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

Abstract

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 bladdersparing 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 bladdersparing 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 CANCER RESEARCH AND TREATMENT (CRT) 4

Neoadjuvant chemotherapy with gemcitabine and cisplatin followed by selective bladder preservation chemoradiotherapy in muscle-invasive urothelial carcinoma of bladder

“…In 64 chemoradiotherapy patients, the probability of surviving metastasis-free by 36 months (i.e., 3-year MFS rate) was encouraging as 70%. The outcomes obtained here compared favorably to those reported in studies involving neoadjuvant chemotherapy for MIBC [ 11 ].…”

“…Although the idea of neoadjuvant chemotherapy followed by concurrent chemoradiotherapy is dated [ 15 16 ], its benefit remains unclear. On the premise of tolerable chemotherapy regimen, studies suggested that patients with downstaging by neoadjuvant chemotherapy could benefit from bladder preservation chemoradiotherapy [ 11 17 ], as well as from radical cystectomy [ 3 4 18 ]. In order to improve the outcomes of neoadjuvant chemotherapy, the addition of immune checkpoint inhibitors to cisplatin-based chemotherapy is a promising strategy.…”

Combined Modality Bladder-Sparing Therapy for Muscle-Invasive Bladder Cancer: How (Should) We Do It? A Narrative Review

“…There is an ongoing debate on the routine utilization of NAC in cisplatin-eligible patients who wish to undergo CMT [ 33 , 34 , 35 ]. The practice often adopted in clinical settings is to administer NAC to patients with MIBC who are fit for cisplatin and offer CMT to those who responded to NAC [ 36 , 37 , 38 ]. Similar selection criteria have been proposed in the SPARE Trial design ( Figure 1 ) [ 39 ].…”

Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature

“…In a phase II study carried out by Shi et al. with the purpose to assess the efficiency of NAC-guided bladder-sparing treatment in MIBC patients, 6 patients who achieved cCR underwent TURBT plus concurrent CRT and all survived with a functional bladder in a median follow-up of 44.6 months ( 76 ). These findings demonstrated the feasibility and safety of bladder preservation strategy in highly selected cCR MIBC patients.…”