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
. 2023 Jun;41(6):1551-1562.
doi: 10.1007/s00345-023-04408-w. Epub 2023 May 5.

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer

Daan J Reesink  1 , Harm H E van Melick  2 , Paul B van der Nat  3   4 , Maartje Los  5 , Simon Horenblas  6 , Ewoudt M W van de Garde  7   8 ; Santeon MIBC Study Group
Collaborators, Affiliations

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer

Daan J Reesink et al. World J Urol. 2023 Jun.

Abstract

Purpose: For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder.

Methods: From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo).

Results: Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674).

Conclusion: There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.

Keywords: Bladder cancer; Effectiveness gap; Efficacy; First-line chemotherapy; Metastatic; Real-world outcomes.

PubMed Disclaimer

Comment in

References

    1. Sternberg CN, Vogelzang NJ (2003) Gemcitabine, paclitaxel, pemetrexed and other newer agents in urothelial and kidney cancers. Crit Rev Oncol Hematol 46(Suppl):S105–S115. https://doi.org/10.1016/s1040-8428(03)00068-4 - DOI - PubMed
    1. Witjes JA, Bruins HM, Cathomas R, Compérat EM, Cowan NC, Gakis G et al (2021) European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol 79:82–104. https://doi.org/10.1016/j.eururo.2020.03.055 - DOI - PubMed
    1. von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ et al (2000) Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 18:3068–3077. https://doi.org/10.1200/JCO.2000.18.17.3068 - DOI - PubMed
    1. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T et al (2005) 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 23:4602–4608. https://doi.org/10.1200/JCO.2005.07.757 - DOI - PubMed
    1. Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A et al (2007) Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol 52:134–141. https://doi.org/10.1016/j.eururo.2006.12.029 - DOI - PubMed

MeSH terms

Grants and funding

LinkOut - more resources