Quality of Life, Functional and Cognitive Outcomes in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Metastatic hormone-sensitive prostate cancer (mHSPC) is a disease stage in which systemic treatment strategies significantly affect survival, functional status, and quality of life. The incorporation of androgen receptor pathway inhibitors (ARPIs) into clinical practice has improved oncological outcomes, yet their influence on cognitive function, fatigue, mood, and sleep requires further real-world investigation.

In this study, the term androgen receptor pathway inhibitors (ARPIs) refer to abiraterone acetate, apalutamide, enzalutamide, and darolutamide. While abiraterone, apalutamide, and enzalutamide are widely used in routine practice in Türkiye, darolutamide may also be included when accessible. All patients will receive ARPIs in combination with standard androgen deprivation therapy (ADT).

This prospective, multicenter, observational cohort study will enroll 102 patients with newly diagnosed mHSPC at Ankara Etlik City Hospital and Gazi University. Assessments will take place at baseline, 3 months, and 6 months.

Validated Turkish patient-reported outcome instruments will be applied:

FACT-Cog: score range 0-148; higher scores = better cognitive functioning.

FACT-F: score range 0-52; higher scores = less fatigue.

PHQ-9: score range 0-27; cut-offs: 5 (mild), 10 (moderate), 15 (moderately severe), 20+ (severe depression).

PSQI: score range 0-21; global score \>5 indicates poor sleep quality.

Additional measures will include ECOG performance status (0-5; higher = worse functioning), demographic and clinical characteristics, comorbidities, and routine laboratory tests. Treatment-related adverse events will be recorded according to CTCAE criteria.

The primary outcomes are longitudinal changes in FACT-Cog and FACT-F scores between baseline, 3 months, and 6 months. Secondary outcomes include changes in PHQ-9 and PSQI scores, ECOG performance status, and laboratory results, as well as adverse event profiles. Exploratory analyses will assess the relationship between clinical or laboratory variables and patient-reported outcomes.

Statistical analyses will include descriptive statistics, group comparisons, and repeated-measures modeling. Multivariable regression will be applied to identify predictors of impaired cognitive or functional outcomes.

By incorporating validated Turkish instruments and explicitly defining ARPI agents, this study aims to generate robust real-world evidence on the cognitive, functional, and quality-of-life effects of ARPI therapy in mHSPC. The findings are expected to guide supportive care strategies and optimize treatment decision-making.

• Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Depression Score [Time frame: Baseline, 3 months, and 6 months after treatment initiation]
• Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Global Score [Time frame: Baseline, 3 months, and 6 months after treatment initiation]
• Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [Time frame: Baseline, 3 months, and 6 months after treatment initiation]
• Change From Baseline in Liver Function Parameters [Time frame: Baseline, 3 months, and 6 months after treatment initiation]
• Change From Baseline in Renal Function Parameters [Time frame: Baseline, 3 months, and 6 months after treatment initiation]
• Change From Baseline in Electrolyte Levels [Time frame: Baseline, 3 months, and 6 months after treatment initiation]
• Change From Baseline in Complete Blood Count (CBC) [Time frame: Baseline, 3 months, and 6 months after treatment initiation]