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Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (15 October 2023) | Viewed by 10662

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Special Issue Editors

Dr. Fumitaka Koga

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Guest Editor

Department of Urology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
Interests: sarcopenia; prognostic biomarkers; urinary bladder neoplasms; prostate neoplasms; renal cell carcinoma

Dr. Hiroshi Fukushima

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Guest Editor

Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan
Interests: sarcopenia; psoas muscles; cachexia; renal cell carcinoma; urinary tract

Special Issue Information

Dear Colleagues,

Sarcopenia is a condition characterized by the degenerative and systemic loss of skeletal muscle mass with the reduction of skeletal muscle strength and physical performance. Sarcopenia reflects not only the frailty of the host and intolerance to cancer therapy but also the presence of cancer cachexia. Thus, sarcopenia is one of the most clinically important factors in the management of cancer-bearing patients.

In the field of urological cancers, including urothelial cancer, kidney cancer, and prostate cancer, a growing number of studies have shown the strong prognostic value of sarcopenia in association with therapeutic modalities according to the disease extent. Currently, minimally invasive robotic surgery is becoming a mainstay of urological cancer surgery. Moreover, the clinical use of novel anti-cancer therapeutics such as immuno-oncology drugs and antibody–drug conjugates is rapidly expanding in urological cancers. With these paradigm shifts in cancer therapy, the prognostic significance of sarcopenia should be verified.

This Special Issue of Cancers focuses on the role of sarcopenia as a prognostic biomarker of urological cancer patients in contemporary clinical practice. This special issue also covers frailty as a treatment outcome biomarker of those patients.

Dr. Fumitaka Koga
Dr. Hiroshi Fukushima
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

sarcopenia
urological cancers
psoas muscles
cancer cachexia
frailty
bladder cancer
renal cell carcinoma
prostate cancer
prognosis
biomarkers

Published Papers (7 papers)

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Research

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13 pages, 5761 KiB

Open AccessArticle

Association between Immune Checkpoint Inhibitor Treatment Outcomes and Body Composition Factors in Metastatic Renal Cell Carcinoma Patients

by Kohei Takei, Toshiki Kijima, Naoya Okubo, Ryo Kurashina, Hidetoshi Kokubun, Toshitaka Uematsu, Hironori Betsunoh, Masahiro Yashi and Takao Kamai

Cancers 2023, 15(23), 5591; https://doi.org/10.3390/cancers15235591 - 26 Nov 2023

Cited by 1 | Viewed by 854

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC); however, validating body composition-related biomarkers for their efficacy remains incomplete. We evaluated the association between body composition-related markers and the prognosis of patients with mRCC who received ICI-based first-line therapies. Patients and Methods: We retrospectively investigated 60 patients with mRCC who underwent ICI-based therapy as their first-line treatment between 2019 and 2023. Body composition variables, including skeletal muscle, subcutaneous fat, and visceral fat indices, were calculated using baseline computed tomography scans. Sarcopenia was defined according to sex-specific cut-off values of the skeletal mass index. The associations between body composition indices and objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results: Patients with sarcopenia had lower ORR and DCR than those without sarcopenia (33.3% vs. 61.1%, p = 0.0436 and 52.4% vs. 94.4%, p = 0.0024, respectively). Patients with sarcopenia had a significantly shorter median PFS (14 months vs. not reached, p = 0.0020) and OS (21 months vs. not reached, p = 0.0023) than patients without sarcopenia did. Sarcopenia was a significant predictor of PFS (hazard ratio [HR], 4.31; 95% confidence interval [CI], 1.65–14.8; p = 0.0018) and OS (HR, 5.44; 95% CI, 1.83–23.4; p = 0.0013) along with poor IMDC risk. No association was found between the subcutaneous, visceral, and total fat indices and the therapeutic effect of ICI-based therapy. Conclusions: Sarcopenia was associated with a lower response and shorter survival rates in patients with mRCC who received first-line ICI-based therapy. Full article

(This article belongs to the Special Issue Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients)

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15 pages, 2173 KiB

Open AccessArticle

Body Composition of Patients Undergoing Radical Cystectomy for Bladder Cancer: Sarcopenia, Low Psoas Muscle Index, and Myosteatosis Are Independent Risk Factors for Mortality

by Simon U. Engelmann, Christoph Pickl, Maximilian Haas, Sebastian Kaelble, Valerie Hartmann, Maximilian Firsching, Laura Lehmann, Miodrag Gužvić, Bas W. G. van Rhijn, Johannes Breyer, Maximilian Burger and Roman Mayr

Cancers 2023, 15(6), 1778; https://doi.org/10.3390/cancers15061778 - 15 Mar 2023

Cited by 6 | Viewed by 1593

Abstract

Background: We assessed a wide array of body composition parameters to identify those most relevant as prognostic tools for patients undergoing radical cystectomy (RC) due to bladder cancer (BC). Methods: In this retrospective, single-center study, preoperative computed tomography (CT) scans of 657 patients were measured at the level of the 3rd lumbar vertebra (L3) to determine common body composition indices including sarcopenia, myosteatosis, psoas muscle index (PMI), subcutaneous and visceral fat index (SFI and VFI), visceral-to-subcutaneous fat ratio (VSR), and visceral obesity. Predictors of overall survival (OS) and cancer-specific survival (CSS) were identified in univariate and multivariate survival analysis. Results: Sarcopenia and a low PMI were independently associated with shorter OS (Sarcopenia: HR 1.30; 95% CI 1.02–1.66; p = 0.04 and a low PMI: HR 1.32; 95% CI 1.02–1.70; p = 0.03) and CSS (Sarcopenia: HR 1.64; 95% CI 1.19–2.25; p < 0.01 and a low PMI: HR 1.41; 95% CI 1.02–1.96; p = 0.04). Myosteatosis, measured as decreasing average Hounsfield units of skeletal muscle, was an independent risk factor for OS (HR 0.98; 95% CI 0.97–1.00; p = 0.01) and CSS (HR 0.98; 95% CI 0.96–1.00; p < 0.05). The assessed adipose tissue indices were not significant predictors for OS and CSS. Conclusions: Sarcopenia, a low PMI, and myosteatosis are independent predictors for OS and CSS in patients undergoing radical cystectomy for bladder cancer. Full article

(This article belongs to the Special Issue Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients)

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12 pages, 3597 KiB

Open AccessArticle

Combination of Muscle Quantity and Quality Is Useful to Assess the Necessity of Surveillance after a 5-Year Cancer-Free Period in Patients Who Undergo Radical Cystectomy: A Multi-Institutional Retrospective Study

by Naoki Fujita, Masaki Momota, Hirotaka Horiguchi, Itsuto Hamano, Jotaro Mikami, Shingo Hatakeyama, Hiroyuki Ito, Takahiro Yoneyama, Yasuhiro Hashimoto, Shoji Nishimura, Kazuaki Yoshikawa and Chikara Ohyama

Cancers 2023, 15(5), 1489; https://doi.org/10.3390/cancers15051489 - 27 Feb 2023

Cited by 1 | Viewed by 1296

Abstract

Background: Although continuous surveillance after a 5-year cancer-free period in patients with bladder cancer (BC) who undergo radical cystectomy (RC) is recommended, optimal candidates for continuous surveillance remain unclear. Sarcopenia is associated with unfavorable prognosis in various malignancies. We aimed to investigate the impact of low muscle quantity and quality (defined as severe sarcopenia) on prognosis after a 5-year cancer-free period in patients who underwent RC. Methods: We conducted a multi-institutional retrospective study assessing 166 patients who underwent RC and had five years or more of follow-up periods after a 5-year cancer-free period. Muscle quantity and quality were evaluated using the psoas muscle index (PMI) and intramuscular adipose tissue content (IMAC) using computed tomography images five years after RC. Patients with lower PMI and higher IMAC values than the cut-off values were diagnosed with severe sarcopenia. Univariable analyses were performed to assess the impact of severe sarcopenia on recurrence, adjusting for the competing risk of death using the Fine-Gray competing risk regression model. Moreover, the impact of severe sarcopenia on non-cancer-specific survival was evaluated using univariable and multivariable analyses. Results: The median age and follow-up period after the 5-year cancer-free period were 73 years and 94 months, respectively. Of 166 patients, 32 were diagnosed with severe sarcopenia. The 10-year RFS rate was 94.4%. In the Fine-Gray competing risk regression model, severe sarcopenia did not show a significant higher probability of recurrence, with an adjusted subdistribution hazard ratio of 0.525 (p = 0.540), whereas severe sarcopenia was significantly associated with non-cancer-specific survival (hazard ratio 1.909, p = 0.047). These results indicate that patients with severe sarcopenia might not need continuous surveillance after a 5-year cancer-free period, considering the high non-cancer-specific mortality. Full article

(This article belongs to the Special Issue Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients)

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11 pages, 1029 KiB

Open AccessArticle

Body Composition as a Comorbidity-Independent Predictor of Survival following Nephroureterectomy for Urothelial Cancer of the Upper Urinary Tract

by Christoph Pickl, Simon Engelmann, Florian Girtner, Miodrag Gužvić, Bas W. G. van Rhijn, Valerie Hartmann, Sonja Holbach, Sebastian Kälble, Maximilian Haas, Bernd Rosenhammer, Johannes Breyer, Maximilian Burger and Roman Mayr

Cancers 2023, 15(2), 450; https://doi.org/10.3390/cancers15020450 - 10 Jan 2023

Cited by 3 | Viewed by 1254

Abstract

Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02–3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18–3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification. Full article

(This article belongs to the Special Issue Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients)

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11 pages, 2187 KiB

Open AccessArticle

Utility of the Age Discrepancy between Frailty-Based Biological Age and Expected Life Age in Patients with Urological Cancers

by Kyo Togashi, Shingo Hatakeyama, Osamu Soma, Kazutaka Okita, Naoki Fujita, Toshikazu Tanaka, Daisuke Noro, Hirotaka Horiguchi, Nozomi Uemura, Takuro Iwane, Teppei Okamoto, Hayato Yamamoto, Takahiro Yoneyama, Yasuhiro Hashimoto and Chikara Ohyama

Cancers 2022, 14(24), 6229; https://doi.org/10.3390/cancers14246229 - 17 Dec 2022

Cited by 3 | Viewed by 1513

Abstract

Background: The estimation of biological age is challenging in patients with cancers. We aimed to investigate frailty-based biological ages using frailty-discriminant scores (FDS) and examined the effect of biological-expected life age discrepancy on the prognosis of patients with urological cancers. Methods: We retrospectively evaluated frailty in 1035 patients having urological cancers. Their frailty-based biological age was then defined by the FDS, which is a comprehensive frailty assessment tool, using 1790 noncancer individuals as controls. An expected life age (=chronological age + life expectancy) was subsequently calculated using the 2019 life expectancy table. The primary outcome was the estimation of the biological-expected life age discrepancy between the frailty-based biological age and expected life age in patients with urological cancers. Secondary outcomes were the evaluation of the effect of the biological-expected life age discrepancy on overall survival. Results: We included 405, 466, and 164 patients diagnosed with prostate cancer, urothelial carcinoma, and renal cell carcinoma, respectively. The median chronological age, life expectancy, and estimated frailty-based biological age were 71, 17, and 83 years, respectively. The biological-expected life age discrepancy in any urological cancers, localized diseases, and metastatic diseases was −4.8, −6.3, and +0.15 years, respectively. The biological-expected life age discrepancy of >5 years was significantly associated with poor overall survival. Conclusions: The biological-expected life age discrepancy between frailty-based biological age and expected life age may be helpful in understanding the role of frailty and patient/doctor conversation. Full article

(This article belongs to the Special Issue Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients)

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12 pages, 818 KiB

Open AccessArticle

Controlling Nutritional Status (CONUT) Score and Sarcopenia as Mutually Independent Prognostic Biomarkers in Advanced Urothelial Carcinoma

by Minami Une, Masaya Ito, Hiroaki Suzuki, Masahiro Toide, Shuichiro Kobayashi, Hiroshi Fukushima and Fumitaka Koga

Cancers 2022, 14(20), 5075; https://doi.org/10.3390/cancers14205075 - 17 Oct 2022

Cited by 8 | Viewed by 1407

Abstract

Background: While the controlling nutritional status (CONUT) score and sarcopenia are objective indices of different aspects of a patient’s general condition, few studies have comprehensively examined their mutual relationship in patients with advanced cancer. Methods: This retrospective study included 200 Japanese patients with advanced urothelial carcinoma (aUC). Sarcopenia was diagnosed using Prado’s definition. The CONUT score and sarcopenia were examined for their possible association, and their prognostic value was analyzed. Results: The CONUT score and sarcopenia were not significantly associated. While sarcopenia occurred in 168 patients (84%), more than half of them had normal or only slightly impaired nutritional status, as indicated by a CONUT score of 0–2. During follow-up (median: 13.3 months), 149 patients died. The CONUT score and sarcopenia were independent prognostic factors (hazard ratio 1.22 and 2.23, respectively; both p < 0.001), whereas performance status was not. Incorporating the CONUT score, sarcopenia, and both into Bajorin’s and Apolo’s prognostic models increased their concordance index as follows: 0.612 for Bajorin’s original model to 0.653 (+the CONUT score), 0.631 (+sarcopenia), and 0.665 (+both), and 0.634 for Apolo’s original model to 0.655 (+the CONUT score), 0.653 (+ sarcopenia), and 0.668 (+both). Conclusion: The CONUT score and sarcopenia were mutually independent in terms of their prognostic value in patients with aUC. These objective indices of a patient’s general condition may help in decision-making when considering treatment for patients with aUC. Full article

(This article belongs to the Special Issue Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients)

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Review

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16 pages, 893 KiB

Open AccessReview

Is It Time to Integrate Frailty Assessment in Onconephrology?

by Henry H. L. Wu, Rajkumar Chinnadurai, Robert J. Walker and Karthik K. Tennankore

Cancers 2023, 15(6), 1674; https://doi.org/10.3390/cancers15061674 - 8 Mar 2023

Cited by 1 | Viewed by 1865

Abstract

Onconephrology has emerged as a novel sub-specialty of nephrology dedicated to the intersection between the kidney and cancer. This intersection is broad and includes a number of important areas of focus, including concurrent chronic kidney disease (CKD) and cancer, acute kidney complications of cancer, and cancer-treatment-induced nephrotoxicity. The importance of onconephrology is even more evident when considering the global growth in the population of older adults, many of whom are living with some degree of frailty. Furthermore, a considerable proportion of older adults have CKD (some of whom eventually progress to kidney failure) and are at high risk of developing solid tumour and hematologic malignancies. Specific to kidney disease, the association between frailty status and kidney disease has been explored in depth, and tools to capture frailty can be used to guide the management and prognostication of older adults living with kidney failure. Whilst there is emerging data regarding the assessment and impact of frailty in onconephrology, there remains a relative paucity of knowledge within this topic. In this article, we evaluate the definition and operationalization of frailty and discuss the significance of frailty within onconephrology. We review evidence on current approaches to assessing frailty in onconephrology and discuss potential developments and future directions regarding the utilization of frailty in this patient population. A greater awareness of the intersections and interactions between frailty and onconephrology and further efforts to integrate frailty assessment in onconephrology to optimize the delivery of realistic and goal-directed management strategies for patients is needed. Full article

(This article belongs to the Special Issue Sarcopenia and Frailty as a Prognostic/Outcome Biomarker of Urological Cancer Patients)

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