Abstract
Frailty syndrome is a functional state that includes a loss of ability to react to stressors, and is associated with poor outcomes, morbidity and premature mortality. The first line treatment in many men with prostate cancer (PCa) consists of an androgen-deprivation therapy (ADT) which can promote or favor frailty syndrome and ADT may therefore favor the progression of frailty over time. Among the pathophysiological bases of frailty, the presence of chronic low-grade inflammation has been associated with its adverse outcomes, but longitudinal studies are needed to validate these biomarkers. In this study, we prospectively evaluate frailty syndrome and blood inflammatory markers (IL1-beta, IL-6, IL-8, TNF alpha, C reactive protein) and leukocytes were measured at baseline and an average of 1 year later in PCa under ADT. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Multinomial regression analysis showed that among the inflammatory biomarkers, those significantly and repeatedly (baseline and follow-up time points) (p < 0.05) associated with frailty syndrome were high IL-6 levels and low lymphocyte counts in blood. Other biomarkers such as IL-8, monocyte counts and C reactive protein were significantly associated with frailty syndrome (p < 0.05) in cross-sectional analyses, but they do not predict frailty progression at 1 year-follow-up. Receiver operating characteristic curve analysis showed that both lymphocyte counts and IL-6 concentration significantly (p < 0.05) (although moderately) discriminate PCa patients that progressed in the severity of frailty syndrome. IL-6 and lymphocytes count are possible biomarkers, useful for identifying frail patients and predicting the progression of frailty in PCa under ADT. Our study suggests the use of these biomarkers to guide clinical decisions on prostate cancer treatment based on a multidisciplinary approach.
Highlights
Prostate cancer (PCa) is the third most common type of tumor in Europe, and the third most frequent cause of death from cancer in men [1]
The drop-outs were due to progression of prostate cancer and the requirements of other pharmacological treatments e.g., five patients became resistant to castration and two metastatic patients switched to chemotherapy treatment
Among the inflammatory markers evaluated in our study, those repeatedly associated with frailty syndrome at both baseline and follow-up were reduced lymphocyte counts and high IL-6 levels. These results obtained in prostate cancer (PCa) patients confirm and extend the observations which correlated frailty syndrome to chronic low-grade inflammation in several populations and involved both the innate and adaptive components of the immune system [56,57,58] and in this study, we reported the role of some inflammatory biomarker confirmed in longitudinal studies which validated some of the biomarkers associated with frailty syndrome in cross-sectional studies
Summary
Prostate cancer (PCa) is the third most common type of tumor in Europe, and the third most frequent cause of death from cancer in men [1]. Treatment selection is based on the disease. Cancers 2020, 12, 1716 risk category, the patient’s age and comorbidities, the patient’s preferences and the adverse effects profile of the treatment [2]. Called androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) analogues or antagonists is the most widely used therapeutic modality in advanced or metastatic and hormone-sensitive PCa [3]. LHRH analogues are more commonly used, and have replaced surgical castration as the standard of care in ADT, because these agents have potential for reversibility and prevent the physical and psychological discomfort associated with orchiectomy [4,5]. The ADT is commonly achieved by administering LHRH agonists is in the first line of treatment of castration-sensitive PCa [4]
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