Neoadjuvant Chemotherapy-Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study

Abstract

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy.

Materials and methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate.

Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory.

Conclusion: After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Keywords: Chemoradiotherapy; Combined modality therapy; Muscle-invasive bladder cancer; Neoadjuvant therapy; Organ sparing treatments.

Fig. 1

Regimen schema of 59 MIBC patients. Different therapies were performed according to the evaluation of NAC efficacy. CRT, chemoradiotherapy; GC, gemcitabine/cisplatin; MDT, multidisciplinary team; MIBC, muscle-invasive bladder cancer; NAC, neoadjuvant chemotherapy; TURBT, transurethral resection of bladder tumor.

Fig. 2

Specific treatments after NAC. Presented by allocated therapy for different groups stratified by NAC efficacy. Definite responders mainly received TURBT plus concurrent TURBT. Incomplete responders received radical cystectomy or partial cystectomy plus pelvic lymphadenectomy. BCG, Bacillus Calmette-Guerin; CRT, chemoradiotherapy; NAC, neoadjuvant chemotherapy; PLND, pelvic lymphadenectomy; TURBT, transurethral resection of bladder tumor.

Fig. 3

Kaplan-Meier plot of the 59 muscle-invasive bladder cancer patients. Error bars are defined as 95% confidence intervals and denoted with a dashed line. The 3-year overall survival rate was 72.8%.

Fig. 4

Kaplan-Meier curves of overall survival with log-rank statistics for the two groups of bladder-sparing treatment and cystectomy. Patients in the bladder-sparing group had significantly better prognosis than those of the cystectomy group (p=0.007).

Fig. 5

Kaplan-Meier curves of relapse-free survival with log-rank statistics for the two groups of bladder-sparing treatment and cystectomy. Patients in the bladder-sparing group had significantly better relapse-free survival than those of the cystectomy group (p=0.002).