Anupam Batra1, Michele Marchioni2, Ardeshir Z Hashmi3, Peter E Lonergan4, Alicia K Morgans5, Kevin T Nead6, Paul L Nguyen7, Eric Winquist8, Joseph L Chin9. 1. Department of Oncology, Cambridge Memorial Hospital, Cambridge, Ontario, Canada. Electronic address: ABatra@cmh.org. 2. G. d'Annunzio University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Dept. of Urology, Chieti, Italy. 3. Center for Geriatric Medicine, Cleveland Clinic, Cleveland, OH, USA. Electronic address: HashmiA@ccf.org. 4. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA. Electronic address: Peter.Lonergan@ucsf.edu. 5. Department of Medicine, Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA. Electronic address: alicia.morgans@northwestern.edu. 6. Department of Epidemiology, Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA. Electronic address: KTNead@mdanderson.org. 7. Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. Electronic address: Paul_Nguyen@dfci.harvard.edu. 8. Department of Oncology, Western University and London Health Sciences Centre, London, Ontario, Canada. Electronic address: Eric.Winquist@lhsc.on.ca. 9. Departments of Surgery (Urology) and Oncology, Western University and London Health Sciences Centre, London, Ontario, Canada. Electronic address: Joseph.Chin@lhsc.on.ca.
Abstract
CONTEXT: Novel androgen receptor axis-targeting drugs (ARATs) have been shown to improve outcomes in men with prostate cancer. Central nervous system androgen blockade may be harmful for older adults who may be at increased risk of adverse cognitive and psychologic effects. OBJECTIVE: To systematically evaluate the effect of ARATs on cognition and depression in men with metastatic prostate cancer. EVIDENCE ACQUISITION: We searched PubMed and EMBASE for articles published in English between September 2012 and September 2019 reporting cognition and depression outcomes in men receiving ARATs for metastatic prostate cancer using validated psychometric tools. The level of evidence and risk of bias were assessed using the GRADE approach for randomized clinical trials and observational studies. RESULTS: 15 reports studying 8954 men with metastatic castration-sensitive and -resistant, or non-metastatic castration-resistant prostate cancer were identified. Data were available for abiraterone, enzalutamide and apalutamide but not darolutamide. The mean (and 95% confidence interval) and median (and min-max) of the absolute scores and changes from baseline were included, when available. There was heterogeneity in the psychometric tools used which obviated statistical pooling of results. Very limited data assessing cognition suggested that abiraterone was associated with improved cognitive functioning or perhaps less cognitive harm versus enzalutamide. Fourteen reports assessed emotional wellbeing. ARATs reduced depressive symptoms when compared to prednisone alone or placebo but not compared to bicalutamide. Abiraterone may improve short-term emotional functioning relative to enzalutamide. The quality of evidence was low when examining ARAT effect on cognitive function and moderate when examining ARAT effect on depression. CONCLUSIONS: Depression was assessed more frequently than cognition in men receiving ARATs. Self-reported depression measures favored abiraterone over enzalutamide and both abiraterone and enzalutamide over placebo. Data evaluating apalutamide and darolutamide are lacking. Further studies of ARATs using validated clinician-based psycho-cognition tools along with self-reported measures in men with metastatic prostate cancer are needed.
CONTEXT: Novel androgen receptor axis-targeting drugs (ARATs) have been shown to improve outcomes in men with prostate cancer. Central nervous system androgen blockade may be harmful for older adults who may be at increased risk of adverse cognitive and psychologic effects. OBJECTIVE: To systematically evaluate the effect of ARATs on cognition and depression in men with metastatic prostate cancer. EVIDENCE ACQUISITION: We searched PubMed and EMBASE for articles published in English between September 2012 and September 2019 reporting cognition and depression outcomes in men receiving ARATs for metastatic prostate cancer using validated psychometric tools. The level of evidence and risk of bias were assessed using the GRADE approach for randomized clinical trials and observational studies. RESULTS: 15 reports studying 8954 men with metastatic castration-sensitive and -resistant, or non-metastatic castration-resistant prostate cancer were identified. Data were available for abiraterone, enzalutamide and apalutamide but not darolutamide. The mean (and 95% confidence interval) and median (and min-max) of the absolute scores and changes from baseline were included, when available. There was heterogeneity in the psychometric tools used which obviated statistical pooling of results. Very limited data assessing cognition suggested that abiraterone was associated with improved cognitive functioning or perhaps less cognitive harm versus enzalutamide. Fourteen reports assessed emotional wellbeing. ARATs reduced depressive symptoms when compared to prednisone alone or placebo but not compared to bicalutamide. Abiraterone may improve short-term emotional functioning relative to enzalutamide. The quality of evidence was low when examining ARAT effect on cognitive function and moderate when examining ARAT effect on depression. CONCLUSIONS:Depression was assessed more frequently than cognition in men receiving ARATs. Self-reported depression measures favored abiraterone over enzalutamide and both abiraterone and enzalutamide over placebo. Data evaluating apalutamide and darolutamide are lacking. Further studies of ARATs using validated clinician-based psycho-cognition tools along with self-reported measures in men with metastatic prostate cancer are needed.
Authors: Evie E M Kolsteren; Esther Deuning-Smit; Alanna K Chu; Yvonne C W van der Hoeven; Judith B Prins; Winette T A van der Graaf; Carla M L van Herpen; Inge M van Oort; Sophie Lebel; Belinda Thewes; Linda Kwakkenbos; José A E Custers Journal: Cancers (Basel) Date: 2022-08-11 Impact factor: 6.575
Authors: Malgorzata K Nowakowska; Xiudong Lei; Mackenzie R Wehner; Paul G Corn; Sharon H Giordano; Kevin T Nead Journal: JAMA Netw Open Date: 2021-12-01
Authors: Shabbir M H Alibhai; Henriette Breunis; Gregory Feng; Narhari Timilshina; Aaron Hansen; Padraig Warde; Richard Gregg; Anthony Joshua; Neil Fleshner; George Tomlinson; Urban Emmenegger Journal: JAMA Netw Open Date: 2021-07-01