Original Study| Volume 21, ISSUE 1, P136-145, February 2023

Download started.


Impact of Body Mass Index on Outcomes in an Asian population of Advanced Renal Cell Carcinoma and Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors

Published:August 05, 2022DOI:



      To clarify the impact of body mass index (BMI) on treatment outcomes including survival, tumor response, and adverse events (AEs) in patients with advanced renal cell carcinoma (RCC) or urothelial carcinoma (UC) treated with immune checkpoint inhibitors (ICIs) in an Asian population.


      We retrospectively evaluated 309 patients with advanced RCC or UC who received ICIs between September 2016 and July 2021. The patients were divided into high- (i.e., ≥25 kg/m2) and low-BMI (<25 kg/m2) groups according to the BMI at the time of treatment initiation.


      Overall, 57 patients (18.4%) were classified into the high-BMI group. In RCC patients treated with ICIs as first-line therapy or UC treated with pembrolizumab, progression-free survival (PFS) (p = 0.309; p = 0.842), overall survival (OS) (p = 0.701; p = 0.983), and objective response rate (ORR) (p = 0.163; p = 0.553) were comparable between the high- and low-BMI groups. In RCC patients treated with nivolumab monotherapy as later-line therapy, OS (p = 0.101) and ORR (p = 0.102) were comparable, but PFS was significantly longer in the high-BMI group (p = 0.0272). Further, multivariate analysis showed that BMI was not an independent factor of PFS or OS in all the treatment groups (any, p>0.05). As for AE profiles, in nivolumab monotherapy, the rate was significantly higher in the high-BMI group (p = 0.0203), whereas in the other two treatments, the rate was comparable.


      BMI was not associated with survival or response rates of advanced RCC or UC patients treated with ICIs in an Asian population. AEs might frequently develop in high-BMI patients with RCC in nivolumab monotherapy.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Xu W
        • Atkins MB
        • McDermott DF
        Checkpoint inhibitor immunotherapy in kidney cancer.
        Nat Rev Urol. 2020; 17 (PMID): 137-150
        • Powles T
        Recent eupdate to the esmo clinical practice guidelines on renal cell carcinoma on cabozantinib and nivolumab for first-line clear cell renal cancer: Renal cell carcinoma: Esmo clinical practice guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2021; 32 (PMID): 422-423
        • Cathomas R
        • Lorch A
        • Bruins HM
        • et al.
        The 2021 updated european association of urology guidelines on metastatic urothelial carcinoma.
        Eur Urol. 2022; 81 (PMID): 95-103
        • Motzer RJ
        • Tannir NM
        • McDermott DF
        • et al.
        Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma.
        N Engl J Med. 2018; 378 (PMID: PMC5972549): 1277-1290
        • Fradet Y
        • Bellmunt J
        • Vaughn DJ
        • et al.
        Randomized phase III keynote-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: Results of >2 years of follow-up.
        Ann Oncol. 2019; 30 (PMID: PMC6594457): 970-976
        • Cortellini A
        • Bersanelli M
        • Santini D
        • et al.
        Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (pd-1)/programmed cell death-ligand 1 (pd-l1) checkpoint inhibitors: a multicentre analysis of immune-related adverse events.
        Eur J Cancer. 2020; 128 (PMID): 17-26
        • Guzman-Prado Y
        • Ben Shimol J
        • Samson O
        Body mass index and immune-related adverse events in patients on immune checkpoint inhibitor therapies: a systematic review and meta-analysis.
        Cancer Immunol Immunother. 2021; 70 (PMID): 89-100
        • Nie RC
        • Chen GM
        • Wang Y
        • et al.
        Association between body mass index and survival outcomes in patients treated with immune checkpoint inhibitors: meta-analyses of individual patient data.
        J Immunother. 2021; 44 (PMID: PMC8500279): 371-375
        • Rogado J
        • Romero-Laorden N
        • Sanchez-Torres JM
        • et al.
        Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-pd-1 antibodies.
        Oncoimmunology. 2020; 9 (PMID: PMC7185216)1751548
        • Cortellini A
        • Bersanelli M
        • Buti S
        • et al.
        A multicenter study of body mass index in cancer patients treated with anti-pd-1/pd-l1 immune checkpoint inhibitors: when overweight becomes favorable.
        J Immunother Cancer. 2019; 7 (PMID: PMC6391761): 57
        • Di Filippo Y
        • Dalle S
        • Mortier L
        • et al.
        Relevance of body mass index as a predictor of systemic therapy outcomes in metastatic melanoma: analysis of the melbase french cohort data.
        Ann Oncol. 2021; 32 (PMID): 542-551
        • Kichenadasse G
        • Miners JO
        • Mangoni AA
        • Rowland A
        • Hopkins AM
        • Sorich MJ
        Association between body mass index and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer.
        JAMA Oncol. 2020; 6 (PMID: PMC6990855): 512-518
        • Boi SK
        • Orlandella RM
        • Gibson JT
        • et al.
        Obesity diminishes response to pd-1-based immunotherapies in renal cancer.
        J Immunother Cancer. 2020; 8 (PMID: PMC7757487)
        • De Giorgi U
        • Procopio G
        • Giannarelli D
        • et al.
        Association of systemic inflammation index and body mass index with survival in patients with renal cell cancer treated with nivolumab.
        Clin Cancer Res. 2019; 25 (PMID): 3839-3846
        • Labadie BW
        • Liu P
        • Bao R
        • et al.
        BMI, IRAE, and gene expression signatures associate with resistance to immune-checkpoint inhibition and outcomes in renal cell carcinoma.
        J Transl Med. 2019; 17 (PMID: PMC6878694): 386
        • De Filippi R
        • Morabito F
        • Santoro A
        • et al.
        Body mass index is not associated with survival outcomes and immune-related adverse events in patients with hodgkin lymphoma treated with the immune checkpoint inhibitor nivolumab.
        J Transl Med. 2021; 19 (PMID: PMC8638339): 489
        • Gülave B
        • Hew MN
        • de Groot JS
        • Rodwell L
        • Teerenstra S
        • Fabriek BO
        High body mass index and pre-existing autoimmune disease are associated with an increased risk of immune-related adverse events in cancer patients treated with pd-(l)1 inhibitors across different solid tumors.
        ESMO Open. 2021; 6 (PMID: PMC8086026)100107
        • Motzer RJ
        • Escudier B
        • McDermott DF
        • et al.
        Nivolumab versus everolimus in advanced renal-cell carcinoma.
        N Engl J Med. 2015; 373 (PMID): 1803-1813
        • Rini BI
        • Plimack ER
        • Stus V
        • et al.
        Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.
        N Engl J Med. 2019; 380 (PMID): 1116-1127
        • Motzer RJ
        • Penkov K
        • Haanen J
        • et al.
        Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.
        N Engl J Med. 2019; 380 (PMID): 1103-1115
        • Bellmunt J
        • de Wit R
        • Vaughn DJ
        • et al.
        Pembrolizumab as second-line therapy for advanced urothelial carcinoma.
        N Engl J Med. 2017; 376 (PMID: PMC5635424): 1015-1026
        • Eisenhauer EA
        • Therasse P
        • Bogaerts J
        • et al.
        New response evaluation criteria in solid tumours: revised recist guideline (version 1.1).
        Eur J Cancer. 2009; 45 (PMID): 228-247
      1. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.4 ( 2022

        • Leiter A
        • Doucette J
        • Krege S
        • et al.
        Obesity and outcomes in patients with metastatic urothelial carcinoma.
        Bladder Cancer. 2016; 2 (PMID: PMC4969712): 341-349
        • Martin L
        • Birdsell L
        • Macdonald N
        • et al.
        Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.
        J Clin Oncol. 2013; 31 (PMID): 1539-1547
        • Ishihara H
        • Kondo T
        • Omae K
        • et al.
        Sarcopenia and the modified glasgow prognostic score are significant predictors of survival among patients with metastatic renal cell carcinoma who are receiving first-line sunitinib treatment.
        Target Oncol. 2016; 11 (PMID): 605-617
        • James BR
        • Tomanek-Chalkley A
        • Askeland EJ
        • Kucaba T
        • Griffith TS
        • Norian LA
        Diet-induced obesity alters dendritic cell function in the presence and absence of tumor growth.
        J Immunol. 2012; 189 (PMID: PMC3401274): 1311-1321
        • Hale M
        • Itani F
        • Buchta CM
        • Wald G
        • Bing M
        • Norian LA
        Obesity triggers enhanced MDSC accumulation in murine renal tumors via elevated local production of ccl2.
        PLoS One. 2015; 10 (PMID: PMC4358922)e0118784
        • Incio J
        • Ligibel JA
        • McManus DT
        • et al.
        Obesity promotes resistance to anti-vegf therapy in breast cancer by up-regulating il-6 and potentially fgf-2.
        Sci Transl Med. 2018; 10 (PMID: PMC5936748)
        • Wang Z
        • Aguilar EG
        • Luna JI
        • et al.
        Paradoxical effects of obesity on t cell function during tumor progression and pd-1 checkpoint blockade.
        Nat Med. 2019; 25 (PMID: PMC6324991): 141-151
        • Bennett DA
        How can i deal with missing data in my study?.
        Aust N Z J Public Health. 2001; 25 (PMID, DOI): 464-469