Positive STAT5 Protein and Locus Amplification Status Predicts Recurrence after Radical Prostatectomy to Assist Clinical Precision Management of Prostate Cancer
Year: 2019
Type: article
Study design: Observational Study
Abstract: Background: A significant fraction of prostate cancer patients experience post–radical prostatectomy (RP) biochemical recurrence (BCR). New predictive markers are needed for optimizing postoperative prostate cancer management. STAT5 is an oncogene in prostate cancer that undergoes amplification in 30% of prostate cancers during progression. Methods: We evaluated the significance of a positive status for nuclear STAT5 protein expression versus STAT5 locus amplification versus combined positive status for both in predicting BCR after RP in 300 patients. Results: Combined positive STAT5 status was associated with a 45% disadvantage in BCR in Kaplan–Meier survival analysis in all Gleason grade patients. Patients with Gleason grade group (GG) 2 and 3 prostate cancers and combined positive status for STAT5 had a more pronounced disadvantage of 55% to 60% at 7 years after RP in univariate analysis. In multivariate analysis, including the Cancer of the Prostate Risk Assessment Postsurgical nomogram (CAPRA-S) variables, combined positive STAT5 status was independently associated with a shorter BCR-free survival in all Gleason GG patients (HR, 2.34; P = 0.014) and in intermediate Gleason GG 2 or 3 patients (HR, 3.62; P = 0.021). The combined positive STAT5 status improved the predictive value of the CAPRA-S nomogram in both ROC-AUC analysis and in decision curve analysis for BCR. Conclusions: Combined positive status for STAT5 was independently associated with shorter disease-free survival in univariate analysis and was an independent predictor for BCR in multivariate analysis using the CAPRA-S variables in prostate cancer. Impact: Our results highlight potential for a novel precision medicine concept based on a pivotal role of STAT5 status in improving selection of prostate cancer patients who are candidates for early adjuvant interventions to reduce the risk of recurrence.
Institutions: Georgetown University, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, University of Helsinki, Institute for Molecular Medicine Finland, Medical College of Wisconsin, Medical College of Wisconsin Cancer Center, Marquette University, University of Turku, Turku University Hospital, Helsinki University Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Bayesian learning algorithms for identifying and classifying heterogeneity of cell types in variety of solid tumors, G5060443699, Novel Strategy to Sensitize Prostate Cancer Cells to Radiation, G6443763734, Stat5 in Progression of Prostate Cancer, Brain Cancer Radio-Pathomics for Predicting Heterogeneous Cytology
OpenAlex ID: W2961357662