{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T09:15:12Z","timestamp":1788340512255,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Second-line chemotherapy is widely used in metastatic urothelial carcinoma after progression on first-line platinum-based therapy, but its independent contribution to survival, as opposed to selection of healthier patients, remains unclear. In this multicenter retrospective cohort of 142 patients treated with first-line platinum-based chemotherapy across seven Turkish centers, overall survival (OS) from first-line progression was compared between patients who received second-line chemotherapy (n = 80) and those who did not (n = 62), using multivariable Cox regression, inverse probability of treatment weighting (IPTW), propensity-score matching, landmark analysis, and a time-dependent Cox model. Median OS was 7.4 versus 4.7 months (log-rank p = 0.064). Second-line chemotherapy was independently associated with improved OS on multivariable analysis (adjusted hazard ratio [aHR] 0.620; 95% confidence interval [CI] 0.423\u20130.907; p = 0.014); Eastern Cooperative Oncology Group (ECOG) performance status \u2265 2 (aHR 3.881; p = 0.001) and lower albumin (aHR 0.671; p = 0.018) were also independent predictors. The association remained significant after IPTW (HR 0.648; p = 0.025) and after a time-dependent Cox model (HR 0.632; p = 0.019), and was unchanged in ECOG-restricted and Bellmunt-adjusted analyses (p = 0.008, p = 0.029); it narrowly missed significance after propensity-score matching (HR 0.645; p = 0.051) and did not reach significance in the 3-month landmark analysis (HR 0.743; p = 0.180). Power was limited (~49%). In a time-dependent Cox model\u2014the analysis least susceptible to immortal-time bias, as it retains the full cohort and classifies pre-treatment person-time as unexposed\u2014second-line chemotherapy remained independently associated with improved OS (HR 0.632; p = 0.019), closely consistent with the primary multivariable estimate. The conventional Cox, IPTW, and propensity-score-matched analyses, which treat second-line receipt as a baseline exposure, were directionally concordant but share a common time-related bias and are therefore not independent confirmations. ECOG performance status was a consistent predictor throughout.<\/jats:p>","DOI":"10.3390\/curroncol33090529","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:53:11Z","timestamp":1788335591000},"page":"529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Outcomes of Second-Line Chemotherapy in Metastatic Urothelial Carcinoma"],"prefix":"10.3390","volume":"33","author":[{"given":"\u0130lkay","family":"\u00c7\u0131takkul","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, Faculty of Medicine, Kocaeli University, Kocaeli 41001, 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Oncology, Faculty of Medicine, Eski\u015fehir Osmangazi University, Eski\u015fehir 26480, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4462-6393","authenticated-orcid":false,"given":"Bahad\u0131r","family":"K\u00f6yl\u00fc","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, School of Medicine, Ko\u00e7 University, Istanbul 34450, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2988-4450","authenticated-orcid":false,"given":"Nazan","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, School of Medicine, Ko\u00e7 University, Istanbul 34450, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"G\u00f6zde","family":"Balkaya Aykut","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, \u00dcmraniye Training and Research Hospital, Istanbul 34764, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1976-3951","authenticated-orcid":false,"given":"Elif","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Kocaeli City Hospital, Kocaeli 41060, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-9628","authenticated-orcid":false,"given":"Mesut","family":"Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Sakarya 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