TY - JOUR
T1 - Development and validation of a novel integrated clinical-genomic risk group classification for localized prostate cancer
AU - Spratt, Daniel E.
AU - Zhang, Jingbin
AU - Santiago-Jiḿenez, Maria
AU - Dess, Robert T.
AU - Davis, John W.
AU - Den, Robert B.
AU - Dicker, Adam P.
AU - Kane, Christopher J.
AU - Pollack, Alan
AU - Stoyanova, Radka
AU - Abdollah, Firas
AU - Ross, Ashley E.
AU - Cole, Adam
AU - Uchio, Edward
AU - Randall, Josh M.
AU - Nguyen, Hao
AU - Zhao, Shuang G.
AU - Mehra, Rohit
AU - Glass, Andrew G.
AU - Lam, Lucia L.C.
AU - Chelliserry, Jijumon
AU - Du Plessis, Marguerite
AU - Choeurng, Voleak
AU - Aranes, Maria
AU - Kolisnik, Tyler
AU - Margrave, Jennifer
AU - Alter, Jason
AU - Jordan, Jennifer
AU - Buerki, Christine
AU - Yousefi, Kasra
AU - Haddad, Zaid
AU - Davicioni, Elai
AU - Trabulsi, Edouard J.
AU - Loeb, Stacy
AU - Tewari, Ashutosh
AU - Carroll, Peter R.
AU - Weinmann, Sheila
AU - Schaeffer, Edward M.
AU - Klein, Eric A.
AU - Karnes, R. Jeffrey
AU - Feng, Felix Y.
AU - Nguyen, Paul L.
N1 - Publisher Copyright:
© 2018 Lippincott Williams and Wilkins. All rights reserved.
PY - 2018/2/20
Y1 - 2018/2/20
N2 - Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorableintermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the threetier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95%CI, 0.65 to 0.84), and 30%of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk formetastasis and can be easily incorporated into current guidelines to better risk-stratify patients.
AB - Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorableintermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the threetier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95%CI, 0.65 to 0.84), and 30%of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk formetastasis and can be easily incorporated into current guidelines to better risk-stratify patients.
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U2 - 10.1200/JCO.2017.74.2940
DO - 10.1200/JCO.2017.74.2940
M3 - Article
C2 - 29185869
AN - SCOPUS:85040829382
SN - 0732-183X
VL - 36
SP - 581
EP - 590
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -