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Abbreviations & Acronyms BPH = benign prostatic hyperplasia CI = confidence interval HoLEP = holmium laser enucleation of the prostate IPSS = International Prostate Symptom Score MRI = magnetic resonance imaging mRUL = minimal residual membranous urethral length MUL = membranous urethral length OR = odds ratio PSC = periurethral sphincter complex PV = prostate volume PVR = post-void residual urine volume Q ave = average flow rate by uroflowmetry Q max = maximum flow rate by uroflowmetry QOL = quality of life RARP = robot-assisted radical prostatectomy ROC = receiver operating characteristic RP = radical prostatectomy tLA = thickness of levator ani TUI = transient urinary incontinence TURP = transurethral resection of the prostate

Purpose Two methods are used to identify sarcopenia by calculating skeletal muscle area on computed tomography: the skeletal muscle index (SMI) and the psoas muscle index (PMI). Programmed death (PD)-1 inhibitors are helpful in treating metastatic renal cell carcinoma (mRCC). However, there remains insufficient information regarding a clear and easy-to-use biomarker for predicting the response to PD-1 inhibitors in patients with mRCC. Therefore, we investigated the influence of sarcopenia on clinical outcomes in patients with mRCC undergoing treatment with nivolumab. Materials and Methods This study evaluated 96 patients with RCC who received nivolumab. The SMI and PMI were calculated for each patient and normalized for stature by use of the following formulas: SMI (cm 2 /m 2 )=([skeletal muscle cross-sectional area at the level of L3]/[height] 2 ) and PMI (cm 2 /m 2 ) = ([left-right sum of the psoas muscle areas at the level of L3]/[height] 2 ). The relationship of the clinical variables with progression-free survival and overall survival (OS) was examined using a Cox proportional hazards model. Results According to the SMI-based definition of sarcopenia, 74.0% of patients had sarcopenia. However, according to the PMI-based definition of sarcopenia, only 34.3% of patients were diagnosed with sarcopenia. Multivariate analysis identified sarcopenia based on PMI (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.04–7.26; p<0.001) and International Metastatic RCC Database Consortium poor risk status (HR, 1.90; 95% CI, 1.03–3.50; p=0.041) as significant and independent prognostic factors of OS. Conclusions PMI-based sarcopenia is a significant prognostic factor for OS in patients with RCC who receive nivolumab therapy.

Recently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60–70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B. longum 420)) with anti-PD-1 and anti-CTLA-4 antibodies in a mouse syngeneic model of RCC to explore possible synergistic effects. We found that B. longum 420 significantly improved the survival of mice bearing RCC tumors treated by anti-PD-1 and anti-CTLA-4 antibodies compared to the mice treated by the antibodies alone. This result suggests that B. longum 420 oral cancer vaccine as an adjunct to ICIs could provide a novel treatment option for RCC patients. Our microbiome analysis revealed that the proportion of Lactobacilli was significantly increased by B. longum 420. Although the detailed mechanism of action is unknown, it is possible that microbiome alteration by B. longum 420 enhances the efficacy of the ICIs.

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