Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer.

Efstathiou, Jason A; Mouw, Kent W; Gibb, Ewan A; Liu, Yang; Wu, Chin-Lee; Drumm, Michael R; da Costa, Jose Batista; du Plessis, Marguerite; Wang, Natalie Q; Davicioni, Elai; Feng, Felix Y; Seiler, Roland; Black, Peter C; Shipley, William U; Miyamoto, David T (2019). Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer. European urology, 76(1), pp. 59-68. Elsevier 10.1016/j.eururo.2019.01.011

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BACKGROUND Bladder-sparing trimodality therapy (TMT) is an alternative to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), and biomarkers to inform therapy selection are needed. OBJECTIVE To evaluate the prognostic value of immune and stromal signatures in MIBC treated with TMT. DESIGN, SETTING, AND PARTICIPANTS We used a clinical-grade platform to perform transcriptome-wide gene expression profiling of primary tumors from 136 MIBC patients treated with TMT at a single institution. We observed 60 overall survival events at 5yr, and median follow-up time for patients without an event was 5.0yr (interquartile range 3.1, 5.0). Expression data from another cohort of 223 MIBC patients treated with neoadjuvant chemotherapy (NAC) and RC were also analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Molecular subtype, immune, and stromal signatures were evaluated for associations with disease-specific survival (DSS) and overall survival (OS) in TMT patients, and in patients treated with NAC and RC. RESULTS AND LIMITATIONS Gene expression profiling of TMT cases identified luminal (N=40), luminal-infiltrated (N=26), basal (N=54), and claudin-low (N=16) subtypes. Signatures of T-cell activation and interferon gamma signaling were associated with improved DSS in the TMT cohort (hazard ratio 0.30 [0.14-0.65], p=0.002 for T cells), but not in the NAC and RC cohort. Conversely, a stromal signature was associated with worse DSS in the NAC and RC cohort (p=0.006), but not in the TMT cohort. This study is limited by its retrospective nature. CONCLUSIONS Higher immune infiltration in MIBC is associated with improved DSS after TMT, whereas higher stromal infiltration is associated with shorter DSS after NAC and RC. Additional studies should be conducted to determine whether gene expression profiling can predict treatment response. PATIENT SUMMARY We used gene expression profiling to study the association between tumor microenvironment and outcomes following bladder preservation therapy for invasive bladder cancer. We found that outcomes varied with immune and stromal signatures within the tumor. We conclude that gene expression profiling has potential to guide treatment decisions in bladder cancer.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Seiler, Roland

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0302-2838

Publisher:

Elsevier

Language:

English

Submitter:

Jeannine Wiemann

Date Deposited:

14 May 2019 14:24

Last Modified:

24 Oct 2019 11:31

Publisher DOI:

10.1016/j.eururo.2019.01.011

PubMed ID:

30712971

Uncontrolled Keywords:

Biomarker Bladder cancer Bladder preservation Bladder-sparing Chemoradiation Gene expression profiling Immune Muscle-invasive bladder cancer Radiation Stromal Trimodality therapy

BORIS DOI:

10.7892/boris.128112

URI:

https://boris.unibe.ch/id/eprint/128112

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