Efficient delivery of radical cystectomy after neoadjuvant chemotherapy for muscle-invasive bladder cancer: a multidisciplinary approach

BACKGROUND:

Cystectomy delay >90 days after a diagnosis of muscle‐invasive bladder cancer (MIBC) adversely affects pathologic stage and survival outcomes in patients who undergo primary surgery. After neoadjuvant chemotherapy (NAC), the impact of the timing of cystectomy delivery on these outcomes is uncertain. Poor communication between urologic and medical oncologists can result in cystectomy delay after systemic treatment. The authors of this report hypothesized that a delay in cystectomy delivery after NAC is associated with adverse survival outcomes.

METHODS:

An eligible cohort of 153 patients with MIBC received NAC and underwent radical cystectomy between 1990 and 2007. At the authors' institution, the genitourinary team strives to schedule patients for surgery at the time of initial evaluation or after their first chemotherapy cycle. Clinicopathologic characteristics, including timing of cystectomy, chemotherapy delivery, vital status, and reasons for excessive surgical delay, were analyzed retrospectively using an institutional database. A Cox proportional regression model was used to test the association between the timing of cystectomy delivery and survival.

RESULTS:

The median follow‐up for all patients was 3.6 years. The median time to cystectomy was 16.6 weeks and 6.9 weeks from the first and last day of NAC, respectively. In multivariate analyses, the timing of cystectomy delivery from the termination of NAC did not significantly alter the risk of survival. The most common reason for cystectomy delivery beyond 10 weeks (28 patients; 18%) was procedural scheduling.

CONCLUSIONS:

Cystectomy delivery within 10 weeks after NAC did not compromise patient survival and, thus, provided a reasonable window for patient recovery and surgical intervention. Cancer 2012;. © 2011 American Cancer Society.     

Urinary diversion and morbidity after radical cystectomy for bladder cancer

BACKGROUND:

The rate of continent urinary diversion after radical cystectomy for bladder cancer varies by patient and provider characteristics. Demonstration of equivalent complication rates, independent of diversion type, may decrease provider reluctance to perform continent reconstructions. The authors sought to determine whether continent reconstructions confer increased complication rates after radical cystectomy.

METHODS:

From the Nationwide Inpatient Sample, the authors used International Classification of Disease (ICD‐9) codes to identify subjects who underwent radical cystectomy for bladder cancer during 2001‐2005. They determined acute postoperative medical and surgical complications from ICD‐9 codes and compared complication rates by reconstruction type using the nearest neighbor propensity score matching method and multivariate logistic regression models.

RESULTS:

Adjusting for case‐mix differences between reconstructive groups, continent diversions conferred a lower risk of medical, surgical, and disposition‐related complications that was statistically significant for bowel (3.1% lower risk; 95% confidence interval [95% CI], ?6.8% to ?0.1%), urinary (1.2% lower risk; 95% CI, ?2.3%, to ?0.4%), and other surgical complications (3.0% lower risk; 95% CI, ?6.2% to ?0.4%), and discharge other than home (8.2% lower risk; 95% CI, ?12.1% to ?4.6%) compared with ileal conduit subjects. Older age and certain comorbid conditions, including congestive heart failure and preoperative weight loss, were associated with significantly increased odds of postoperative medical and surgical complications in all subjects.

CONCLUSIONS:

Mode of urinary diversion after radical cystectomy for bladder cancer is not associated with increased risk of immediate postoperative complications. These results may encourage broader consideration of continent urinary diversion without concern for increased complication rates. Cancer 2010. © 2010 American Cancer Society.     

Current status of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer

Muscle-invasive transitional cell carcinoma occurs in approximately 30% of patients and is associated with a high risk of distant metastasis. Radical local therapy in the form of cystectomy or radiotherapy is curative in a portion of patients. Systemic therapy to treat occult micrometastasis at the time of local control is necessary to improve outcomes. Neoadjuvant chemotherapy is associated with a 5–6% improvement in overall survival at 5 years, and adjuvant chemotherapy may achieve similar results, although this remains unproven. Operative complications are not increased with neoadjuvant therapy. Perioperative treatment strategies remain underutilized, and many patients are not offered treatment to reduce the risk of relapse. Neoadjuvant strategies are a potent tool for research and should be employed to test new agents for the treatment of transitional cell carcinoma.     

Neoadjuvant and adjuvant chemotherapy in bladder cancer

State of the art treatment for invasive bladder cancer is cystectomy. Intensive clinical investigation has been performed in the last years about the role of neoadjuvant and adjuvant chemotherapy. Although neoadjuvant treatment seems not to increase long-term survival, it seems to play a role in the possibility of bladder preservation strategies. Adjuvant chemotherapy, in high-risk patients, seems to improve disease-free survival and time to progression. Nevertheless, new prospective studies should be performed to clarify its role in improving survival.      

Superior efficacy of neoadjuvant chemotherapy and radical cystectomy in cT3-4aN0M0 compared to cT2N0M0 bladder cancer

In this study, we compared complete pathological downstaging (pCD, ≤(y)pT1N0) and overall survival (OS) in patients with cT2 versus cT3–4aN0M0 UC of the bladder undergoing radical cystectomy (RC) with or without neoadjuvant chemo- (NAC) or radiotherapy (NAR). A population-based sample of 5,517 patients, who underwent upfront RC versus NAC + RC or NAR + RC for cT2-4aN0M0 UC between 1995–2013, was identified from the Netherlands Cancer Registry. Data were retrieved from individual patient files and pathology reports. pCD-rates were compared using Chi-square tests and OS was estimated by Kaplan–Meier analyses. Multivariable analyses were conducted to determine odds (OR) and hazard ratios (HR) for pCD-status and OS, respectively. We included 4,504 (82%) patients with cT2 and 1,013 (18%) with cT3–4a UC. Median follow-up was 9.2 years. In cT2 UC, pCD-rate was 25% after upfront RC versus 43% (p < 0.001) and 33% (p = 0.130) after NAC + RC and NAR + RC, respectively. In cT3–4a UC, pCD-rate was 8% after upfront RC versus 37% (p < 0.001) and 16% (p = 0.281) after NAC + RC and NAR + RC, respectively. In cT2 UC, 5-year OS was 57% and 51% for NAC + RC and upfront RC, respectively (p = 0.135), whereas in cT3–4a UC, 5-year OS was 55% for NAC + RC versus 36% for upfront RC (p < 0.001). In multivariable analysis for OS, NAC was beneficial in cT3–4a UC (HR: 0.67, 95%CI 0.51–0.89) but not in cT2 UC (HR: 0.91, 95%CI 0.72–1.15). NAR did not influence OS. In conclusion, NAC + RC was associated with superior pCD compared to RC alone and NAR + RC. Superior OS for NAC + RC compared to RC alone was especially evident in cT3–4a disease.     

Radical cystectomy for bladder cancer:oncologic outcome in 271 Chinese patients

Few large scale studies have reported the oncologic outcome of radical cystectomy for treating bladder cancer in China; hence, we lack long-term prognostic information. The aim of the current study was to determine the survival rate and prognostic factors of patients who underwent radical cystectomy for bladder cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic data from 271 bladder cancer patients who underwent radical cystectomy between 2000 and 2011. Univariate and multivariate analyses were conducted to identify independent prognostic predictors for this cohort. Median follow-up was 31.7 months(range, 0.2–139.1 months). Thirty-day mortality was(1.4%). The 5-year recurrence-free survival, cancer-specific survival(CSS), and overall survival rates were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS rates of patients with T1–T4 disease were 90.7%, 85.0%, 51.0%, and 18.0%, respectively. Patients with organ-confined disease had a higher 5-year CSS rate than those with extravesical disease(81.4% vs. 34.9%, P 0.001). For the 38 patients(14%) with lymph node involvement, the 5-year CSS rate was 27.7%—significantly lower than that of patients without lymph node metastasis(P 0.001). The 5-year CSS rate was much higher in patients with low grade tumor than in those with high grade tumor(98.1% vs. 68.1%, P 0.001). Multivariate Cox regression showed that patient age(hazard ratio, 2.045; P = 0.013) and T category(hazard ratio, 2.213; P 0.001) were independent predictors for CSS. These results suggest that radical cystectomy is a safe and effective method for treating bladder cancer in Chinese patients. Old age and high T category were associated with poor prognosis in bladder cancer patients who underwent radical cystectomy.     

A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy improves survival in muscle-invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has similar efficacy and less toxicity than MVAC in metastatic disease, but is untested as neoadjuvant treatment. METHODS: The authors retrospectively evaluated patients with muscle-invasive urothelial carcinoma who received neoadjuvant GC before radical cystectomy between November 2000 and December 2006 at Memorial Sloan-Kettering Cancer Center. Post-therapy pathological downstaging to either residual disease at cystectomy (pT0) or no residual muscle-invasion (相似文献   

保留膀胱的综合治疗与根治性手术治疗肌层浸润性膀胱癌预后的荟萃分析

目的 比较保留膀胱手术+术后化疗与根治性手术治疗肌层浸润性膀胱癌的预后.方法 检索保留膀胱手术+术后化疗与根治性手术治疗肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)的对照研究,比较两种治疗方案的术后5年生存率,计算合并优势比(OR)和95%CI.结果 共纳入7项研究,累积876例患者.1组研究的OR=1.03,95%CI为1.03(0.52~2.02),4组研究的OR及其95%CI﹤1,2组研究的OR及其95%CI﹥1;7个研究的总OR=1.05,95%CI为1.05(0.53~2.06),跨过"无差异线",故认为根治性膀胱全切术(radical cystectomy,RC)与保留膀胱的综合治疗预后差异无统计学意义(Z=0.13,P=0.89).结论 对于部分肌层浸润性膀胱癌患者,保留膀胱的综合治疗不会降低患者的5年生存率,且能保留患者膀胱的正常功能,提高了患者的生存质量,但适应证需严格把握.     

Combining surgery and chemotherapy for invasive bladder cancer: current and future directions

More than 13,000 patients died from invasive bladder cancer in 2005 alone. Radical cystectomy is the most commonly prescribed treatment for patients with muscle-invasive bladder cancer, or for those with a nonmuscle-invasive disease that is refractory to intravesical therapy. Despite advances in surgical technique and improved understanding of the role of pelvic lymphadenectomy, 5-year survival probabilities suggest that improvements in treatment are necessary. The maturation of several randomized clinical trials on perioperative chemotherapy, and particularly neoadjuvant chemotherapy, clearly suggest that an integrated treatment program of systemic chemotherapy and definitive locoregional therapy may improve the outcome for bladder cancer patients. The next frontier is the molecular characterization of this spectrum of diseases that make up invasive bladder cancer and targeted therapeutics. Prospective validation of molecular markers and evaluation of novel therapeutic agents, alone or in combination with established cytotoxic agents, provide hope of better outcomes for bladder cancer patients.     

Treatment of muscle-invasive bladder cancer: progress and new challenges

The management of muscle-invasive bladder cancer has evolved over the last 20 years. Radical surgery, while curative for a significant number of patients, is inadequate for a subgroup with aggressive features including, but not limited to, advanced local stage, lymphovascular invasion on transurethral resection specimen, or variant histology such as small cell carcinoma. It is now clear that chemotherapy can improve the outcome for such patients. Combination platinum-based neoadjuvant chemotherapy is associated with a survival advantage of 5–8% at 5 years over local therapy alone. Improvements in surgical technique are also important and need to be further refined. Biologic-based staging and targeted therapies hold promise for the future. The critical issue in multimodal therapy for this very heterogeneous disease is individualized patient selection. In this review, data are presented with emphasis on the practical application of current knowledge to the management of patients with muscle-invasive bladder cancer.     

Lymphatic invasion is a prognostic factor for bladder cancer treated with radical cystectomy

Background We aimed to elucidate the significance of pathological prognostic factors in patients with bladder cancer treated with radical cystectomy and pelvic lymphadenectomy focusing on the association between lymphatic invasion and disease recurrence. Methods Ninety-one patients with ladder cancer who had undergone radical cystectomy were examined retrospectively. Clinicopathological findings and clinical outcomes were analyzed. Patients who received palliative cystectomy or neoadjuvant chemotherapy and patients who did not receive lymphadenectomy owing to a poor general condition or far advanced local disease status were excluded. Results Lymphatic invasion and lymph node involvement were present in 45.1% and 23.1% of patients, respectively. Multivariate analyses, using the Cox proportional hazards model, indicated that lymphatic invasion (hazard ratio [HR], 5.30; P = 0.007) and lymph node involvement (HR = 3.05; P = 0.016) were independent prognostic factors for disease-specific survival. Of the 91 patients, 29 (31.9%) had recurrent disease during the follow-up period. The rate of recurrence in patients with lymphatic invasion and without lymph node involvement was 50% (11/22), which was not significantly different from that in patients with both lymphatic invasion and lymph node involvement (73.7%; 14/19; P = 0.121), indicating a high risk of disease recurrence in patients with bladder cancer with lymphatic invasion even in the absence of the lymph node involvement. Conclusion In patients with bladder cancer treated with radical cystectomy, lymphatic invasion is an independent prognostic factor for disease-specific and disease-free survival. Patients with lymphatic invasion have a high risk of disease recurrence after radical cystectomy even in the absence of lymph node involvement.     

膀胱癌膀胱全切除术后早期并发症的相关影响因素研究

目的探讨膀胱癌膀胱全切除术后早期并发症发生的相关因素。方法收集200例膀胱癌患者的手术资料和术后3个月的随访资料,包括手术时间、术中出血量、术中输血量、术后住院时间等。根据改良的Clavien分级系统对膀胱癌患者术后早期并发症进行分级。分析膀胱癌患者术后早期并发症发生的影响因素。结果200例膀胱癌患者中,124例患者术后出现早期并发症。有并发症膀胱癌患者和无并发症膀胱癌患者的年龄、糖尿病史、美国麻醉医师协会(ASA)分级、入院症状、尿流改道方式、术后住院时间比较,差异均有统计学意义(P<0.05);多因素分析结果显示:年龄、糖尿病史、入院症状、术后住院时间、ASA分级为膀胱癌患者术后早期并发症发生的独立影响因素。结论膀胱癌患者膀胱全切除术后早期并发症的发生率较高,年龄较大、有糖尿病史、ASA分级高、有入院症状、术后住院时间长的膀胱癌患者术后早期并发症的发生风险较高,因此要加强对该部分人群的重点关注和预防控制。     

A nonrandomized,prospective, clinical study on the impact of circulating tumor cells on outcomes of urothelial carcinoma of the bladder patients treated with radical cystectomy with or without adjuvant chemotherapy

To investigate outcomes of urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) according to the presence of circulating tumor cells (CTC) and the administration of adjuvant chemotherapy (AC). We prospectively enrolled 226 UCB patients treated with RC without neoadjuvant chemotherapy at our institution between 2007 and 2013. Blood samples were obtained from all patients preoperatively and analyzed for CTC using the CellSearch^® system. Platinum‐based AC was administered in 50 patients (27.0%). Cox regression models evaluated the association of CTC with disease recurrence, cancer‐specific and overall mortality according to AC administration. 185 patients were available for analyses. CTC were present in 41 patients (22.2%). Patients with presence of CTC received AC more frequently, compared to patients without CTC (p = 0.027). At a median follow‐up of 31 months, the presence of CTC was associated with disease recurrence, cancer‐specific and overall mortality (p‐values < 0.001) in patients without AC administration. In patients who received AC, there was no difference in either endpoint between patients with or without presence of CTC. In multivariable analysis of patients without AC administration, the presence of CTC was an independent predictor for disease recurrence (HR: 4.9; p < 0.001), cancer‐specific (HR: 4.2; p = 0.003) and overall mortality (HR: 4.2; p = 0.001). The CTC status may be implemented in decision‐making regarding AC administration in UCB patients following RC. CTC measurement should be implemented in future UCB studies on systemic chemotherapy to validate our findings.     

Urologist referral delay and its impact on survival after radical cystectomy for bladder cancer

Background

Evidence shows that wait times before bladder cancer surgery have been increasing, and wait time can negatively affect survival. We aimed to determine if a long delay caused by an indirect referral before a first urologist visit affects the survival of patients undergoing radical cystectomy for bladder cancer.

Methods

We analyzed data from 1271 patients who underwent surgery for bladder cancer during the decade 2000–2009. The cohort was obtained by linking two administrative databases in the province of Quebec. Patients were considered to have been directly referred to a urologist if they had 5 or fewer visits with a general practitioner before their first urologist visit; otherwise, they were considered to have been indirectly referred. The effect on survival after surgery of a longer delay before a first urologist visit was assessed using Cox regression models.

Results

Median referral delay for the study population was 30 days (56 days for women, 23 days for men; p < 0.0001). Indirect referral was observed for 49% of women and 33% of men. Compared with patients who were directly referred, those who were indirectly referred after first symptoms of bladder cancer experienced poorer survival (hazard ratio: 1.29; 95% confidence interval: 1.10 to 1.52). Women who were indirectly referred had a significant 47% greater risk of death after radical cystectomy. Men who were indirectly referred also experienced decreased survival (adjusted hazard ratio: 1.25; 95% confidence interval: 1.03 to 1.51).

Conclusions

Patients indirectly referred to a urologist had an increased risk of mortality after surgery. Compared with men, women had longer wait times and poorer survival.     

The role of adjuvant combination chemotherapy after cystectomy in locally advanced bladder cancer: What we do not know and why

Background:Radical cystectomy is the standard treatment forpatients with muscle invasive bladder cancer. Three to four cycles of adjuvantchemotherapy is widely used in patients with pT3-pT4a and/or pN+ M0 diseasein an effort to delay recurrence and prolong survival. Although a number ofclinical trials have been carried out, this paper questions whether the useof adjuvant combination chemotherapy is actually justified. Patients and methods:A review of published randomized trials ofadjuvant cisplatin-containing combination chemotherapy in locally advancedbladder cancer was undertaken. Four trials including a total of 278 randomizedpatients were identified. Results:Although these trials appear to show a significantdifference in favor of adjuvant chemotherapy, serious methodological flawswere found. They have major deficiencies in terms of sample size, earlystopping of patient entry, statistical analyses, reporting of results anddrawing conclusions. Conclusions:These trials provide insufficient evidence to supportthe routine use of adjuvant chemotherapy in clinical practice due to smallsample sizes, confusing analyses and terminology, and the reporting ofquestionable conclusions. Analyses of the duration of survival were either notdone or were inconclusive and quality of life has not been considered. Newlarge scale, multicenter trials are imperative in order to provide convincingresults.