Abstract
Background
While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC), information regarding health related quality of life (HR-QoL) is sparse. We aimed at summarizing current evidence on the impact of ARSIs on HR-QoL.
Methods
We performed a systematic review of the published literature on PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane libraries between January 2011 and April 2022. We included only phase III randomized controlled trials (RCT), which were selected according to the PRISMA guidelines. We aimed at evaluating differences in HR-QoL, assessed by validated patient reported outcomes instruments. We analyzed global scores and sub-domains such as sexual functioning, urinary symptoms, bowel symptoms, pain/fatigue, emotional and social/family wellbeing. We reported data descriptively.
Results
Six RCTs were included: two used enzalutamide with ADT as intervention arms (ARCHES, ENZAMET); one used apalutamide with ADT (TITAN); two abiraterone acetate and prednisone (AAP) with ADT (STAMPEDE, LATITUDE); and one darolutamide with ADT (ARASENS). Enzalutamide or AAP with ADT increase overall HR-QoL in comparison with ADT alone, ADT with first generation nonsteroideal anti-androgens or ADT with docetaxel, whereas apalutamide and darolutamide with ADT maintain HR-QoL similarly to ADT alone or ADT with docetaxel, respectively. Time to first deterioration of pain was longer with combination therapy with enzalutamide, AAP or darolutamide, but not with apalutamide. No worsening of emotional wellbeing was reported from the addition of ARSIs to ADT than ADT alone.
Conclusions
The addition of ARSIs to ADT in mHSPC tends to increase overall HR-QoL and prolong time to first deterioration of pain/fatigue compared with ADT alone, ADT with first generation nonsteroideal anti-androgens, and ADT with docetaxel. ARSIs show a complex interaction with remaining HR-QoL domains. We advocate a standardization of HR-QoL measurement and reporting to allow further comparisons.
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Data availability
All data generated or analyzed during this study are included in this published article and its supplementary information files.
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Conceptualization: LA, ML, FE; study design: LA, ML, FE, MM, GG, RC; data collection: LA, ML, FE; data analysis: LA, ML; data interpretation: LA, ML; writing: ML, LA; revision: ML, LA, MM, GG, AKM, RC, AM, AB, RMS, RP, CDN, FE; final approval: ML, LA, MM, GG, AKM, RC, AM, AB, RMS, RP, CDN, FE; accountability: ML, LA, MM, GG, AKM, RC, AM, AB, RMS, RP, CDN, FE.
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RC: Advisory role for Astellas, Janssen, Bayer, Sanofi, MSD, Roche, BMS, Merck, Pfizer, Ipsen; honoraria from Astellas, Janssen, Merck. The remaining authors declare no competing interests.
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Afferi, L., Longoni, M., Moschini, M. et al. Health-related quality of life in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors: the role of combination treatment therapy. Prostate Cancer Prostatic Dis (2023). https://doi.org/10.1038/s41391-023-00668-0
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DOI: https://doi.org/10.1038/s41391-023-00668-0