Systemic Treatment, Subjective Cognitive Function, and Survival in Prostate and Breast Cancer: Evidence from Patient Reported Outcomes and Real-World Data

Abstract

Prostate and Breast cancer are the most commonly diagnosed malignancies and the second leading causes of cancer-related death for men and women, respectively. In the United States, there are more than 3.5 million prostate cancer survivors, and more than 4 million breast cancer survivors, with these populations projected to continue to grow in the coming years. Improvements in screening practices, earlier detection, and advancements in treatment have prolonged survival among those diagnosed across both cancer sites. For cancer survivors with metastatic prostate cancer and those with hormone receptor-positive (HR+) breast cancer, systemic hormone therapies play a critical role in reducing mortality by targeting distinct biological pathways. Despite these therapeutic advancements, there remains a limited understanding of the long-term role hormone therapies play in cancer survivorship, particularly with respect to sustained use. In addition, methods for measuring treatment adherence using real-world data are not well established. This dissertation aims to bridge these research gaps by investigating various aspects of cancer survivorship, with a focus on the long-term use of systemic hormone therapies and on measuring adherence in real-world settings. In Chapter 1, we utilized data from the International Registry for Men with Advanced Prostate Cancer (IRONMAN) to examine the association between first-line systemic hormonal treatment and subjective cognitive function trajectories among men with metastatic hormonesensitive prostate cancer (mHSPC). We fit joint longitudinal and survival models for two subjective cognitive function scales administered to IRONMAN patients at enrollment and during follow-up for up to 2 years. We found that there was no evidence of worse cognitive decline over time for individuals treated with androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitors (ARPIs), nor ADT + chemotherapy, when compared to individuals treated with ADT monotherapy. Our study suggests that additional systemic hormonal therapies used to treat mHSPC survivors do not negatively impact subjective cognitive function. In Chapter 2, we further examined subjective cognitive function near diagnosis and longitudinal trajectories and their association with mortality in the IRONMAN registry, among those with metastatic prostate cancer. This association was evaluated by fitting joint longitudinal and survival models for a follow-up period of up to 4 years. The findings from this study revealed that poor subjective cognitive function near diagnosis and longitudinally was associated with higher mortality. Our study highlights that subjective cognitive function can provide an additional point of intervention to improve overall survival in this patient population. In Chapter 3, we compared measurements of adherence for endocrine therapy when using electronic health records (EHR) and health claims data among a population of 79 hormone receptor-positive breast cancer survivors. We investigated whether there were differences across race and ethnicity, primary language spoken, and insurance status. We found that when adherence is measured using only EHR data, adherence estimates are consistently higher than when measured from health insurance claims data. Our study highlights the importance of data source selection when assessing adherence to endocrine therapy and that EHR and claims data offer complementary insights. In conclusion, investigating research questions that extend beyond survival to encompass life after diagnosis, while also highlighting the need to refine approaches to measuring treatment adherence, is essential for informing care for cancer survivors. This work provides a foundation to facilitate research and interventions aimed at enhancing the well-being and quality of life of the continuously growing population of prostate and breast cancer survivors.