A Propensity Score Analysis: Exploring the Effect of Adjuvant Chemotherapeutic Agent with Radiation Therapy and Androgen Deprivation Therapy in Patients with High Risk Prostate Cancer Público

Abstract

Introduction: Prostate cancer is still among the most prevalent cancers in men. Despite falling rates of mortality, it is still one of the leading causes of death. Accounting for the most important predictors in prostate cancer, patients are classified into three different prognostic categories, consisting of low, intermediate, and high risk groups. We define high risk prostate cancer as patients one of the following criteria - Gleason score >= 8, PSA >= 20, clinical T stage >= 2c, or pathological T stage >= 2c. The rates of mortality are significantly higher for those patients in the "high-risk" subset. For localized high risk patients, the most common treatment is the use of radiation therapy and long-term hormone therapy. More recent studies however have begun exploring the use of adjuvant chemotherapy. The objective of this study was to conduct a NCDB outcomes analysis of patients with localized high risk prostate cancer in order to examine the effect chemotherapy on overall survival.

Methods: A retrospective outcomes study was conducted using data from the National Cancer Database (NCDB). Patients must additionally be treated with radiation therapy, hormone therapy, or chemotherapy. Unadjusted overall survival was first estimated with univariate and multivariate Cox proportional hazards model. An adjusted overall survival was recalculated after accounting for baseline covariates using propensity score methods such as matching, weighting, and propensity score covariate adjustment.

Results: The final cohort contained 29,659 subjects of which only 177 patients received chemotherapy adjuvant. Unadjusted Univariate (HR=1.05[0.79, 1.4], p=0.723) and multivariate (HR= 0.89[0.67 -1.19], p=0.43) analysis concluded no survival benefits for the adjuvant chemotherapy. Use of propensity score analysis found that only matching was able to successfully balance the covariates between the treatment and control cohort, ultimately finding that there was still no benefit to the use of adjuvant chemotherapy (0.87[0.65-1.16], p=0.377).

Conclusion: Results from this analysis suggests that there were no clinical benefits to use of chemotherapeutic agent in addition to radiation therapy and hormone treatment such the additional treatment provided no survival benefits. For future analysis, a larger treatment cohort defined by use of docetaxel and higher radiation dose may provide reliable results.

Table of Contents

1. Introduction ... 1

2. Background ... 2

2.1 Diagnosis ... 2

2.2 Classification ... 2

2.3 Treatment ...4

2.4 Literature Review ... 4

2.5 Study Population ... 6

3. Statistical Methods ... 7

3.1 Data Source and Study Design ... 7

3.2 Variables and Measurements ... 7

3.3 Statistical Analysis ... 8

3.4 Propensity Score Methodology ... 10

3.4.1 Propensity Score Estimation ... 10

3.4.2 Matching ...11

3.4.3 Weighting ... 12

3.4.4 Propensity Score as a Covariate ... 12

3.4.5 Subclassification ... 13

3.4.6 Diagnostics ... 13

3.5 Propensity Score Analysis ... 14

4. Results ... 15

4.1 Descriptive Statistics ... 15

4.2 Univariate Association with Chemotherapy ... 16

4.3 Multivariate Association with Chemotherapy ... 16

4.4 Univariate Association with Overall Survival ... 17

4.5 Multivariate Association with Overall Survival ...18

4.6 Propensity Score Results ...19

5. Discussion ... 21

5.1 Conclusion ... 23

6. References ... 24

7. Appendix ... 28

About this Master's Thesis

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School	Rollins School of Public Health
Department	Biostatistics and Bioinformatics
Subfield / Discipline	Biostatistics - MPH & MSPH
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Statistics Health Sciences, Public Health Health Sciences, Oncology
Palavra-chave	observational studies survival analysis NCDB Prostate Cancer Oncology Propensity Score
Committee Chair / Thesis Advisor	Liu, Yuan, Emory University
Committee Members	Manatunga, Amita, Emory University
Partnering Agencies	Does not apply (no collaborating organization)

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