Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going?

Abstract

Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the recommended treatment, with the highest level of evidence, for patients with muscle-invasive bladder cancer (MIBC). However, only a minority of patients receive this treatment, mainly due to patient comorbidities, the relatively small survival benefit, and the lack of predictive biomarkers to select those patients most likely to benefit from this multimodal approach. In addition, adjuvant chemotherapy has been recommended for patients with high-risk MIBC, although randomized trials have not provided conclusive evidence on the impact of this approach. At present, however, this situation is changing, largely due to our improved knowledge of the molecular biology of bladder cancer, which has enabled us to identify new prognostic and predictive biomarkers that can be used to select the most appropriate treatment for each patient. Moreover, new active treatments, especially immunotherapy, have shown promising results in the neoadjuvant setting. In addition, the gene expression profile of bladder tumors can be used to classify them into different subtypes, which correlate with specific clinical-pathological characteristics and with treatment response or resistance. Therefore, the main objective for the near future is to introduce these translational breakthroughs into routine clinical practice in order to personalize treatment for each patient.

The Dependence between Urinary Levels of Angiogenesis Factors, 8-Iso-prostaglandin F2α, ɣ-Synuclein, and Interleukin-13 in Patients with Bladder Cancer: A Pilot Study

“…To date, there is no reliable method for the prediction of response to chemotherapy, resulting in a possible overtreatment in nonresponders with unnecessary toxicity that might render patients in a deteriorated physical condition without the opportunity for additional, alternative therapy [ 39 ]. The parameters presented in our study, determined in the urine of patients with BC, reflect the multifaceted processes occurring during the course of the disease, such as angiogenesis, oxidative stress, and immune response.…”

The biological function of m6A reader YTHDF2 and its role in human disease

“…Bladder cancer is the most common malignant tumor of the urinary tract and the treatment of bladder cancer has not been improved significantly since 30 years ago [31]. Recently, researchers constantly pay attention to the biological role of m6A modification in bladder cancer.…”

HYAL4-V1/Chondroitinase (Chase) Drives Gemcitabine Resistance and Predicts Chemotherapy Failure in Patients with Bladder Cancer

“…Neoadjuvant chemotherapy is intended for down-staging of the disease and for treating micrometastases prior to cystectomy (4). Although immunotherapy regimens have been approved as both first and secondline treatments for metastatic disease, the response rate is ≤ 25% and chemotherapy in the adjuvant and salvage setting remains the standard of care (5)(6)(7). Chemotherapy regimens for BC are largely platinum-based.…”

“…Chemotherapy regimens for BC are largely platinum-based. Due to its better tolerability, Gemcitabine plus Cisplatin (Gem+Cis) is a preferred chemotherapy regimen versus the MVAC (Methotrexate, Vinblastine sulfate, Adriamycin, and Cisplatin) in the neoadjuvant and adjuvant/salvage settings (6,(8)(9)(10).…”

“…Although the terms prognostic and predictive biomarkers have been used interchangeably, the former predicts a patient's overall health outcome (e.g., overall survival, cancer-specific survival), whereas the latter refers to the prediction of response to a particular treatment and can even be a target for therapy (11). Due to the availability of tissues from the transurethral resection and radical cystectomy, as well as, urine as the optimal non-invasive liquid biopsy for assaying markers, several potential prognostic and predictive biomarkers have been identified for BC, especially MIBC, where prediction of therapy response is critical for improving the clinical outcome of patients with advanced BC (6,12). In the last few years MIBC molecular subtypes have gained prominence due to their promise as predictors of clinical outcome and for guiding treatment Research.…”