TY - JOUR
T1 - Unified model involving genomics, magnetic resonance imaging and prostate-specific antigen density outperforms individual co-variables at predicting biopsy upgrading in patients on active surveillance for low risk prostate cancer
AU - Beksac, Alp Tuna
AU - Ratnani, Parita
AU - Dovey, Zachary
AU - Parekh, Sneha
AU - Falagario, Ugo
AU - Roshandel, Reza
AU - Sobotka, Stanislaw
AU - Kewlani, Deepshikha
AU - Davis, Avery
AU - Weil, Rachel
AU - Bashorun, Hafis
AU - Jambor, Ivan
AU - Lewis, Sara
AU - Haines, Kenneth
AU - Tewari, Ashutosh K.
N1 - Funding Information:
Z.D. is Medical Director and stock owner (by shares) of MedTech Holdings Ltd. AKT as of 2020 listed as company type, relationship type and financial. Urethral Catheterless Radical Prostatectomy, Patent, No. DNA Based Bicistronic Vectors with Inducible and Constitutive Promoters ‐ ID#: 16060, Patent, No. High Intensity Focus Ultrasound and CPG‐Brachyurys iRNA for Treatment of Prostate Cancer ‐ ID# 160403, Patent, No. Patent for a Catheterless Device and Approach, Patent, No. *Promaxo, Leadership position, Yes. *Promaxo, Equity Ownership, yes. Global Prostate Cancer Research Foundation, Leadership position, No. Kalyani Prostate Cancer Institute, Leadership Position, No. Prostate Cancer Foundation, Leadership Position, No. Roivant, Consultant, No. Blank Family Foundation, Grant, Yes. Intuitive Surgical, Scientific Study or Trial, Yes. Department of Defense (DOD), Scientific Study or Trial, Yes. AxoGen, Inc., Scientific Study or Trial, Yes. Oncovir, Inc ‐ Poly ICLC, Scientific Study or Trial, Yes. National Institute of Health (NIH/DHHS), Scientific Study or Trial, Yes. National Cancer Institute, Scientific Study or Trial, Yes. National Institute on Drug Abuse, Scientific Study or Trial, Yes. Dr. Ash Tewari (the Principal Investigator in this study and Chairman of Milton and Carroll Petrie Department of Urology at the Icahn School of Medicine at Mount Sinai) owns equity in the form of stock certificates in Promaxo, for which he serves as an advisor. Promaxo is a privately traded company which develops MRI technology with a focus on prostate cancer. Kite Pharma, Scientific Study or Trial, Yes. Lumicell, Inc, Scientific Study or Trial, Yes. Dendreon, Scientific Study or Trial, Yes. *PROMAXO: Common Stock Certificate VALUE: 51,205% SHARE RELATED PARTY: 0.63; Intuitive – no salary/see referenced COI’s; Promaxo – no salary/investment – see referenced COI’s; Kite Pharma: Serve as PI. Industry funded for research procedures. Site PI performance – no salary; Poly ICLC: serve as site PI. Phase I Study of IN SITU Autologous Vaccination Against Prostate Cancer With Intratumoral and Systemic HILTONOL (POLY‐ICLC) Prior to Radical Prostatectomy. Product provided free of charge – no other funding ‐ no salary.
Publisher Copyright:
© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.
PY - 2022/3
Y1 - 2022/3
N2 - Background: Active surveillance (AS) is the reference standard treatment for the management of low risk prostate cancer (PCa). Accurate assessment of tumor aggressiveness guides recruitment to AS programs to avoid conservative treatment of intermediate and higher risk patients. Nevertheless, underestimating the disease risk may occur in some patients recruited, with biopsy upgrading and the concomitant potential for delayed treatment. Aim: To evaluate the accuracy of mpMRI and GPS for the prediction of biopsy upgrading during active surveillance (AS) management of prostate cancer (PCa). Method: A retrospective analysis was performed on 144 patients recruited to AS from October 2013 to December 2020. Median follow was 4.8 (IQR 3.6, 6.3) years. Upgrading was defined as upgrading to biopsy grade group ≥2 on follow up biopsies. Cox proportional hazard regression was used to investigate the effect of PSA density (PSAD), baseline Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score and GPS on upgrading. Time-to-event outcome, defined as upgrading, was estimated using the Kaplan–Meier method with log-rank test. Results: Overall rate of upgrading was 31.9% (n = 46). PSAD was higher in the patients who were upgraded (0.12 vs. 0.08 ng/ml2, p =.005), while no significant difference was present for median GPS in the overall cohort (overall median GPS 21; 22 upgrading vs. 20 no upgrading, p =.2044). On univariable cox proportional hazard regression analysis, the factors associated with increased risk of biopsy upgrading were PSA (HR = 1.30, CI 1.16–1.47, p = <.0001), PSAD (HR = 1.08, CI 1.05–1.12, p = <.0001) and higher PI-RADS score (HR = 3.51, CI 1.56–7.91, p =.0024). On multivariable cox proportional hazard regression analysis, only PSAD (HR = 1.10, CI 1.06–1.14, p = <.001) and high PI-RADS score (HR = 4.11, CI 1.79–9.44, p =.0009) were associated with upgrading. A cox regression model combining these three clinical features (PSAD ≥0.15 ng/ml2 at baseline, PI-RADS Score and GPS) yielded a concordance index of 0.71 for the prediction of upgrading. Conclusion: In this study PSAD has higher accuracy over baseline PI-RADS score and GPS score for the prediction of PCa upgrading during AS. However, combined use of PSAD, GPS and PI-RADS Score yielded the highest predictive ability with a concordance index of 0.71.
AB - Background: Active surveillance (AS) is the reference standard treatment for the management of low risk prostate cancer (PCa). Accurate assessment of tumor aggressiveness guides recruitment to AS programs to avoid conservative treatment of intermediate and higher risk patients. Nevertheless, underestimating the disease risk may occur in some patients recruited, with biopsy upgrading and the concomitant potential for delayed treatment. Aim: To evaluate the accuracy of mpMRI and GPS for the prediction of biopsy upgrading during active surveillance (AS) management of prostate cancer (PCa). Method: A retrospective analysis was performed on 144 patients recruited to AS from October 2013 to December 2020. Median follow was 4.8 (IQR 3.6, 6.3) years. Upgrading was defined as upgrading to biopsy grade group ≥2 on follow up biopsies. Cox proportional hazard regression was used to investigate the effect of PSA density (PSAD), baseline Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score and GPS on upgrading. Time-to-event outcome, defined as upgrading, was estimated using the Kaplan–Meier method with log-rank test. Results: Overall rate of upgrading was 31.9% (n = 46). PSAD was higher in the patients who were upgraded (0.12 vs. 0.08 ng/ml2, p =.005), while no significant difference was present for median GPS in the overall cohort (overall median GPS 21; 22 upgrading vs. 20 no upgrading, p =.2044). On univariable cox proportional hazard regression analysis, the factors associated with increased risk of biopsy upgrading were PSA (HR = 1.30, CI 1.16–1.47, p = <.0001), PSAD (HR = 1.08, CI 1.05–1.12, p = <.0001) and higher PI-RADS score (HR = 3.51, CI 1.56–7.91, p =.0024). On multivariable cox proportional hazard regression analysis, only PSAD (HR = 1.10, CI 1.06–1.14, p = <.001) and high PI-RADS score (HR = 4.11, CI 1.79–9.44, p =.0009) were associated with upgrading. A cox regression model combining these three clinical features (PSAD ≥0.15 ng/ml2 at baseline, PI-RADS Score and GPS) yielded a concordance index of 0.71 for the prediction of upgrading. Conclusion: In this study PSAD has higher accuracy over baseline PI-RADS score and GPS score for the prediction of PCa upgrading during AS. However, combined use of PSAD, GPS and PI-RADS Score yielded the highest predictive ability with a concordance index of 0.71.
KW - PSA density
KW - active surveillance
KW - biomarker
KW - genomic prostate score
KW - multiparametric MRI
KW - oncotype
KW - prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85121446630&partnerID=8YFLogxK
U2 - 10.1002/cnr2.1492
DO - 10.1002/cnr2.1492
M3 - Article
C2 - 34931468
AN - SCOPUS:85121446630
VL - 5
JO - Cancer Reports
JF - Cancer Reports
SN - 2573-8348
IS - 3
M1 - e1492
ER -