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  string(1508) "Background: The survival outcome of nonmetastatic CRPC (nmCRPC) is significantly prolonged by androgen-receptor signaling inhibitors (ARSI). The benefit  of prolonged metastasis-free survival should be weighted against the increased incidence of adverse events of long-term medication. Furthermore, identifying patients with variable outcomes after ARSI may facilitate further investigation of intensify or de-intensify treatment.
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Participants: Men with nmCRPC.
Main Outcome Measure(s); is MFS and will be defined as the time from date of random assignment to the first detection of distant metastasis on imaging or death of any cause.
Statistical Analysis: We will evaluate the predictive ability of the prognostic model based on discrimination and calibration. We will first apply the estimated parameters from the prognostic model to the validation dataset and compute a risk score for every patient. The predictive performance of the model will be evaluated by computing the area under the receiver operating characteristic curve (AUC). The prognostic model will be assessed for its calibration. Decision curve analysis will be performed to assess the clinical value of using prediction model." ["project_brief_bg"]=> string(892) "The survival outcome of nonmetastatic CRPC (nmCRPC) is significantly prolonged by novel androgen-receptor signaling inhibitors (ARSI). Median metastasis-free survival (MFS) was 40.5 months in the apalutamide group in the SPARTAN trial [1]. nmCRPC, however, is a heterogenous group of lethal prostate cancer with nearly one-third of patients developed metastases within 2 year follow-up after ARSI. Unlikely to mCRPC, prediction model was rarely investigated in nmCRPC and PSA doubling time was the only well recognized stratification factor [2]. Thus, prediction model is strongly needed to explain the variability in the expected outcome of nmCRPC and further prompt individualized treatment [3]. We have collected nmCRPC patients from Fudan University Shanghai Cancer Center and plan to develop a prognostic model. The model was not externally validated in an independent cohort using ARSI." ["project_specific_aims"]=> string(241) "We seek to externally validate a prognostic model developed from our center in an independent cohort of nmCRPC treated with abiraterone. We will evaluate the predictive ability of the prognostic model based on discrimination and calibration." ["project_study_design"]=> string(0) "" ["project_study_design_exp"]=> string(0) "" ["project_purposes"]=> array(1) { [0]=> array(2) { ["value"]=> string(50) "Research on clinical prediction or risk prediction" ["label"]=> string(50) "Research on clinical prediction or risk prediction" } } ["project_purposes_exp"]=> string(0) "" ["project_software_used"]=> array(2) { ["value"]=> string(7) "RStudio" ["label"]=> string(7) "RStudio" } ["project_software_used_exp"]=> string(0) "" ["project_research_methods"]=> string(172) "Data from the phase II trial of nmCRPC will be utilized to validate the prognostic model of MFS. We need the access to the data from the IMAAGEN trial in the YODA platform." ["project_main_outcome_measure"]=> string(469) "The primary endpoint is metastasis-free survival (MFS) and will be defined as the time from date of random assignment to the first detection of distant metastasis on imaging or death of any cause.
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1. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8. PMID: 29420164.
2. Whitney CA, Howard LE, Freedland SJ, DeHoedt AM, Amling CL, Aronson WJ, Cooperberg MR, Kane CJ, Terris MK, Daskivich TJ. Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2019 May;22(2):252-260. doi: 10.1038/s41391-018-0095-0. Epub 2018 Oct 2. PMID: 30279582.
3. Lokeshwar SD, Klaassen Z, Saad F. Treatment and trials in non-metastatic castration-resistant prostate cancer. Nat Rev Urol. 2021 Jul;18(7):433-442. doi: 10.1038/s41585-021-00470-4. Epub 2021 May 17. PMID: 34002069.

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2022-4942

General Information

How did you learn about the YODA Project?: Scientific Publication

Conflict of Interest

Request Clinical Trials

Associated Trial(s):
  1. NCT01314118 - A Multicenter, Open-label, Single-arm, Phase 2 Study of Abiraterone Acetate Plus Prednisone in Subjects With Advanced Prostate Cancer Without Radiographic Evidence of Metastatic Disease
  2. NCT01946204 - A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study of ARN-509 in Men With Non-Metastatic (M0) Castration-Resistant Prostate Cancer
What type of data are you looking for?:

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Data Request Status

Status: Ongoing

Research Proposal

Project Title: External Validation of a Prognostic Model of Metastasis-Free Survival In Men with Nonmetastatic Castration-Resistant Prostate Cancer

Scientific Abstract: Background: The survival outcome of nonmetastatic CRPC (nmCRPC) is significantly prolonged by androgen-receptor signaling inhibitors (ARSI). The benefit of prolonged metastasis-free survival should be weighted against the increased incidence of adverse events of long-term medication. Furthermore, identifying patients with variable outcomes after ARSI may facilitate further investigation of intensify or de-intensify treatment.
Objective: We seek to externally validate a prognostic model developed from our center in an independent cohort of nmCRPC.
Study Design: We will utilize data from a phase II trial of nmCRPC treated by abiraterone to validate the prognostic model of metastasis-free survival (MFS).
Participants: Men with nmCRPC.
Main Outcome Measure(s); is MFS and will be defined as the time from date of random assignment to the first detection of distant metastasis on imaging or death of any cause.
Statistical Analysis: We will evaluate the predictive ability of the prognostic model based on discrimination and calibration. We will first apply the estimated parameters from the prognostic model to the validation dataset and compute a risk score for every patient. The predictive performance of the model will be evaluated by computing the area under the receiver operating characteristic curve (AUC). The prognostic model will be assessed for its calibration. Decision curve analysis will be performed to assess the clinical value of using prediction model.

Brief Project Background and Statement of Project Significance: The survival outcome of nonmetastatic CRPC (nmCRPC) is significantly prolonged by novel androgen-receptor signaling inhibitors (ARSI). Median metastasis-free survival (MFS) was 40.5 months in the apalutamide group in the SPARTAN trial [1]. nmCRPC, however, is a heterogenous group of lethal prostate cancer with nearly one-third of patients developed metastases within 2 year follow-up after ARSI. Unlikely to mCRPC, prediction model was rarely investigated in nmCRPC and PSA doubling time was the only well recognized stratification factor [2]. Thus, prediction model is strongly needed to explain the variability in the expected outcome of nmCRPC and further prompt individualized treatment [3]. We have collected nmCRPC patients from Fudan University Shanghai Cancer Center and plan to develop a prognostic model. The model was not externally validated in an independent cohort using ARSI.

Specific Aims of the Project: We seek to externally validate a prognostic model developed from our center in an independent cohort of nmCRPC treated with abiraterone. We will evaluate the predictive ability of the prognostic model based on discrimination and calibration.

Study Design:

What is the purpose of the analysis being proposed? Please select all that apply.: Research on clinical prediction or risk prediction

Software Used: RStudio

Data Source and Inclusion/Exclusion Criteria to be used to define the patient sample for your study: Data from the phase II trial of nmCRPC will be utilized to validate the prognostic model of MFS. We need the access to the data from the IMAAGEN trial in the YODA platform.

Primary and Secondary Outcome Measure(s) and how they will be categorized/defined for your study: The primary endpoint is metastasis-free survival (MFS) and will be defined as the time from date of random assignment to the first detection of distant metastasis on imaging or death of any cause.
1. Date of Randomization (MM/DD/YYYY)
2. Date of Progression/Metastasis (MM/DD/YYYY)
2. Survival Status (Alive, dead)
3. Date of Last Observation or Follow-up (MM/DD/YYYY)
4. Date of Death (MM/DD/YYYY) or time to death since random assignment

Main Predictor/Independent Variable and how it will be categorized/defined for your study: The main predictors are:
1. ECOG Performance Status: 0, 1, 2, 3+
2. PSA doubling time
3. Gleason score
4. No. of previous hormonal therapies: 1, 2+
5. Hemoglobin
6. PSA
7. Alkaline phosphatase
8. Age

Other Variables of Interest that will be used in your analysis and how they will be categorized/defined for your study: In addition, previous treatment (prostatectomy, radiation, other treatment) will be needed to describe the population and to assess the performance of the model in these subgroups.

Statistical Analysis Plan: We will evaluate the predictive ability of the prognostic model based on discrimination and calibration. We will first apply the estimated parameters from the prognostic model to the validation dataset and compute a risk score for every patient. The predictive performance of the model will be evaluated by computing the area under the receiver operating characteristic curve (AUC). The prognostic model will be assessed for its calibration. Decision curve analysis will be performed to assess the clinical value of using prediction model.

Narrative Summary: The survival outcome of nonmetastatic CRPC (nmCRPC) is significantly prolonged by androgen-receptor signaling inhibitors (ARSI). The benefit of prolonged metastasis-free survival should be weighted against the increased incidence of adverse events of long-term medication. Furthermore, identifying patients with different outcomes after ARSI may facilitate further investigation of intensify or de-intensify treatment. We seek to externally validate a prognostic model developed from our center in an independent cohort of nmCRPC. If promising in discrimination and calibration, the model may help explain the heterogeneity of nmCRPC and serve as a valid stratification tool in clinical practice.

Project Timeline: We plan to submit an abstract for EAU in 2023. It is expected that it will take 6 months to complete the analysis. It is anticipated that a manuscript will be submitted by early 2023.

Dissemination Plan: The results of these analyses will be submitted as abstracts and will be presented at International meetings such as EAU or AUA . The first abstract is planned for EAU in 2023. Manuscripts will be written and will be submitted for Publication in peer review journals, such as European Urology, and Journal of Urology. Abstracts and manuscripts will be sent to the sponsor for review.

Bibliography:

1. Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. doi: 10.1056/NEJMoa1715546. Epub 2018 Feb 8. PMID: 29420164.
2. Whitney CA, Howard LE, Freedland SJ, DeHoedt AM, Amling CL, Aronson WJ, Cooperberg MR, Kane CJ, Terris MK, Daskivich TJ. Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2019 May;22(2):252-260. doi: 10.1038/s41391-018-0095-0. Epub 2018 Oct 2. PMID: 30279582.
3. Lokeshwar SD, Klaassen Z, Saad F. Treatment and trials in non-metastatic castration-resistant prostate cancer. Nat Rev Urol. 2021 Jul;18(7):433-442. doi: 10.1038/s41585-021-00470-4. Epub 2021 May 17. PMID: 34002069.