Neoadjuvant or adjuvant chemotherapy: what is the best treatment of muscle invasive bladder cancer?

Bladder cancer is the fourth most common cancer for men and the eighth most common cancer for women. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting the treatment is based on cisplatin chemotherapy regimens type MVAC, MVAC-HD or gemcitabine plus cisplatin. The standard treatment of muscle invasive operable bladder cancer (T2–T4) used widely was radical cystectomy with pelvic lymph nodes dissection; the anatomical extent of pelvic lymphadenectomy has not accurately been defined so far. However, in the last decade, the treatment of tumors was improved by the introduction of chemotherapy as part of the management of the disease. Neoadjuvant chemotherapy should be considered at first, as standard treatment of choice, before local treatment for patients with good performance status (0–1) and good renal function–glomerular filtration rate (GFR) >60 mL/min. For patients treated with primary surgery, adjuvant chemotherapy is a valuable option in the case of lymph nodes involvement. This brief review would provide the evidence of the role of neoadjuvant chemotherapy in the management of operable muscle invasive (T2–T4) bladder cancer.     

Recent progress in the treatment for urothelial cancer

Recent progress in the treatment for urothelial cancer is reviewed, especially concerning systemic chemotherapy and surgical techniques. A guideline for chemotherapy of urothelial cancer according to clinical stage is shown on the basis of evidence level in Japan. MVAC chemotherapy is regarded as the gold standard for advanced metastatic urothelial cancer. Randomized controlled trial revealed that gemcitabine in combination with cisplatin (GC therapy) has an efficacy similar to MVAC and is less toxic. Thus, GC therapy will become the standard treatment for advanced metastatic urothelial cancer instead of MVAC. Many chemotherapeutic regimens including gemcitabine and taxane have been introduced for patients with MVAC refractory or recurrent urothelial cancer. It was not yet clarified whether neoadjuvant chemotherapy provides survival benefits. Recent metaanalysis, however, revealed that neoadjuvant chemotherapy, especially cisplatin-based chemotherapy, has a survival advantage compared with total cystectomy alone. Intravesical BCG instillation is the standard treatment for carcinoma in situ and prophylaxis of recurrence for high-risk superficial bladder cancer. For higher efficacy and lower adverse effect, maintenance instillation and low-dose therapy are proposed, respectively, but further investigation is needed. Laparoscopic surgery in the urological field is widely performed and regarded as a minimally invasive surgery. Laparoscopic nephroureterectomy for patients with upper urinary tract cancer is reported to show the same efficacy at point of cancer control in comparison with traditional open surgery. Endoscopic treatment for upper tract urothelial cancer using laser can be safe and effective for a properly selected patient with a normal contralateral kidney.     

Risk factors and clinical outcomes of patients with node-positive muscle-invasive bladder cancer

Radical cystectomy and lymphadenectomy is a standard treatment for patients with high-grade, invasive bladder cancer. Although the absolute limits of lymphadectomy at the time of surgery have not been precisely defined, there is a growing body of evidence to suggest that an extended lymph node dissection may be beneficial for staging and survival in both node-negative and -positive bladder cancer patients. For lymph node-positive patients, several prognostic factors have been identified to provide risk stratification and direct the need for adjuvant treatment. These include: the pathological stage of the bladder tumor, extent of the lymphadenectomy and nodal tumor burden. The concept of lymph node density has also been identified as a prognostic factor. The literature and data on the extent of lymphadenectomy will be reviewed as well as the current prognostic variables and the benefits of adjuvant chemotherapy.     

Risk factors and clinical outcomes of patients with node-positive muscle-invasive bladder cancer

Radical cystectomy and lymphadenectomy is a standard treatment for patients with high-grade, invasive bladder cancer. Although the absolute limits of lymphadectomy at the time of surgery have not been precisely defined, there is a growing body of evidence to suggest that an extended lymph node dissection may be beneficial for staging and survival in both node-negative and -positive bladder cancer patients. For lymph node-positive patients, several prognostic factors have been identified to provide risk stratification and direct the need for adjuvant treatment. These include: the pathological stage of the bladder tumor, extent of the lymphadenectomy and nodal tumor burden. The concept of lymph node density has also been identified as a prognostic factor. The literature and data on the extent of lymphadenectomy will be reviewed as well as the current prognostic variables and the benefits of adjuvant chemotherapy.     

Standard or accelerated methotrexate,vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?

BackgroundThere is continuing controversy regarding the optimal regimen for neoadjuvant chemotherapy (NAC) in bladder cancer.Patients and methodsWe performed a retrospective analysis of 241 consecutive bladder cancer patients who received a combination of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) using a standard (52 patients) or an accelerated schedule (189 patients) as NAC before radical cystectomy in 17 centres of the French GEnito-urinary TUmour Group from March 2004–May 2013.ResultsThe median age was 62 years. As expected, the median number of cycles, the median total dose of cisplatin and the median cisplatin dose intensity were higher in patients treated with the accelerated regimen. Conversely, the median duration of chemotherapy was shorter. Regarding toxicity, grade III/IV neutropenia, grade III thrombocytopenia and grade III anaemia as well were more frequently observed in patients treated with the standard regimen. Among 211 (88%) patients who proceeded to cystectomy, 75 (35%) patients achieved an ypT0 pN0 status (no pathologic residual tumour cells) with no significant difference according to the MVAC schedule. Three-year overall survival rates were 66.5% (95% confidence interval [CI], 56–79) and 72% (95% CI, 59.5–88) in the standard and accelerated cohorts, respectively. In the multivariate analysis, two independent prognostic parameters were retained: the ypT0 stage and the ypN0 stage. Heterogeneity test did not show any interaction with NAC regimens.ConclusionSimilar pathological response and survival rates were observed whatever the chemotherapy regimen used. Haematological toxicity was greater in patients who received standard MVAC.     

Systemic chemotherapy options for metastatic bladder cancer

Systemic chemotherapy has reached a therapeutic plateau in the treatment of transitional cell carcinomas of the urothelium. Since the advent of the combination of methotrexate, vinblastine, adriamycin and cisplatin (MVAC) in the 1980s, no chemotherapy regimen has been proven to be superior to this therapy. Only one regimen, a combination of gemcitabine and cisplatin, has been equivalent. With a similar response rate and survival, plus the benefit of an improved toxicity profile, the gemcitabine cisplatin combination has largely supplanted MVAC in physician's practices. Although a recent dose-intense version of MVAC has shown an improved toxicity profile compared with traditional MVAC, it is clear that, for many patients, a full-dose cisplatin-based chemotherapy regimen may not be a tolerable option. Tobacco use, which is a common risk factor predisposing for the development of transitional cell carcinoma, may also cause morbidities that preclude treatment with aggressive combination therapy. Therefore, there is a clear need for regimens with improved toxicity, especially for the frequently frail or elderly patient population with poor renal function. There is an additional unmet requirement in rare bladder tumors, for which treatment has traditionally been based upon anecdotal evidence, limited by small patient numbers. Currently, there is newfound hope for all bladder cancer patients, with investigators studying new combinations and novel treatment paradigms, with recent studies focusing on frail, or 'cisplatin-unfit', patients and additional studies in the setting of rare small cell or urachal carcinoma patients.     

Squamous cell carcinoma of the bladder treated with a new combined chemotherapy regimen, intraarterial nedaplatin and pirarubicin plus intravenous methotrexate and vincristine--second case report in Japan

We report our second patient treated successfully with a new combined chemotherapy regimen of intra-arterial pirarubicin and nedaplatin plus intravenous methotrexate and vincristine for squamous cell carcinoma (SCC) of the bladder. A 57-year-old man consulted our hospital in September 2005 for treatment of bladder tumors diagnosed in another hospital. Magnetic resonance imaging (MRI) showed an extravesical invasive tumor on the anterior wall of the bladder, and clinical stage T2bN0M0 was diagnosed. Transurethral cold-cup biopsy was performed, and pathological examination revealed SCC. After he received two courses of this new combined intra-arterial chemotherapy regimen using nedaplatin, tumors were detected in MRI and cystoscopy.We performed partial cystectomy in January 2006. Postoperative pathological examination revealed no tumor cells (pathological CR). There were no severe adverse reactions by this chemotherapy regimen. He has been alive without evidence of disease.     

Curative radiotherapy following chemotherapy for invasive bladder carcinoma (a preliminary report)

Twenty-five patients with invasive transitional cell carcinoma of the bladder (Stage T2, T3, T4) received combined modality therapy using four cycles of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by surgery or radiation therapy (RT). Sixteen patients had complete (N = 8) or partial (N = 8) response to MVAC. Curative RT was delivered to 11 responders with T2 or T3 disease and to 2 patients with T4 disease. All 11 with T2 and T3 disease are currently alive, 7 with normal bladder function. The two with T4 disease are dead of disease. Three patients required salvage cystectomy for local recurrence and one patient had cystectomy for bladder stones. Follow-up ranged from 11 to 50 months with a median of 31 months. No late chemo-radiotherapy treatment-related complications to the intestines or in bladder function (other than one bladder stone formation) occurred. These preliminary results are encouraging and warrant further evaluation of this innovative approach in treating invasive carcinoma of the bladder. T2 and T3 patients with a complete or partial response to MVAC may be excellent candidates for a bladder-sparing treatment.     

Systemic chemotherapy options for metastatic bladder cancer

Systemic chemotherapy has reached a therapeutic plateau in the treatment of transitional cell carcinomas of the urothelium. Since the advent of the combination of methotrexate, vinblastine, adriamycin and cisplatin (MVAC) in the 1980s, no chemotherapy regimen has been proven to be superior to this therapy. Only one regimen, a combination of gemcitabine and cisplatin, has been equivalent. With a similar response rate and survival, plus the benefit of an improved toxicity profile, the gemcitabine cisplatin combination has largely supplanted MVAC in physician’s practices. Although a recent dose-intense version of MVAC has shown an improved toxicity profile compared with traditional MVAC, it is clear that, for many patients, a full-dose cisplatin-based chemotherapy regimen may not be a tolerable option. Tobacco use, which is a common risk factor predisposing for the development of transitional cell carcinoma, may also cause morbidities that preclude treatment with aggressive combination therapy. Therefore, there is a clear need for regimens with improved toxicity, especially for the frequently frail or elderly patient population with poor renal function. There is an additional unmet requirement in rare bladder tumors, for which treatment has traditionally been based upon anecdotal evidence, limited by small patient numbers. Currently, there is newfound hope for all bladder cancer patients, with investigators studying new combinations and novel treatment paradigms, with recent studies focusing on frail, or ‘cisplatin-unfit’, patients and additional studies in the setting of rare small cell or urachal carcinoma patients.     

Chemotherapy in Metastatic Urothelial Cancer

For more than a decade, the cisplatin plus doxorubicin and methotrexate plus vinblastine (MVAC) regimen has been the gold standard chemotherapy in bladder cancer, although the toxicity associated with this therapy has hampered its use in many older patients with metastatic disease. In recent years, new active agents have been identified, combinations of new agents with established drugs followed and results have become available on the combination of gemcitabine and cisplatin vs MVAC that have revealed an efficacy-toxicity profile in favor of the gemcitabine-cisplatin regimen. Other new doublet and triplet combinations, comprising new agents as well as incorporating one or two new agents into established regimens have demonstrated significant activity in phase II studies. However, there are no randomized data to show that any of these regimens improves patient survival as compared with either MVAC or cisplatin-gemcitabine. Advances in the understanding of the molecular biology of urothelial cancer will help to identify new biochemical targets for the development of novel therapeutic approaches to treat this cancer.     

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.     

Restaging procedures, criteria of response, and relationship between pathological response and survival

The first priorities for upfront chemotherapy in TCCB are to prove in randomized phase III trials that the addition of toxic chemotherapy to toxic standard locoregional treatment can improve survival and/or permit bladder preservation. If such proof is obtained, we will need to distinguish patients who benefit from chemotherapy from those who do not. One way to make such a distinction is to separate responders from nonresponders. The prognostic value of downstaging to P0 or noninvasive cancer is significantly different from the prognosis associated with the continued presence of invasive disease. The available data regarding clinical assessment of response still appear to indicate that only the demonstration of a lack of response (see Table 2: cIR, cSD, cPD, greater than or equal to cT2) is reliable, However, there may be some patients, who after two courses of chemotherapy, still show the presence of invasive bladder cancer together with signs of tumor cell kill and may be further downstaged to P0 during the next two courses of chemotherapy. The clinical assessment of cCR and cPR is too inaccurate to be used as a basis for decisions concerning continuation of chemotherapy or bladder preservation. The decision to leave the bladder untreated after a cCR carries the risk of jeopardizing cure. More studies on the evaluation of response of the primary tumor are needed, probably with a central role for the pathologist to evaluate not only the gross presence, minimal residual disease, or true absence of cancer but also the adequacy of site and deepness of the restaging TUR biopsy.     

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.     

Role of complete lymphadenectomy in endometrioid uterine cancer

Although surgical pathological staging is the standard of care for uterine carcinoma, the benefits of a complete lymphadenectomy remain controversial. Evidence suggests that this procedure provides prognostic information and directs the use of appropriate adjuvant treatment in patients who are node-positive. Furthermore, it eliminates the need for adjuvant treatment in low-risk patients with negative nodes and no extrauterine spread of disease. Although the complications associated with this procedure raise the question as to whether all low-risk patients need a complete lymphadenectomy, the limitations of preoperative and intraoperative pathological analyses mean that lymphadenectomy in low-risk patients might still have merit. Future advances are warranted to enhance preoperative radiological and intraoperative pathological assessment to establish the risk of nodal disease. In this review, we assess the evidence on the prognostic and therapeutic benefits of a complete versus selective lymphadenectomy. Moreover, we discuss the complications associated with lymphadenectomy and identify subsets of low-risk patients who might not need to undergo this procedure.     

保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床研究

目的 评价保留膀胱手术联合动脉化疗治疗浸润性膀胱癌的临床疗效.方法 2003年4月～2006年12月,对35例浸润性膀胱癌患者采用经尿道膀胱肿瘤电切或膀胱部分切除术联合GC(吉西他滨 顺铂)方案动脉化疗治疗,总结分析肿瘤控制情况、膀胱保存率和患者的生存率.结果 33例患者获随访,2例失访,平均随访24.3个月(3～45个月).27例无瘤生存,2例带瘤生存,4例死于肿瘤转移,2年生存率为88.8%;19例无复发及转移,5例浅表性复发,3例浸润性复发,6例转移;25例保留膀胱生存,4例行挽救性全膀胱切除,4例死亡,2年膀胱保存率为74.1%.全部患者对动脉化疗耐受良好,无严重全身和局部不良反应.结论 保留膀胱手术联合GC方案动脉化疗治疗浸润性膀胱移行细胞癌近期疗效满意,毒副作用轻,值得临床进一步观察研究.     

Chemotherapy in Locally Advanced and Metastatic Bladder Cancer

Chemotherapy plays an important role in the management of patients with locally advanced and metastatic transitional cell carcinoma of the urothelial tract. Chemotherapeutic regimens have evolved from use of single drugs with low response rates and a short median survival to combination chemotherapy with inclusion of new active drugs which achieve response rates up to 75–80% and the possibility of cure in about 15% of patients with good performance status and without visceral metastases. Patients with a primary good response are candidates for subsequent surgery or radiotherapy of residual disease. A standard regimen in patients with good prognosis and normal renal function has, for a number of years, been the four-drug combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). However, this is now replaced in most centers with gemcitabine and cisplatin (GC), which has similar efficacy but less toxicity. New promising regimens include the combinations of gemcitabine and one of the taxanes, with or without cisplatin and the triple combination of cisplatin, paclitaxel and ifosfamide. The three-drug combination of gemcitabine, cisplatin and paclitaxel is presently being compared with the GC regimen in a large, international, randomized, phase III trial. Other two- and three-drug combinations have been proposed as alternative possibilities, but these regimens have to be compared with GC or MVAC in randomized trials to explore their potential use as a new standard of care in this patient group. No data so far have suggested the best treatment for patients with poor prognostic features, including impaired renal function. The use of drugs without renal toxicity (e.g. gemcitabine in combination with paclitaxel) is effective, but the rate of hematologic toxicity seems to increase profoundly in patients with poor prognosis. Thus, the goal for an appropriate chemotherapeutic regimen for these patients is to find an acceptable balance between efficacy and toxicity. Results of second-line chemotherapy have been disappointing, and treatment of patients requiring second-line therapy should primarily be performed as part of a clinical trial. An exception is gemcitabine, where efficacy seems to be independent of whether or not patients have received prior cisplatin-containing chemotherapy. Presently, new drugs such as pemetrexed and vinflunine are being investigated as second-line treatment. However, it should be emphasized that patients with a primary good response to chemotherapy such as MVAC or GC and a long recurrence-free interval generally should be offered re-induction combination chemotherapy and not included in trials with new second-line drugs.     

Management of bladder cancer

Bladder cancer is a paradigm of malignancy, representing the spectrum from localized to metastatic disease, and manifesting varied histologic types, including transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. Preclinical and clinical data suggest that a common stem cell of origin gives rise to the different histologic types and that these patterns are of clonal origin. Localized bladder cancer is managed optimally by transurethral resection, with or without adjuvant intravesical chemotherapy. Invasive cancer or relapsed superficial disease may require more radical surgery or radical radiotherapy. In recent years, the evolution of techniques of continent urinary diversion or of bladder replacement has revolutionized the management of invasive disease. However, the 5-year survival for invasive bladder cancer is still approximately 50%, and innovative strategies have been developed, combining definitive local treatment and systemic chemotherapy, in an attempt to improve survival. For patients with metastatic disease, the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (the MVAC regimen) has achieved response rates as high as 70% but with a median survival of only 12 months. Until cure rates are improved, one of the hallmarks of effective management of metastatic disease will remain the provision of thorough and well-structured palliative treatment programs. Recently, the introduction of new agents (such as paclitaxel, gallium, ifosfamide, and gemcitabine) has led to promising response rates, and further clinical trials of these agents alone and in combination are in progress. In addition, an improved understanding of the mechanisms of resistance to treatment, including the implications of the expression of p-glycoprotein, p53 proteins, and other biochemical predictors of outcome, and of strategies to overcome such resistance, may lead to more effective management of advanced disease. Furthermore, real progress will be made only through the application of well-designed clinical trials to test the efficacy and toxicity of the new strategies of treatment.     

Surgical management of bladder cancer in 2003

Recent advances in molecular and cell biology have led to a greater understanding of the basic biology of bladder cancer. However, despite these advances, surgery remains a key component of modern bladder cancer treatment. Endoscopy is the mainstay of the diagnosis and treatment of superficial bladder cancer. Adjuvant intravesical therapy is recommended for patients with high-risk superficial bladder cancer (Ta/T1 high grade). Select patients with invasive bladder cancer (T2/T3) are candidates for bladder-sparing approaches, incorporating transurethral resection of bladder tumor (TURBT), radiation and chemotherapy. The results and complications of endoscopic therapy are discussed. The role of partial cystectomy, radical cystoprostatectomy, prostate-sparing cystectomy, laparoscopic radical cystectomy, lymphadenectomy and urethrectomy in invasive bladder cancer are discussed. The tumor control outcomes and complications of radical cystoprostatectomy (still the gold standard) for organ-confined and node-positive bladder cancer are reported. Surgery remains an integral part of the management of patients with bladder cancer. Improved understanding of the biology of bladder cancer, combined with better surgical techniques and safety, continues to improve the survival and quality of life of patients with bladder cancer.     

Surgical management of bladder cancer in 2003

Recent advances in molecular and cell biology have led to a greater understanding of the basic biology of bladder cancer. However, despite these advances, surgery remains a key component of modern bladder cancer treatment. Endoscopy is the mainstay of the diagnosis and treatment of superficial bladder cancer. Adjuvant intravesical therapy is recommended for patients with high-risk superficial bladder cancer (Ta/T1 high grade). Select patients with invasive bladder cancer (T2/T3) are candidates for bladder-sparing approaches, incorporating transurethral resection of bladder tumor (TURBT), radiation and chemotherapy. The results and complications of endoscopic therapy are discussed. The role of partial cystectomy, radical cystoprostatectomy, prostate-sparing cystectomy, laparoscopic radical cystectomy, lymphadenectomy and urethrectomy in invasive bladder cancer are discussed. The tumor control outcomes and complications of radical cystoprostatectomy (still the gold standard) for organ-confined and node-positive bladder cancer are reported. Surgery remains an integral part of the management of patients with bladder cancer. Improved understanding of the biology of bladder cancer, combined with better surgical techniques and safety, continues to improve the survival and quality of life of patients with bladder cancer.     

The current status of perioperative chemotherapy for invasive bladder cancer: a multiinstitutional retrospective study in Japan

Background We conducted a multiinstitutional analysis to clarify the clinical significance of perioperative chemotherapy, in invasive bladder cancers in Japan, and to identify the patient subpopulations who could benefit from perioperative chemotherapy.Methods A total of 913 consecutive patients aged less than 80 years who underwent radical cystectomy for invasive bladder cancer from 1990 to 2000 at 32 Japanese hospitals were retrospectively analyzed. Median follow-up was 3.8 years (range, 0.1 to 11.8 years).Results In total, 341 patients (37.3%) were treated with perioperative chemotherapy, including neoadjuvant chemotherapy (n = 174), adjuvant chemotherapy (n = 114), or a combination of both chemotherapies (n = 53). With cisplatin-based combination chemotherapy, the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was the one most frequently used for perioperative chemotherapy, but the average number of cycles was distinctly less than that in reported randomized trials. MEC (methotrexate, epirubicin, and cisplatin) chemotherapy had efficacy similar to that of the MVAC regimen. On analysis of patients stratified by stage, the overall survival of patients with adjuvant chemotherapy was significantly better than that of those without adjuvant chemotherapy, in patients with pT2b, pN0 or pT3, pN0 (P = 0.016 or 0.020, respectively), but adjuvant chemotherapy had no, or the opposite, effect on patients with pT2a, pN0, pT4, pN0, or pTany, pN+. On the other hand, neoadjuvant chemotherapy provided a statistically significant survival benefit only for patients with clinical T3N0 (P = 0.015). Of note, in the high-risk subgroup, the overall survival rate for patients with complete response (CR) after neoadjuvant chemotherapy was significantly better than that of patients with partial response (PR) or no change (NC)/progressive disease (PD) (P = 0.043).Conclusion In Japan, cisplatin-based combination chemotherapy has been the main modality adopted perioperatively for high-risk patients with radical cystectomy. This studys clinical results indicated that perioperative chemotherapy may improve survival in patients with T3N0 or pT2b/pT3, pN0 bladder cancer.