Health-related Quality of Life in Patients with Advanced Prostate Cancer: A Systematic Review
Abstract
Context:
The assessment of “soft” endpoints such as health-related quality of life (HRQOL) is increasingly relevant when evaluating the optimal treatment sequence of novel therapeutic options in patients with advanced prostate cancer (PCa).
Objective:
To systematically review contemporary data regarding HRQOL outcomes in patients with advanced PCa.
Evidence Acquisition:
A systematic review of the literature published between January 2011 and March 2019 was performed using the PubMed/Medline Database, Web of Sciences, and Embase according to PRISMA guidelines. Inclusion criteria encompassed phase II or III trials enrolling at least 100 patients with advanced PCa (metastatic hormone-naive, nonmetastatic castration-resistant, or metastatic castration-resistant). HRQOL had to be assessed via a standardized, validated HRQOL-specific tool. Studies were screened and selected according to European Association of Urology recommendations.
Evidence Synthesis:
Fourteen studies including 12,661 patients were included. The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire was used in 11 studies, the European Quality of Life 5-Dimensions (EQ-5D) in six, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) in two, and its prostate-specific amendment QLQ-PR25 in one study. Three studies in metastatic castration-sensitive prostate cancer (mHNPC) found beneficial HRQOL effects for abiraterone acetate and docetaxel compared with standard androgen deprivation therapy (ADT). Two studies in nonmetastatic castration-resistant prostate cancer (nmCRPC) observed positive HRQOL effects for enzalutamide and apalutamide. Nine studies focused on metastatic castration-resistant prostate cancer (mCRPC), reporting beneficial HRQOL outcomes for enzalutamide, abiraterone acetate, and radium-223. Most studies had a low risk of bias. Limitations included heterogeneity in HRQOL tools, lack of baseline values, and unclear impact of supportive care.
Conclusions:
There is strong evidence from several phase III trials supporting a beneficial effect of current systemic treatment options on HRQOL outcomes in patients with advanced PCa compared with standard ADT.
Patient Summary:
This systematic review summarizes contemporary data from large clinical trials on the effect of current treatment strategies on health-related quality of life (HRQOL) in advanced prostate cancer. Robust data support positive HRQOL effects of numerous agents at different clinical stages.
Introduction
Since the introduction of taxane-based chemohormonal therapy in the early 2000s, multiple new agents have become available for advanced prostate cancer (PCa), including docetaxel, abiraterone acetate, enzalutamide, radium-223, apalutamide, and darolutamide. These options span various stages: metastatic hormone-naive (mHNPC), nonmetastatic castration-resistant (nmCRPC), and metastatic castration-resistant (mCRPC) PCa. Optimal therapy selection should consider individual risk profiles and HRQOL, as all treatments can induce side effects impacting HRQOL. Patient-reported outcomes (PROMs) are increasingly incorporated into clinical trials using validated questionnaires.
Evidence Acquisition
A systematic review was conducted for literature from January 2011 to March 2019 using PubMed, Web of Sciences, and Embase, following PRISMA guidelines. Inclusion required phase II/III/IV trials with ≥100 advanced PCa patients and HRQOL assessed by a validated tool. For phase II trials, HRQOL had to be a prespecified primary endpoint; for phase III/IV, HRQOL was accepted as a secondary endpoint. Keywords included “health related quality of life,” “prostate cancer,” “advanced,” and “metastatic.” After screening 873 articles, 14 studies were included.
Evidence Synthesis
Study Selection and Quality Assessment
Fourteen studies with 12,661 patients were included. Risk of bias was generally low, with some open-label designs showing potential for performance or detection bias.
HRQOL Assessment Tools
FACT-P: Used in 11 studies, assesses physical, social/family, emotional, and functional well-being, plus 12 PCa-specific items. Scores range 0–156; higher scores indicate better HRQOL.
EQ-5D: Used in six studies, evaluates general HRQOL with a utility index and visual analog scale (0–100).
QLQ-C30: Used in two studies, assesses cancer-specific HRQOL (five functional, three symptom scales, global health status).
QLQ-PR25: Used in one study, PCa-specific module assessing urinary, bowel, and hormone therapy-related symptoms.
Metastatic Hormone-Naive Prostate Cancer (mHNPC)
Three phase III trials assessed HRQOL: Hussain et al.: Intermittent vs. continuous ADT; intermittent ADT favored for physical functioning, vitality, libido, and mental health, with physical functioning reaching statistical significance.
LATITUDE trial: Abiraterone acetate plus ADT vs. ADT alone; abiraterone prolonged time to deterioration in FACT-P and EQ-5D scores (median 12.9 vs. 8.3 months; HR 0.85, p = 0.032).
CHAARTED trial: Docetaxel plus ADT vs. ADT; initial decline in FACT-P scores with docetaxel at 3 months, but higher scores at 12 months compared to ADT alone.
Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)
Two phase III trials:
PROSPER: Enzalutamide plus ADT vs. placebo plus ADT; preservation of general HRQOL (FACT-P) with enzalutamide.
SPARTAN: Apalutamide plus ADT vs. placebo plus ADT; HRQOL maintained with apalutamide, with no clinically meaningful deterioration before symptomatic progression.
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Nine studies:
Abiraterone acetate: In both post-chemotherapy and chemotherapy-naïve settings, abiraterone improved FACT-P scores and prolonged time to HRQOL deterioration compared to placebo.
Enzalutamide: In both post-chemotherapy (AFFIRM) and pre-chemotherapy (PREVAIL) settings, enzalutamide resulted in less decline or improvement in HRQOL (FACT-P and EQ-5D) compared to placebo.
Radium-223 (ALSYMPCA trial): Radium-223 improved or maintained HRQOL (FACT-P, EQ-5D) compared to placebo.
Other agents: Additional studies with docetaxel, cabazitaxel, and supportive care interventions reported HRQOL outcomes, generally favoring newer agents over standard ADT.
Limitations
Comparability between studies was limited by the use of different validated questionnaires.Some studies lacked baseline HRQOL values.The impact of supportive care on HRQOL outcomes was unclear.
Conclusions
Strong evidence from several phase III trials supports the beneficial effect of current systemic treatments-including abiraterone acetate, docetaxel, enzalutamide, apalutamide, and radium-223-on HRQOL in advanced prostate cancer compared with standard ADT. HRQOL should be an integral part of treatment decision-making and sequencing in advanced PCa.
Patient Summary
This systematic review summarizes evidence from large clinical trials demonstrating that many modern treatments for advanced prostate cancer can improve or maintain health-related quality of life. Several validated questionnaires are available to assess HRQOL, and robust data support the positive effects ARN-509 of these therapies at different disease stages.