Significant Cognitive Decline Undetected During mCRPC Therapy

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: A study of metastatic castration-resistant prostate cancer (mCRPC) patients aged at least 65 years shows no significant decline in attention, executive function or global cognition during treatment with docetaxel, abiraterone, enzalutamide or radium-223 therapy.   

The research suggests that “most older men do not experience significant cognitive decline while undergoing treatment for mCRPC regardless of the treatment used”, say Shabbir Alibhai, from Toronto General Hospital in Ontario, Canada, and co-workers in JAMA Network Open. 

They explain that their study “focused on older adults, who have historically been excluded in clinical oncology research, despite being at a higher risk of cognitive decline.” 

And they add: “Thus, this research adds substantially to the limited published studies describing the cognitive changes of older men with advanced prostate cancer, which is significant because older adults with cancer are less willing than younger adults to accept adverse effects (particularly cognitive or functional decline) in return for gains in survival.” 

The team collated information from 155 men who consecutively attended one of four academic cancer centres in Ontario between July 2015 and December 2019 and received docetaxel (n=51), abiraterone (n=29), enzalutamide (n=54) or radium-223 (n=21).  

The patients were assessed before and after treatment using three measures – the Montreal Cognitive Assessment and the Trail Making Tests A (motor function) and B (executive function). 

Shabbir Alibhai et al report that the patients in the four therapeutic groups had “similar” baseline cognitive function and that their cognitive scores on the three measures “remained stable or improved slightly” after treatment. 

Although patients given docetaxel or radium-223 were more likely than those given abiraterone or enzalutamide to experience a standard deviation (SD) decline of at least 1.5 on one of the three measures, the differences between the groups was not statistically significant.  

Moreover, none of the patients had a clinically meaningful decline in cognition, defined by the International Cognition and Cancer Task Force as a 1.5 SD or greater decline on at least two measures, the researchers said. 

Initial analysis revealed a significant and positive correlation between greater age and increasing decline on the Trails A score but multivariable analysis found that baseline test score was the only characteristic significantly associated with cognitive decline.  

Acknowledging the small size of the study groups and the lack of an untreated control group, Shabbir Alibhai and co-authors say that “future trials using a more thorough neuropsychological assessment, self-reported measures, and a larger sample with multiple times are warranted.” 

Nevertheless, they note the cognitive test confidence intervals for each treatment “were smaller than the minimum clinically important difference, suggesting that few men would have a noticeable decline in any of these cognitive measures.” 

Reference  

Alibhai SMH, Breunis H, Feng G, et al. Association of chemotherapy, enzalutamide, abiraterone, and radium 223 with cognitive function in older men with metastatic castration-resistant prostate cancer. JAMA Netw Open; 4:e2114694. doi:10.1001/jamanetworkopen.2021.14694