Association of PTEN loss with outcome of patients (pts) with early high-risk prostate cancer (CaP) treated with adjuvant docetaxel following radical prostatectomy (RP)

Autor: D. Keizman, Z. Zhang, A. DeMarzo, B. Gurel, T. Lotan, J. Hicks, E. Rosenbaum, E. S. Antonarakis, M. A. Carducci, M. A. Eisenberger
Rok vydání: 2011
Předmět:
Zdroj: Journal of Clinical Oncology. 29:43-43
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2011.29.7_suppl.43
Popis: 43 Background: Loss of the PTEN tumor suppressor and subsequent activation of the PI3K pathway is common and has potential clinical and therapeutic value in CaP. We examined the PTEN status of primary tumors in pts who underwent adjuvant docetaxel tx in a prospective clinical trial. Methods: Of the 77 pts enrolled in a prospective multi-institutional adjuvant docetaxel trial (TAX 2501, J Urol 2007), we prospectively collected 56 primary tumor pathology specimens suitable for analysis of PTEN status by immunoreactivity (IHC) and/or fluorescence in situ hybridisation (FISH) assay. Protocol defined progression included a PSA of ≥ 0.4 ng/mL, radiological/pathological evidence of recurrent disease or death from any cause. Univariate and multivariable analyses based on the Cox proportional hazards regression model were used to analyze the independent association of PTEN and other known prognostic factors with progression free survival (PFS). Results: PTEN loss was observed in 37/56 pts (66%). Pts with PTEN loss vs detectable PTEN were balanced regarding clinical stage, combined Gleason score, seminal vesicles and surgical margins involvement, and lymph nodes status. Pts with a detectable PTEN had a significantly higher pre-RP PSA (median 14 vs 8.6 ng/mL, p=0.015). 41/56 (73.2%, median followup of 37.5 months, range 10.4 to 44.5) progressed with an overall median PFS of 13 months (mos) (95% CI 9.8–15.8). Independent prognostic factors of progression by multivariate analysis were: seminal vesicles involvement (HR 2.19, p=0.024), combined Gleason score 9–10 (HR 2.46, p=0.027) and PTEN loss (HR 2.36, p=0.037). PFS on pts without PTEN loss (median not reached at a followup time of 37.5 mos, range 10.4–44.5 mos) was significantly longer (log rank test, p = 0.026) compared to those with undetectable PTEN (median PFS 12.9 mos, 95% CI 9.7–15.3). Conclusions: PTEN loss may be an independent prognostic factor associated with poorer outcome of pts with early high-risk CaP treated with adjuvant docetaxel following RP. These findings may have important prognostic and therapeutic implications in CaP. No significant financial relationships to disclose.
Databáze: OpenAIRE
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