date 2004 Jul 15
PubMed ID 28016190
Abstract

9604 Background: Prognostic groupings using PSA, grade and stage still leave significant unexplained outcome variability. Biological heterogeneity is likely a factor, emphasizing the importance of integrating biomarker data into predictive and prognostic paradigms. Novel therapy targeting options might also be identified along the way. The status of one such biomarker, p53, could alter curative-intent radiotherapy outcomes based on its position in radioresponse pathways. We therefore identified a cohort of low-to-moderate risk, previously-treated radiotherapy patients and determined PSA failure rates as a function of pretreatment p53 tumor status. A prognostically matched surgery group was studied in parallel to test whether p53 had true predictive specificity for radiation outcome or was only a global prognostic factor.A total of 81 and 53 patients were identified who previously underwent a radical prostatectomy or radiotherapy(68-70 Gy), respectively, and who shared similarly favorable characteristics (PSA ≤ 20 ng/ml, Gleason score ≤ 7; no hormonal therapy before failure; 6 yr median follow-up). Abnormal p53 status (≥ 10% labeling index) was determined immunohistochemically in pretreatment biopsy specimens.About 34% of both surgery and radiation patient biopsy specimens had abnormal p53 labeling. The two groups had very similar 5-year actuarial PSA failure rates of about 31%. Multivariate analyses including stage, grade and initial PSA revealed that abnormal p53 strongly correlated with actuarial PSA failure in radiotherapy (hazard ratio of 4.6; p < 0.001), but not in surgery patients (hazard ratio of 2.14; p = 0.22).Abnormal pretreatment p53 status in favorable patients strongly and independently predicted for PSA failure after radiotherapy but not radical prostatectomy. This radiation-specific predictive power for outcome, if further validated, could significantly influence patient management. Beyond simple stratification, pretreatment p53 testing could identify a role for altered treatment – perhaps aggressive dose escalation or a novel p53 targeting strategy. No significant financial relationships to disclose.


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