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string(122) "A novel risk stratification system of metastatic castration-sensitive prostate cancer using CHAARTED and LATITUDE criteria"
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string(540) "The CHAARTED and LATITUDE classifications are commonly used to stratify patients with metastatic castration-sensitive prostate cancer. However, these classifications may lead to the overuse of upfront treatment in certain cases. By integrating these two classifications, we aim to develop a novel risk stratification system that more accurately predicts prognosis. This approach could enable more appropriate selection of candidates for upfront treatment, ensuring that patients receive optimal therapy while avoiding unnecessary treatment."
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["property_scientific_abstract"]=>
string(1756) "Background
Upfront therapy has become more common for metastatic castration-sensitive prostate cancer (mCSPC). However, the current CHAARTED and LATITUDE classifications may lead to the overuse of upfront treatment. A novel classification that integrates these criteria could help better stratify patients and optimize treatment selection.
Objective
To develop a new risk classification system for mCSPC by combining CHAARTED and LATITUDE criteria, aiming to refine prognosis stratification and identify patients who may achieve favorable outcomes without upfront treatment.
Study Design
A post-hoc analysis, using data on the TITAN trial. Patients with mCSPC were categorized into three risk groups based on CHAARTED (high/low volume) and LATITUDE (high/low risk) classifications.
1. Double-low group: low volume & low risk
2. Intermediate group: low volume & high risk or high volume & low risk
3. Double-high group: high volume & high risk
Participants
Patients with mCSPC, treated with androgen deprivation therapy in combination with apalutamide or placebo.
Primary and Secondary Outcome Measures
Primary outcomes: Overall survival and second progression-free survival.
Secondary outcomes: Time to castration-resistant prostate cancer.
Statistical Analysis
Patients will be classified into three risk groups based on a combination of the CHAARTED and LATITUDE approaches. Time-to-event outcomes will be analyzed using Kaplan-Meier methods and compared via the log-rank test, with multiple comparisons adjusted using the Holm-Bonferroni method. PSA decline rates are compared between groups."
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string(1353) "In recent years, novel androgen receptor signaling inhibitors (ARSIs) have significantly transformed the treatment landscape for metastatic castration-sensitive prostate cancer (mCSPC), making them the preferred first-line option.[1] The risk stratification in mCSPC is primarily guided by the CHAARTED (high/low volume) and LATITUDE (high/low risk) classifications. However, these systems do not always align, leading to discordant prognostic assessments.[2] This inconsistency may contribute to the overuse of upfront therapy, including androgen deprivation therapy combined with ARSIs and/or chemotherapy. While upfront treatment has been shown to improve overall survival, it remains unclear whether all patients, particularly those classified as low risk and low volume, derive equal benefit from upfront therapy, as some may achieve favorable outcomes without it. [1]
The current risk classification systems may not adequately identify patients who can achieve long-term survival without upfront therapy. By integrating CHAARTED and LATITUDE criteria, this study aims to refine prognostic stratification and develop a novel risk classification for mCSPC. This approach could help optimize treatment selection, minimizing unnecessary exposure to intensive therapy while ensuring that high-risk patients receive appropriate treatment."
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string(1110) "The primary objective of this study is to refine the prognostic stratification of metastatic castration-sensitive prostate cancer (mCSPC) by integrating the CHAARTED (high/low volume) and LATITUDE (high/low risk) classifications. By incorporating both criteria, we aim to establish a more precise risk classification system that can optimize patient selection for upfront therapy.
The following hypotheses will be evaluated in this study:
1. The combination of CHAARTED and LATITUDE classifications will allow for a more granular risk stratification of mCSPC patients.
2. Patients classified as "Double-low" (low volume and low risk) may achieve favorable outcomes without upfront intensive therapy.
3. The newly proposed classification system will help identify patient subgroups for whom upfront therapy may be unnecessary, leading to a more personalized treatment approach.
By addressing these hypotheses, this study aims to improve treatment decision-making, potentially reducing unnecessary upfront therapy while maintaining optimal oncological outcomes."
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Exclusion criteria: Patients with missing outcome data"
["project_main_outcome_measure"]=>
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["project_other_variables_interest"]=>
string(905) "The following variables will be used as covariates in the analysis:
- Age (categorical)
- Race (categorical)
- Eastern Cooperative Oncology Group performance status (categorical)
- Baseline prostate-specific antigen (continuous)
- Gleason score at diagnosis (categorical)
- Prior local therapy (categorical)
- Presence of visceral metastasis (categorical)
- Presence of lymph node metastasis (categorical)
- Presence of liver metastasis (categorical)
- Presence of lung metastasis (categorical)
- Metastasis stage at initial diagnosis (categorical)
- Baseline hemoglobin (continuous)
- Baseline albumin (continuous)
- Baseline alkaline phosphatase (continuous)
- Baseline lactate dehydrogenase (continuous)
- Previous docetaxel use (categorical)
- Baseline disease volume (categorical)"
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string(365) "Descriptive statistics will be used to summarize the baseline characteristics. Patients will be classified into three risk groups based on a combination of the CHAARTED and LATITUDE approaches. Time-to-event outcomes will be analyzed using Kaplan-Meier methods and compared via the log-rank test, with multiple comparisons adjusted using the Holm-Bonferroni method."
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string(195) "Day 0: Approval of the project
Day 60: Data transfer
Day 90: Data processing
Day 120: Data analysis
Day 240: Manuscript writing
Day 360: Manuscript submission"
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string(835) "[1] Iwamoto H, Hori T, Nakagawa R, Kano H, Makino T, Naito R, Yaegashi H, Kawaguchi S, Nohara T, Shigehara K, Izumi K, Mizokami A. Novel Treatment Strategies for Low-Risk Metastatic Castration-Sensitive Prostate Cancer. Cancers (Basel). 2024 Sep 19;16(18):3198. doi: 10.3390/cancers16183198. PMID: 39335169; PMCID: PMC11430633.
[2] Kawahara T, Yoneyama S, Ohno Y, Iizuka J, Hashimoto Y, Tsumura H, Tabata KI, Nakagami Y, Tanabe K, Iwamura M, Uemura H, Miyoshi Y. Prognostic Value of the LATITUDE and CHAARTED Risk Criteria for Predicting the Survival of Men with Bone Metastatic Hormone-Naïve Prostate Cancer Treated with Combined Androgen Blockade Therapy: Real-World Data from a Japanese Multi-Institutional Study. Biomed Res Int. 2020 Jul 1;2020:7804932. doi: 10.1155/2020/7804932. PMID: 32714984; PMCID: PMC7352129.
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Research Proposal
Project Title:
A novel risk stratification system of metastatic castration-sensitive prostate cancer using CHAARTED and LATITUDE criteria
Scientific Abstract:
Background
Upfront therapy has become more common for metastatic castration-sensitive prostate cancer (mCSPC). However, the current CHAARTED and LATITUDE classifications may lead to the overuse of upfront treatment. A novel classification that integrates these criteria could help better stratify patients and optimize treatment selection.
Objective
To develop a new risk classification system for mCSPC by combining CHAARTED and LATITUDE criteria, aiming to refine prognosis stratification and identify patients who may achieve favorable outcomes without upfront treatment.
Study Design
A post-hoc analysis, using data on the TITAN trial. Patients with mCSPC were categorized into three risk groups based on CHAARTED (high/low volume) and LATITUDE (high/low risk) classifications.
1. Double-low group: low volume & low risk
2. Intermediate group: low volume & high risk or high volume & low risk
3. Double-high group: high volume & high risk
Participants
Patients with mCSPC, treated with androgen deprivation therapy in combination with apalutamide or placebo.
Primary and Secondary Outcome Measures
Primary outcomes: Overall survival and second progression-free survival.
Secondary outcomes: Time to castration-resistant prostate cancer.
Statistical Analysis
Patients will be classified into three risk groups based on a combination of the CHAARTED and LATITUDE approaches. Time-to-event outcomes will be analyzed using Kaplan-Meier methods and compared via the log-rank test, with multiple comparisons adjusted using the Holm-Bonferroni method. PSA decline rates are compared between groups.
Brief Project Background and Statement of Project Significance:
In recent years, novel androgen receptor signaling inhibitors (ARSIs) have significantly transformed the treatment landscape for metastatic castration-sensitive prostate cancer (mCSPC), making them the preferred first-line option.[1] The risk stratification in mCSPC is primarily guided by the CHAARTED (high/low volume) and LATITUDE (high/low risk) classifications. However, these systems do not always align, leading to discordant prognostic assessments.[2] This inconsistency may contribute to the overuse of upfront therapy, including androgen deprivation therapy combined with ARSIs and/or chemotherapy. While upfront treatment has been shown to improve overall survival, it remains unclear whether all patients, particularly those classified as low risk and low volume, derive equal benefit from upfront therapy, as some may achieve favorable outcomes without it. [1]
The current risk classification systems may not adequately identify patients who can achieve long-term survival without upfront therapy. By integrating CHAARTED and LATITUDE criteria, this study aims to refine prognostic stratification and develop a novel risk classification for mCSPC. This approach could help optimize treatment selection, minimizing unnecessary exposure to intensive therapy while ensuring that high-risk patients receive appropriate treatment.
Specific Aims of the Project:
The primary objective of this study is to refine the prognostic stratification of metastatic castration-sensitive prostate cancer (mCSPC) by integrating the CHAARTED (high/low volume) and LATITUDE (high/low risk) classifications. By incorporating both criteria, we aim to establish a more precise risk classification system that can optimize patient selection for upfront therapy.
The following hypotheses will be evaluated in this study:
1. The combination of CHAARTED and LATITUDE classifications will allow for a more granular risk stratification of mCSPC patients.
2. Patients classified as "Double-low" (low volume and low risk) may achieve favorable outcomes without upfront intensive therapy.
3. The newly proposed classification system will help identify patient subgroups for whom upfront therapy may be unnecessary, leading to a more personalized treatment approach.
By addressing these hypotheses, this study aims to improve treatment decision-making, potentially reducing unnecessary upfront therapy while maintaining optimal oncological outcomes.
Study Design:
Individual trial analysis
What is the purpose of the analysis being proposed? Please select all that apply.:
New research question to examine treatment effectiveness on secondary endpoints and/or within subgroup populations
Software Used:
RStudio
Data Source and Inclusion/Exclusion Criteria to be used to define the patient sample for your study:
Inclusion criteria: All patients involved in this trial
Exclusion criteria: Patients with missing outcome data
Primary and Secondary Outcome Measure(s) and how they will be categorized/defined for your study:
Overall survival and second progression-free survival as per the trial protocol. Time to castration-resistant prostate cancer is defined as the time from randomization to the onset of castration resistance.
Main Predictor/Independent Variable and how it will be categorized/defined for your study:
Patient risk classification based on the combination of CHAARTED and LATITUDE approaches.
Other Variables of Interest that will be used in your analysis and how they will be categorized/defined for your study:
The following variables will be used as covariates in the analysis:
- Age (categorical)
- Race (categorical)
- Eastern Cooperative Oncology Group performance status (categorical)
- Baseline prostate-specific antigen (continuous)
- Gleason score at diagnosis (categorical)
- Prior local therapy (categorical)
- Presence of visceral metastasis (categorical)
- Presence of lymph node metastasis (categorical)
- Presence of liver metastasis (categorical)
- Presence of lung metastasis (categorical)
- Metastasis stage at initial diagnosis (categorical)
- Baseline hemoglobin (continuous)
- Baseline albumin (continuous)
- Baseline alkaline phosphatase (continuous)
- Baseline lactate dehydrogenase (continuous)
- Previous docetaxel use (categorical)
- Baseline disease volume (categorical)
Statistical Analysis Plan:
Descriptive statistics will be used to summarize the baseline characteristics. Patients will be classified into three risk groups based on a combination of the CHAARTED and LATITUDE approaches. Time-to-event outcomes will be analyzed using Kaplan-Meier methods and compared via the log-rank test, with multiple comparisons adjusted using the Holm-Bonferroni method.
Narrative Summary:
The CHAARTED and LATITUDE classifications are commonly used to stratify patients with metastatic castration-sensitive prostate cancer. However, these classifications may lead to the overuse of upfront treatment in certain cases. By integrating these two classifications, we aim to develop a novel risk stratification system that more accurately predicts prognosis. This approach could enable more appropriate selection of candidates for upfront treatment, ensuring that patients receive optimal therapy while avoiding unnecessary treatment.
Project Timeline:
Day 0: Approval of the project
Day 60: Data transfer
Day 90: Data processing
Day 120: Data analysis
Day 240: Manuscript writing
Day 360: Manuscript submission
Dissemination Plan:
The project is expected to produce a manuscript suitable for publication in a urology journal, with results to be presented at appropriate urology conferences.
Bibliography:
[1] Iwamoto H, Hori T, Nakagawa R, Kano H, Makino T, Naito R, Yaegashi H, Kawaguchi S, Nohara T, Shigehara K, Izumi K, Mizokami A. Novel Treatment Strategies for Low-Risk Metastatic Castration-Sensitive Prostate Cancer. Cancers (Basel). 2024 Sep 19;16(18):3198. doi: 10.3390/cancers16183198. PMID: 39335169; PMCID: PMC11430633.
[2] Kawahara T, Yoneyama S, Ohno Y, Iizuka J, Hashimoto Y, Tsumura H, Tabata KI, Nakagami Y, Tanabe K, Iwamura M, Uemura H, Miyoshi Y. Prognostic Value of the LATITUDE and CHAARTED Risk Criteria for Predicting the Survival of Men with Bone Metastatic Hormone-Naïve Prostate Cancer Treated with Combined Androgen Blockade Therapy: Real-World Data from a Japanese Multi-Institutional Study. Biomed Res Int. 2020 Jul 1;2020:7804932. doi: 10.1155/2020/7804932. PMID: 32714984; PMCID: PMC7352129.