Forty years of cisplatin-based chemotherapy in muscle-invasive bladder cancer: are we understanding how, who and when?
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For 40 years cisplatin-based chemotherapy has been administered to patients with muscle-invasive bladder cancer (MIBC). The best evidence of its efficacy is found in the context of neoadjuvant chemotherapy (NAC). However, the benefit to the patient is modest, with an improvement in 5-year overall survival of only 5–8%. Approximately 60% of patients still have muscle-invasive disease at cystectomy despite NAC. Selecting patients based on the likelihood of response appears to be a promising strategy to improve on this modest benefit. To realize this promise, researchers are investigating biomarkers for identifying responders and non-responders prior to NAC.
In this review, we discuss a number of tissue- and liquid-based biomarkers associated with the response to NAC.
Results and conclusions
We elaborate biomarkers at the methylation, DNA, RNA and protein levels and give their current status in clinical trials and/or their implementation in daily clinical practice. In particular, detection of alterations in DNA damage repair pathways as well as molecular subtypes seems to be a promising method for identifying responders to NAC. Furthermore, we illustrate liquid-based biomarkers. Circulating tumor DNA (ctDNA) in patient blood and urine appear to offer an elegant way for biological characterization of MIBC. Recent data show that the presence of ctDNA is limited in patients with localized MIBC being considered for NAC. At this disease stage, ctDNA in patient urine may be more promising for the genomic characterization of MIBC. However, ctDNA in blood or urine has not yet been rigorously investigated in this clinical context.
KeywordsMuscle-invasive bladder cancer Neoadjuvant chemotherapy Cisplatin resistance Second-line treatment Molecular subtypes Gene expression analysis
Protocol/project development: RS, JS. Data collection or management: RS, JS. Data analysis: NA. Manuscript writing/editing: RS, JS, BR.
Compliance with ethical standards
Conflict of interest
The authors have no direct or indirect commercial financial incentive associated with publishing this review article.
Experimental protocol and ethics
For this review, no tissue was analyzed or patient data collected. Therefore, no ethical approval was obtained.
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