The Efficacy Of Comprehensive Therapy Guided By Neoadjuvant Chemotherapy For Muscle-Invasive Bladder Cancer

ObjectivesIn the past,radical cystectomy(RC)was the standard treatment for muscle-invasive bladder cancer(MIBC).Current researches showed that neoadjuvant chemotherapy(NAC),such as Gemcitabine/Cisplatin(GC),combined with RC could improve prognosis of MIBC patients compared with RC alone.NAC plus RC have become the standard of treatment for MIBC patients.As the poor quality of life after RC,the exploration of comprehensive treatment on bladder preservation without affecting prognosis has been a hotspot.Previous studies showed that NAC could achieve significant tumor downgrading,even complete response(CR).However,previous bladder-preserving treatments mostly consisted of maximum Transurethral Resection of Bladder Tumor(TURBT)before NAC,which influenced the true evaluation of NAC.The purposes of this research were to explore the authentic effectiveness ofNAC in MIBC patients without being affected by the efficacy of TURBT,then to evaluate the bladder preservation rate,prognosis and quality of life after the subsequent treatments,such as TURBT plus concurrent chemoradiotherapy or partial cystectomy plus pelvic lymphadenectomy,and to explore the prognosis of patients after radical cystectomy.MethodsFrom September 2015 to September 2018,bladder urothelial carcinoma patients of clinical stage T2-4aN0M0 confirmed by imaging and cystoscope biopsy were intended to enroll in this study.2-4 courses of NAC were performed with GC regimen.GC regimen consisted of 1,000 mg/m2 gemcitabine intravenously on day 1 and day 8,75 mg/m2 cisplatin intravenously on day 1 administered every 21 days.After NAC,imaging,cystoscopy and urine cytology were used to assess the efficacy of NAC consulted with the multiple disciplinary team(MDT)discussion.Definite responders(DR:T≤T1)would receive comprehensive treatment of bladder preservation(TURBT plus concurrent chemoradiotherapy).Incomplete responders(IR)would receive either RC or partial cystectomy plus pelvic lymphadenectomy after MDT discussion.The primary endpoint was bladder preservation rate,and secondary endpoints were overall survival(OS)and life quality of bladder-sparing patients.Results59 patients(53 men&6 women)with MIBC were enrolled in the study,with a median age of 63 years(39-70).According to the 7th edition of American Joint Committee on Cancer(AJCC)TNM Staging system,numbers of patients at each clinical stage were:cT215,cT3 39,cT4a 5.All pathologies of biopsy were urothelial carcinoma.The rate of DR was 52.5%(31/59),and CR accounted for 10.2%(6/59);IR was 44.1%(26/59);progressive disease(PD)rate was 3.4%(2/59).59.3%(35/59)patients received comprehensive treatments of bladder preservation including TURBT plus concurrent chemoradiotherapy(42.4%),partial cystectomy plus pelvic lymphadenectomy(6.8%),TURBT plus bacillus calmette-guerin(BCG)instillation(6.8%)and TURBT alone(3.4%).The median follow-up period was 28.3 months(9.2 to 47.2),and the 3-year OS was 71.2%for all patients.The 3-year OS was 88.0%of bladder-sparing patients,and the 3-year relapse-free survival(RFS)was 70.5%.In the SF-36 questionnaires,all patients had considerable scores of total physical health and total mental health.In terms of the preserved bladder functions,the results of Overactive Bladder Symptom Score(OABSS)were satisfied.The 3-year OS and RFS of radical cystectomy group were 57.1%and 36.3%,which were significantly worse than bladder-sparing group.89.8%(53/59)of patients experienced adverse events after neoadjuvant chemotherapy,and most were grade 2(34/59,57.6%).Concurrent chemoradiotherapy related adverse events accounted for 28%(7/25)and mostly were grade 1.The rate of postoperative complications was 15%(3/20)of radical cystectomy,but all patients were safely discharged.ConclusionsPatients with muscle-invasive bladder cancer can receive a good efficacy and tolerable side-effect of neoadjuvant chemotherapy.After stratifying MIBC patients by the true efficacy of NAC,DR could benefit from comprehensive treatments of bladder preservation resulting in satisfied bladder-sparing rate,prognosis and quality of life.For IR,the curative effect of radical cystectomy was not optimistic,and further related researches were urged.In this research,comprehensive treatments guided by neoadjuvant chemotherapy for muscle-invasive bladder cancer patients deserve further verification by multicenter and prospective researches.