Liquid Biopsies to Select Patients for Perioperative Chemotherapy in Muscle-invasive Bladder Cancer: A Systematic Review

Neoadjuvant chemotherapy (NAC) is considered the standard treatment for muscle-invasive bladder cancer (MIBC). However, its overall survival benefit is limited and toxicity is significant; hence, NAC has not been adopted universally. To systematically evaluate whether biomarkers can guide the administration of perioperative chemotherapy in MIBC patients. A systematic search of the PubMed database was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). In total, 215 papers were screened and 22 were selected to assess the potential clinical value of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in selecting MIBC patients for perioperative chemotherapy. We found that the presence of one or more CTCs before radical cystectomy, as determined by the CellSearch technique, is a robust marker for poor recurrence-free and overall survival. Consequently, whether NAC can be withheld in patients without the presence of CTCs is a subject of ongoing investigation. Studies investigating various approaches to detect cfDNA showed that cfDNA is present in the blood of MIBC patients, but varying results on its prognostic value have been reported. Successful cfDNA-based approaches are likely to encompass at least a multitude of genes using next-generation sequencing, as there are generally few hotspot somatic mutations in MIBC. Liquid biopsies hold promise in selecting MIBC patients for perioperative chemotherapy, but instead of more proof-of-principle studies, prospective studies investigating true clinical applicability for treatment decision making are urgently needed. Liquid biopsies appear to be a promising tool to guide the administration of chemotherapy in patients with muscle-invasive bladder cancer; however, the optimal way to implement these remains to be determined.