Biomarkers for Predicting Clinical Outcomes of Chemoradiation-Based Bladder Preservation Therapy for Muscle-Invasive Bladder Cancer

Fumitaka Koga, Kosuke Takemura, Hiroshi Fukushima, Fumitaka Koga, Kosuke Takemura, Hiroshi Fukushima

Abstract

Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have a favorable prognosis and quality of life with a preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting the clinical outcomes of chemoradiation-based BPT. The biomarkers studied were categorized into those related to apoptosis, cell proliferation, receptor tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and others. Among these biomarkers, the Ki-67 labeling index (Ki-67 LI) and meiotic recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both the chemoradiation response and the prognosis of patients on BPT. Concurrent use of trastuzumab and a combination of carbogen and nicotinamide can overcome chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia. Further studies are needed to confirm the practical utility of these biomarkers for progress on biomarker-directed personalized management of MIBC patients.

Keywords: biomarker; bladder neoplasm; bladder preservation; chemoradiation; prognosis; urothelial carcinoma.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Biomarkers that may be used for predicting and improving the chemoradiation response. Biomarkers in bold letter are also associated with favorable prognosis on bladder preservation therapy. Overexpression of erbB2 is associated with unfavorable chemoradiation response, which can be overcome by trastuzumab. ADC, apparent diffusion coefficient value on diffusion-weighted magnetic resonance imaging; erbB2, erythroblastic leukemia viral oncogene homolog 2; ERCC1, excision repair cross-complementing group 1; Hsp60, heat shock protein 60; Uro subtype, urobasal subtype in the Lund University subtyping model;↑, high value;↓, low value.
Figure 2
Figure 2
Biomarkers that may be used for predicting and improving prognosis on bladder preservation therapy. Biomarkers in bold letter are also associated with favorable chemoradiation response. Biomarkers in dark shadow are associated with unfavorable clinical outcomes, which can be overcome by CON. BPT, bladder preservation therapy; CON, carbogen and nicotinamide; CRP, C-reactive protein; DDR, DNA damage response; EGFR, epidermal growth factor receptor; erbB2, erythroblastic leukemia viral oncogene homolog 2; HIF-1α, hypoxia-inducible factor-1α; MRE11, meiotic recombination 11; NRP2, neutropilin 2; VEGF, vascular endothelial growth factor;↑, increased expression;↓, decreased expression or low value.

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