Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar-Apr;38(2):873-880.
doi: 10.21873/invivo.13513.

Efficacy of Platinum-based Chemotherapy in Patients With Metastatic Urothelial Carcinoma With Variant Histology

Akinori Minato  1 , Kazuki Murooka  2 , Yutaka Okumura  3 , Tomohisa Takaba  3 , Katsuyoshi Higashijima  3 , Yujiro Nagata  3 , Ikko Tomisaki  3 , Kenichi Harada  3 , Naohiro Fujimoto  3
Affiliations

Efficacy of Platinum-based Chemotherapy in Patients With Metastatic Urothelial Carcinoma With Variant Histology

Akinori Minato et al. In Vivo. 2024 Mar-Apr.

Abstract

Background/aim: Variant urothelial carcinoma (VUC, defined herein as urothelial carcinoma with any histological variant) is frequently observed at an advanced stage. However, the efficacy of systemic chemotherapy against VUC in metastatic disease has rarely been reported. This study assessed the therapeutic response and survival outcomes of platinum-based chemotherapy as first-line treatment in patients with metastatic VUC.

Patients and methods: We retrospectively analyzed consecutive patients with metastatic bladder and upper urinary tract cancer who received gemcitabine plus cisplatin (or carboplatin) at the University of Occupational and Environmental Health Hospital between November 2008 and November 2022. Progression-free survival and overall survival were evaluated using the Kaplan-Meier method and Cox proportional hazard models.

Results: Out of 131 patients recorded, 86 (65.6%) had pure urothelial carcinoma (PUC) and 45 (34.4%) had VUC. The most common variant element was squamous differentiation (44.4%). Compared to those with PUC, patients with VUC showed a comparable objective response rate (33.3% vs. 41.9%, p=0.451) and disease control rate (64.5% vs. 75.6%, p=0.221). They also had poorer progression-free survival (median=4.9 months vs. 7.9 months, p=0.014) and overall survival (median=10.9 months vs. 18.2 months, p=0.037) than those with PUC. On multivariate analysis, VUC was an independent predictor of progression (hazard ratio=1.79; 95% confidence interval=1.19-2.69; p=0.005) and mortality (hazard ratio=1.64; 95% confidence interval=1.08-2.48; p=0.020).

Conclusion: Although the response of metastatic VUC to platinum-based chemotherapy was not inferior to that of PUC, VUC had progressed faster than PUC. VUC was significantly associated with a poor prognosis after platinum-based chemotherapy as first-line treatment.

Keywords: Variant histology; chemotherapy; prognosis; urothelial carcinoma.

PubMed Disclaimer

Conflict of interest statement

The Authors declare that they have no competing interests in relation to this study.

Figures

Figure 1
Figure 1. Kaplan-Meier curves for (A) progression-free survival and (B) overall survival after the initiation of platinum-based chemotherapy in patients with PUC and VUC. PUC: Pure urothelial carcinoma; VUC: variant urothelial carcinoma.
Figure 2
Figure 2. Kaplan-Meier curves for (A) progression-free survival and (B) overall survival after initiation of platinum-based chemotherapy in patients with squamous differentiation and other histological variants.
Figure 3
Figure 3. Kaplan-Meier curves for overall survival after initiation of platinum-based chemotherapy in patients with PUC and VUC with the use of subsequent ICI therapy. PUC: Pure urothelial carcinoma; VUC: variant urothelial carcinoma; ICI: immune checkpoint inhibitor.
Figure 4
Figure 4. Kaplan-Meier curves for overall survival after initiation of platinum-based chemotherapy in patients with VUC with or without the use of subsequent ICI therapy. VUC: Variant urothelial carcinoma; ICI: immune checkpoint inhibitor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Flaig TW, Spiess PE, Abern M, Agarwal N, Bangs R, Boorjian SA, Buyyounouski MK, Chan K, Chang S, Friedlander T, Greenberg RE, Guru KA, Herr HW, Hoffman-Censits J, Kishan A, Kundu S, Lele SM, Mamtani R, Margulis V, Mian OY, Michalski J, Montgomery JS, Nandagopal L, Pagliaro LC, Parikh M, Patterson A, Plimack ER, Pohar KS, Preston MA, Richards K, Sexton WJ, Siefker-Radtke AO, Tollefson M, Tward J, Wright JL, Dwyer MA, Cassara CJ, Gurski LA. NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. J Natl Compr Canc Netw. 2022;20(8):866–878. doi: 10.6004/jnccn.2022.0041. - DOI - PubMed
    1. Cathomas R, Lorch A, Bruins HM, Compérat EM, Cowan NC, Efstathiou JA, Fietkau R, Gakis G, Hernández V, Espinós EL, Neuzillet Y, Ribal MJ, Rouanne M, Thalmann GN, van der Heijden AG, Veskimäe E, Alfred Witjes J, Milowsky MI. The 2021 updated European Association of Urology Guidelines on metastatic urothelial carcinoma. Eur Urol. 2022;81(1):95–103. doi: 10.1016/j.eururo.2021.09.026. - DOI - PubMed
    1. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–4608. doi: 10.1200/JCO.2005.07.757. - DOI - PubMed
    1. Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF, KEYNOTE-045 Investigators Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–1026. doi: 10.1056/NEJMoa1613683. - DOI - PMC - PubMed
    1. Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020;383(13):1218–1230. doi: 10.1056/NEJMoa2002788. - DOI - PubMed

MeSH terms