{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:01:44Z","timestamp":1790492504019,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non\u2013muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence rate and the potential to progress, especially among high-risk patients. Limitations of Bacillus Calmette\u2013Gu\u00e9rin (BCG), including treatment failure, high recurrence rates, adverse events, and global shortages, create an unmet need for alternative agents. Objective: To assess the efficacy and safety of intravesical gemcitabine and docetaxel (GEM\/DOCE) in the treatment of na\u00efve and BCG-failure high-risk and very high-risk NMIBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and meta-analysis was prospectively registered (PROSPERO: CRD420251050582) and conducted in accordance with PRISMA 2020 guidelines. Databases were searched from January 2014 to March 2025. Eligible studies enrolled adult patients with NMIBC treated with intravesical sequential GEM\/DOCE. Data were synthesized using random-effects and common-effects meta-analysis models for oncological and safety outcomes, incorporating subgroup analyses by prior BCG status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine studies comprising 883 patients were included. At 12 months, the pooled recurrence-free survival (RFS) was 73.75% and high-grade recurrence-free survival (HG-RFS) was 75.78%. BCG-na\u00efve patients demonstrated significantly superior 12-month RFS (82.50% vs. 60.00%, p &amp;lt; 0.001) and HG-RFS (84.09% vs. 63.79%, p &amp;lt; 0.001) compared to BCG-failure cohorts. Progression-free survival (95.57%), cancer-specific survival (99.18%), overall survival (97.32%), and cystectomy-free survival (94.41%) remained high at 12 months. GEM\/DOCE was generally well tolerated. The pooled proportion of patients experiencing treatment-related adverse events was 52.59%, with an overall treatment intolerance rate of only 3.55%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intravesical GEM\/DOCE represents an effective and well-tolerated intravesical therapeutic option in patients with high- and very high-risk NMIBC, demonstrating favorable recurrence outcomes with preserved survival. The regimen appears particularly effective in BCG-na\u00efve disease, while also providing clinically meaningful disease control in BCG-failure populations. However, the available evidence is limited by heterogeneity across studies and the predominance of retrospective designs. Further prospective, adequately powered studies are required to better define its role and optimize treatment protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251050582<\/jats:ext-link>\n                      , identifier CRD420251050582.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1859461","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:26Z","timestamp":1783571006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sequential gemcitabine\u2013docetaxel in BCG-na\u00efve and BCG-failure non\u2013muscle-invasive bladder cancer: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Bandar","family":"Alhubaishy","sequence":"first","affiliation":[{"name":"Department of Urology, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"King Abdulaziz University Hospital","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Beshawri","sequence":"additional","affiliation":[{"name":"King Saud bin Abdulaziz University for Health Science\u060c Collage of Medicine","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inam","family":"Abulreish","sequence":"additional","affiliation":[{"name":"Umm Al-Qura University, College of Medicine","place":["Makkah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Alnajar","sequence":"additional","affiliation":[{"name":"King Abdulaziz University, Collage of Medicine - Rabigh Branch","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamad","family":"Radhi","sequence":"additional","affiliation":[{"name":"King Saud bin Abdulaziz University for Health Science\u060c Collage of Medicine","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abduljawad","family":"Saleh","sequence":"additional","affiliation":[{"name":"King Saud bin Abdulaziz University for Health Science\u060c Collage of Medicine","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saher","family":"Alwafi","sequence":"additional","affiliation":[{"name":"King Saud bin Abdulaziz University for Health Science\u060c Collage of Medicine","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulghafour","family":"Halawani","sequence":"additional","affiliation":[{"name":"Department of Urology, King Abdulaziz University","place":["Jeddah, Saudi 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