Understanding treatment toxicity patterns through remote symptom monitoring and examining the effect of frailty in older men with metastatic prostate cancer.
Authors: Parthipan Milothy , Feng Gregory , Breunis Henriette , Timilshina Narhari , Soto Pérez de Celis Enrique , Hansen Aaron Richard , Emmenegger Urban , Finelli Antonio , Warde Padraig , Tomlinson George , Krzyzanowska Monika K. , Matthew Andrew , Clarke Hance , Santa Mina Daniel , Puts Martine , Alibhai Shabbir M.H. 
Published: June 2023

12054

Background: Advancements in metastatic prostate cancer (mPC) treatments have increased survival, but using multiple lines of therapy has increased the prevalence and severity of toxicities. Older men and those living with frailty experience higher symptom burden associated with treatment. Although toxicities have been described in previous trials, much of the focus has been on pain and fatigue among fit and younger men, and only a few trials have examined the effects of frailty on toxicity. Thus, the aims of this study were to (1) understand the prevalence, duration, and changes in symptom severity among older men receiving mPC treatments; and (2) examine differences among frail and non-frail men. Methods: Men aged 65+ with mPC starting chemotherapy (chemo), androgen receptor-axis-targeted (ARAT) therapies, or radium-223 (Rad223) from two academic Canadian cancer centres were enrolled in a prospective cohort study. Participants self-reported symptoms daily using the Edmonton Symptom Assessment Scale (ESAS) for the first treatment cycle via internet or telephone. Frailty status was determined using the Vulnerable Elders Survey (VES-13). Study outcomes were the development of moderate-to-severe symptoms (ESAS≥4), their duration, and the proportion of participants who had improvements in symptom severity (ESAS<4) after reporting moderate-to-severe symptoms at baseline. Outcomes were determined using descriptive statistics. Associations between symptom prevalence, duration, and frailty were assessed using t-tests and chi-square tests. Results: 90 men (mean age=77 +/- 6.1 years, 58% frail (VES-13≥3)) starting chemo (n=34), an ARAT (n=43), or Rad223 (n=13) were included. The most common moderate-to-severe symptoms across cohorts were fatigue (46.8%), insomnia (42.9%), poor wellbeing (41.2%), decreased appetite (37.1%), and pain (35.9%). These symptoms were numerically higher in frail men, but differences between frail and non-frail were only statistically significant for poor wellbeing (62.5% in frail vs. 31.4% in non-frail, p=0.039). On average, poor wellbeing lasted 6.5 days (SD=7.6) days, decreased appetite lasted 5.5 days (SD=4.9), fatigue lasted 5.1 days (SD=7.3), pain lasted 4.7 days (SD=5.6), and insomnia lasted 4.6 days (SD=6.2) across cohorts. Fatigue and pain lasted numerically longer in frail men whereas insomnia, poor wellbeing, and decreased appetite lasted numerically longer in non-frail men, but these differences were not statistically significant. Among participants who reported moderate-to-severe symptoms at baseline, 15.4%, 10.7%, 7.7%, 5.3% and 3.6% had improvements in pain, appetite, wellbeing, insomnia, and fatigue, respectively. Conclusions: Understanding temporal patterns of symptoms and the impact of frailty in older men receiving mPC treatments may help inform supportive care approaches. Clinical trial information: NCT04193657 .