Novel coumarone-derived(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol inhibits muscle-invasive bladder cancer cells by repressing the S and G2 cell cycle phases

Background:This study aimed to select compounds with unique inhibitory effects on muscle-invasive bladder cancer(MIBC)from coumarone derivatives with similar parent nuclear structures and to reveal their tumor-suppressive effects using various approaches.Methods:Bladder cancer cell lines SW780 and T24,as well as human normal bladder epithelial cell line SV-HUC-1 were selected as the study model,and these urinary system cells were co-incubated with various concentrations of(S,E)-4-(4-methylbenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-isocyanobenzylidene)-3-phenylchroman-3-ol,(S,E)-4-(4-fluorobenzylidene)-3-phenylchroman-3-ol(FPO),and(S,E)-3-phenyl-4-(4-(trifluoromethoxy)benzylidene)chroman-3-ol.Cell activity was detected using cell counting kit-8.FPO showed the strongest inhibitory effect on MIBC cells;therefore,it was selected for further experiments.We monitored the FPO-induced T24 cell morphological changes with an inverted microscope.The FPO-inhibited migration of T24 cells was examined using a cell scratch assay.We detected the clonogenic ability of T24 cells through a clone formation test and evaluated their proliferative ability using a 5-ethynyl-2’-deoxyuridine fluorescence staining kit.The inhibitory effect of FPO against the cell cycle was monitored using flow cytometry,and its suppressive effect on the DNA replication ability of T24 cells was detected using double fluorescence staining(Ki67 and phalloidin).Results:Among the four candidate coumarone derivatives,FPO showed the most significant inhibitory effect on MIBC cells and was less toxic to normal urothelial cells.FPO inhibited T24 cell growth in time and dose-dependent manners(the half-inhibitory concentration is 8μM).FPO significantly repressed the proliferation,migration,and clonogenic ability of bladder cancer T24 cells.Cell mobility was significantly inhibited by FPO:30μM FPO almost completely repressed migration occurred at after 24 h treatment.Moreover,FPO significantly suppressed the clonogenicity of bladder cancer cells in a dose-dependent manner.Mechanistically,FPO targeted the cell cycle,arresting the S and G2 phases on bladder cancer T24 cells.Conclusion:We discovered a novel anticancer chemical,FPO,and proposed a potential mechanism,through which it suppresses MIBC T24 cells by repressing the cell cycle in the S and G2 phases.This study contributes to the development of novel anticancer drugs for MIBC.

A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer

Objective:Conservative approaches in muscle-invasive bladder cancer(MIBC)have been evolved to avoid aggressive surgery,but are limited to elderly,frail,and patients medically unfit for surgery.Our study aimed to assess the response rate of neoadjuvant chemotherapy(NACT)before radiotherapy(RT)in MIBC patients.Methods:Forty patients with urothelial carcinoma of stage T2-T4a,N0,M0 were enrolled between November 2013 and November 2015,and treated with three cycles of NACT with gemcitabine-cisplatin.Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors(RECIST)criteria.Patients who achieved complete response(CR)and partial response(PR)>50%were treated with radical RT,and those who had PR<50%,stable disease(SD),and progressive disease(PD)underwent radical cystectomy(RC).Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model.Results:After NACT,35(87.5%)patients achieved either PR>50%or CR,and were treated with RT.Five(12.5%)patients who had PR<50%,SD,or PD underwent RC.All patients who received radiation showed CR after 6 weeks.Median follow-up was 43 months(range:10-66 months)and median overall survival(OS)was not reached.Three-year OS,local control,and disease-free survival were 70.1%,60.9%,50.6%,respectively,and 50%of patients preserved their functioning bladder.Three-year OS rate was 88.9%in patients who achieved CR to NACT,73.1%in patients with PR≥50%and 40%in patients with PR<50%.Conclusion:NACT followed by RT provides a high probability of local response with bladder preservation in CR patients.Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.

Comparison of the survival outcomes between primary and secondary muscle-invasive bladder cancer: a propensity score-matched study

Background:Studies have classified muscle-invasive bladder cancer(MIBC)into primary(initially muscle-invasive,PMIBC)and secondary subtypes(initially non-muscle-invasive but progresses,SMIBC),for which controversial survival outcomes were demonstrated.This study aimed to compare the survival outcomes between PMIBC and SMIBC patients in China.Methods:Patients diagnosed with PMIBC or SMIBC at West China Hospital from January 2009 to June 2019 were retrospectively included.Kruskal-Wallis and Fisher tests were employed to compare clinicopathological characteristics.Kaplan-Meier curves and Cox competing proportional risk model were used to compare survival outcomes.Propensity score matching(PSM)was employed to reduce the bias and subgroup analysis was used to confirm the outcomes.Results:A total of 405 MIBC patients were enrolled,including 286 PMIBC and 119 SMIBC,with a mean follow-up of 27.54 and 53.30 months,respectively.The SMIBC group had a higher proportion of older patients(17.65%[21/119]vs.9.09%[26/286]),chronic disease(32.77%[39/119]vs.22.38%[64/286]),and neoadjuvant chemotherapy(19.33%[23/119]vs.8.04%[23/286]).Before matching,SMIBC had a lower risk of overall mortality(OM)(hazard ratios[HR]0.60,95%confidence interval[CI]0.41-0.85,P=0.005)and cancer-specific mortality(CSM)(HR 0.64,95%CI 0.44-0.94,P=0.022)after the initial diagnosis.However,higher risks of OM(HR 1.47,95%CI 1.02-2.10,P=0.038)and CSM(HR 1.58,95%CI 1.09-2.29,P=0.016)were observed for SMIBC once it became muscle-invasive.After PSM,the baseline characteristics of 146 patients(73 for each group)were well matched,and SMIBC was confirmed to have an increased CSM risk(HR 1.83,95%CI 1.09-3.06,P=0.021)than PMIBC after muscle invasion.Conclusions:Compared with PMIBC,SMIBC had worse survival outcomes once it became muscle-invasive.Specific attention should be paid to non-muscle-invasive bladder cancer with a high progression risk.

Cryoablation techniques in bladder cancer: A review

Bladder cancer(BC)ranks as the tenth most common cancer globally.Histopathologically,BC is broadly categorized into urothelial and non-urothelial BC.Urothelial carcinoma represents over 90%of BC in most regions worldwide.The standard treatment procedure for diagnosing and treating non-muscle-invasive bladder cancer(NMIBC)is transurethral resection of bladder tumors(TURBT).Currently,the standard of care for muscle-invasive bladder cancer(MIBC)is neoadjuvant chemotherapy followed by radical cystectomy.Cryoablation therapy is a medical technique that uses extremely low temperatures to destroy diseased tissue.This treatment serves as a therapeutic tool for both benign and malignant diseases in organs such as the kidney,prostate gland,lung,liver,and breast,and is particularly effective for unresectable tumors,offering less trauma,quick recovery,good tolerability,and symptom control.However,cryoablation has its limitations.Over the past few years,cryoablation therapy has emerged as a new method for treating early BC.This treatment is minimally invasive,precise,and offers quick recovery,providing patients with a new treatment option.Although randomized studies are still limited,increasing evidence suggests its potential application in bladder cancer combined with transurethral resection(TURBT)or medication.Cryoablation is not standard therapy for bladder cancer.Treatment decisions should be discussed by a multidisciplinary team of urologists,oncologists,and interventional physicians and require more randomized controlled trials to define patient selection criteria and treatment approaches.

术前全身炎症反应指数对中高危非肌层浸润性膀胱癌预后的影响

目的:探讨术前全身炎症反应指数(systemic inflammatory response index,SIRI)对中高危非肌层浸润性膀胱癌(nonmuscle invasive bladder cancer,NMIBC)预后的影响。方法:回顾性分析2013年1月至2015年7月于天津医科大学肿瘤医院行经尿道膀胱肿瘤电切术(transurethral resection of bladder tumor,TURBT)治疗的103例NMIBC患者的临床资料,根据术后患者有无复发或进展分为复发组和未复发组以及进展组和未进展组。根据组间比较结果,绘制SIRI的受试者工作特征曲线(receiver operating characteristic curve,ROC),求得最优截断值对患者进行分组。通过Kaplan-Meier法和Cox单因素及多因素分析确定影响NMIBC患者预后的危险因素。结果:SIRI值在复发患者和未复发患者间差异无统计学意义(P=0.393);患者的年龄(P=0.016)、性别(P=0.030)、肿瘤数目(P=0.008)、分期(P<0.001)、分级(P<0.001)、是否初发(P=0.002)、单核细胞计数(P=0.042)以及SIRI(P=0.044)差异具有统计学意义;根据ROC曲线确定SIRI鉴定患者术后是否出现进展的最佳临界值,将患者分为低SIRI组和高SIRI组,生存分析对比两组间的无进展生存期(progression-free survival,PFS)差异具有统计学意义(P=0.005)。Cox多因素分析结果显示,肿瘤数目(P=0.041)、是否初发(P=0.041)及SIRI≥0.725(P=0.025)是NMIBC患者TURBT术后PFS的独立预后因素。结论:SIRI是影响中高危NMIBC患者进展的独立危险因素,术前SIRI对预测肿瘤分期有一定的应用价值。

Clinical practice guideline on bladder cancer(Part Ⅲ)

Bladder cancer(BC)has become a significantly prevalent disease in China,with an incidence rate of 5.80 per 100000 in 2015,ranking it as the thirteenth most common type of cancer within the nation.This illness presents a serious public health concern,highlighting the imperative need to unify the standards for diagnosis and treatment to improve patient outcomes.The section of the clinical practice guideline in question is dedicated to addressing muscle-invasive bladder cancer(MIBC)and metastatic BC.The primary treatment strategies for MIBC are well-defined:preoperative(neoadjuvant)chemotherapy combined with radical cystectomy stands as the conventional treatment protocol.For patients with locally advanced MIBC,integrating systemic and local therapies is advocated to enhance treatment effectiveness.In cases of metastatic BC,the focus shifts to systemic treatment supplemented by supportive care measures.The guideline also succinctly presents the pros and cons of various urinary diversion surgeries,which are critical considerations following radical cystectomy.It provides an in-depth exploration of the treatment modalities for metastatic urothelial carcinoma of the bladder.Additionally,this part delves into the integrated approach to treatment and the use of radiotherapy in bladder preservation for localized disease.Moreover,it offers a concise overview of the classification,diagnosis,and therapeutic approaches for nonurothelial carcinoma of the bladder.Lastly,this part emphasizes the importance of recommended posttreatment follow-up for MIBC patients to ensure comprehensive and ongoing care management.

肌层浸润性膀胱癌的新辅助化疗研究进展

肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)是指临床分期为cT2-cT4的膀胱癌。根治性膀胱全切术是肌层浸润性膀胱癌的标准治疗,但是根治术后MIBC患者5年生存率差异巨大。新辅助化疗则可以提高MIBC患者的5年生存率。本文将对新辅助化疗的最佳化疗方案、现状以及研究方向等方面进行综述。

肌层浸润性膀胱癌化疗的临床应用与进展

肌层浸润性膀胱癌(MIBC)的标准治疗手段是根治性膀胱切除术,该手术并发症多,术后肿瘤复发及转移风险高,术前或术后予以辅助化疗能有效地提高患者生存率,降低复发率,同时能增加部分患者保留膀胱的可能性,笔者就肌层浸润性膀胱癌的不同辅助化疗手段研究进展及临床应用情况作一综述。

膀胱癌原位新膀胱术后切口相关并发症预防与干预的研究进展

膀胱癌发病率在我国呈逐年上升趋势,每年新诊断的病例中近三分之一为肌层浸润性膀胱癌(muscle invasive bladder cancer,MIBC),MIBC的标准治疗方案仍是行膀胱根治性切除(radical cystectomy,RC)及盆腔淋巴结清扫术。原位新膀胱术(orthotopic neobladder,ONB)是RC术后尿流改道的主要方式,但术后尿路、肠道以及切口相关并发症较多,本文将就ONB术后切口并发症发生机制以及预防和处理措施进行综述,以期为临床提供帮助。

TURBt术前髂内动脉灌注化疗治疗T2、T3期肌层浸润性膀胱癌的疗效及其对患者术后生活质量的影响

目的探讨经尿道膀胱肿瘤切除术(TURBT)术前髂内动脉灌注化疗治疗T_2、T_3期肌层浸润性膀胱癌的疗效及其对患者术后生活质量的影响。方法选取中南大学湘雅二医院2012年12月至2015年2月收治的肌层浸润性膀胱癌患者共80例,按随机数表法分为对照组和观察组,每组40例。对照组患者单纯行TURBt,观察组患者在TURBt术前1周经双侧髂内动脉注入吉西他滨1 000 mg/m^2和卡铂300 mg/m^2。比较两组患者围手术期临床指标(手术时间、术中出血量、引流管留置时间、住院时间)。随访2年,比较两组患者的复发率,生存率以及不良反应(下泌尿道症候群、骨髓抑制、胃肠道反应),并以中文版SF-36生活质量评分表评估观察组术前、术后的躯体相关生活质量、心理相关生活质量。结果观察组患者的手术时间、术中出血量、导尿管留置时间及住院时间分别为(34.42±7.19)min、(25.76±4.58)mL、(8.21±2.43)d、(14.13±5.73)d,均明显优于对照组的(61.75±3.70)min、(52.32±7.43)mL、(6.94±3.20)d、(16.56±4.83)d,差异均有统计学意义(P<0.05);观察组患者的骨髓抑制发生率为7.50%,明显高于对照组的0,差异有统计学意义(P<0.05),但两组患者在下泌尿道症候群、胃肠道反应及总不良反应发生率方面比较差异均无统计学意义(P>0.05);观察组患者随访6个月、1年和2年时的复发率分别为2.50%、7.50%、15.00%,均明显低于对照组的15.00%、27.50%、32.50%,差异均有统计学意义(P<0.05);观察组患者1年、2年的无复发生存率及平均生存时间分别为92.50%、85.00%、(22.1±1.3)个月,均明显高于对照组的72.50%、67.50%、(18.3±1.6)个月,差异均有统计学意义(P<0.05),但1年、2年的总体生存率及平均生存时间两组比较差异均无统计学意义(P>0.05);观察组患者术后1个月的躯体相关生活质量评分及总分明显高于术前,差异均有统计学意义(P<0.05),而术后1个月心理相关生活质量评分与术前比较差异无统计学意义(P>0.05);观察组患者术后1年的躯体相关生活质量评分、心理相关生活质量评分和总分均明显高于术前及术后1个月,差异均有统计学意义(P<0.05)。结论 TURBt术前髂内动脉化疗栓塞治疗T_2~T_3期肌层浸润性膀胱癌在2年随访期内可降低术后复发率,提高患者躯体和心理相关生活质量,但要注意骨髓抑制的风险。

TURBT术后即刻灌注吡柔比星预防肌层浸润性膀胱癌复发的疗效及安全性观察

目的评估TURBT术后即刻膀胱灌注吡柔比星对预防肌层浸润性膀胱癌复发的疗效及安全性。方法回顾性分析我院于2013年1月至2019年6月收治的64例肌层浸润性膀胱癌病例资料。治疗模式均为TURBT+膀胱灌注。治疗组(n=26)术后24 h内行膀胱灌注,对照组(n=38)术后24~48 h内行膀胱灌注。比较两组1、3、6、12个月复发率,对比肿瘤分期进展和不良反应发生情况。结果治疗组术后1、3、6个月复发率(11.54%,23.08%,38.46%)明显低于对照组(44.74%,63.16%,65.79%),差异有统计学意义(P<0.05);两组术后12个月复发率相似(61.54%vs.60.53%,P>0.05);治疗组发热(38.46%)及膀胱刺激征(42.31%)发生率与对照组(26.32%,23.68%)比较差异无统计学意义(P>0.05);治疗组血尿发生率高于对照组(61.54%vs.26.32%,P<0.05);两组肿瘤分期进展(23.08%vs.31.58%)比较差异无统计学意义(P>0.05)。结论肌层浸润性膀胱癌TURBT术后即刻灌注吡柔比星可显著降低肿瘤早期复发率,提高患者早期获益,不会增加患者肿瘤分期进展风险,值得临床借鉴,但可能增加患者血尿的发生率。

肌层浸润性膀胱癌的精准新辅助化疗进展研究

膀胱癌是泌尿系统最常见的恶性肿瘤,其中肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)占25%~30%。MIBC的标准治疗方式为新辅助化疗(neoadjuvant chemotherapy,NAC)+膀胱癌根治术,而只行根治术的5年生存率低。NAC虽可杀灭微转移癌病灶,使肿瘤降期,提高患者的总生存率,仅化疗后病理降期可使患者生存获益,无效的化疗可能会延误患者治疗,如何精准选择行NAC的患者是临床面临的难题。本文将对MIBC的NAC的应用现状及疗效预测进行综述。

Galectin-9阳性肿瘤相关巨噬细胞在肌层浸润性膀胱癌中的表型、功能及临床治疗意义

目的·分析半乳糖凝集素9阳性肿瘤相关巨噬细胞(galectin-9^(+)tumor-associated macrophages,galectin-9^(+)TAMs)在肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)组织中的表型特征,探究MIBC微环境对galectin-9^(+)TAMs的调控作用,galectin-9^(+)TAMs抑制CD8^(+)T细胞反应的机制及其临床治疗意义。方法·通过流式细胞术检测MIBC与癌旁组织中galectin-9^(+)TAMs的表型特征。利用TCGA (The Cancer Genome Atlas)数据库筛选与LGALS9和LGALS9巨噬细胞基因集显著相关的细胞因子。用人重组细胞因子体外刺激巨噬细胞,分为人重组巨噬细胞集落刺激因子(recombinant human macrophage-stimulating factor,rh M-CSF)刺激组、人重组白介素-16 (recombinant human interleukin-16,rh IL-16)刺激组和人重组干扰素γ (recombinant human interferon-γ,rh IFN-γ)刺激组,并通过流式细胞术检测3组galectin-9表达情况。流式细胞术检测加入rh M-CSF中和性抗体后巨噬细胞表达galectin-9的情况。Anti-galectin-9抗体处理MIBC单细胞悬液后,通过流式细胞术检测TAMs的效应功能变化。分选癌与癌旁组织中galectin-9^(+)TAMs和人外周血CD8^(+)T细胞并进行体外共培养,通过流式细胞术检测CD8^(+)T细胞效应功能变化。采用anti-galectin-9抗体和程序性死亡受体1 (programmed cell death protein 1,PD-1)抗体单独及协同处理体外培养的肿瘤组织,通过流式细胞术检测肿瘤细胞凋亡及CD8^(+)T细胞效应功能变化。结果·Galectin-9^(+)TAMs高表达人类白细胞DR抗原(human leukocyte antigen DR,HLA-DR)、CD86、CD206和细胞程序性死亡-配体1 (programmed cell death-ligand 1,PD-L1),分泌IL-10和转化生长因子-β (transforming growth factor-β,TGF-β)增加,分泌肿瘤坏死因子-α (tumor necrosis factor-α,TNF-α)减少。TCGA数据库筛选结果显示,M-CSF、IL-16和IFN-γ与LGALS9和LGALS9巨噬细胞基因集的相关性最显著。用rh M-CSF、rh IL-16和rh IFN-γ体外刺激巨噬细胞,rh M-CSF刺激组中galectin-9的表达显著升高,加入中和性抗体后表达显著下调。阻断galectin-9后,TAMs表型从高表达抑制性分子向促炎症分子转换,其表面表达PD-L1显著下降。体外共培养galectin-9^(+)TAMs和CD8^(+)T细胞后,galectin-9^(+)TAMs能够抑制CD8^(+)T细胞的效应功能,该作用部分依赖于galectin-9。联合阻断galectin-9和PD-1后,肿瘤细胞凋亡比例、CD8^(+)T细胞的增殖能力和效应分子的分泌与单独阻断PD-1相比,均显著增多或增强。结论·Galectin-9^(+)TAMs具有免疫抑制表型和功能。肿瘤来源M-CSF诱导TAMs高表达galectin-9。Galectin-9^(+)TAMs抑制CD8^(+)T细胞功能从而促进MIBC免疫逃逸。联合阻断galectin-9和PD-1能够更有效地重激活CD8^(+)T细胞功能。

老年肌层浸润性膀胱癌患者行根治性经尿道膀胱肿瘤电切术效果探究

目的:探究老年MIBC患者行TURBt的治疗效果。方法:收集某院收治的79例老年MIBC患者,收集时间为2015年9月～2017年9月,分为试验组(n=39)和对照组(n=40)。对照组采纳开放手术膀胱部分切除术,试验组采纳TURBt术,比较手术情况、并发症。结果:与对照组术中出血量比较,试验组较少,具有统计学差异,P<0.05;与对照组手术时间、尿管留置时间、住院时间比较,试验组较短,具有统计学差异,P<0.05;与对照组并发症发生率比较,试验组较低,具有统计学差异,P<0.05。结论:TURBt术可有效缩短老年MIBC患者的治疗时间,减少并发症,值得推广。

Natural bioactive compounds:a potential therapeutic strategy to sensitize bladder cancer to cisplatin treatment?

Bladder cancer(BC)is the tenth most common cancer,and its incidence is steadily rising worldwide,with the highest rates in developed countries.Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the standard therapy for patients with muscle-invasive bladder cancer.However,less than 50%of patients initially respond to this treatment and nearly all of them eventually develop resistance,which is an important barrier to long-term survival.Therefore,there is an urgent need to understand the mechanisms of cisplatin resistance in BC and develop ways to counteract them.Several preclinical studies have demonstrated that naturally derived bioactive compounds,such as phytochemicals and flavonoids,can enhance the antitumor activity of cisplatin,with minimal side effects,by targeting different pathways involved in cisplatin sensitivity and resistance.However,their poor bioavailability has been one of the main problems for their successful introduction into clinical practice.At present,however,many new formulations with greatly increased bioavailability are under study in several clinical trials with encouraging results.

Adjuvant chemotherapy after radical cystectomy:Do all patients who need chemotherapy after surgery actually receive it?

Background:Compliance with the guideline recommendations for neoadjuvant chemotherapyin patients with muscle-invasive bladder cancer is incomplete.The adjuvant chemotherapy approach has the advantage of pathology-based decision-making,allowing for patient selection.In addition,radical surgery is not delayed and treatment-related toxicity does not impair surgical fitness.The proportion of patients who completed chemotherapy after cystectomy among those who were fit and in need of treatment were evaluated.The reasons for not completing adjuvant chemotherapy were determined.Materials and methods:We retrospectively evaluated all patients who had undergone radical cystectomy at our center over thelast 7 years.Indications for adjuvant chemotherapy included pathological T>2,any node+,or surgical margin involvement.Only patients who were fit for chemotherapy before surgery were included in the study.Results:Of the 52 patients with muscle-invasive bladder cancer,14 received neoadjuvant chemotherapy or unfit for chemotherapy were excluded.Of the remaining 38 patients,14(37%)had bladder-confined cancers and did not require additional chemotherapy.Of the 24 patients who needed chemotherapy and were fit to receive it,8 patients completed treatment(33%),and 3 discontinued treatment due to toxicity.Twelve patients(50%)declined chemotherapy,whereas 1 patient became unfit for chemotherapy after surgery.Conclusions:While the adjuvant chemotherapy approach could save unnecessary treatment in 37%of patients,two-thirds of those who needed chemotherapy did not complete it.Patient refusal was the primary reason for not receiving treatment.

碳离子放射治疗肌层浸润性膀胱癌Ⅰ/Ⅱ期临床研究的初步疗效观察

目的评估Ⅰ/Ⅱ期临床研究中碳离子放疗(CIRT)治疗肌层浸润性膀胱癌的可行性和安全性。方法研究对象为2020年3月至2022年1月就诊甘肃省武威肿瘤医院的9例肌层浸润性膀胱癌患者(不伴远处转移),临床分期为T2~3。治疗包括3分次,由12 Gy增加到24 Gy的局部照射和11分次44 Gy的全膀胱照射。碳离子照射剂量均为相对生物学有效性(RBE)为3.0时的剂量。膀胱肿瘤总剂量为56~68 Gy,分14次。主要观察终点包括肿瘤的治疗相关不良反应和剂量限制毒性(DLT)、局部控制率(LC)。次要终点为无进展生存期(PFS)。结果9例患者完成了试验研究中各剂量段CIRT,剂量递增至68 Gy。未发生DLT和≥3级的急性放疗不良反应和生存期内的晚期放疗不良反应。肿瘤剂量达到68 Gy时,出现2例2级急性泌尿生殖道反应,1例急性下消化道症状;62 Gy以上剂量组观察到3例1级晚期放射性膀胱反应,表现为尿频和镜下血尿。所有病例治疗结束时血尿均消失,排尿不畅缓解,尿红细胞值显著下降。治疗后3个月、6个月局部控制率分别为100%和88.9%,客观缓解率均为88.9%。1例患者在治疗后6个月出现局部复发,采用挽救性手术治疗。结论碳离子放射治疗肌层浸润性膀胱癌初步疗效观察,未见剂量限制性毒性,安全可行,近期疗效显著,症状缓解明显,患者耐受性好。