TY - JOUR
T1 - Incorporation of Urinary Prostate Cancer Antigen 3 and TMPRSS2:ERG into Prostate Cancer Prevention Trial Risk Calculator
AU - Ankerst, Donna P.
AU - Goros, Martin
AU - Tomlins, Scott A.
AU - Patil, Dattatraya
AU - Feng, Ziding
AU - Wei, John T.
AU - Sanda, Martin G.
AU - Gelfond, Jonathan
AU - Thompson, Ian M.
AU - Leach, Robin J.
AU - Liss, Michael A.
N1 - Funding Information:
Other: None. Financial disclosures : Donna P. Ankerst and Michael A. Liss certy that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: The University of Michigan has been issued a patent on the detection of ETS gene fusions in prostate cancer, on which Tomlins is listed as a coinventor. The University of Michigan licensed the diagnostic field of use to Hologic/Gen-Probe, Inc., which sublicensed some rights to Ventana Medical Systems. Tomlins has received honoraria from, and served as a consultant to Ventana Medical Systems. Funding/Support and role of the sponsor : Funded by U01 CA086402, P30 CA054174, U01 CA113913, U01 CA214170, and R01 CA179115. The work of Dr. Liss was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program under Award Number W81XWH-15-1-0441. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.
Publisher Copyright:
© 2018
PY - 2019/1
Y1 - 2019/1
N2 - Background: The Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) is a commonly used risk tool for predicting the outcome on biopsy based on the established risk factors. Objective: To determine whether incorporation of the novel urinary markers prostate cancer antigen 3 (PCA3) and TMPRSS2:ERG (T2:ERG) into the PCPTRC improves its discrimination, accuracy, and clinical net benefit. Design, setting, and participants: Since PCA3 and T2:ERG were not measured as part of the PCPTRC, a Bayesian modeling approach was used to combine data where the markers were measured in a Michigan cohort with the PCPTRC as prior probabilities to form an updated PCPTRC. This update was compared to the existing PCPTRC on an independent Early Detection Research Network cohort in terms of discrimination, calibration, and decision curve analysis. Results and limitations: Among the 1225 Michigan biopsies, 57.7%, 24.0%, and 18.3% were negative, with low- and high-grade (Gleason grade ≥ 7) prostate cancer, respectively. Evaluated on the Early Detection Research Network validation set comprising 854 biopsies, areas under the curve (95% confidence interval) for predicting high-grade cancer in the 854 biopsies comprising the validation set were 70.0% (66.0–74.0%), 76.4% (72.8–80.0%), and 77.1% (73.6–80.6%) for the PCPTRC alone, with PCA3 added, and PCA3 and T2:ERG added, respectively. Net benefit was improved for the updated PCPTRC, while calibration was not. Limitations are that the updated PCPTRC is based on two different cohorts, the PCPT and Michigan, and that 20% of the validation set came from the Michigan center. More validation is required; hence, the updated risk tool is posted online. Conclusions: Incorporation of PCA3 into the PCPTRC improved validation on an independent cohort, whereas T2:ERG offered negligible utility in addition to PCA3. Patient summary: After passing external validation, prostate cancer antigen 3 has been added to the online Prostate Cancer Prevention Trial Risk Calculator for use by patients in deciding whether to proceed to biopsy. TMPRSS2:ERG did not improve prediction on the external validation set, but is included for further validation.
AB - Background: The Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) is a commonly used risk tool for predicting the outcome on biopsy based on the established risk factors. Objective: To determine whether incorporation of the novel urinary markers prostate cancer antigen 3 (PCA3) and TMPRSS2:ERG (T2:ERG) into the PCPTRC improves its discrimination, accuracy, and clinical net benefit. Design, setting, and participants: Since PCA3 and T2:ERG were not measured as part of the PCPTRC, a Bayesian modeling approach was used to combine data where the markers were measured in a Michigan cohort with the PCPTRC as prior probabilities to form an updated PCPTRC. This update was compared to the existing PCPTRC on an independent Early Detection Research Network cohort in terms of discrimination, calibration, and decision curve analysis. Results and limitations: Among the 1225 Michigan biopsies, 57.7%, 24.0%, and 18.3% were negative, with low- and high-grade (Gleason grade ≥ 7) prostate cancer, respectively. Evaluated on the Early Detection Research Network validation set comprising 854 biopsies, areas under the curve (95% confidence interval) for predicting high-grade cancer in the 854 biopsies comprising the validation set were 70.0% (66.0–74.0%), 76.4% (72.8–80.0%), and 77.1% (73.6–80.6%) for the PCPTRC alone, with PCA3 added, and PCA3 and T2:ERG added, respectively. Net benefit was improved for the updated PCPTRC, while calibration was not. Limitations are that the updated PCPTRC is based on two different cohorts, the PCPT and Michigan, and that 20% of the validation set came from the Michigan center. More validation is required; hence, the updated risk tool is posted online. Conclusions: Incorporation of PCA3 into the PCPTRC improved validation on an independent cohort, whereas T2:ERG offered negligible utility in addition to PCA3. Patient summary: After passing external validation, prostate cancer antigen 3 has been added to the online Prostate Cancer Prevention Trial Risk Calculator for use by patients in deciding whether to proceed to biopsy. TMPRSS2:ERG did not improve prediction on the external validation set, but is included for further validation.
KW - PCA3
KW - Prostate cancer
KW - Prostate-specific antigen
KW - T2:ERG
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U2 - 10.1016/j.euf.2018.01.010
DO - 10.1016/j.euf.2018.01.010
M3 - Article
C2 - 29422418
AN - SCOPUS:85041582899
SN - 2405-4569
VL - 5
SP - 54
EP - 61
JO - European Urology Focus
JF - European Urology Focus
IS - 1
ER -