Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy

Abstract

<jats:p>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 &lt; 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 &lt; 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 &lt; 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.</jats:p>

Lymphocytes as a Biomarker of Frailty Syndrome: A Scoping Review

“…The relationship between total lymphocyte counts and frailty percentages has also been evaluated in three longitudinal studies conducted in cancer patients [ 28 , 29 ] and institutionalized older women [ 32 ]. However, only one of them validated the associations observed in cross-sectional studies, showing that in addition to being associated with frailty at the beginning of the study, low lymphocyte counts predicted its progression at one year of follow-up, with a moderate sensitivity of 65.2% and a specificity of 68.7% [ 28 ].…”

“…In both geriatrics research and clinical settings, the most-used definitions of frailty were developed by Fried and co-workers (physical frailty phenotype) and Rockwood and co-workers (the frailty index based on accumulative deficits). Among the studies analyzed in the review, the tools mostly used were the Fried model [10,12,13,[16][17][18]20,[23][24][25][26][27][28], which defines a phenotype that includes the presence of three or more of the following clinical criteria: Involuntary weight loss in the last year, muscle weakness, gait slow, self-reported fatigue, and low physical activity [5]. For their part, Gilmore et al [29] assessed frailty using a modified version of Fried's frailty score, using four of the five available criteria (weakness, exhaustion, walking speed, and physical activity).…”

Implication of Interleukin Family in Cancer Pathogenesis and Treatment

“…Some of the most important interleukins in inflammatory processes are IL-6 and IL-10. In this edition, two different articles deal with both interleukins [ 5 , 6 ]. One study evidences the use of IL-6 and lymphocyte count as a possible biomarker to guide clinical decisions on prostate cancer treatment based on a multidisciplinary approach [ 5 ].…”

“…In this edition, two different articles deal with both interleukins [ 5 , 6 ]. One study evidences the use of IL-6 and lymphocyte count as a possible biomarker to guide clinical decisions on prostate cancer treatment based on a multidisciplinary approach [ 5 ]. By way of confirming the impact of IL-6 and IL-10 polymorphisms on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), the group of Kewan [ 6 ] showed no significant differences in the distribution of all IL-10 polymorphisms studied of DLBCL between patients and controls.…”

Circulating interleukin 6, androgen deprivation therapy, and fatigue in prostate cancer: Is inflammation the link?

“…Exercise improves many ADT‐related adverse effects in patients with prostate cancer, including fatigue, with resistance training providing the most substantial gains in muscular strength and endurance 15 . Although high IL‐6 levels are associated with frailty syndrome in patients with prostate cancer on ADT, 16 data on the effect of physical conditioning on IL‐6 levels are mixed. In one study, a 20‐week resistance training program had no effect on CRP, IL‐6, or TNF‐α serum levels.…”