Abstract
Sarcopenia is a muscle loss syndrome known as a risk factor of various carcinomas. The impact of sarcopenia and sarcopenia-related inflammatory/nutritional markers in metastatic urothelial carcinoma (mUC) treated with pembrolizumab was unknown, so this retrospective study of 27 patients was performed. Psoas muscle mass index (PMI) was calculated by bilateral psoas major muscle area at the L3 with computed tomography. The cut-off PMI value for sarcopenia was defined as ≤6.36 cm2/m2 for men and ≤3.92 cm2/m2 for women. Neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 and sarcopenia correlated with significantly shorter progression-free survival (PFS) (hazard ratio (HR) 3.81, p = 0.020; and HR 2.99, p = 0.027, respectively). Multivariate analyses identified NLR ≥ 4.0 and sarcopenia as independent predictors for PFS (HR 2.89, p = 0.025; and HR 2.79, p = 0.030, respectively). Prognostic nutrition index < 45, NLR ≥ 4.0 and sarcopenia were correlated with significantly worse for overall survival (OS) (HR 3.44, p = 0.046; HR 4.26, p = 0.024; and HR 3.92, p = 0.012, respectively). Multivariate analyses identified sarcopenia as an independent predictor for OS (HR 4.00, p = 0.026). Furthermore, a decrease in PMI ≥ 5% in a month was an independent predictor of PFS and OS (HR 12.8, p = 0.008; and HR 6.21, p = 0.036, respectively). Evaluation of sarcopenia and inflammatory/nutritional markers may help in the management of mUC with pembrolizumab.
Highlights
Immune checkpoint inhibitors (ICIs), including programmed cell death 1 (PD-1)inhibitors, such as nivolumab and pembrolizumab, have been shown to have promising effects in the treatment of various types of cancer [1,2,3,4,5]
We investigated the impacts of sarcopenia and different inflammatory and nutritional markers on the efficacy of the use of pembrolizumab to treat unresectable metastatic urothelial cancer in clinical practice
Skeletal muscle loss, which is often reported as a predictor of perioperative complications and chemotherapy-related adverse events (AEs), and as a prognostic factor for various malignant tumors, has been reported to be associated with poorer overall survival (OS) and the occurrence of early acute limiting toxicity in melanoma and non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) [17,29,30]
Summary
Immune checkpoint inhibitors (ICIs), including programmed cell death 1 (PD-1)inhibitors, such as nivolumab and pembrolizumab, have been shown to have promising effects in the treatment of various types of cancer [1,2,3,4,5]. Pembrolizumab has been widely used in Japan since 2017 for treating unresectable mUC that is resistant to conventional cytotoxic chemotherapy, including that using platinum. Biomarkers for predicting the effects of ICIs have been sought out using various approaches. Such possible biomarkers reported in past studies have included programmed death ligand 1 (PD-L1), tumor mutation burden, and circulating immune markers [10,11]. These markers are incomplete at least when used alone [11]. Predictive and measurable biomarkers are needed to select patients for whom treatment with ICIs is suitable
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