肌层浸润性膀胱癌新辅助化疗研究进展

膀胱癌是泌尿系统常见恶性肿瘤之一,初诊时约1/3为肌层浸润性,其治疗以根治性膀胱切除术为主,但术后存在较高的肿瘤复发与转移风险。新辅助化疗在一定程度上提高患者生存率,降低复发率,并增加保留膀胱功能的可能性,但目前仍存在争议。本文从新辅助化疗的临床应用价值与依据、化疗方案的选择以及在保留膀胱治疗中的应用等方面阐述肌层浸润性膀胱癌新辅助化疗研究的新进展。     

新辅助动脉化疗在肌层浸润性大体积膀胱癌保留膀胱治疗中的价值

目的评估术前新辅助动脉化疗联合经尿道手术在直径超过3cm的肌层浸润性膀胱癌保留膀胱治疗的临床价值。方法对于较大体积(直径3cm)的28例肌层浸润性膀胱肿瘤(T2N0M0~T4aN0M0)采用新辅助动脉化疗联合手术治疗,观察动脉化疗效果,分析肿瘤降期率、保留膀胱率、肿瘤复发率,Kaplan-Meier法计算总体生存率、无肿瘤复发生存率,并绘制生存曲线。结果 26例(92.9%)患者动脉化疗有效,肿瘤可见明显缩小,经3~5次动脉介入治疗后行经尿道切除术+膀胱灌注完成保留膀胱治疗;动脉化疗无效2例,立即行根治性全膀胱切除术。26例完成保留膀胱治疗的患者,术后肿瘤病理分期降低19例(73.1%),无变化为7例。肿瘤复发8例(复发率为30.8%),其中,浅表性复发5例,局部浸润性复发2例,远处转移1例。28例患者总体生存率:3年69%,5年62.1%。无肿瘤复发生存率:5年44.07%。最终25例患者得到保留膀胱(保留膀胱率89.3%)。结论直径3cm的较大体积浸润性膀胱肿瘤采用术前新辅助动脉化疗治疗,可使肿瘤降期降级及体积缩小,有利于经尿道完全切除,可有效提高患者生存率,同时保留了膀胱,大大提高患者生存质量,对不愿或不宜行膀胱全切的患者是一个理想的选择。     

膀胱癌新辅助化疗研究进展

根治性膀胱切除加盆腔区域淋巴结清扫是治疗浸润性膀胱癌的标准术式,但对于非器官局限性膀胱癌,局部复发与远处转移的风险较高。对这部分患者进行以顺铂为基础的新辅助化疗,可以降低复发率,改善手术疗效,提高生存率。对新辅助化疗敏感的患者,可以考虑保留膀胱的保守治疗。     

肌层浸润性膀胱癌新辅助化疗敏感性标志物的研究现状

膀胱癌是我国男性十大恶性肿瘤之一,其中20%~30%的患者初诊时即诊断为肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)。既往,根治性膀胱切除术(radical cystectomy,RC)是MIBC的一线治疗方案。现有多项研究结果表明,对于MIBC患者选择新辅助化疗联合RC,相比于仅行RC,可提高肿瘤完全反应率并延长患者总生存期,已成为治疗MIBC的1类推荐标准方案,而且有保留膀胱的可能性。多项研究结果表明,以顺铂为基础的新辅助化疗在MIBC患者中的应用越来越普遍,但仍存在化疗无效或肿瘤进展的可能,因此探讨术前新辅助化疗敏感性一直是泌尿肿瘤研究的热点,本文就膀胱尿路上皮癌新辅助化疗的敏感性问题作一综述,以期对临床工作起到指导和帮助作用。     

吉西他滨联合顺铂新辅助化疗治疗肌层浸润性膀胱癌的疗效分析

目的:探讨肌层浸润性膀胱癌接受吉西他滨联合顺铂(GC)新辅助化疗的临床效果。方法:回顾性分析2010年12月—2020年6月首都医科大学附属北京友谊医院收治的55例肌层浸润性膀胱癌新辅助化疗患者的临床资料,接受GC方案新辅助化疗后,行膀胱根治性切除+盆腔淋巴结清扫术。分析化疗前后病理缓解、预后和毒副作用情况。计数资料组...     

膀胱癌动脉介入化疗38例分析

目的　探讨浸润性膀胱癌的微创治疗方法。　方法　 1991年 1月～ 2 0 0 1年 2月应用髂内动脉灌注化疗治疗浸润性膀胱癌 38例 ,其中 2 4例行化疗泵植入术。　结果　完全缓解率 (CR) 17.1% ( 6 /35 ) ,部分缓解率 (PR) 77 1% ( 2 7/35 ) ,总有效率 94 3% ( 33/35 )。　结论　动脉介入化疗可以作为不能手术切除的浸润性膀胱癌的治疗或作为术前辅助治疗。     

经尿道手术联合化疗治疗肌层浸润性膀胱癌的应用进展

肌层浸润性膀胱癌（MIBC）的标准治疗方式是膀胱根治性切除术（RC）联合盆腔淋巴结清扫术,但因其存在手术风险大、部分患者需尿流改道等因素,导致部分患者不能或不愿实施该手术。经尿道手术联合化疗、放疗等治疗方式可以使部分MIBC患者保留膀胱,其中化疗是应用最为广泛的辅助治疗方式。化疗包括术前新辅助化疗（NAC）、术后辅助化疗、髂内动脉化疗及膀胱灌注化疗,每种化疗方式实施时间及特点有所不同。本文就目前经尿道手术联合化疗治疗肌层浸润性膀胱癌的应用进展作一综述。     

肌层浸润性膀胱癌新辅助与辅助免疫治疗的现状与展望

<正>根治性膀胱切除术(radical cystectomy,RC)是肌层浸润性膀胱癌(muscle-invasive bladde cancer,MIBC)的主要治疗方式,国内外指南推荐为T_2～4aN₀M₀期及高危非肌层浸润性膀胱癌患者提供RC^[1]。但MIBC患者接受RC后,仍有50%的患者出现术后复发^[1],从新辅助和辅助治疗的层面减少复发,提高患者生存率和生活质量就显得尤其重要。新辅助和辅助化疗的研究已从二十世纪八十年代开展,推荐c T_2～4aN₀M₀期MIBC患者采用以顺铂为基础的新辅助化疗,未行新辅助化疗的p T₃～p T₄或淋巴结转移的患者建议术后辅助化疗^[1]。     

肌层浸润性膀胱癌新辅助化疗的临床应用及进展

肌层浸润性膀胱癌（MIBC）恶性程度高,易多发、复发和转移,手术治疗能提高患者的总生存率,但术后大部分患者将出现远处转移。新辅助化疗对肌层浸润性膀胱癌患者微转移灶的控制和生存率的改善等作用,推动其逐步成为肌层浸润性膀胱癌的标准治疗方式,其临床利用率也逐步提高,但还存在一些有待解决的问题,本文将对肌层浸润性膀胱癌的新辅助化疗的临床应用及进展作一综述。     

肌层浸润性膀胱癌新辅助化疗的研究进展

膀胱癌为泌尿系统最常见的恶性肿瘤之一,其中90％病理类型为膀胱尿路上皮癌,全世界每年新发病例约30多万人,约1/3的患者初次诊断时即为肌层浸润性膀胱癌.随着根治性膀胱切除手术技术不断提高,总体预后有一定程度的改善,但5年生存率仍不到50％.新辅助化疗已成为国际上治疗肌层浸润性膀胱癌的热点,能有效减少膀胱癌术后复发与进展风险.目前,吉西他滨联合顺铂方案(Gemcitabine+ Cisplatin,GC)已逐渐成为临床新辅助化疗标准.现主要综述肌层浸润性膀胱癌新辅助化疗的研究进展.     

Outcome of Patients Who Refuse Cystectomy after Receiving Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer

Objectives

To determine the outcome of patients who refuse cystectomy after receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer.

Methods

Between 1995 and 2001, 63 patients were evaluated who declined to undergo a planned cystectomy, because they achieved a complete clinical response to neoadjuvant cisplatin-based chemotherapy. Patient, tumor, and treatment features were assessed prospectively, and correlated in univariate and multivariate analyses with overall survival. The median follow-up was 86 mo and all patients were followed for more than 5 yr.

Results

Forty patients (64%) survived, with 54% of them having an intact functioning bladder. The number and size of invasive tumors were strongly associated with overall survival. The most significant treatment variable predicting better survival was complete resection of the invasive tumor on re-staging transurethral resection before starting chemotherapy. Of 23 patients (36%) who subsequently died of disease, 19 (30%) relapsed with invasive cancer in the bladder. Over 90% of surviving patients had solitary, small, and low-stage invasive tumors completely resected, and 83% survived without relapses in the bladder.

Conclusions

Selected patients with muscle-invasive bladder cancers may survive after transurethral resection and neoadjuvant chemotherapy, and tumor features can identify which patients responding completely to chemotherapy may survive without cystectomy.     

Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

Background: Standard of care for patients with muscle-invasive bladder cancer (MIBC) includes neoadjuvant cisplatin-based chemotherapy (NAC) followed by consolidative therapy with either chemoradiation or radical cystectomy (RC). Some patients experience robust pathologic responses to NAC, and these have been reported to associate with somatic mutations in specific gene pathways including DNA damage response genes.Objective: To evaluate the ability of post-NAC clinical restaging, with or without tumor sequencing, to predict final RC pathologic staging.Design, setting, and participants: We reviewed our institutional review board–approved institutional database to identify patients with MIBC who underwent NAC followed by RC from 2003 to 2016. Following NAC prior to RC, cystoscopy was performed routinely, with resection of residual visible tumor and/or tumor base (transurethral resection [TUR]). For patients with pre-NAC tumor tissue available, tumor sequencing was performed.Outcome measurements and statistical analysis: Clinical restaging and tumor sequencing were evaluated for their ability to predict the final pathologic stage accurately at RC using chi-square or Fisher’s exact test.Results and limitations: A total of 114 patients underwent restaging TUR following NAC and prior to RC. The diagnostic accuracy of post-NAC clinical restaging including TUR was poor, with 32% of patients being downstaged falsely when compared with their final RC pathology. Forty-nine patients had sequencing of pre-NAC tumor tissue, of whom 32 showed at least one mutation of interest. However, NAC responses and rates of false downstaging did not differ significantly according to tumor mutation status.Conclusions: This study highlights the inaccuracy of post-NAC clinical restaging TUR with or without adjunctive tumor mutation analysis, to assess pathologic residual disease accurately. Caution must be taken when performing post-NAC restaging, especially when considering conservative management strategies such as active surveillance on this basis.Patient summary: Several groups are evaluating whether certain patients, whose bladder cancer responds well to upfront chemotherapy, may be able to forego cystectomy safely. We demonstrate that currently available staging tools and tumor DNA sequencing cannot identify such patients reliably and accurately.     

Genomic Differences Between “Primary” and “Secondary” Muscle-invasive Bladder Cancer as a Basis for Disparate Outcomes to Cisplatin-based Neoadjuvant Chemotherapy

Background

Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). It is unknown whether this treatment strategy is appropriate for patients who progress to MIBC after treatment for prior noninvasive disease (secondary MIBC).

Correlation of Pathologic Complete Response with Survival After Neoadjuvant Chemotherapy in Bladder Cancer Treated with Cystectomy: A Meta-analysis

ContextNeoadjuvant chemotherapy before radical cystectomy (RC) is the preferred initial option for muscle-invasive bladder cancer (BCa). As in rectal and breast cancer, pathologic downstaging is associated with increased overall survival (OS).ObjectiveWe conducted a meta-analysis to determine whether pathologic complete response (pCR) (pT0N0M0) after neoadjuvant chemotherapy is associated with a better outcome in muscle-invasive BCa.Evidence acquisitionA systematic search was conducted in PubMed, Web of Science, Cochrane Collaboration's Central register of controlled trials, and Embase for publications reporting outcomes of patients with and without pCR. All patients underwent neoadjuvant cisplatin-based polychemotherapy and RC. The primary outcome reported as relative risk (RR) was OS. Secondary end points were recurrence-free survival (RFS) and cancer-specific survival other than distant and locoregional RFS. A meta-analysis was performed using the fixed effects model or random effects model. Overall heterogeneity for RFS and OS was assessed with forest plots and the Q test.Evidence synthesisA total of 13 trials were included, for a total of 886 patients analysed after neoadjuvant chemotherapy and RC, without any postoperative treatment. The pCR rate was 28.6%. Patients who achieved pCR in the primary tumour and the lymph nodes presented an RR for OS of 0.45 (95% confidence interval [CI], 0.36–0.56; p < 0.00001). The number needed to treat to prevent 1 death was 3.7 (absolute risk difference: −26%). The summary RR for RFS was 0.19 (95% CI, 0.09–0.39; p < 0.00001).ConclusionsPatients with BCa who achieved pCR (pT0N0M0 stage) after neoadjuvant chemotherapy have a better OS and RFS than do patients without pCR.     

多学科协作诊治模式下结直肠癌不同周期新辅助化疗联合手术的方案研究

目的 通过在多学科协作诊治模式下运用不同周期的结直肠癌新辅助化疗联合手术的多种方案,探讨适合于我国结直肠癌患者的有效治疗方案.方法 回顾性研究了2006年10月至2007年4月期间四川大学华西医院普外三科收治的结直肠癌患者,并根据新辅助化疗的周期数将资料分为单周期组、双周期组和三周期组,比较3组在运用不同周期新辅助化疗和手术的联合方案下治疗时间、新辅助化疗效果、手术结果 等指标之间的差异.结果 从新辅助化疗完成到手术时间3组[单周期组(5.64±2.00)d,双周期组(5.80±3.74)d,三周期组(6.22±2.76)d]间差异无统计学意义(P＞0.05).从治疗效果上看,3组内新辅助化疗后较化疗前的CEA值均有下降(P<01)；双周期组和三周期组患者的便血、肛门坠胀/刺激感、大便不畅感等主观感受指标比单周期组明显改善(P＜0.01).在评估肿瘤病灶缓解情况中,双周期组和三周期组中出现CR和PR的构成比较单周期组更多,肿瘤缓解率(CR+PR)更高(P＜0.01).而新辅助化疗的治疗不良反应中,新辅助化疗后较化疗前的WBC值在双周期组和三周期组内均明显下降(P＜0.01),新辅助化疗前后WBC差值,在单周期组[(0.16±0.20)×109/L]分别比双周期组[(2.41±2.16)×109/L]和三周期组[(2.63±1.48)×109/L]下降更少(P＜0.01).三周期组的恶心和呕吐反应明显多于单周期组(P＜0.01)和双周期组(P＜0.01)；但是腹胀和腹泻反应在3组之间差异无统计学意义(P＞0.05).采用不同的新辅助化疗周期患者对方案接受程度的调查发现,单周期组和双周期组对于方案的接受程度均为100％,并表示有信心进行辅助化疗；而三周期组的方案接受率为66.7％(12/18).所有患者均顺利完成手术,手术后肛门排气时间单周期组与双周期组间差异有统计学意义(P＜0.05)；术后进食时间,三周期组与单周期组、三周期组与双周期组的患者之间的差异均有统计学意义(P＜O.05).而3组在伤口愈合时间上差异无统计学意义(P＞0.05).结论 综合分析新辅助化疗周期与手术安排之间的时间、治疗效果和手术结果 ,选择双周期短时间的新辅助治疗方案对我国西部地区患者可能是一套具有可行性和安全性的结直肠癌多学科治疗方案.     

Outcomes in Patients with Muscle-invasive Bladder Cancer Treated with Neoadjuvant Chemotherapy Followed by (Chemo)radiotherapy in the BC2001 Trial

BackgroundBC2001 demonstrated improved local control with the addition of chemotherapy to radiotherapy in 360 patients with muscle-invasive bladder cancer.ObjectiveTo establish whether such benefit remained in BC2001 patients who received prior neoadjuvant chemotherapy.Design, setting, and participantsA total of 117 patients (33%) received neoadjuvant chemotherapy and were randomised to radiotherapy with (48%) or without (52%) concomitant chemotherapy. Patients were recruited between August 2001 and April 2008 from 28 UK centres.InterventionPlatinum-based neoadjuvant chemotherapy, followed by radiotherapy with (cRT) or without (RT) synchronous 5-fluorouracil and mitomycin-C.Outcome measurements and statistical analysisToxicity, locoregional control (LRC), overall survival (OS), and quality of life (QoL) were measured.Results and limitationsOf the patients, 74% received gemcitabine plus cisplatin or carboplatin. Compliance rates with full-dose radiotherapy were cRT 93% and RT 92%. An excess of grade ≥3 toxicities while on (chemo)radiation occurred for cRT 33% versus RT 22%, although nonstatistically significant (p = 0.16). With 110 mo median follow-up for survival (interquartile range 96–123), cRT showed improved LRC though not statistically significant (adjusted hazard ratio [aHR] = 0.64, 95% confidence interval [CI] 0.33–1.23, p = 0.18). No differences in OS (aHR = 0.95, 95% CI 0.57–1.57, p = 0.8) were observed. No significant detriment in QoL was observed between cRT and RT in this subgroup of patients.ConclusionsNeoadjuvant chemotherapy does not compromise the delivery of radical curative treatment. Although underpowered due to a small sample size, the benefit of chemoradiotherapy to improve local control in this group of patients receiving neoadjuvant chemotherapy is consistent with that observed in the main trial. Although a nonsignificant excess of toxicity was observed, there was no evidence of impaired QoL.Patient summaryChemotherapy before radical chemo(radiotherapy) is feasible and well tolerated.     

乳腺癌新辅助化疗的研究进展

目的探讨乳腺癌新辅助化疗的研究进展。方法从乳腺癌新辅助化疗的理论基础、临床意义、适用范围、常用药物及方案、疗效预测因子及其与保乳手术、前哨淋巴结活检的关系等方面总结乳腺癌新辅助化疗的研究进展。结果新辅助化疗可降低临床分期,增加保乳手术机会,了解化疗药物敏感性,防止远处转移,但对前哨淋巴结活检的影响存在争议。结论新辅助化疗是乳腺癌全身治疗重要的部分,但在如何选择高效的化疗药物、制订个体化方案、预测治疗效果等方面仍需进一步研究。     

Neoadjuvant Chemotherapy for Invasive Bladder Cancer

Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.     

晚期乳腺癌新辅助化疗的临床报告

目的　探讨新辅助化疗在晚期乳腺癌治疗中的远期临床效果。方法　对 31例Ⅲ、Ⅳ期的乳腺癌患者行新辅助化疗 ,手术前行 2周期的CAF方案化疗〔CTX 5 0 0mg/m2 静脉推注 (第 1、8天 ) ,5 FU 5 0 0mg/m2 静脉推注 (第 1、8天 ) ,ADM 30mg/m2 静脉推注 (第 1天 ) ,每 2 1天为 1周期〕 ,并与同期未行任何术前治疗的可手术的30例Ⅲa期患者作对比分析。结果　新辅助化疗组的总有效率为 87.1% (2 7/31) ,有 6 1.3% (19/31)的患者分期降低 ,其中 6例降为Ⅲa期 ,8例降为Ⅱb期 ,4例降为Ⅱa期 ,1例降为 0期 ,临床完全缓解 1例 ,无病理完全缓解。新辅助化疗组的无病生存期为 5 6 .3个月 ,明显高于未行化疗组的 4 3.5个月 (P<0 .0 5 ) ,新辅助化疗组的 5年无病生存率为 38.7% ,略高于未化疗组的 33.3% ,两组间差异无显著性意义。结论　新辅助化疗能降低晚期乳腺癌患者的分期 ,为手术创造最佳机会 ,能明显延长晚期乳腺癌患者的无病生存期 ,减少或延缓肿瘤的复发、转移。