Liquid biopsy can evaluate minimally residual disease. Hotspot mutations are also common in non-coding regions among the MIBC patients. We evaluated the status of MIBC with hotspot mutations with cfDNA.Tumor and blood from MIBC patients were collected prospectively. We evaluate the VAF of mutations (TERT, PLEKHS1, ADGRG6 and WDR74) with digital PCR in tumor and cfDNA as somatic mutation. We originally designed and validated primers and probes. VAF of cfDNA and clinical imaging were matched. This study was approved by the Institutional Review Board (#2022-157).37 MIBC patients were enrolled and 28 (76%) patients had any hotspot. Among the 21 patients of follow-up cohort, cfDNA predicted recurrence 58 days earlier than the diagnosis by CT scan. Furthermore, the detection of ctDNA at the first visit after radical cystectomy was associated with recurrence free survival (P = 0.0043) and overall survival (P = 0.017). The patient who received neoadjuvant chemotherapy (NAC) and diagnosed as ypT0 belonged to the nonrecurrence group with negative ctDNA.Hotspot mutation is promising biomarker to predict earlier recurrence than CT-scan. Multiple detection of mutations in cfDNA contributes to reliable recurrence prediction.