A genomic classifier independently prognostic of prostate cancer death in a high-risk surgical cohort.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 60-60
Author(s):  
Matthew R. Cooperberg ◽  
Anamaria Crisan ◽  
Anirban Pradip Mitra ◽  
Mercedeh Ghadessi ◽  
Christine Buerki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cox Model ◽  
Ratio Test ◽  
Net Benefit ◽  
Prognostic Information ◽  
Full Data ◽  
Combined Model ◽  
Prostate Cancer Death ◽  
Cox Analysis

60 Background: Biomarkers may improve ascertainment of progression risk after radical prostatectomy (RP). We compared two validated post-RP classifiers: the Decipher genomic classifier (GC) and CAPRA-S (based on standard clinicopathologic parameters), to predict prostate cancer-specific mortality (CSM) in a contemporary cohort of RP patients. Methods: From a cohort of 1,010 RP patients treated from 2000-06, a case-cohort design was used to analyze a subset of 219 men with one or more high risk features and available paraffin-embedded tissue. Median follow-up was 6 years. The GC, derived from expression levels of 22 biomarkers and dichotomized to denote low- and high-risk, and CAPRA-S, calculated from preoperative PSA and pathologic grade and staging variables, scores were determined. The scores were evaluated individually and in combination using concordance index, decision curve, (DC), re-classification, and Cox analyses for prediction of CSM. Results: 212 men had full data available to calculate the CAPRA-S; 27 experienced CSM. The c-index for GC (0.78) and CAPRA-S (0.76) were similar, although GC showed improved calibration and higher net-benefit on DC analysis. In 103 patients with high-risk CAPRA-S scores (≥6), GC scores were likewise high-risk for 49, among whom 19 had CSM events. The other 54 men were reclassified as low-risk by GC; among these only 1 CSM event was observed. In multivariable Cox analysis both GC and CAPRA-S were independently prognostic of CSM, with hazard ratios of 1.62 (p<0.001) and 1.22 (p=0.01), respectively for unit score increases. A combined model defined based on the Cox model as (0.20*CAPRA-S + 5.68*GC) was more accurate than either score alone (p<0.001 by likelihood ratio test). DC analysis indicated greater net benefit for the combined model than for either score alone. Conclusions: In men treated with RP at high risk of recurrence based on clinical and pathologic variables, both GC and CAPRA-S were significant predictors of CSM. Notably, GC was able to 'down-risk' >50% of men stratified to high risk based on CAPRA-S alone. Thus the GC provides independent prognostic information, and a model integrating GC and CAPRA-S may further improve the prediction of lethal prostate cancer.

2243 COMBINED VALUE OF GENOMIC BIOMARKERS AND CAPRA-S IN PREDICTING PROSTATE CANCER DEATH IN A HIGH-RISK SURGICAL COHORT

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Matthew Cooperberg ◽  
Anamaria Crisan ◽  
Anirban Mitra ◽  
Mercedeh Ghadessi ◽  
Christine Buerki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cancer Death ◽  
Genomic Biomarkers ◽  
Prostate Cancer Death

Is clinical stage T2c prostate cancer intermediate- or high-risk disease? Results from the SEARCH database.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 123-123
Author(s):  
Abhay A Singh ◽  
Leah Gerber ◽  
Stephen J. Freedland ◽  
William J Aronson ◽  
Martha K. Terris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Risk Stratification ◽  
Predictive Accuracy ◽  
Cox Model ◽  
Clinical Stage ◽  
Prostate Cancer Risk ◽  
Clinical Staging ◽  
Intermediate Risk ◽  
Concordance Index

123 Background: Clinical stage T2c is a nebulous factor in the algorithm for prostate cancer risk stratification. According to D’Amico risk stratification cT2c is high-risk category where NCCN guidelines place this stage in intermediate-risk. As diagnostic work up with the use of MRI continues to escalate clinical staging may become more important. As cT2c represents a possible decision fork in treatment decisions we sought to investigate which risk group the clinical behavior of cT2c tumors more closely resembles. Methods: We retrospectively analyzed data from 1089 men who underwent radical prostatectomy (RP) from 1988 to 2009 who did not have low-risk CaP from the SEARCH database. We compared time to BCR between men with cT2c disease, those with intermediate-risk (PSA 10-20 ng/ml or Gleason sum (GS) =7), and those with high-risk (PSA>20 ng/ml, GS 8-10, cT3) using Cox regression models adjusting for age, race, year of RP, center, and percent cores positive. We also compared predictive accuracy of two Cox models wherein cT2c was considered either intermediate- or high-risk by calculating concordance index c. Results: A total of 68 men (3.4%) had cT2c tumors. After a median follow-up of 47.5 months, there was no difference in BCR risk between men with intermediate-risk CaP and those with cT2c tumors (HR=0.90; p=0.60). In contrast, there was a trend for men with high-risk CaP to have nearly 50% increased BCR risk compared to men with cT2c tumors (HR=1.50; 95% CI=0.97-2.30; p=0.07) which did not reach statistical significance. Concordance index c was higher in the Cox model wherein cT2c tumors were considered intermediate-risk (c=0.6147) as opposed to high-risk (c=0.6106). Conclusions: BCR risk for patients with clinical stage T2c was more comparable to men who had intermediate-risk CaP than men with high-risk. In addition, a model which incorporates cT2c disease as intermediate-risk has better predictive accuracy. These findings suggest men with cT2c disease should be offered treatment options for men with intermediate-risk CaP. As clinical staging more routinely incorporates MRI there is the potential to better identify bilateral organ-confined CaP and further establish risk classification.

The effect of pathologic T-stage and Gleason score on cancer-specific survival for specimen-confined high-risk prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 114-114
Author(s):  
Lorenzo Tosco ◽  
Hendrik Van Poppel ◽  
Thomas Van den Broeck ◽  
Patrick Bastian ◽  
Alberto Briganti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Cox Proportional Hazards Model ◽  
Cancer Specific Survival ◽  
High Risk Prostate Cancer ◽  
Kaplan Meier ◽  
Risk Prostate Cancer

114 Background: High-risk prostate cancer (HRPC) is a challenging disease and the role of surgery is often considered in the context of a multimodal approach. The indication for adjuvant therapy after surgery for HRPC patients who have specimen-confined disease (R0, pN0, <pT3b) is still difficult. The current study aims to analyze postoperative pathological features which help to predict CSS in specimen-confined HRPC and thus may aid in the decision to administer adjuvant EBRT or ADT. Methods: From a multi-institutional retrospective cohort of 5876 HRPC patients treated by radical prostatectomy and pelvic lymph node dissection, 1391 patients with specimen-confined disease were selected. Following surgery, adjuvant EBRT and/or ADT were delivered according to institutional protocols. Patients were subdivided into four groups according to pT stage (pT≥3 and pT<3) and final Gleason score (GS≥8 and GS<8). Kaplan-Meier plots with log-rank tests and a Cox proportional hazards model were applied to study CSS. All significance levels were set at 0.05. MedCalc was used for all statistical analyses. Results: Median age was 65 years (43-84). Of all patients, 346 (24.9%) had GS≥8 and 794 (57.1%) had pT≥3 at definitive histopathology. Patients were classified into COMBO groups: C1 (478; 34.4%; GS<8,pT<3), C2 (567; 40.8%; GS<8, pT≥3), C3 (119; 8.6%; GS≥8, pT<3), C4 (227; 16.3%; GS≥8, pT≥3). Adjuvant EBRT and ADT, respectively, were delivered in C1 2%/2%, C2 15%/22%, C3 3%/10%, C4 18%/25%. Kaplan Meier plots demonstrated statistically different 10-yr CSS between groups: C1 97.4%, C2 95.2%, C3 89.9% and C4 84.4% (p<0.0001). COMBO groups were also compared using a Cox model and results are shown in the Table. Conclusions: COMBO groups demonstrated to be able to subdivide specimen-confined HRPC into 4 demarcated groups with significantly different CSS. This subdivision could be considered an easy-to-use tool which can help for counseling patients for adjuvant treatment strategies. [Table: see text]

The effect of pathologic T-stage and Gleason score on cancer-specific survival in patients with positive surgical margins after surgery for high-risk prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 140-140
Author(s):  
Lorenzo Tosco ◽  
Hendrik Van Poppel ◽  
Thomas Van den Broeck ◽  
Patrick Bastian ◽  
Alberto Briganti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Cox Proportional Hazards Model ◽  
Cancer Specific Survival ◽  
High Risk Prostate Cancer ◽  
Kaplan Meier ◽  
Risk Prostate Cancer

140 Background: High-risk prostate cancer (HRPC) is a challenging disease and the role of surgery is often considered in the context of a multimodal approach but patients with positive section margins (R1) disease have not always the same cancer-specific survival (CSS). The current study aims to analyze current postoperative pathological features in order to predict CSS of HRPC patients with R1, but with negative lymph nodes (pN0), treated with surgery. Methods: From a multi-institutional retrospective cohort of 5,876 HRPC patients treated by radical prostatectomy and pelvic lymph node dissection, 1541 patients with pN0 and R1 were selected. Following surgery, adjuvant EBRT and/or ADT were delivered according to institutional protocols. Patients were subdivided into four groups according to pT stage (pT≥3 and pT<3) and p-Gleason score (pGS≥8 and pGS<8). Kaplan-Meier plots with log-rank tests and a Cox proportional hazards model were applied to study CSS. All significance levels were set at 0.05. MedCalc was used for all statistical analyses. Results: Median age at surgery was 66 years (42-89). Of all patients, 399 (25.9%) had GS≥8 and 999 (64.8%) had pT≥3 at definitive histopathology. Patients were classified as COMBO groups: C1 (423; 27.4%; GS<8,pT<3), C2 (674; 43.7%; GS<8, pT≥3), C3 (83; 5.4%; GS≥8, pT<3), C4 (362; 23.5%; GS≥8, pT≥3). Adjuvant EBRT and ADT, respectively, were delivered in C1 3%/5%, C2 15%/21%, C3 21%/20%, C4 28%/40%. Kaplan-Meier plots demonstrated statistically different 10-yr CSS between groups: C1 97%, C2 93.8%, C3 85.1% and C4 77.3% (p<0.0001). COMBO groups were also compared using a Cox model and results are shown in the Table. Conclusions: COMBO groups demonstrated to be able to subdivide margin-positive, pN0 HRPC into 4 demarcated groups with significantly different CSS. This subdivision could be considered an easy-to-use tool which can help for counseling patients for adjuvant treatment strategies. [Table: see text]

THE RISK OF PROSTATE CANCER DEATH FOR ELDERLY MEN WITH TREATED HIGH-RISK PROSTATE CANCER AND NO OR CORRECTED CARDIOVASCULAR DISEASE

2009 ◽  
Vol 181 (4S) ◽  
pp. 207-207
Author(s):  
Karen E Hoffman ◽  
Ming-Hui Chen ◽  
Brian J. Moran ◽  
Michelle H. Braccioforte ◽  
Daniel Dosoretz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Cancer Death ◽  
Elderly Men ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Prostate Cancer Death

scholarly journals MP07-01 VALIDATION OF A GENOMIC RISK CLASSIFIER TO PREDICT PROSTATE CANCER DEATH IN HIGH RISK PATIENTS

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
R. Jeffrey Karnes ◽  
Ashley Ross ◽  
Edward Schaeffer ◽  
Eric Klein ◽  
Nicholas Erho ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cancer Death ◽  
High Risk Patients ◽  
Prostate Cancer Death ◽  
Risk Patients ◽  
Genomic Risk

Validation of a genomic-clinical classifier for predicting clinical progression in high-risk prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4565-4565
Author(s):  
Christine Buerki ◽  
Anirban Pradip Mitra ◽  
Peter C. Black ◽  
Mercedeh Ghadessi ◽  
Eric J. Bergstralh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Disease Progression ◽  
Mayo Clinic ◽  
Curve Analysis ◽  
Clinical Progression ◽  
Prognostic Information ◽  
Decision Curve Analysis ◽  
High Risk Cohort

4565 Background: The efficient delivery of adjuvant therapy after radical prostatectomy (RP) in patients with prostate cancer is limited by the lack of biomarkers, beyond clinicopathologic factors, that are able to assess the risk of clinically significant disease progression. Previously, routine FFPE patient specimens from the Mayo Clinic Radical Prostatectomy Registry with long term follow-up were selected to develop a genomic classifier (GC) to predict clinical progression. Here, we present the validation of a GC in a cohort of patients at high risk of disease progression. Methods: A case-cohort study of high-risk RP patients from the Mayo Clinic (N=219) was used to validate the genomic classifier (GC) for predicting clinical progression (defined by positive bone or CT scan post-RP). Its performance was compared to a multivariable clinical classifier (CC) and a genomic-clinical classifier (GCC) which combines GC with established clinicopathologic variables. Concordance index, Cox modeling and decision curve analysis were used to compare the different models. Results: GC and GCC were predictive of clinical progression in the high-risk cohort with c-indices of 0.79 and 0.82, respectively, compared to the clinical classifier (0.70). Multivariable survival analysis showed that the majority of prognostic information of GCC came from the GC with a minor contribution from Gleason score. Decision curve analysis showed that GCC had a higher overall net benefit compared to CC over a wide range of ‘decision-to-treat’ thresholds for the risk of progression. Conclusions: In this high-risk cohort, GC and GCC classifiers showed improved performance over CC in prediction of clinical progression. GC is an independent prognostic factor in this cohort and captures the majority of prognostic information. GC and GCC’s prognostic performance and their usefulness in guiding decision-making in the adjuvant setting after RP need further testing in studies of additional prostate cancer risk groups.

Patient NCCN risk classification based on combined clinical cell cycle risk (CCR) score.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 249-249 ◽  
Author(s):  
Steven Stone ◽  
Julia E. Reid ◽  
Michael K. Brawer
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
High Risk ◽  
Outcome Data ◽  
Risk Category ◽  
Intermediate Risk ◽  
Clinicopathologic Features ◽  
Prognostic Information ◽  
Nccn Guidelines ◽  
Risk Reclassification

249 Background: Improved prognostic tools for newly diagnosed prostate cancer are needed to more appropriately match treatment to a patient’s risk of progression. The cell cycle progression (CCP) score is a highly validated prognostic RNA expression signature which has been combined with CAPRA (CCR, combined clinical cell cycle risk score) to generate an estimate of prostate cancer mortality (PCM) within 10-years of diagnosis. Here, we evaluate how the prognostic information from CCR can reclassify patients compared to their initial assignment to an NCCN risk category based on clinicopathologic features alone. Methods: The CCR score was previously validated and is calculated as a linear combination of CAPRA and CCP score (0.39 x CAPRA + 0.57 x CCP). A risk reclassification scheme was applied to patients tested by the Myriad Genetics commercial laboratory (N = 16,442). First, PCM risk was assigned based on the patient’s CCR score. Next, patients whose PCM risks were outside the interquartile range (IQR) of their NCCN risk category were reclassified according to whether their PCM risks fell within the IQR of another NCCN risk category. Finally, patients whose PCM risks were below (or above) the IQR of the NCCN low (or high) category were reclassified as low (or high). Results: Based on clinicopathologic features alone the commercial cohort was classified according to NCCN Guidelines as low (N = 8,695), favorable intermediate (N = 3,347), intermediate (N = 3,086), or high risk (N = 1,224). After calculating patient risk of PCM based on CCR, 25% of the NCCN low risk men were reclassified to favorable intermediate or intermediate risk; 47% of the NCCN favorable intermediate risk men were reclassified (24% lower and 23% higher); 49% of the NCCN intermediate risk men were reclassified (24% lower and 25% higher); and 25% of the NCCN high risk were reclassified to favorable intermediate or intermediate risk. There is no outcome data associated with commercial samples. Conclusions: The prognostic information in the CCR score results in significant amounts of risk reclassification for all patients with localized disease when compared to stratification based only on NCCN risk categories.

986 HOW SOON CAN WE IDENTIFY MEN AT HIGH RISK FOR PROSTATE CANCER DEATH? AN EARLY SURVEILLANCE STRATEGY FOR PROSTATE CANCER

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Andrew Vickers ◽  
Caroline Savage ◽  
Thomas Bjork ◽  
Axel Gerdtsson ◽  
Jonas Manjer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cancer Death ◽  
Surveillance Strategy ◽  
Prostate Cancer Death
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