Julian Schardt1, Beat Roth2, Roland Seiler3. 1. Department of Medical Oncology, University of Bern, Bern, Switzerland. 2. Department of Urology, University of Bern, 3010, Bern, Switzerland. 3. Department of Urology, University of Bern, 3010, Bern, Switzerland. r_seiler@gmx.ch.
Abstract
PURPOSE: 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. METHODS: 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.
PURPOSE: 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. METHODS: 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.
Authors: Francesca Sanguedolce; Magda Zanelli; Andrea Palicelli; Stefano Ascani; Maurizio Zizzo; Giorgia Cocco; Lars Björnebo; Anna Lantz; Ugo Giovanni Falagario; Luigi Cormio; Giuseppe Carrieri Journal: Int J Mol Sci Date: 2022-07-15 Impact factor: 6.208
Authors: Jochen Rutz; Andrea Janicova; Katja Woidacki; Felix K-H Chun; Roman A Blaheta; Borna Relja Journal: Int J Mol Sci Date: 2020-05-26 Impact factor: 5.923