{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T16:12:58Z","timestamp":1775923978720,"version":"3.50.1"},"reference-count":39,"publisher":"PAGEPress Publications","issue":"1","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Ital Urol Androl"],"abstract":"<jats:p>Introduction: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence. Intravesical Bacillus Calmette-Gu\u00e9rin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC. Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results. We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. Methods: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC\/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. Results: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p &lt; 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p&lt;0.001). Some RCT\u2019s had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. Conclusions: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.<\/jats:p>","DOI":"10.4081\/aiua.2024.12154","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T10:17:17Z","timestamp":1708424237000},"source":"Crossref","is-referenced-by-count":1,"title":["A systematic review and meta-analysis of intraarterial chemotherapy for non muscle invasive bladder cancer: Promising alternative therapy in high tuberculosis burden countries"],"prefix":"10.4081","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2442-0996","authenticated-orcid":false,"given":"Zakaria Aulia","family":"Rahman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-2704","authenticated-orcid":false,"given":"Furqan","family":"Hidayatullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-1834","authenticated-orcid":false,"given":"Jasmine","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1518-8010","authenticated-orcid":false,"given":"Lukman","family":"Hakim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2549","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"118879","doi-asserted-by":"crossref","unstructured":"Abern MR, Owusu RA, Anderson MR, et al. Perioperative intravesical chemotherapy in non-muscle-invasive bladder cancer: A systematic review and meta-analysis. J Natl Compr Canc Netw. 2013;11:477-84.","DOI":"10.6004\/jnccn.2013.0060"},{"key":"118880","doi-asserted-by":"crossref","unstructured":"Huang B, Wang H, Lin H, et al. Evaluation of the effects of intraarterial chemotherapy combined with intravesical chemotherapy against intravesical chemotherapy alone after transurethral resection of bladder tumor in T1-staged Grade 3 bladder cancer. J Cancer Res Clin Oncol. 2019;145:487-94.","DOI":"10.1007\/s00432-018-2811-5"},{"key":"118881","doi-asserted-by":"crossref","unstructured":"Sun F, Zhao R, Zhu Y, et al. A prospective comparison of intraarterial chemotherapy combined with intravesical chemotherapy and intravesical chemotherapy alone after transurethral resection with a thulium laser in high-risk non-muscle invasive bladder cancer. Cancer Chemother Pharmacol. 2017;79:1099-107.","DOI":"10.1007\/s00280-017-3305-x"},{"key":"118882","unstructured":"European Association of Urology. Non-Muscle-Invasive Bladder Cancer. EAU Guidelines. Available from: https:\/\/uroweb.org\/guidelines\/non-muscle-invasive-bladder-cancer"},{"key":"118883","doi-asserted-by":"crossref","unstructured":"Katafigiotis I, Sfoungaristos S, Martini A, et al. Bladder cancer to patients younger than 30 years: a retrospective study and review ofthe literature. Urologia. 2017;84:231-5.","DOI":"10.5301\/uj.5000264"},{"key":"118884","doi-asserted-by":"crossref","unstructured":"Burger M, Catto JWF, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63:234-41.","DOI":"10.1016\/j.eururo.2012.07.033"},{"key":"118885","doi-asserted-by":"crossref","unstructured":"Van Den Bosch S, Witjes JA. Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: A systematic review. Eur Urol 2011;60:493-500.","DOI":"10.1016\/j.eururo.2011.05.045"},{"key":"118886","doi-asserted-by":"crossref","unstructured":"Martin-Doyle W, Leow JJ, Orsola A, et al. Improving selection criteria for early cystectomy in high-grade T1 bladder cancer: A metaanalysis of 15,215 patients. J Clin Oncol. 2015;33:643-50.","DOI":"10.1200\/JCO.2014.57.6967"},{"key":"118887","doi-asserted-by":"crossref","unstructured":"Sylvester RJ, Brausi MA, Kirkels WJ, et al. Long-Term Efficacy Results of EORTC Genito-Urinary Group Randomized Phase 3 Study 30911 Comparing Intravesical Instillations of Epirubicin, Bacillus Calmette-Gu\u00e9rin, and Bacillus Calmette-Gu\u00e9rin plus Isoniazid in Patients with Intermediate- and High-Risk. Eur Urol. 2010;57:766-73.","DOI":"10.1016\/j.eururo.2009.12.024"},{"key":"118888","doi-asserted-by":"crossref","unstructured":"Shen PL, Lin ME, Hong YK, He XJ. Bladder preservation approach versus radical cystectomy for high-grade non-muscle-invasive bladder cancer: A meta-analysis of cohort studies. World J Surg Oncol. 2018;16:1-15.","DOI":"10.1186\/s12957-018-1497-0"},{"key":"118889","doi-asserted-by":"crossref","unstructured":"Chang SS, Cookson MS. Non-muscle-invasive bladder cancer: The role of radical cystectomy. Urology. 2005;66:917-22.","DOI":"10.1016\/j.urology.2005.05.003"},{"key":"118890","doi-asserted-by":"crossref","unstructured":"Alhunaidi O, Zlotta AR. The use of intravesical BCG in urothelial carcinoma of the bladder. Ecancermedicalscience. 2019;13:1-9.","DOI":"10.3332\/ecancer.2019.905"},{"key":"118891","doi-asserted-by":"crossref","unstructured":"Sylvester RJ, Oosterlinck W, Van Der Meijden APM. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: A meta-analysis of published results of randomized clinical trials. J Urol. 2004;171:2186-90.","DOI":"10.1097\/01.ju.0000125486.92260.b2"},{"key":"118892","doi-asserted-by":"crossref","unstructured":"Wansaula Z, Wortham JM, Mindra G, et al. Bacillus calmettegu\u00e9rin cases reported to the national tuberculosis surveillance system, United States, 2004-2015. Emerg Infect Dis. 2019;25:451-6.","DOI":"10.3201\/eid2503.180686"},{"key":"118893","doi-asserted-by":"crossref","unstructured":"To U, Kim J, Chia D. Disseminated BCG: complications of intravesical bladder cancer treatment. Case Rep Med 2014;2014:362845.","DOI":"10.1155\/2014\/362845"},{"key":"118894","doi-asserted-by":"crossref","unstructured":"Buffen, Kathrin et al. 2014. Autophagy controls BCG-induced trained immunity and the response to intravesical BCG therapy for bladder cancer. PLoS Pathog 2014;10:e1004485.","DOI":"10.1371\/journal.ppat.1004485"},{"key":"118895","unstructured":"Stewart DJ, Benjamin RS, Zimmerman S, et al. Clinical pharmacology of intraarterial cis-diamminedichloroplatinum (II). Cancer Res. 1983;43:917-20."},{"key":"118896","doi-asserted-by":"crossref","unstructured":"Mokarim A, Uetani M, Hayashi N, et al. Combined intraarterial chemotherapy and radiotherapy in the treatment of bladder carcinoma. Cancer. 1997;80:1776-85.","DOI":"10.1002\/(SICI)1097-0142(19971101)80:9<1776::AID-CNCR12>3.0.CO;2-2"},{"key":"118897","doi-asserted-by":"crossref","unstructured":"Tester W, Caplan R, Heaney J, et al. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: Results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol. 1996;14:119-26.","DOI":"10.1200\/JCO.1996.14.1.119"},{"key":"118898","doi-asserted-by":"crossref","unstructured":"Eapen L, Stewart D, Collins J, Peterson R. Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer. J Urol. 2004;172:1276-80.","DOI":"10.1097\/01.ju.0000140456.42509.b6"},{"key":"118899","doi-asserted-by":"crossref","unstructured":"Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647.","DOI":"10.1136\/bmj.g7647"},{"key":"118900","doi-asserted-by":"crossref","unstructured":"MacLennan GT, Kirkali Z, Cheng L. Histologic Grading of Noninvasive Papillary Urothelial Neoplasms. Eur Urol. 2007;51:889-98.","DOI":"10.1016\/j.eururo.2006.10.037"},{"key":"118901","doi-asserted-by":"crossref","unstructured":"Sobin LH, Fleming ID. TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer. 1997;80:1803-4.","DOI":"10.1002\/(SICI)1097-0142(19971101)80:9<1803::AID-CNCR16>3.0.CO;2-9"},{"key":"118902","doi-asserted-by":"crossref","unstructured":"Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:1-16.","DOI":"10.1186\/1745-6215-8-16"},{"key":"118903","doi-asserted-by":"crossref","unstructured":"Grant J, Hunter A. Measuring inconsistency in knowledgebases. J Intell Inf Syst 2006;27:159-84.","DOI":"10.1007\/s10844-006-2974-4"},{"key":"118904","doi-asserted-by":"crossref","unstructured":"Schmidt FL, Oh IS, Hayes TL. Fixed- versus random-effects models in meta-analysis: Model properties and an empirical comparison of differences in results. Br J Math Stat Psychol. 2009;62:97-128.","DOI":"10.1348\/000711007X255327"},{"key":"118905","doi-asserted-by":"crossref","unstructured":"Borenstein M, Hedges LV., Higgins JPT, Rothstein HR. 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Meta-analysis, funnel plots and sensitivity analysis. Biostatistics. 2000;1:247-62.","DOI":"10.1093\/biostatistics\/1.3.247"},{"key":"118910","doi-asserted-by":"crossref","unstructured":"Richardson M, Garner P, Donegan S. Interpretation of subgroup analyses in systematic reviews: A tutorial. Clin Epidemiol GlobHealth. 2019;7:192-8.","DOI":"10.1016\/j.cegh.2018.05.005"},{"key":"118911","doi-asserted-by":"crossref","unstructured":"Eapen L, Stewart D, Collins J, Peterson R. Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer. J Urol. 2004;172:1276-80.","DOI":"10.1097\/01.ju.0000140456.42509.b6"},{"key":"118912","doi-asserted-by":"crossref","unstructured":"Lian F, Chen W, Liu Y, et al. Intra-arterial chemotherapy combined with intravesical chemotherapy is effective in preventing recurrence in non-muscle invasive bladder cancer. 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Intra-arterial chemotherapy combined with intravesical chemotherapy compared with intravesical BCG immunotherapy retrospectively in high-risk non-muscle-invasive bladder cancer after transurethral resection of the bladder tumor. J Cancer Res Clin Oncol 2021;147:1781-8.","DOI":"10.1007\/s00432-020-03453-x"},{"key":"118916","doi-asserted-by":"crossref","unstructured":"Chen MK, Qin ZK, Zhou FJ, et al. Intra-arterial chemotherapy is reliable in preventing high-risk superficial bladder cancer from recurrence and progression. J Chemother. 2009;21:681-6.","DOI":"10.1179\/joc.2009.21.6.681"},{"key":"118917","unstructured":"International SRI, Avenue R, Park M. Cancer chemotherapy and pharmacology. Growth (Lakeland). 1985;127:160-4."}],"container-title":["Archivio Italiano di Urologia e Andrologia"],"original-title":[],"link":[{"URL":"https:\/\/www.pagepressjournals.org\/index.php\/aiua\/article\/download\/12154\/11713","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/download\/12154\/11713","content-type":"application\/zip","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/download\/12154\/11713","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T07:47:40Z","timestamp":1711525660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/view\/12154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,16]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,3,27]]}},"URL":"https:\/\/doi.org\/10.4081\/aiua.2024.12154","relation":{},"ISSN":["2282-4197","1124-3562"],"issn-type":[{"value":"2282-4197","type":"electronic"},{"value":"1124-3562","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2,16]]}}}