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Original research
Impact of consensus molecular subtypes on survival with and without adjuvant chemotherapy in muscle-invasive urothelial bladder cancer
  1. Florestan J Koll1,2,3,
  2. Claudia Döring4,
  3. Leon Herwig4,
  4. Benedikt Hoeh1,
  5. Mike Wenzel1,
  6. Cristina Cano Garcia1,
  7. Severine Banek1,
  8. Luis Kluth1,
  9. Jens Köllermann4,
  10. Andreas Weigert5,
  11. Felix K-H Chun1,
  12. Peter Wild2,4,6,
  13. Henning Reis4
  1. 1 Department of Urology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
  2. 2 Frankfurt Cancer Institute (FCI), Hospital of the Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
  3. 3 University Cancer Center (UCT) Frankfurt, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
  4. 4 Dr. Senckenberg Institute of Pathology, Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany
  5. 5 Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Frankfurt am Main, Hessen, Germany
  6. 6 Frankfurt Institute for Advanced Studies (FIAS), Frankfurt am Main, Hessen, Germany
  1. Correspondence to Dr Florestan J Koll; florestanjohannes.koll{at}kgu.de

Abstract

Aims Adjuvant chemotherapy after radical cystectomy can reduce the risk of recurrence and death in advanced muscle-invasive urothelial bladder cancer (MIBC). Molecular subtypes have been shown to be associated with survival. However, their predictive value to guide treatment decisions is controversial and data to use subtypes as guidance for adjuvant chemotherapy is sparse. We aimed to assess survival rates based on MIBC consensus molecular subtypes with and without adjuvant chemotherapy.

Methods Gene expression profiles of 143 patients with MIBC undergoing radical cystectomy were determined from formalin-fixed, paraffin-embedded specimen to assign consensus molecular subtypes. Expression of programmed cell death ligand-1 (PD-L1) and immune cell infiltration were determined using multiplex immunofluorescence. Matched-pair analysis was performed to evaluate the effect of adjuvant chemotherapy on overall survival (OS) for molecular subtypes applying Kaplan-Meier and Cox regression survival analyses.

Results Samples were luminal papillary: 9.1% (n=13), luminal non-specified: 6.3% (n=9), luminal unstable: 4.9% (n=7), stroma-rich: 27.9% (n=40), basal/squamous (Ba/Sq): 48.9% (n=70) and neuroendocrine-like (NE-like): 2.8% (n=4). Ba/Sq tumours had the highest concentration of PD-L1+ tumour and immune cells. Patients with luminal subtypes had better OS than those with NE-like (HR 0.2, 95% CI 0.1 to 0.7, p<0.05) and Ba/Sq (HR 0.5, 95% CI 0.2 to 0.9, p<0.05). No survival benefit with adjuvant chemotherapy was observed for luminal tumours, whereas Ba/Sq had significantly improved survival rates with adjuvant chemotherapy. Retrospective design and sample size are the main limitations.

Conclusion Consensus molecular subtypes can be used to stratify patients with MIBC. Luminal tumours have the best prognosis and less benefit when receiving adjuvant chemotherapy compared with Ba/Sq tumours.

  • CHEMOTHERAPY
  • MOLECULAR BIOLOGY
  • Urinary Bladder
  • Medical Oncology
  • Biomarkers, Tumor

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/jcp-2023-208973

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    Data availability statement

    Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Handling editor Murali Varma.

    • Contributors All authors contributed substantially to the study conception and design. Conception and design: FJK, PW and HR. Acquisition of data: FJK, CD, MW, CCG, SB, JK, AW and HR. Analysis and interpretation of data: FJK, CD, AW and BH. Drafting of the manuscript: FJK and HR. Critical revision of the manuscript for important intellectual content: BH, CCG, MW, PW, LK and HR. Statistical analysis: FJK and CD. Obtaining funding: FJK, FKHC and PW. Administrative, technical or material support: LH, CD and AW. Supervision: LK, FKHC, PW and HR. Responsible for the overall content as guarantor: FJK.

    • Funding FJK was funded by the Mildred Scheel Career Center Frankfurt (Deutsche Krebshilfe). The work was further supported by Hessen State Ministry for Higher Education, Research and the Arts and LOEWE Center Frankfurt Cancer Institute (FCI) (III L 5 – 519/03/03.001 – (0015)). HTG Transcriptome Panel was performed as part of a collaboration agreement with HTG Molecular Diagnostics. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

    • Competing interests PW has received consulting fees and honoraria for lectures by Bayer, Janssen-Cilag, Novartis, Roche, MSD, Astellas Pharma, Bristol-Myers Squibb, Thermo Fisher Scientific, Molecular Health, Guardant Health, Sophia Genetics, Qiagen, Eli Lilly, Myriad, Hedera Dx and AstraZeneca. Research Support was provided by AstraZeneca and Roche. HTG Transcriptome Panel was funded by HTG Molecular Diagnostics. HR was on an advisory board of Bristol-Myers Squibb, received honoraria from Roche, Bristol-Myers Squibb, Janssen-Cilag, Novartis, AstraZeneca, MCI, CHOP GmbH and Diaceutics, received travel support from Philips, Roche, and Bristol-Myers Squibb, and received grants from Bristol-Myers Squibb.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.