Lauren E Howard1,2, Jingbin Zhang3, Nick Fishbane3, Amanda M De Hoedt2, Zachary Klaassen4, Daniel E Spratt5, Adriana C Vidal6, Dechen Lin7,8, Megan P Hitchins7,8, Sungyong You6,9, Michael R Freeman6,9, Kosj Yamoah10, Elai Davicioni3, Stephen J Freedland11,12. 1. Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA. 2. Department of Surgery, Division of Urology, Veteran Affairs Healthcare System, Durham, NC, USA. 3. Decipher Biosciences, Inc, Vancouver, BC, Canada. 4. Department of Surgery, Section of Urology, Augusta University - Medical College of Georgia, Augusta, GA, USA. 5. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. 6. Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 7. Department of Medicine, Cedars-Sinai, Los Angeles, CA, USA. 8. Center for Bioinformatics and Functional Genomics, Cedars-Sinai, Los Angeles, CA, USA. 9. Department of Biomedical Sciences, Cedars-Sinai, Los Angeles, CA, USA. 10. Section of Genitourinary Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 11. Department of Surgery, Division of Urology, Veteran Affairs Healthcare System, Durham, NC, USA. stephen.freedland@cshs.org. 12. Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. stephen.freedland@cshs.org.
Abstract
BACKGROUND: The Decipher 22-gene genomic classifier (GC) may help in post-radical prostatectomy (RP) decision making given its superior prognostic performance over clinicopathologic variables alone. However, most studies evaluating the GC have had a modest representation of African-American men (AAM). We evaluated the GC within a large Veteran Affairs cohort and compared its performance to CAPRA-S for predicting outcomes in AAM and non-AAM after RP. METHODS: GC scores were generated for 548 prostate cancer (PC) patients, who underwent RP at the Durham Veteran Affairs Medical Center between 1989 and 2016. This was a clinically high-risk cohort and was selected to have either pT3a, positive margins, seminal vesicle invasion, or received post-RP radiotherapy. Multivariable Cox models and survival C-indices were used to compare the performance of GC and CAPRA-S for predicting the risk of metastasis and PC-specific mortality (PCSM). RESULTS: Median follow-up was 9 years, during which 37 developed metastasis and 20 died from PC. Overall, 55% (n = 301) of patients were AAM. In multivariable analyses, GC (high vs. intermediate and intermediate vs. low) was a significant predictor of metastasis in all men (all p < 0.001). Consistent with prior studies, relative to CAPRA-S, GC had a higher C-index for 5-year metastasis (0.78 vs. 0.72) and 10-year PCSM (0.85 vs. 0.81). There was a suggestion GC was a stronger predictor in AAM than non-AAM. Specifically, the 5-year metastasis risk C-index was 0.86 in AAM vs. 0.69 in non-AAM and the 10-year PCSM risk C-index was 0.91 in AAM vs. 0.78 in non-AAM. However, the test for interaction of race and the performance of the GC in the Cox model was not significant for either metastasis or PCSM (both p ≥ 0.3). CONCLUSIONS: GC was a very strong predictor of poor outcome and performed well in both AAM and non-AAM. Our data support the use of GC for risk stratification in AAM post-RP. While our data suggest that GC may actually work better in AAM, given the limited number of events, further validation is needed.
BACKGROUND: The Decipher 22-gene genomic classifier (GC) may help in post-radical prostatectomy (RP) decision making given its superior prognostic performance over clinicopathologic variables alone. However, most studies evaluating the GC have had a modest representation of African-American men (AAM). We evaluated the GC within a large Veteran Affairs cohort and compared its performance to CAPRA-S for predicting outcomes in AAM and non-AAM after RP. METHODS: GC scores were generated for 548 prostate cancer (PC) patients, who underwent RP at the Durham Veteran Affairs Medical Center between 1989 and 2016. This was a clinically high-risk cohort and was selected to have either pT3a, positive margins, seminal vesicle invasion, or received post-RP radiotherapy. Multivariable Cox models and survival C-indices were used to compare the performance of GC and CAPRA-S for predicting the risk of metastasis and PC-specific mortality (PCSM). RESULTS: Median follow-up was 9 years, during which 37 developed metastasis and 20 died from PC. Overall, 55% (n = 301) of patients were AAM. In multivariable analyses, GC (high vs. intermediate and intermediate vs. low) was a significant predictor of metastasis in all men (all p < 0.001). Consistent with prior studies, relative to CAPRA-S, GC had a higher C-index for 5-year metastasis (0.78 vs. 0.72) and 10-year PCSM (0.85 vs. 0.81). There was a suggestion GC was a stronger predictor in AAM than non-AAM. Specifically, the 5-year metastasis risk C-index was 0.86 in AAM vs. 0.69 in non-AAM and the 10-year PCSM risk C-index was 0.91 in AAM vs. 0.78 in non-AAM. However, the test for interaction of race and the performance of the GC in the Cox model was not significant for either metastasis or PCSM (both p ≥ 0.3). CONCLUSIONS: GC was a very strong predictor of poor outcome and performed well in both AAM and non-AAM. Our data support the use of GC for risk stratification in AAM post-RP. While our data suggest that GC may actually work better in AAM, given the limited number of events, further validation is needed.
Authors: Kevin H Kensler; Shivanshu Awasthi; Mohamed Alshalalfa; Bruce J Trock; Stephen J Freedland; Michael R Freeman; Sungyong You; Brandon A Mahal; Robert B Den; Adam P Dicker; R Jeffrey Karnes; Eric A Klein; Priti Lal; Yang Liu; Elai Davicioni; Walter Rayford; Kosj Yamoah; Timothy R Rebbeck Journal: Eur Urol Open Sci Date: 2022-04-26
Authors: Stephen J Freedland; Kosj Yamoah; Shivanshu Awasthi; Anders Berglund; Julieta Abraham-Miranda; Robert J Rounbehler; Kevin Kensler; Amparo Serna; Adriana Vidal; Sungyong You; Michael R Freeman; Elai Davicioni; Yang Liu; R Jeffrey Karnes; Eric A Klein; Robert B Den; Bruce J Trock; Joshua D Campbell; David J Einstein; Raavi Gupta; Steven Balk; Priti Lal; Jong Y Park; John L Cleveland; Timothy R Rebbeck Journal: Clin Cancer Res Date: 2020-10-09 Impact factor: 13.801
Authors: Adam B Weiner; Thiago Vidotto; Yang Liu; Adrianna A Mendes; Daniela C Salles; Farzana A Faisal; Sanjana Murali; Matthew McFarlane; Eddie L Imada; Xin Zhao; Ziwen Li; Elai Davicioni; Luigi Marchionni; Arul M Chinnaiyan; Stephen J Freedland; Daniel E Spratt; Jennifer D Wu; Tamara L Lotan; Edward M Schaeffer Journal: Nat Commun Date: 2021-02-10 Impact factor: 17.694
Authors: Junhee Yoon; Minhyung Kim; Edwin M Posadas; Stephen J Freedland; Yang Liu; Elai Davicioni; Robert B Den; Bruce J Trock; R Jeffrey Karnes; Eric A Klein; Michael R Freeman; Sungyong You Journal: Prostate Cancer Prostatic Dis Date: 2021-02-02 Impact factor: 5.554