Sarcopenic Obesity and its Prognostic Impact on Urological Cancers: A Systematic Review

You have accessJournal of UrologyReview Article1 Oct 2021Sarcopenic Obesity and its Prognostic Impact on Urological Cancers: A Systematic Review J. Stangl-Kremser, A. Mari, L. Y. Lai, C. T. Lee, R. Vince, A. Zaslavsky, S. S. Salami, H. Fajkovic, S. F. Shariat, and G. S. Palapattu J. Stangl-KremserJ. Stangl-Kremser Department of Urology, Medical University of Vienna, Vienna, Austria Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan Department of Urology, Michigan Medicine, Ann Arbor, Michigan More articles by this author , A. MariA. Mari Department of Urology, University of Florence, Careggi Hospital, Florence, Italy More articles by this author , L. Y. LaiL. Y. Lai Department of Urology, Michigan Medicine, Ann Arbor, Michigan Supported by NIH/National Cancer Institute T32CA180984. More articles by this author , C. T. LeeC. T. Lee Department of Urology, Michigan Medicine, Ann Arbor, Michigan Department of Urology, The Ohio State University, Columbus, Ohio Financial interest and/or other relationship with Merck. More articles by this author , R. VinceR. Vince Department of Urology, Michigan Medicine, Ann Arbor, Michigan Supported by NIH/National Cancer Institute T32CA180984. Supported by the National Institutes of Health. More articles by this author , A. ZaslavskyA. Zaslavsky Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan More articles by this author , S. S. SalamiS. S. Salami Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan Department of Urology, Michigan Medicine, Ann Arbor, Michigan More articles by this author , H. FajkovicH. Fajkovic Department of Urology, Medical University of Vienna, Vienna, Austria More articles by this author , S. F. ShariatS. F. Shariat Department of Urology, Medical University of Vienna, Vienna, Austria Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria Karl Landsteiner Institute, Vienna, Austria Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan Department of Urology, Weill Cornell Medical College, New York, New York Department of Urology, University of Texas Southwestern, Dallas, Texas Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic European Association of Urology Research Foundation, Arnhem, Netherlands More articles by this author , and G. S. PalapattuG. S. Palapattu §Correspondence: Department of Urology, University of Michigan Medical School, 1500 E. Medical Center Dr., 7306 Rogel Cancer Center, Ann Arbor, Michigan 48109-5948 telephone: 734-763-9269; FAX: 734-936-9127; E-mail Address: [email protected] Department of Urology, Medical University of Vienna, Vienna, Austria Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan Department of Urology, Michigan Medicine, Ann Arbor, Michigan Financial interest and/or other relationship with ImmunityBio and SynDev. More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001873AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment. Materials and Methods: We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity. Results: A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51–0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4−16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11–63). Conclusions: There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer. Abbreviations and Acronyms BMI body mass index CHT chemotherapy CSS cancer-specific survival L3 third lumbar vertebra NOS Newcastle–Ottawa Scale OS overall survival PCa prostate cancer PFS progression-free survival RCC renal cell carcinoma SMI skeletal muscle index UC urothelial carcinoma Urological cancers account for a large and increasing health burden across the world, with approximately 2.1 million new cases of renal cell carcinoma (RCC), urothelial carcinoma (UC) and prostate cancer (PCa) worldwide.1 Mortality rate increased 1.6-fold between 1990 and 2013 despite advances in medical and surgical treatments.1 Better prognostic patient-specific factors are needed to identify at-risk patients suitable for appropriate intervention. Traditionally, cancer staging and baseline comorbidities have been used to predict survival outcomes of patients with cancer undergoing treatment. Also, the use of performance status and clinical frailty indices have supported physician therapeutic decision making by estimating cancer survival.2 Recently, there has been an increasing interest in utilizing body composition phenotype as an additional indicator of cancer prognosis. Studies have found that patients who experience loss of muscle mass and function have worse outcomes than their counterparts a decline in muscle mass and function.3,4 While this phenomenon known as sarcopenia is primarily age-related, it can also be secondary to malnutrition, endocrine dysfunction and immobility.5,6 In chronic diseases, eg cancer cachexia, specific T-cells combined with increased levels of inflammatory cytokines have been implicated in the process of muscle destruction.7,8 Sarcopenia has also been studied in conjunction with body composition. Sarcopenia, obesity and sarcopenic obesity are considered syndromes of disordered body composition within a spectrum of relative muscle mass and the percentage of body fat (fig. 1).9 Sarcopenic obesity, first introduced by Baumgartner et al,10 is predicted to become a public health problem.11 There are different, evolving definitions of sarcopenic obesity. To date, there is no standardized method to assess for this syndrome. Numerous underlying mechanisms can explain the over presence of sarcopenic obesity in the elderly, including anabolic resistance, reduced muscle perfusion and deposition of intramyocellular lipids (6).12,13 Muscle degeneration promotes insulin resistance which is the foundation for excess fat and muscle wasting.14 Figure 1. Venn diagram depicts relationship of sarcopenia and obesity. Coexistence of these 2 diseases is defined as sarcopenic obesity (SO). Some recent studies in patients with various cancers have suggested a relationship of sarcopenic obesity with mortality and reported its association with survival outcomes.15–19 However, others reported no significant association between the two.20–22 This systematic review aims to assess the prevalence and impact of sarcopenic obesity on outcomes in patients with urological cancers, with a focus on RCC, UC and PCa. Findings from this study may inform clinical management of patients with sarcopenic obesity. Materials and Methods Literature Search Our methodology is summarized in a completed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Protocols checklist (supplementary table 1, https://www.jurology.com). The protocol was prospectively registered in the International Prospective Register of Systematic Reviews database (PROSPERO: CRD42020190483). We searched the PubMed®, EMBASE® and Scopus® databases for studies that evaluated the prevalence and prognostic impact of sarcopenic obesity on outcomes among patients with urological cancers undergoing treatment. Search terms are provided in supplementary table 2 (https://www.jurology.com). Eligibility Criteria We applied the Population, Interventions, Comparators and Outcomes (PICO) design to specify the eligibility criteria based on the PRISMA guidelines. To be eligible, studies must have included patients with urological cancers and sarcopenic obesity (Population) who underwent cancer treatment (Intervention) and patients with urological cancers without sarcopenic obesity (Comparator) for evaluation of prevalence of sarcopenic obesity and association between sarcopenic obesity and survival outcomes (Outcome). Inclusion and Exclusion of Systematic Review All original studies reporting the prevalence of sarcopenic obesity and survival outcomes of patients with urological cancers were included in the present systematic review. Patients must have 1) a diagnosis of urological cancer confirmed with pathology, 2) undergone cancer treatment and 3) initiation of assessment of their body composition (eg muscle and fat) before cancer treatment. Editorials, letters, replies from authors, reviews, commentaries and case reports were excluded. If multiple articles were published by the same working group based on similar patient cohorts and/or data set suspicious for double use, only the publication with the largest patient cohort was included. Outcomes and Data Extraction Our primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) among patients with sarcopenic obesity and urological cancer who were undergoing treatment. The secondary outcome was prevalence of sarcopenic obesity. All potentially eligible studies were independently reviewed by 2 authors (JS-K, AM). Discrepancies were resolved by the corresponding author of this review (GSP). After the full-text screening, the following data were extracted: the name of the first author, year of publication, cancer type, cancer stage, number of patients, age, followup time, methods of assessing sarcopenic obesity, cutoffs criteria for sarcopenic obesity and the number of patients with sarcopenic obesity. When available, median survival times and interquartile ranges, median survival rates and/or hazard ratios with confidence intervals for OS, CSS and PFS were extracted. Studies that did not report on survival outcomes were also included if they addressed the prevalence of sarcopenic obesity. Quality Evaluation We used the Newcastle–Ottawa Scale (NOS)23 to assess the quality of selection, comparability and outcomes on the decision rules published by Hartling et al.24 A followup of 24 months or greater was deemed adequate for outcomes assessments. Results Literature Search and Selection Our search on February 10, 2021 retrieved 2,984 publications (fig. 2). An additional relevant study was identified from further up-to-date literature search. After removing duplicates, 1,885 results were screened independently, leading to the exclusion of 1,438 publications by title review and 447 publications by abstract review. A total of 97 publications were screened by full-text review for inclusion, of which 15 original studies met criteria to be included in this systematic review. Figure 2. Article selection process. SO, sarcopenic obesity. Studies and Patient Characteristics Of 15 studies included in this review, 12 examined the prevalence of sarcopenic obesity and 9 assessed for relationships between sarcopenic obesity and cancer outcomes in patients with urological cancers undergoing treatment. Characteristics of the studies are summarized in table 1. Of the 9 studies assessing cancer outcomes, all had evaluated OS, 2 studies assessed for PFS and 2 studies reported on CSS. Table 1. Baseline characteristics of included studies References Publication Yr Study Period Region Study Design Age (yrs) Followup Cancer Site Tumor Type Treatment Xu et al33 2020 2012–2017 U.S. r Median 71 (range 50–97) Median 33.9 mos (IQR 20.4–55.2) Prostate adv Various Darbas et al30 2020 2006–2017 France r Median 66 (range 43–89) Median 36.5 mos (range 0.5–137.0) Kidney (RCC) loc NE (partial or complete) Stangl-Kremser et al25 2019 2005–2016 Austria r Median 69 (IQR 65–75) Median 24.1 mos (IQR 12.8–40.8) Prostate met CHT Mavuduru et al28 2019 . India p . . Bladder loc RC Di Palma et al29 2018 . France . Mean 70 (range 50–86) . Prostate adv Castration±CHT Mayr et al34 2018 2004–2014 Germany r Median 72 (IQR 65–78) Median 35.0 mos (IQR 20.0–58.0) Bladder loc RC Stangl-Kremser et al32 2018 2004–2015 Austria r Median 82 (IQR 75−86) Median 12.5 mos (IQR 5.1−23.5) Bladder loc RT Kocher et al31 2017 2002–2016 U.S. r Mean 7.5 (±SD 10.2) Mean 31.2 mos (range 5.0–122.0) Upper tract (UC) adv RNU Gu et al38 2017 2008–2014 China r Median 60 . Kidney (RCC) met TKI+mTOR-I Fukushima et al26 2017 2001–2015 Japan r Median 71 (IQR 41–87) Median 41.0 mos (range 4.0–170.0) Upper tract (UC) adv RNU Cushen et al27 2016 2008–2013 Ireland r Median 69 (range 46–81) . Prostate met CHT Wu et al37 2015 2004–2012 U.S. r . . Prostate met CHT Psutka et al20 2015 2000–2008 U.S. r . Median 6.3 yrs (IQR 5.7–9.5) Bladder loc RC Psutka et al22 2015 2000–2010 U.S. r . . Kidney (RCC) loc RNU Huillard et al21 2013 2006–2012 France r Median 60 (range 29–83) . Kidney (RCC) met TKI adv, advanced. loc, localized. met, metastasized. mTOR-I, mammalian target of rapamycin inhibitors. NE, nephrectomy. p, prospective. r, retrospective. RC, radical cystectomy. RNU, radical nephroureterectomy. RT, radiation therapy. TKI, tyrosine kinase inhibitors. Seven studies were conducted in Europe, 5 in North America and 3 in Asia. Studies were published between January 2010 and October 2020 (including Epub), with urologic oncology cancer patients treated between 2000 and 2017. Five studies included patients with PCa, 4 studies included patients with RCC and 6 studies included patients with UC. The methods for assessment and cutoffs for sarcopenic obesity used in the included studies are presented in table 2. Briefly, all studies used skeletal muscle areas based on cross-sectional imaging to assess for sarcopenia. The definition of obesity varied among studies. Most studies used the body mass index (BMI) to classify patients as obese, while some used an elevated fat mass index or visceral fat-to-muscle ratio. Table 2. Overview of methods and cutoffs classifying cases as sarcopenic obese Authors, Yr Muscle Assessment Software Muscle Assessment Sarcopenia Definition No. Pts Included No. Pts Analyzed Obesity Assessment No. SO Pts SO Prevalence No. SO Men No. SO Women Cutoff SMI Men (cm2/m2) Cutoff SMI Women (cm2/m2) Xu et al, 2020 L3 SMI sliceOmatic™ 53 N/A 188 182 BMI ≥30 kg/m2 69 38% 69 N/A - - Darbas et al, 2020 L3 SMI AW Server (GE Healthcare Inc) 53 41 620 96 BMI ≥30 kg/m2 45 47% 118 N/A Stangl-Kremser et al, 2019 L3 SMI OsiriX™ 53 N/A 186 186 BMI ≥25 kg/m2 118 63% - - Mavuduru et al, 2019 L3 SMI - 53 41 54 54 BMI ≥25 kg/m2 8 15% 6 N/A Di Palma et al, 2018 L3 SMI - 55 N/A 55 55 - 6 11% - - Mayr et al, 2018 L3 SMI Osirix 52 43 860 709 BMI ≥25 kg/m2 121 17% - - Stangl-Kremser et al, 2018 L3 SMI Osirix 53 43 94 68 BMI ≥25 kg/m2 30 44% - - Kocher et al, 2017 L3 SMI Aquarius iNtuition (U.S. Department of Veterans Affairs) 55 39 133 100 BMI ≥30 kg/m2 18 18% - - Gu et al, 2017 L3 SMI ImageJ (U.S. National Institutes of Health) 40.8 34.9 142 101 BMI ≥23 kg/m2 - - - - Fukushima et al, 2017 L3 SMI Osirix 53 41 85 81 BMI ≥25 kg/m2 11 14% - NA Cushen et al, 2016 L3 SMI and SMD Osirix 53 N/A 82 63 BMI ≥25 kg/m2 8 13% - N/A Wu et al, 2015 L3–4 SMA ImageJ - N/A 378 333 VMR >median - - - - Psutka et al, 2015 L3 SMI sliceOmatic 55 39 515 262 FMI >9 kg/m2 (men), FMI >13 kg/m2 (women) 71 27% - - Psutka et al, 2015 L3 SMI sliceOmatic 55 39 390 250 FMI >9 kg/m2 (men), FMI >13 kg/m2 (women) - - - - Huillard et al, 2013 L3 SMI ImageJ 55.4 38.9 84 61 BMI ≥25 kg/m2 12 20% 11 1 FMI, fat mass index. N/A, not applicable. SO, sarcopenic obesity. SMA, skeletal muscle area. SMD, skeletal muscle density. VMR, visceral fat-to-muscle area ratio. Prevalence of Sarcopenic Obesity Among the patients included in 12 studies evaluating the prevalence of sarcopenic obesity, the mean prevalence was 27% with a range between 11% and 63%.20,21,25–34 For kidney cancer, 1 study reported a 20% prevalence of sarcopenic obesity among patients with metastatic RCC.21 The authors defined sarcopenic obesity based on the skeletal muscle index (SMI) assessed by cross-sectional imaging at the height of the third lumbar vertebra (L3) and a BMI ≥25 kg/m2. Gender-specific thresholds for the assessment of sarcopenia according to Fearon et al35 were applied. Another study, including patients with localized disease, revealed a prevalence of 47%.30 For UC of the bladder, the range of patients displaying sarcopenic obesity was between 15% and 44%.20,28,32,34 Notably, the cut-offs for L3 SMI and the definition of obesity were different in these studies.20,28,32 In regard to advanced upper tract UC, 14% to 18% of the patients with advanced upper tract UC were found to have sarcopenic obesity.31,36 For PCa, a range of 11%–38% of cohorts of 55 and 182 men, respectively, with advanced disease were reported to be sarcopenic obese.29,33 Another series reported a prevalence of 63% among 154 men with castration-resistant PCa.25 Prognostic Value of Sarcopenic Obesity Ten studies assessed the prognostic value of sarcopenic obesity. In regard to OS (supplementary table 3, https://www.jurology.com), 7 studies found no statistically significant association between sarcopenic obesity and OS. Cushen et al stratified the patients with metastatic PCa into BMI categories.27 The authors reported that patients with low attenuation of the skeletal muscles, an image-derived surrogate measure of greater intramuscular adipose tissue, were associated with shorter OS compared to patients with a high muscle attenuation (10.7 months versus 19.2 months; p=0.04, respectively) in patients with normal BMI. However, there was no association of low muscle attenuation in obese patients (BMI ≥25) with OS (p=0.21).27 Psutka et al evaluated the impact of obesity after adjusting for skeletal muscle wasting in patients with UC.20 In univariable analysis, they assessed skeletal muscle attenuation but could not detect a statistically significant impact on OS (p=0.12). However, in this study, the definition of sarcopenia was based on the SMI. Patients with the coexistence of increased fat mass and sarcopenia were not at risk to experience a shorter OS (HR 1.29, 95% CI 0.74–2.27, p=0.40).20 Another study assessing patients with RCC reported a nonsignificant hazard ratio of 1.50 (p=0.10) for all-cause mortality in multivariate analysis.22 Similarly, Huillard et al did not observe significant differences regarding OS between patients with RCC displaying sarcopenia and BMI <25 kg/m2 and patients without sarcopenia or BMI ≥25 kg/m2 (p=0.21).21 Darbas et al reported that sarcopenic obese patients tend to have an increased risk to experience a shorter OS (p=0.05).30 Notably, 1 study used visceral fat-to-muscle area ratio to define sarcopenic obesity, eg focusing on imaging-based assessment to determine sarcopenic obesity. In this analysis, an increased ratio was associated with OS (HR 0.71, 95% CI 0.51–0.89, p=0.04) in patients with PCa. However, no significant differences in time to death of any cause were found anymore between high and low visceral fat-to-muscle area ratio stratified by BMI categories.37 In a study that stratified patients with RCC by BMI and muscle loss, the authors detected statistically significant group differences (p=0.01) with a median OS ranging from 11.6 months in those with muscle loss and low BMI to 25.9 months in patients with muscle loss and high BMI.38 We found little consensus on the prognostic impact of sarcopenic obesity on PFS, as only 2 studies of patients with RCC reported on this outcome.21,38 Gu et al found that skeletal muscle loss was associated with PFS for patients with various BMI and muscle mass changes (p <0.01).38 For instance, patients with muscle loss and a low BMI had a PFS of 8.4 months whereas patients patient with muscle loss and a high BMI had a PFS of 13.9 months. In another study, the authors reported no significant differences regarding OS between patients with sarcopenia and BMI <25 kg/m2 and the remaining patients (p=0.10; supplementary table 4, https://www.jurology.com).21 Two studies compared the CSS of patients with and without sarcopenic obesity.22,32 One study could detect a statistically significant adverse impact of sarcopenic obesity in patients with advanced UC of the bladder (HR 5.0, 95% CI 1.4−16.7, p=0.01) in a subgroup analysis.32 Among patients with kidney cancer, those with sarcopenic obesity had a 2.0 times higher hazard ratio of poor CSS compared to those without sarcopenic obesity (HR 2.0, p=0.05; supplementary table 5, https://www.jurology.com).22 The reported survival outcomes are summarized in table 3. The detailed NOS analysis is shown in supplementary table 6 (https://www.jurology.com). Briefly, the risk of bias of the included studies ranged from poor (eg a high risk of bias) to good (eg low risk of bias). The quality of selection and comparability was fair or good. However, we detected poor quality concerning reporting of review-specific outcome data for 6 of the 15 included studies. Table 3. Overview of reported survival outcomes Color legend: blue: analysis performed; orange: no analysis performed. adj, adjustment (in multivariate analysis). pN, pathological N stage. pT, pathological T stage. Outcomes by Cancer Type Renal cell carcinoma Results were mixed among the studies investigating the outcomes of patients with RCC. Patients treated with nephrectomy for clinically localized disease displaying sarcopenic obesity had a trend for higher risk of experiencing shorter OS (p=0.05).30 By comparison, the other study supported no association between death of any cause and sarcopenic obesity (HR 1.5, 95% CI not reported, p=0.10).22 Similarly, Psutka et al could not show that sarcopenic obesity was an independent unfavorable prognostic factor for CSS after adjusting for cancer staging and age (HR 2.0, 95% CI not reported, p=0.05).22 For patients with metastatic RCC, time to death of any cause did not differ significantly in a study comparing 12 patients with sarcopenic obesity and 49 patients without sarcopenic obesity (median OS 19.3 months [IQR 14.0–20.0] versus 23.5 months [IQR 12.5–40.7], p=0.21).21 In contrast, Gu et al analyzed 101 patients with metastatic RCC and found that individuals with a BMI <23 kg/m2 and muscle loss had the worst OS and PFS (p=0.01, respectively).38 Bladder cancer One study evaluated the impact of sarcopenic obesity on OS in patients with UC of the bladder undergoing radical cystectomy. Neither study found any statistically significant differences in the OS of sarcopenic obese patients and those without sarcopenic obesity.20 The 5-year OS rate was 40.0% in individuals displaying excessive fat and sarcopenia and 37.4% in those without sarcopenic obesity (p=0.72). The authors could not show that sarcopenic obesity was significantly associated with OS in univariable analysis (HR 1.29, 95% CI 0.74–2.27, p=0.40).20 One other study evaluated for the prognostic value of sarcopenic obesity in patients undergoing bimodal therapy. The authors reported that patients who display sarcopenia and concomitant obesity have limited CSS but no shorter OS (p=0.01 and p=0.32, respectively).32 No studies have evaluated the impact of sarcopenic obesity on PFS of patients with UC of the bladder. Prostate cancer Of the 2 studies evaluating the prognostic impact of sarcopenic obesity for patients with PCa.27,37 Among patients with metastatic castration-resistant disease undergoing docetaxel chemotherapy (CHT) who have a normal BMI, patients with low muscle quality had shorter survival compared to patients with high muscle quality (10.7 months [IQR 3.9–17.5] versus 19.2 months [IQR 10.6–27.9], p=0.04). In contrast, this association was no longer significant in patients with BMI greater than 25 kg/m2 (p=0.21). Of note, patients with an elevated BMI displayed greater muscle mass than their counterparts with normal BMI (p <0.01) and had a better OS (HR 0.35, CI 0.16–0.78, p=0.01).27 Moreover, Wu et al demonstrated a protective impact of an elevated visceral fat-to-muscle area ratio in the same setting (HR 0.71, 95% CI 0.51–0.98, p=0.04).37 Even though not included in our analysis for outcomes due to the divergent definition of sarcopenic obesity, but of relevance, 1 other study reported that patients with high BMI experienced longer OS independent of sarcopenia and myosteatosis (p=0.01).33 No study has examined the prognostic value of sarcopenic obesity in patients with localized disease. There are also no available data on the impact of sarcopenic obesity on CSS or PFS among patients with PCa. Discussion Sarcopenia and obesity are 2 health conditions that are growing in prevalence in the older population.6 While body composition is a known prognostic factor in many conditions, including solid tumors,39–41 the impact of the concordance of these 2 conditions, sarcopenic obesity, on cancers remains unknown. In reviewing the literature on sarcopenic obesity in the context of urological cancer, we found that almost 1 in 4 patients with urological cancer has sarcopenic obesity. However, with the limited number of studies available, current evidence on the impact of sarcopenic obesity on survival outcomes is conflicting. Much work needs to be done to understand the impact of sarcopenic obesity on cancer outcomes in order to support management recommendations for nutrition, exercise and additional therapies as adjuncts to standard cancer care. Body composition changes have been associated with clinical outcomes in various pathologies, including several cancers. As shown in our conceptual model (fig. 3), the cause of sarcopenic obesity for patients with cancer is multifactorial, where age-related metabolism changes and environmental obesogenic factors are compounded by increased levels of inflammatory cytokines secondary to cancer inflammation.7,8 This is a constellation that even further promotes gain in fat mass and loss of mass and muscle quality. The imbalance of protein synthesis and degradation results in muscle loss linked with increased physical disability, surgical complications and toxicity during cancer treatment. Functionally, these body composition changes lead to progressive impairment as patients are depleted of muscle strength needed to carry their body weight.10 However, future studies are needed to evaluate the association between muscle mass quality, eg by the assessment of the skeletal muscle attenuation as determined by computerized tomography and physical performance. Figure 3. Conceptual model demonstrates dynamic changes between losing fat-free and gaining fat masses. In patients with cancer, 1 extreme alteration of fat mass might be present: 1) cachexia with low muscle mass and low fat mass, or 2) sarcopenic obesity. Sarcopenic obesity is common in patients with cancer with a prevalence of 15% among patients with lung/gastrointestinal cancer and 9% in patients with advanced solid tumors.42 Reviewing the mean prevalence of this condition in urological cancer patients is 27%. Our results are not enough to draw a conclusion for the prognostic impact of sarcopenic obesity in urological cancer patients. However, patients with sarcopenic obesity, regardless of cancer status, may have an increased 10-year cardiovascular disease risk score.43 In the context of the heightened risk for cardio