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.
Highlights
Bladder cancer is the second most common malignancy of the genitourinary tract after prostate cancer in the United States, with approximately 81,000 new cases and 17,000 deaths each year as of 2018 [1]
This study suggests that meiotic recombination 11 (MRE11) expression status may allow patient selection for radiotherapy or radical cystectomy (RC)
A phase III clinical trial showed that hypoxia modification with carbogen and nicotinamide (CON) significantly improved prognosis of invasive bladder cancer patients treated with radiotherapy [51]
Summary
Bladder cancer is the second most common malignancy of the genitourinary tract after prostate cancer in the United States, with approximately 81,000 new cases and 17,000 deaths each year as of 2018 [1]. Bladder preservation therapy (BPT), consisting of transurethral resection, chemotherapy, and radiation, has yielded oncological outcomes and QOL comparable to or more favorable than RC when select MIBC patients undergo BPT [5]. MIBC patients with favorable oncological and QOL outcomes after BPT are those achieving complete response (CR) to chemoradiation; such patients account for 50–90% of MIBC patients treated with chemoradiation-based BPT [5] Those who do not achieve CR are advised to undergo salvage RC, MIBC patients who do not achieve CR to chemoradiation show unfavorable cancer-specific survival (CSS) regardless of salvage RC with curative intent due to metastatic recurrences [5,9]; such patients may benefit from neoadjuvant chemotherapy plus RC in terms of CSS. Case series and phase I/II studies demonstrated possible activity of gemcitabine [12] and paclitaxel [13] as radiosensitizers for MIBC
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