Hindawi Journal of Oncology Volume 2022, Article ID 1997507, 7 pages https://doi.org/10.1155/2022/1997507 Research Article Diabetes Is a Risk Factor for the Prognosis of Patients with Bladder Cancer: A Meta-Analysis 1 2 2 3 4 Lv Dong, Xiang Ying, Song Tao, Zhou Guang-Peng, and Shen Tai-Ming Department of Urology, Deyang People’s Hospital, Deyang, Sichuan, China Department of Urology, Eastern Hospital, Sichuan Academy of Medical Sciences &Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China Department of Endocrinology, Eastern Hospital, Sichuan Academy of Medical Sciences &Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China Health Management Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China Correspondence should be addressed to Shen Tai-Ming; email@example.com Received 21 April 2022; Accepted 17 August 2022; Published 26 September 2022 Academic Editor: Shahid Mumtaz Copyright © 2022 Lv Dong et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. To systematically evaluate the impact of diabetes on the prognosis of bladder cancer patients after radical cystectomy (RC). Methods. PubMed, Embase, and Cochrane Library databases were selected from inception to October 2021. e studies on the e‰ects of diabetes on bladder cancer patients after RC were included for analysis. e inclusion and exclusion criteria were independently selected for literature screening, the quality of the included studies was evaluated, and data were extracted. Results. A total of 5 cohort studies were included, with a total of 2 661 subjects, including 391 cases in the diabetic group, non-diabetes. Meta-analysis results show that diabetes increases the overall risk of death in patients after RC (HR 1.36, 95% CI: 1.30∼1.43, P < 0.001) and the risk of tumor-speci˜c death (HR 1.59, 95% CI: 1.29∼1.95, P < 0.001). Sensitivity analysis shows that the stability of this study is well. Conclusion. Diabetes was an independent risk factor in terms of overall and cancer-speci˜c survival in patients who underwent RC. patients have muscle-invasive bladder cancer (MIBC), and 1. Introduction the standard treatment is radical cystectomy [4, 5]. Although Bladder cancer is one of the most common malignant tu- MIBC has made some progress in the treatment in recent mors of the urinary tract, and its incidence is higher in men years, the overall prognosis remains poor. than in women . More than 80% of bladder cancer pa- Diabetes is the most common chronic metabolic disease tients will experience painless hematuria or symptoms of in the world, and it may have an important impact on the overactive bladder such as frequent urination and urgency pathogenesis, progression, and prognosis of bladder cancer [2, 3]. Although bladder cancer is not among the top ten through various mechanisms [6, 7]. e paper will discuss causes of cancer death in China, it is one of the most the e‰ect of diabetes on the survival of patients with bladder common malignant tumors in urinary tract diseases. e cancer after RC surgery and provide evidence for improving incidence of bladder cancer ranks 10th among malignant the prognosis of patients with bladder cancer. tumors in the world. About 80,000 new bladder cancer patients were diagnosed in the United States in 2017, while 2. Methods the age-standardized incidence rates of bladder cancer in European men and women reached 19.1 and 4.0, re- 2.1. Literature Review. e databases including PubMed, spectively. About 30% of all newly diagnosed bladder cancer Embase, and Cochrane Library were all screened for related 2 Journal of Oncology studies from their inception to November 2021. *e search cut-and-ﬁll method was used to verify whether the publi- terms included “diabetes,” “bladder cancer,” “urothelial cation bias aﬀected the stability of the combined eﬀect size. carcinoma,” “bladder neoplasms,” “urinary bladder neo- plasms,” “cystectomy,” “mortality,” “survival,” and 3. Results “prognosis.” 3.1.BaselineCharacteristicsoftheIncludedStudies. After the screening of the studies, we got 1245 studies from the da- 2.2.InclusionCriteria. Inclusion criteria were as follows: (1) tabases. After the duplications were excluded, 1097 studies a cohort study with bladder cancer patients as the research were left. After the assessment of title and the abstract of the object; (2) pathologically diagnosed patients with high-risk studies, 365 studies were left. And we performed the full-text non-muscle-invasive bladder cancer or muscle-invasive screening, we ﬁnally 5 studies in the present analysis [8–12]. bladder cancer, and the selected treatment method is RC; *e screening procedure is shown in Figure 1. *e baseline (3) in the diabetes group, the diagnosis of diabetes should be characteristics of the included studies are presented in before RC; (4) outcome indicators include overall survival Table 1. (OS) or cancer-speciﬁc mortality and other related prog- nostic indicators; (5) the hazard ratio (HR) and conﬁdence 3.2. Overall Survival. As shown in Figure 2, the meta- interval (95%CI) are provided in the literature or the HR and analysis showed that diabetes was signiﬁcantly associated 95% CI can be extracted from the Kaplan–Meier curve in the with the poor overall survival of the patients (HR � 1.36, 95% literature; and (6) if the same study has published results CI: 1.30∼1.43, P< 0.001). Also, the funnel plot demon- from diﬀerent periods, the latest research data will be strated that there was no signiﬁcant publication bias. included. *en, we performed the subgroup analysis based on the analysis type of the included studies. We ﬁrst pooled the 2.3.ExclusionCriteria. Exclusion criteria were as follows: (1) results from the univariate analysis results. As shown in epidemiological investigation, case-control study, and other Figure 3(a), the results in univariate analysis were consistent research types; (2) research using partial cystectomy or with the above results. In Figure 3(b), we observed that the transurethral resection of bladder tumor and other methods diabetes was still signiﬁcantly associated with the overall of treatment; (3) literature types such as review, medical survival of the patients in the multivariate analysis. record report, meta-analysis, conference paper, and so on; (4) studies with poor research quality and without full text; 3.3. Cancer-Speciﬁc Survival and Recurrence. We studied and (5) studies without reporting relevant outcome cancer-speciﬁc survival next. As shown in Figure 4, diabetes indicators. was signiﬁcantly associated with the cancer-speciﬁc survival of the included patients. Figure 5 shows the results on the 2.4. Literature Quality Evaluation. Two reviewers in- recurrence rate. Diabetes was signiﬁcantly associated with dependently screened the literature and evaluated the quality the recurrence of the disease. of the literature according to the inclusion and exclusion criteria and then cross-compared the extracted study data. 4. Discussion *e Newcastle-Ottawa Scale (NOS) cohort study scoring table was used to evaluate the quality of the literature, and Bladder cancer is the most common malignant tumor of the the literature with a score of ≥6 was considered as high- urinary system . In 2018, about 200,000 people died of quality literature and could be included in meta studies. bladder cancer worldwide, accounting for 2.1% of cancer- related deaths. *e most common histological type of bladder cancer is urothelial carcinoma, accounting for about 2.5.DataExtraction. *e data mainly extracted according to 90% of all bladder cancers [14, 15]. For urothelial cell the purpose of the study included the ﬁrst author’s name, muscle-invasive bladder cancer and non-urothelial cell publication time, country, cohort age, sample size, age, bladder cancer, active RC is recommended. *e standard gender, follow-up time, HR, and 95% CI for survival risk or treatment for RC is “total cystectomy + distal ureter- death risk. ectomy + pelvic lymph node dissection + urinary diversion.” RC can be open, laparoscopic, or robotic, and each treatment 2.6. Statistical Analysis. Meta-analysis was performed by technique has its own advantages and disadvantages. RevMan software, and the HR and 95% CI in each study However, RC is a complex surgical procedure, the incidence were pooled. *e I test was used to test the heterogeneity of of postoperative complications can be as high as 64%, the 30- the included studies. If I ≥ 50%, P≤ 0.10, there was het- day postoperative mortality rate is 1% to 3%, and the erogeneity among the studies, and a random-eﬀects model postoperative mortality rate will increase for patients aged was used for analysis; if I < 50%, P> 0.10, there was no >80 years . signiﬁcant heterogeneity, and a ﬁxed-eﬀects model was used Diabetes is a chronic metabolic disease. Due to the for analysis. Sensitivity analysis was performed on the results absolute or relative lack of insulin, the blood sugar in the of the meta-analysis, and funnel plots were drawn for body remains at a high level for a long time. If it is not publication bias analysis. If there was publication bias, the eﬀectively controlled, it will eventually lead to cardiovascular Journal of Oncology 3 Records identified through database searching (n = 1245, PubMed = 546, Embase = 612, Cochrane library = 87) Records after duplicates removed (n = 1097) Records screened Records excluded (n = 365) (n = 732) Full-text articles assessed Full-text articles excluded, for eligibility with reasons (n = 365) (n = 360) Studies included in qualitative synthesis (n = 5) Studies included in quantitative synthesis (meta-analysis) (n = 5) Figure 1: *e ﬂowchart of the literature screening. and cerebrovascular diseases, kidney damage, retinopathy, positively associated with serious complications. *e study and peripheral neuropathy . Diabetes is one of the most by Goodenough et al. pointed out that glycated hemoglobin serious health problems in the world today. *ere are 22 ≥6.5% and perioperative hyperglycemia were associated with million people living with diabetes in the United States, and an increased incidence of major complications after ab- this number is expected to climb to 40 million by 2030. *ere dominal surgery, emphasizing that elective surgery should are about 69.1 million diabetics in India and 69.1 million in be more reasonably controlled for blood sugar. Mossanen et al. included 57 553 patients with RC surgery in 360 China. *e total number of people with diabetes and pre- diabetes has reached 140 million. *ere is a close re- hospitals in the United States. *e meta-analysis showed that lationship between diabetes and bladder cancer, and many the increase in complications will lead to an increase in the studies have shown that diabetes can increase the incidence mortality rate of patients. (2) Diabetes can lead to tumor and mortality of bladder cancer [18–21]. recurrence and progression. Type 2 diabetes is the most In this study, meta-analysis conﬁrmed that diabetes can common type of diabetes, and insulin resistance and signiﬁcantly increase the risk of death in bladder cancer hyperinsulinemia often exist in the body. Insulin can patients after RC, resulting in poor prognosis of patients. *e combine with the insulin receptor on the surface of tumor remainder of this paper is arranged as the following two cells to promote the mitosis of tumor cells. reasons why diabetes increases the risk of death in patients *ere are few studies on the eﬀect of diabetes on the after RC surgery. (1) *e incidence of complications in prognosis of patients with RC after surgery, and there is no relevant meta-analysis conducted by scholars at present, so diabetic patients is higher. Studies have demonstrated that diabetes is an independent risk factor for perioperative life- the topic selection of this study is relatively new, and the threatening complications in cystectomy patients and is quality of the included literature is high. However, this study Included Eligibility Screening Identification 4 Journal of Oncology Table 1: *e baseline characteristics of the included studies. Sample size Gender Study Study Author Year Region Age (male/ Follow-up NOS type period DM Non-DM female) Rieken et al.  2014 USA, Canada, Australia, and Europe R 1992–2008 120 1302 65.5 1108/314 34 8 Oh et al.  2015 Korea R 2004–2014 28 172 65.8 176/24 38 7 Dybowski et al.  2015 Poland R 2004–2006 10 53 67 46/17 81 8 Froehner et al.  2017 Germany R 1993–2012 225 707 68 726/206 84 7 Kwiatkowska et al.  2017 Poland P 2014–2016 8 36 67 25/19 16 8 Note. DM: diabetes, R: retrospective study, and P: perspective study. Journal of Oncology 5 Weight Hazard Ratio Hazard Ratio Study or Subgroup log [Hazard Ratio] SE (%) IV, Fixed, 95% CI IV, Fixed, 95% CI Dybowski 2015 1.2149 0.4899 0.3 3.37 [1.29, 8.80] Froehner 2017 0.3075 0.027 89.8 1.36 [1.29, 1.43] 0.1 3.40 [0.57, 20.28] Kwiatkowska 2017 1.2238 0.9112 Oh 2015 0.2469 0.1011 6.4 1.28 [1.05, 1.56] Rieken 2014 0.4187 0.1379 3.4 1.52 [1.16, 1.99] Total (95% CI) 100.0 1.36 [1.30, 1.43] 2 2 Heterogeneity: Chi = 5.44, df = 4 (P = 0.25); I = 26% 0.05 0.2 15 20 Test for overall effect: Z = 12.14 (P < 0.00001) DM Non-DM 0.2 0.4 0.6 0.8 0.05 0.2 1 5 20 Hazard Ratio Figure 2: *e forest and funnel plots of the overall survival. Weight Hazard Ratio Hazard Ratio Study or Subgroup log[Hazard Ratio] SE (%) IV, Fixed, 95% CI IV, Fixed, 95% CI Kwiatkowska 2017 1.2238 0.9112 0.2 3.40 [0.57, 20.28] Oh 2015 0.3557 0.0447 90.5 1.43 [1.31, 1.56] Rieken 2014 0.4383 0.1392 9.3 1.55 [1.18, 2.04] Total (95% CI) 100.0 1.44 [1.33, 1.57] 2 2 Heterogeneity: Chi = 1.21, df = 2 (P = 0.55); I = 0% 0.05 0.2 1 5 20 Test for overall effect: Z = 8.59 (P < 0.00001) DM Non-DM (a) Weight Hazard Ratio Hazard Ratio Study or Subgroup log [Hazard Ratio] SE (%) IV, Random, 95% CI IV, Random, 95% CI Dybowski 2015 1.2149 0.4899 3.6 3.37 [1.29, 8.80] Froehner 2017 0.3075 0.1569 25.0 1.36 [1.00, 1.85] Oh 2015 0.2469 0.1011 41.8 1.28 [1.05, 1.56] Rieken 2014 0.4187 0.1379 29.6 1.52 [1.16, 1.99] Total (95% CI) 100.0 1.42 [1.18, 1.70] 2 2 2 Heterogeneity: Tau = 0.01, Chi = 4.37, df = 3 (P = 0.22); I = 31% 0.1 0.2 0.5 1 21 5 0 Test for overall effect: Z = 3.68 (P = 0.0002) DM Non-DM (b) Figure 3: *e forest plot for the overall survival in (a) univariate analysis and (b) multivariate analysis. SE (log [Hazard Ratio]) 6 Journal of Oncology Weight Hazard Ratio Hazard Ratio Study or Subgroup log [Hazard Ratio] SE (%) IV, Fixed, 95% CI IV, Fixed, 95% CI Oh 2015 0.5822 0.1832 32.4 1.79 [1.25, 2.56] Rieken 2014 0.4055 0.1268 67.6 1.50 [1.17, 1.92] Total (95% CI) 100.0 1.59 [1.29, 1.95] 2 2 Heterogeneity: Chi = 0.63, df = 1 (P = 0.43); I = 0% 0.1 0.2 0.5 1 21 5 0 Test for overall effect: Z = 4.44 (P < 0.00001) DM Non-DM Figure 4: *e forest plot for the cancer-speciﬁc survival. DM Non-DM Weight Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total (%) M-H, Fixed, 95% CI M-H, Fixed, 95% CI Oh 2015 67 120 520 1302 81.5 1.90 [1.30, 2.77] Rieken 2014 8 28 44 172 18.5 1.16 [0.48, 2.83] Total (95% CI) 148 1474 100.0 1.76 [1.25, 2.49] Total events 75 564 2 2 Heterogeneity: Chi = 0.99, df = 1 (P = 0.32); I = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.23 (P = 0.001) DM Non-DM Figure 5: *e forest plot for the recurrence rate. also has some limitations. First, only 5 cohort studies were Conflicts of Interest included, and only 2 studies reported tumor-speciﬁc mor- *e authors declare that they have no conﬂicts of interest. tality risk. None of the 5 studies analyzed glycemic control after RC. Second, the sample sizes of the two studies were Authors’ Contributions small, so further large-sample prospective studies are still needed for demonstration and analysis. Finally, this study Dong Lv and Ying Xiang contributed equally to this study. only retrieved published Chinese and English studies and did not include dissertations, conference papers, and un- Acknowledgments published studies. *ere may be publication bias caused by incomplete literature inclusion. It is proved that the stability Sichuan Provincial Health and Health Commission Project and robustness of the results of this meta-analysis are high. (16PJ437). *e results of this study prove that diabetes can sig- niﬁcantly increase the risk of death after radical cystectomy References in bladder cancer patients. For the future improved treat- ments of bladder cancer patients with diabetes, close follow-  J. Bellmunt, “Bladder cancer,”Hematology-OncologyClinicsof up should be performed during the perioperative period and North America, vol. 29, no. 2, 2015,xiii-xiv.  R. H. Martinez Rodriguez, O. Buisan Rueda, and L. Ibarz, postoperative period to monitor and control blood sugar “Bladder cancer: present and future,” Medicina Clınica, levels to reduce the risk of related complications. vol. 149, no. 10, pp. 449–455, 2017.  S. Siracusano, R. Rizzetto, and A. B. Porcaro, “Bladder cancer 5. Conclusion genomics,” Urologia, vol. 87, no. 2, pp. 49–56, 2020.  K. B. Farling, “Bladder cancer: risk factors, diagnosis, and Diabetes was an independent risk factor in terms of overall management,” 6e Nurse Practitioner, vol. 42, no. 3, pp. 26– and cancer-speciﬁc survival in patients who underwent 33, 2017. radical cystectomy.  M. Pecoraro, M. Takeuchi, H. A. Vargas et al., “Overview of VI-rads in bladder cancer,” American Journal of Roentgen- Data Availability ology, vol. 214, no. 6, pp. 1259–1268, 2020.  National Collaborating Centre for Cancer (UK), “Bladder *e data used to support this study are available from the cancer: diagnosis and management of bladder cancer: © NICE corresponding author upon request. (2015) Bladder cancer: diagnosis and management of bladder cancer,” BJU International, vol. 120, no. 6, pp. 755–765, 2017.  A. Pham and L. K. Ballas, “Trimodality therapy for bladder Disclosure cancer: modern management and future directions,” Current A preprint has previously been published. Opinion in Urology, vol. 29, no. 3, pp. 210–215, 2019. Journal of Oncology 7  B. Dybowski, K. Ossolinski, ´ A. Ossolinska, ´ M. Peller, E. Bres- Niewada, and P. Radziszewski, “Impact of stage and comorbidities on ﬁve-year survival after radical cystectomy in Poland: single centre experience,”CentralEuropeanjournalof urology, vol. 68, no. 3, pp. 278–283, 2015.  M. Froehner, R. Koch, U. Heberling, V. Novotny, M. Hubler, and M. P. Wirth, “An easily applicable single condition-based mortality index for patients undergoing radical prostatectomy or radical cystectomy,” Urologic Oncology: Seminars and Original Investigations, vol. 35, no. 1, pp. 32.e17–32.e23, 2017.  M. Kwiatkowska, B. Dybowski, O. Kuczkiewicz-Siemion et al., “Factors aﬀecting one-year survival after radical cystectomy: a prospective study,” Central European journal of urology, vol. 70, no. 3, pp. 238–244, 2017.  J. J. Oh, M. Y. Kang, J. K. Jo et al., “Association between diabetes mellitus and oncological outcomes in bladder cancer patients undergoing radical cystectomy,” International Jour- nal of Urology, vol. 22, no. 12, pp. 1112–1117, 2015.  M. Rieken, E. Xylinas, L. Kluth et al., “Eﬀect of diabetes mellitus and metformin use on oncologic outcomes of pa- tients treated with radical cystectomy for urothelial carci- noma,” Urologic Oncology: Seminars and Original Investigations, vol. 32, no. 1, pp. 49.e7–14, 2014.  X. M. Piao, Y. J. Byun, W. J. Kim, and J. Kim, “Unmasking molecular proﬁles of bladder cancer,” Investigative and clinical urology, vol. 59, no. 2, pp. 72–82, 2018.  S. C. Skeldon and S. Larry Goldenberg, “Bladder cancer: a portal into men’s health,” Urologic Oncology: Seminars and Original Investigations, vol. 33, no. 1, pp. 40–44, 2015.  F. Vakar Lopez, “Molecular subtyping bladder cancer: is it ready for clinical practice?” Turkish Journal of Medical Sci- ences, vol. 50, no. 7, pp. 1677-1678, 2020.  T. Viˇsnjar, R. Romih, and D. Zupanˇciˇc, “Lectins as possible tools for improved urinary bladder cancer management,” Glycobiology, vol. 29, no. 5, pp. 355–365, 2019.  S. Daneshmand and A. Nazemi, “Neoadjuvant chemotherapy in variant histology bladder cancer: current evidence,” Eu- ropean urology focus, vol. 6, no. 4, pp. 639–641, 2020.  J. L. Gore and S. M. Gilbert, “Improving bladder cancer patient care: a pharmacoeconomic perspective,” Expert Re- view of Anticancer 6erapy, vol. 13, no. 6, pp. 661–668, 2013.  L. Dong, Y. Xiang, S. Tao, Z. Guang-Peng, and S. Tai-Ming, 6e Prognostic Value of Diabetes in Patients Underwent Radical Cystectomy: A Meta-Analysis, Research square, Durham, NC, USA, 2022.  Z. Zhu, X. Wang, Z. Shen, Y. Lu, S. Zhong, and C. Xu, “Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies,” BMC Cancer, vol. 13, no. 1, p. 310, 2013.  S. C. Larsson, N. Orsini, K. Brismar, and A. Wolk, “Diabetes mellitus and risk of bladder cancer: a meta-analysis,” Dia- betologia, vol. 49, no. 12, pp. 2819–2823, 2006.
Journal of Oncology
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Published: Sep 26, 2022