Cell cycle progression genes and recurrence after radical prostatectomy.

Genitourinary Cancer
Session Type and Session Title: 
Oral Abstract Session B: Prostate, Testis, Bladder, and Other GU Neoplasms
Reception and General Poster Session D: Testis, Bladder, Renal and Other GU Neoplasms
Abstract Number: 


G. P. Swanson, A. R. Brothman, J. E. Reid, V. O. Speights Jr., A. Younus, J. Park, D. D. Flake II, A. Gutin, J. S. Lanchbury, S. Stone; University of Texas Health Science Center at San Antonio, San Antonio, TX; University of Utah, Salt Lake City, UT; Myriad Genetics, Inc., Salt Lake City, UT; Scott and White Clinic, Temple, TX

Abstract Disclosures


Background: About 35% of patients undergoing radical prostatectomy (RP) eventually have biochemical recurrence. Predicting recurrence would help focus interventions on at risk patients, and spare those for whom no further treatment is warranted. Clinical parameters are often combined into prognostic models and although reasonably accurate, appear to have reached the upper limits of predictive accuracy. Specifically, there is the enigma of patients with what appears to be low-risk disease that eventually fail therapy. Therefore, there is need for biomarkers that improve our ability to predict disease outcome. Methods: Using quantitative RT-PCR on RNA from formalin fixed paraffin-embedded tumor samples, we measured the expression level of genes involved with cell cycle progression (CCP) in a retrospective post-RP cohort of 442 patients (median follow-up 9.5 years). The cohort was divided into training (N = 195) and validation sets (N = 247). Expression was associated with biochemical recurrence. Using traditional factors(organ confined, PSA and Gleason), we identified low- and high-risk patients and determined how the markers predicted outcome in each group. Results: The CCP signature alone was a significant predictor of biochemical recurrence in the training and validation cohorts (p-values of 0.01 and 5.8 × 10-8, respectively). After adjusting for clinical parameters, the signature was a significant predictor of disease outcome for low-risk patients in both the training (p-value = 0.0071) and validation cohorts (p-value = 1.9×10-4) with a validated negative predictive value of 0.95. Patients in the low-risk group with a low CCP score had a 5% 10 year recurrence rate versus 22% with a high CCP score. In the validation cohort only, the CCP signature was also prognostic in high-risk patients (p-value = 0.0026). For high-risk patients with a low CCP score, the recurrence rate was 36%, and 70% for patients with high CCP score. Conclusions: We developed and validated an expression signature that defines the risk of disease recurrence after RP. In combination with commonly employed postsurgical clinical parameters, the signature dramatically improves the prediction of recurrence in men with clinically defined low-risk disease.