Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy

Seiler, Roland; Ashab, Hussam Al-Deen; Erho, Nicholas; Rhijn, Bas W.G. van; Winters, Brian; Douglas, James J.; Kessel, Kim E.M. van; Putte, Elisabeth E. Fransen van de; Sommerlad, Matthew; Wang, Natalie Q.; Choeurng, Voleak; Gibb, Ewan A.; Palmer-Aronsten, Beatrix; Lam, Lucia L.C.; Buerki, Christine; Davicioni, Elai; Sjödahl, Gottfrid; Kardos, Jordan; Hoadley, Katherine A.; Lerner, Seth P.; McConkey, David J.; Choi, Woonyoung; Kim, William Y.; Kiss, Bernhard; Thalmann, George N.; Todenhöfer, Tilman; Crabb, Simon J.; North, Scott; Zwarthoff, Ellen C.; Boormans, Joost L.; Wright, Jonathan L.; Dall′Era, Marc; Heijden, Michiel S. van der; Black, Peter C.

doi:10.1016/j.eururo.2017.03.030

Cited by 689 publications

(623 citation statements)

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“…Such cancers have low risk for progression, and preliminary data suggests a low likelihood of response to cisplatin-based neoadjuvant chemotherapy (NAC) (Seiler et al, 2017). The frequency of FGFR3 alterations in luminal papillary tumors suggests that tyrosine kinase inhibitors of FGFR3 may be an effective treatment approach, especially since early phase clinical trials show benefit of pan-FGFR inhibitor agents in FGFR3-selected advanced solid tumors (Karkera et al, 2017; Nogova et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

Robertson¹,

Kim²,

Al‐Ahmadie³

et al. 2017

Cell

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Summary We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival ‘neuronal’ subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, lncRNA, and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma-in-situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

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Section: Discussionmentioning

confidence: 99%

“…* For luminal-papillary cases, the low predicted likelihood of response is based on preliminary data from (Seiler et al, 2017). See Discussion.…”

Section: Figurementioning

confidence: 99%

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

Robertson¹,

Kim²,

Al‐Ahmadie³

et al. 2017

Cell

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1,624

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“…Genomic 'subtypes' and genetic alterations with distinct molecular profiles and varied response to NAC have been described [19][20][21][22][23] . As our understanding of MIBC biology continues to evolve, more 'personalized' treatment decisions will allow us to better select chemo sensitive tumors.…”

Section: Cuaj -Original Researchmentioning

confidence: 99%

Trends and disparities in the use of neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma

Duplisea

Mason

Reichard

et al. 2018

CUAJ

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Introduction: Neoadjuvant chemotherapy (NAC) prior to radical or partial cystectomy is considered the standard of care for eligible patients with muscle-invasive urothelial carcinoma. Despite guideline recommendations, adoption of NAC has historically been low, although prior studies have suggested that use is increasing. In this contemporary study, we examine trends in the use of NAC and explore factors associated with its receipt. Methods: We identified patients in the National Cancer Database who underwent radical or partial cystectomy for cT2-cT4N0M0 urothelial carcinoma from 2006-2014. The proportion of patients receiving NAC during each year was examined. Logistic regression models were used to evaluate clinical and socioeconomic factors associated with the receipt of NAC. Results: A total of 18 188 patients were identified who underwent radical or partial cystectomy for muscle-invasive bladder cancer. Overall, 3940 (21.7%) received NAC. We noted a significant increase in the use of NAC over time, from 9.7% in 2006 to 32.2% in 2014. Factors associated with lower use of NAC include older age, higher comorbidity score, lower cT stage, lower hospital radical cystectomy volume, treatment at a non-academic facility, lower patient income, and receipt of partial cystectomy (all p<0.001). Interestingly, neither sex nor race were associated with receipt of NAC. Conclusions: Use of NAC has increased significantly over time to a modest rate of 32%. However, disparities still exist in the receipt of NAC and future efforts aimed at mitigating these disparities are warranted.

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“…High-quality evidence demonstrating the clinical benefits of the therapeutic hypotheses generated by this and other molecular analyses is now needed. Already, evidence has been presented indicating superior responses of tumours of the basal subtype to neoadjuvant chemotherapy 10 , and of the relative resistance of other subtypes to this approach 8 . A finer-grained understanding of sensitivity to the range of chemotherapy, targeted therapy and immune-based therapeutics is now required.…”

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confidence: 99%

Multi-omic profiling refines the molecular view

Hurst

Knowles

2017

Nat Rev Clin Oncol

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Standfirst |Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease for which treatment has, historically, lagged behind that of many other solid tumour types. A more detailed understanding of the biology of individual tumours and the identification of molecular features that provide prognostic and predictive information is key to the application of personalized care for patients with this disease. The recent publication of the complete TCGA study of 412 MIBC samples 1 now provides such data. Estimates suggest that >400,000 new cases of bladder cancer and 165,000 bladder-cancer-related deaths occur worldwide each year 2 . Approximately 25% of cases are muscle-invasive bladder cancers (MIBC). These comprise a heterogeneous group of tumours, and for patients with metastatic disease, the prognosis is generally poor. Until the recent approval of immune-checkpoint inhibitors for use in some patients with advanced MIBC, no new drugs had been approved for the treatment of bladder cancer in more than two decades and no significant changes in survival outcomes had been recorded 3 . Refers to Robertson

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Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy

Cited by 689 publications

References 20 publications

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer

Trends and disparities in the use of neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma

Multi-omic profiling refines the molecular view

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