Preoperative concurrent chemoradiotherapy against muscle-invasive bladder cancer: results of partial cystectomy in elderly or high-risk patients

BACKGROUND: Good local control has been reported in cases of muscle-invasive bladder cancer treated by chemoradiotherapy and transurethral resection (TUR). However, definitive irradiation or extensive chemotherapy is often intolerable for elderly or poor-risk patients. We report here benefits of partial cystectomy after concurrent low-dose chemoradiotherapy for high-risk patients. METHODS: Thirty-seven patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (50-100 mg/body x 2 courses) and pelvic irradiation (40 Gy) preoperatively. Among 17 patients (46%) who achieved complete response (CR), 10 were not suitable for radical cystectomy and underwent partial cystectomy. Radical cystectomy was performed in 24 cases [CR = 6, partial response (PR) = 18]. Two patients (one CR and one PR) rejected open surgery and were treated by TUR of the primary site. One no change (NC) patient received no further treatment because of mental disorder. RESULTS: Median follow-up was 12 months (range 2-37 months). Fifteen of 36 evaluable cases (42%) achieved a pathological T0 response (no residual tumor). Estimated 3-year disease-free survival was 56% for all patients and 100% for T0 responders. Seven of 21 patients with pathological persistent tumor developed local recurrence (three patients) or distant metastasis (four patients). All of the 10 patients (eight with T0 response and two with a small residual tumor nest) who underwent partial cystectomy were recurrence-free for an observation period of up to 3 years. CONCLUSIONS: Bladder preservation by partial cystectomy may be a choice for patients who show a good response to preoperative chemoradiotherapy and are not suitable for radical cystectomy.     

Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer: a multi-institutional, long-term experience

BACKGROUND: The authors evaluated their long-term experience with combined-modality, conservative treatment in patients with muscle-invasive bladder cancer. METHODS: In total, 121 patients with T2, T3, or T4 bladder cancer (mean age, 63 years; ratio of men to women, 3:1) underwent induction by transurethral resection (TUR) of the tumor and received 2 cycles of neoadjuvant chemotherapy followed by radiotherapy (RT) (n = 43 patients) or radiochemotherapy (RCT) (n = 78 patients). Six weeks after RT or RCT, responses were evaluated by restaging TUR. Patients who achieved a complete response (CR) were observed at regular intervals. In patients who had persistent or recurrent invasive tumor, further treatment was recommended. RESULTS: Local response evaluation by restaging TUR was possible in 119 patients, and 102 of those patients (85.7%) achieved a CR. After a median follow-up of 66 months (range, 6-182 months), no local or distant disease recurrences were observed in 67 of 102 complete responders (65.7%), 17 of 102 complete responders (16.7%) experienced superficial local disease recurrence, and 18 of 102 complete responders (17.6%) had a muscle-invasive relapse. The 5-year tumor-specific, overall, and bladder-intact survival rates were 73.5%, 67.7%, and 51.2%, respectively. Treatment modality, tumor classification, and resection status after initial TUR had an impact on survival rates (P = .04, P = .02, and P = .02, respectively). CONCLUSIONS: The current results indicated that conservative combined treatment is a reasonable alternative to radical cystectomy in selected patients with muscle-invasive bladder cancer.     

Stellenwert der Radiochemotherapie beim Harnblasenkarzinom

Radical cystectomy remains the standard of care for muscle-invasive bladder cancer, while for high-risk superficial carcinoma an organ-preserving approach, including transurethral resection (TUR) and intravesical therapy, is recommended. This review summarizes the chemotherapy and radiotherapy options for high risk T1 or muscle-invasive bladder cancer as alternative to or as neoadjuvant therapy before radical surgery. Multimodality therapy, including TUR, radiation and chemotherapy, is associated with recurrence and progression rates of 30% and 15% in high-risk T1 bladder cancer, respectively. For muscle-invasive disease, 5-year survival rates in the range of 50–60% have been published, which is comparable to primary cystectomy series. Approximately 80% of surviving patients retained their own well functioning bladder. Close coordination among all disciplines is required to achieve optimal results. An integral part of the concept is salvage cystectomy for non-responder or muscle-invasive recurrence. Ideal candidates for the organ preserving approach are those with early-stage unifocal tumors (T1/T2). Preoperative chemoradiation is likely to improve the results of cystectomy alone in patients with locally advanced bladder cancer (T3b, T4).     

Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results.

PURPOSE: To evaluate our long-term experience with combined modality treatment and selective bladder preservation and to identify factors that may predict treatment response, risk of relapse, and survival. PATIENTS AND METHODS: Between 1982 and 2000, 415 patients with bladder cancer (high-risk T1, n = 89; T2 to T4, n = 326) were treated with radiotherapy (RT; n = 126) or radiochemotherapy (RCT; n = 289) after transurethral resection (TUR) of the tumor. Six weeks after RT/RCT, response was evaluated by restaging-TUR. In case of complete response (CR), patients were observed at regular intervals. In case of persistent or recurrent invasive tumor, salvage-cystectomy was recommended. Median follow-up was 60 months (range, 6 to 199 months). RESULTS: CR was achieved in 72% of patients. Local control after CR without muscle-invasive relapse was maintained in 64% of patients at 10 years. Distant metastases were diagnosed in 98 patients with an actuarial rate of 35% at 10 years. Ten-year disease-specific survival was 42%, and more than 80% of survivors preserved their bladder. Early tumor stage and a complete TUR were the most important factors predicting CR and survival. RCT was more effective than RT alone in terms of CR and survival. Salvage cystectomy for local failure was associated with a 45% disease-specific survival rate at 10 years. Cystectomy because of a contracted bladder was restricted to 2% of patients. CONCLUSION: TUR with RCT is a reasonable option for patients seeking an alternative to radical cystectomy. Ideal candidates are those with early-stage and unifocal tumors, in whom a complete TUR is accomplished.     

Invasive bladder cancer: a single-institution experience with bladder-sparing approach

Our objective was to assess the efficacy and safety of a selective bladder-preserving approach by transurethral resection and sequential chemoradiotherapy in patients with muscle-invasive bladder cancer. From 1989 through 1997, 40 patients with biopsy-confirmed bladder cancer, clinical stages T2-4NxM0, were treated with induction by aggressive transurethral resection (TUR) and three cycles of methotrexate, cisplatin, and vinblastine (MCV) chemotherapy. Tumor response was evaluated by cystoscopy and biopsy. In complete responders, the treatment was continued by radiotherapy (60 Gy to the bladder and 50 Gy to pelvic lymph nodes). Radical cystectomy was recommended to patients with residual tumor. Clinical complete response rate to TUR and MCV chemotherapy was 70%. The 4-year actuarial overall survival rate for the whole series was 80.5%. Among 36 patients who completed chemotherapy and radiotherapy, the 4-year actuarial survival was 84%, with 82.6% surviving with their bladders intact. Freedom from local failure in complete responders to TUR-chemotherapy was 84%. Multivariate analysis revealed that the extent of initial TUR and status after TUR-chemotherapy were independent prognostic factors associated with survival and disease-free survival. This study confirms that the combination of aggressive TUR and sequential chemoradiotherapy with bladder preservation is an alternative treatment option to primary cystectomy for selected patients with invasive bladder carcinoma.     

Radiochemotherapy with cisplatin and 5-fluorouracil after transurethral surgery in patients with bladder cancer

PURPOSE: To give an update on the long-term outcome of an intensified protocol of combined radiochemotherapy (RCT) with 5-fluorouracil (5-FU) and cisplatin after initial transurethral resection of bladder tumor (TURBT) with selective organ preservation in bladder cancer. METHODS AND MATERIALS: One hundred twelve patients with muscle-invading or high-risk T1 (G3, associated Tis, multifocality, diameter >5 cm) bladder cancer were enrolled in a protocol of TURBT followed by concurrent cisplatin (20 mg/m(2)/day as 30-min infusion) and 5-FU (600 mg/m(2)/day as 120-h continuous infusion), administered on Days 1-5 and 29-33 of radiotherapy. Response to treatment was evaluated by restaging TURBT 4-6 weeks after RCT. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. RESULTS: Ninety-nine patients (88.4%) had no detectable tumor at restaging TURBT; 71 patients (72%) have been continuously free from local recurrence or distant metastasis. Superficial relapse occurred in 13 patients and muscle-invasive recurrence in 11 patients. Overall and cause-specific survival rates for all patients were 74% and 82% at 5 years, respectively. Of all surviving patients, 82% maintained their own bladder, 79% of whom were delighted or pleased with their urinary condition. Hematologic Grade 3/4 toxicity occurred in 23%/6% and Grade 3 diarrhea in 21% of patients. One patient required salvage cystectomy due to a shrinking bladder. CONCLUSION: Concurrent RCT with 5-FU/cisplatin has been associated with acceptable acute and long-term toxicity. Overall and cause-specific survival rates are encouraging. More than 80% of patients preserved their well-functioning bladder.     

Prognostic factors in invasive bladder carcinoma treated by combined modality protocol (organ-sparing approach)

PURPOSE: The results of bladder sparing approach for the treatment of muscle-invasive bladder cancer, using a combination of transurethral resection (TUR), chemotherapy, and radiotherapy, are encouraging. The survival of patients treated by this method is similar to the survival of patients treated by radical cystectomy. The aim of our study was to find out which pretreatment characteristics influence the survival of patients treated by organ sparing approach that would enable us to identify the patients most suitable for this type of treatment. METHODS AND MATERIALS: The prognostic value of different factors, such as age, gender, performance status, hemoglobin level, clinical stage, histologic grade, presence of obstructive uropathy, and completeness of TUR, has been studied in 105 patients with invasive bladder cancer, who received a bladder sparing treatment in the period from 1988 to 1995. They were treated with a combination of TUR, followed by 2-4 cycles of methotrexate, cisplatinum, and vinblastine polychemotherapy. In complete responders the treatment was completed by radiotherapy (50 Gy to the bladder and 40 Gy to the regional lymph nodes), whereas nonresponders underwent cystectomy whenever feasible. RESULTS: Our study has confirmed an independent prognostic value of performance status, histologic grade, and obstructive uropathy, for the disease-specific survival (DSS) of bladder cancer patients treated by a conservative approach. We believe that performance status best reflects the extent of disease and exerts significant influence on the extent and course of treatment, while obstructive uropathy is a good indicator of local spread of the disease, better than clinical T-stage. Our finding that histologic grade is one of the strongest prognostic factors shows that tumor biology also is a very important prognostic factor in patients treated by conservative approach. CONCLUSION: Patients with muscle-invasive bladder cancer who are most likely to benefit from conservative treatment approach include those with good performance status, absence of hydronephrosis, and histologic low grade transitional cell carcinoma.     

Organ preservation in patients with invasive bladder cancer: initial results of an intensified protocol of transurethral surgery and radiation therapy plus concurrent cisplatin and 5-fluorouracil

To assess safety, tolerance, and disease control of transurethral resection of the bladder tumor (TURB) plus concurrent cisplatin, 5-fluorouracil (5-FU), and radiation therapy (RT) with selective organ preservation in patients with bladder cancer.

Forty-five patients with muscle-invading or high-risk T1 (G3, associated carcinoma in situ, multifocality, >5 cm) bladder cancer were entered into a protocol of TURB followed by concurrent cisplatin (20 mg/m²/day, 20-min infusion) and 5-FU (600 mg/m²/day, 120-hour continuous infusion), administered on Day 1–5 and 29–33 of RT (single dose 1.8 Gy, total dose to the bladder 54–59.4 Gy). Response was evaluated by restaging TURB 6 weeks later. In case of invasive residual or recurrent tumor, salvage cystectomy was recommended. Median follow-up was 35 months (range: 8–80 months).

Thirty-nine patients (87%) had no detectable tumor at restaging TURB; 29 patients (64%) have been continuously free of tumor in their bladders. A superficial relapse occurred in 4 patients, a muscle-invasive relapse in 6 patients. Overall survival and survival with preserved bladder was 67% and 54%, respectively, at 5 years. Hematologic Grade 3/4 toxicity occurred in 10%/4%; Grade 3 diarrhea occurred in 9%. Thirty-four patients (76%) completed the protocol as scheduled or with only minor deviations. One patient required salvage cystectomy because of a shrinking bladder.

Conclusion: This protocol of concurrent cisplatin/5-FU and RT has been associated with acceptable toxicity. The complete response rate of 87% and the 5-year survival with intact bladder of 54% are encouraging and compare favorably with our historical control series using RT with carboplatin and cisplatin alone.     

Optimal timing of radical cystectomy in T1 high-grade bladder cancer

T1 high-grade (formerly T1G3) bladder cancer is a challenging clinical entity representing approximately 10-15% of all new bladder cancer cases. The variable natural history of the disease and possible impairment in quality of life associated with radical treatment makes T1 high-grade one of the most challenging uro-oncological patient groups to manage. In particular, the risk of clinical understaging and not recognizing muscle-invasive disease may have detrimental effects on patient outcome. The cornerstone of contemporary staging is restaging transurethral resection (TUR), which helps in defining further management. In patients with restaging TUR stage less than T1, induction bacillus Calmette-Guérin combined with maintenance offers good results. The option of radical cystectomy should be discussed with patients with restaging TUR stage T1 or higher and it is highly recommended to all patients with recurrent T1 of carcinoma in situ during bacillus Calmette-Guérin maintenance. In addition to restaging TUR stage, several other clinicopathological factors, such T1 substaging, associated carcinoma in situ, tumor size and appearance, lymphovascular invasion, and hydronephrosis, aid in the decision making between radical and conservative treatment. Future prospects include improved staging and molecular markers that may guide toward conservative therapy or allow more cT1 patients to be offered nerve-sparing cystectomies and neobladders and, thus, improving quality of life for patients undergoing radical surgery.     

Can patient selection for bladder preservation be based on response to chemotherapy?

BACKGROUND: Neoadjuvant chemotherapy for patients with muscle-invasive bladder carcinoma is given to treat micrometastases and to preserve the bladder. The objective of this study was to evaluate the possibility of bladder preservation in patients with muscle-invasive bladder carcinoma who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy. METHODS: One hundred four consecutive patients with T2-T4,N0,M0 transitional cell carcinoma of the bladder were treated with 3 cycles of neoadjuvant M-VAC chemotherapy. After clinical restaging, 52 patients underwent transurethral resection of the bladder (TURB) alone, 13 patients underwent partial cystectomy, and 39 patients underwent radical cystectomy. RESULTS: The median survival for the entire group was 7.49 years (95% confidence interval, 4.86-10.0 years). Forty-nine patients (49%) were T0 at the time of TURB after receiving M-VAC. Thirty-one of 52 patients (60%) who received chemotherapy and underwent TURB alone were alive at a median follow-up of 56 + months (range, 10-160 + months): Twenty-three patients (44%) in that TURB group maintained an intact bladder. Of 13 responding patients with monofocal lesions who underwent partial cystectomy, only 1 patient required salvage cystectomy, and survival generally was good. The 5-year survival rate for this group was 69%. With a long median follow-up of 88 + months (range, 16-158 months), 4 patients (31%) were alive with a functioning bladder. In the radical cystectomy group, the median follow-up was 45 months (range, 4-172 + months), and 15 of 39 patients (38%) patients remained alive. In 77 patients who had their tumors down-staged to T0 or superficial disease, the median follow-up was 63 months (range, 4-172 + months), and the 5-year rate survival was 69%. This is in contrast to a 5-year survival rate of only 26% in 27 patients who failed to respond and had a status >/= T2 after receiving chemotherapy (median follow-up, 31 months; range, 7-156 + months). The median survival for 27 elderly patients (age >/= 70 years; median age, 73 years; range, 70-82 years) was 90 months (7.5 years). For elderly patients who underwent TURB and partial cystectomy, the 5-year survival rate was 67% with a 109-month (9-year) median survival; 47% of patients preserved their bladders intact. The median follow-up of the living elderly patients was 61 months (range, 20-120 + months). CONCLUSIONS: Bladder sparing in selected patients on the basis of response to neoadjuvant chemotherapy is a feasible approach that should be confirmed in prospective, randomized trials. Selected elderly patients are candidates for this approach.     

Neoadjuvant versus Adjuvant Chemotherapy in Patients with Resectable Muscle-Invasive Bladder Cancer

Introduction: In regards to resectable muscle-invasive bladder cancer (MIBC) patients, contemporary guidelines recommend treatment with radical cystectomy and perioperative chemotherapy (neoadjuvant or adjuvant). In addition, the 5-year survival rate ranges from 36% to 48% in connection to T3 or T4 staged tumors or lymph node metastatic tumors. Perioperative treatment can improve overall survival, and the most robust evidence are in favor of neoadjuvant chemotherapy. The purpose of this study was to assess the impact of perioperative chemotherapy on the survival of patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC). Methods: The medical records of ninety-four patients with muscle-invasive bladder cancer (MIBC) that were treated with radical cystectomy and perioperative chemotherapy from 2008 to 2018 were retrospectively analyzed at Songklanagarind hospital. Neoadjuvant and adjuvant chemotherapy groups were classified. Univariable and multivariable regression analyses were used to predict overall survival (OS) after treatment. The survival rates for each group were estimated and compared using long-rank testing. Results: Overall, we identified 94 eligible patients of whom 20 patients (21.2%) received neoadjuvant and 74 patients (78.8%) received adjuvant chemotherapy. The 5-year survival rate of the neoadjuvant group was 55.7%, and in regards to the adjuvant group it was 30.4%. A multivariable analysis yielded that, patients treated with neoadjuvant chemotherapy had longer survival than those treated with adjuvant chemotherapy (p =0.039).  The median survival here as log rank compares median survival. Conclusion: The overall survival of neoadjuvant chemotherapy (NAC) was better than adjuvant chemotherapy (AC) in regards to muscle-invasive bladder cancer. These data could support the use of neoadjuvant chemotherapy in MIBC prior to radical cystectomy.     

Favorable outcome of preoperative low dose chemoradiotherapy against muscle-invasive bladder cancer

To investigate the feasibility of preoperative low-dose chemoradiotherapy, 50 patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (100 mg/body x 2 courses) and pelvic irradiation (40 Gy). Among 20 patients (40%) who achieved clinical complete regression, 11 with solitary tumor underwent partial cystectomy because of advanced age, poor condition of the patients, or a reluctance to have radical surgery. Radical cystectomy was carried out in the remaining 39 cases (complete regression 9, partial regression 30). Pathologic T0 response (no residual tumor) was achieved in 18 (36%) of all the cases. Median follow-up was 19 months (range 2-59 months). Estimated 3-year disease-free survival was 75% for all patients and 100% for T0 responders. Local recurrence (2 patients) or distant metastasis (6 patients) developed in 8 of 32 patients with pathologic persistent tumor. All of the 11 patients (9 with T0 response and 2 with a small residual tumor nest) who underwent partial cystectomy were recurrence free for observation periods up to 59 months. Low-dose chemoradiotherapy is as effective as other neoadjuvant protocols and is applicable to high-risk patients. The bladder can be preserved by partial cystectomy in selected cases with clinical complete regression.     

Tissue factor expression correlates with disease-specific survival in patients with node-negative muscle-invasive bladder cancer

Tissue factor (TF), a transmembrane glycoprotein responsible for initiating the extrinsic pathway of blood coagulation plays a key role in cancer growth, metastasis and angiogenesis. Various studies have demonstrated the prognostic potential of TF expression in several cancers. However, its role in bladder cancer is unclear. This study evaluated the prognostic potential of TF expression in muscle-invasive bladder tumors from patients treated with radical cystectomies. Immunohistochemical staining using a monoclonal antibody (mAb) anti-TF was carried out on sections of tissue microarray blocks containing cores of muscle-invasive bladder tumors (4 cores/tumor) from 218 patients. The intensity of the staining was evaluated on a scale from 0 to 3 by two independent observers who were both unaware of the clinicopathological characteristics of the samples. TF was expressed in 77.6% of tumors, independently from baseline characteristics (age, gender, stage and grade) as assessed using the chi(2) and Student t tests. During follow-up (median: 2.6 years), 45.4% of the patients died from the progression of their cancer. Kaplan-Meier survival showed that among the 103 patients with node-negative (N0) transitional cell carcinoma (TCC), those with TF-positive tumors had shorter bladder cancer-specific survival (p = 0.0276). Moreover, multivariate Cox regression analysis showed they had a 3.15-fold greater risk of dying from bladder cancer (95% CI: 1.1-9.0; p = 0.032). In conclusion, TF expression was an independent predictor of disease-specific survival in N0 muscle-invasive TCCs treated by radical cystectomy and therefore, might help identify patients at higher risk of disease progression. These patients could potentially benefit from adjuvant chemotherapy.     

肌层浸润性膀胱癌患者根治术后预后相关因素分析

目的:探讨肌层浸润性膀胱癌根治术预后相关因素。方法:回顾性分析156例腹腔镜下根治性膀胱全切除术及盆腔淋巴结清扫术后肌层浸润性膀胱癌患者生存数据,选择17种可能对预后产生影响的因素,采用Kaplan-Meier法及Cox比例风险模型统计分析。结果:单因素分析示年龄、肿瘤T分期、有无淋巴结转移、肾积水、是否侵犯输尿管下段、是否侵犯淋巴脉管、是否行新辅助化疗、术后辅助放化疗对患者预后的影响差异有统计学意义（P<0.05）。多因素分析示年龄（P<0.001）、肿瘤T分期（P=0.003）、淋巴结转移（P=0.031）、新辅助化疗（P=0.015）为肌层浸润性膀胱癌根治术预后影响因素。结论:年龄、肿瘤T分期、淋巴结转移为影响肌层浸润性膀胱癌根治术患者生存的独立危险因素。新辅助化疗是肌层浸润性膀胱癌根治术预后保护因素。     

TP53 accumulation predicts improved survival in patients resistant to systemic cisplatin-based chemotherapy for muscle-invasive bladder cancer.

To examine retrospectively the prognostic significance of TP53 immunoreactivity for both tumor response and patient survival in 83 patients with nonmetastatic muscle-invasive bladder cancer treated with a single transurethral resection (TUR) of tumor and combined cisplatin-based systemic chemotherapy followed by repeat TUR, paraffin-embedded sections of a bladder tumor obtained at TUR before chemotherapy (1 T2, 52 T3, and 30 T4) were immunostained for TP53 using monoclonal PAb1801 and DO-7 antibodies. For the entire cohort, TP53 immunopositivity (PAb1801 or DO-7) did not predict complete response (CR), complete or partial response (PR), progressive disease, or time to death from bladder cancer. There was a highly significant correlation between PAb1801 and DO-7 nuclear immunoreactivity (r = 0.8242; P<0.0001). In 76 patients in which complete clinical data were available, tumor stage (T2/T3; P = 0.0499), CR and PR (P = 0.0016) and CR (P<0.0001) were associated with patient survival. In a multivariate model, CR (P<0.0001) was the only independent predictor of improved survival. In complete responders, neither TP53 immunostaining nor clinicopathological factors stratified patients into prognostic groups. However, in the subset of patients (n = 38) who were chemoresistant (PR or progressive disease), improved survival was associated with > or =20% TP53 immunoreactivity (PAb1801; P = 0.0191) and tumor stage (T2/T3; P = 0.0358). TP53 immunopositivity (PAb1801 or DO-7) did not predict overall survival or response to systemic chemotherapy in patients with nonmetastatic but predominantly clinical stage > or =T3 bladder cancer, but it had prognostic significance within the chemoresistant subgroup.     

Radiochemotherapie des Harnblasenkarzinoms

Although radical cystectomy remains the standard of care for muscle-invasive bladder cancer, many groups are exploring the use of trimodality therapy, including transurethral resection of the bladder tumor (TURBT), radiation, and chemotherapy. With these programs, cystectomy has been reserved for patients with incomplete response or local relapse after combined modality treatment (CMT). Five-year survival rates in the range of 50–60% have been published in these series, and approximately three quarters of the surviving patients maintained their own, well-functioning bladder. Thus, CMT with selective organ preservation has become a reasonable option for patients seeking an alternative to radical cystectomy. Ideal candidates are those with early-stage and unifocal tumors, in which a complete TUR (R0 resection) is accomplished.     

Organ preservation in invasive bladder cancer: Brachytherapy,an alternative to cystectomy and combined modality treatment?

PURPOSE: To evaluate our long-term results of bladder preservation with brachytherapy in the treatment of bladder cancer. METHODS AND MATERIALS: Between 1987 and 2000, 108 patients with T1-G3 and T2-T3a stages of bladder cancer were treated with a transurethral resection (TUR) and a course of external beam radiotherapy (30 Gy in 15 fractions) followed by brachytherapy (40 Gy). All tumors were solitary lesions with a diameter < or =5 cm. Median follow-up was 54 months (range, 1-178 months). RESULTS: The 5-year and 10-year overall survival rates were 62% and 50%, respectively. The 5-year and 10-year disease-specific survival rates were 73% and 67%, respectively. The actuarial local control rate was 73% at 5 and 73% at 10 years, respectively. The 5-year and 10-year disease-specific survival rates for patients with a preserved bladder were 68% and 59%, respectively. Of all long-term surviving patients, 90% preserved their native bladders. The treatment was well tolerated. Acute toxicity was mild. Two patients experienced serious late toxicity: 1 patient developed a persisting vesicocutaneous fistula and the other a stricture of the urethra and ureters. CONCLUSION: For patients with solitary, organ confined invasive bladder cancer < or =5 cm, bladder preservation with brachytherapy is an excellent alternative to radical cystectomy and combined modality treatment.     

Human leukocyte antigen class I down-regulation in muscle-invasive bladder cancer: Its association with clinical characteristics and survival after cystectomy

Using a novel monoclonal anti-pan human leukocyte antigen (HLA) class I heavy chain antibody (EMR 8-5) reacting with paraffin-embedded sections, we examined the prognostic significance of HLA class I molecules in muscle-invasive bladder cancer patients who underwent radical cystectomy. Immunohistochemical staining for HLA class I molecules with monoclonal antibody EMR 8-5 was performed on specimens from 65 clinically muscle-invasive bladder cancer patients who underwent radical cystectomy and pelvic lymph node dissection without neoadjuvant chemotherapy. We analyzed the clinicopathological and prognostic significance of HLA class I expression. Immunohistochemical analysis revealed HLA class I down-regulation in 22 (33.8%) invasive bladder cancers. This down-regulation had no correlation with clinicopathological parameters such as pathologic stage, nodal status, and grade. The recurrence-free survival of patients with HLA class I–positive tumors was significantly better than that of those with down-regulation (log rank, P  =   0.0337). Multivariate analysis revealed that HLA class I expression was a significant factor influencing the recurrence-free survival of bladder cancer patients after cystectomy ( P  =   0.0155). Our data demonstrate that HLA class I down-regulation in tumor cells was clearly observed in about one-third of the patients. HLA class I expression could be a prognostic marker for muscle-invasive bladder cancer patients after cystectomy. ( Cancer Sci 2009; 100: 2331–2334)     

Independent predictors of cancer-specific survival in transitional cell carcinoma of the upper urinary tract: multi-institutional dataset from 3 European centers

BACKGROUND: The objective of the current study was to identify variables that were predictive of cancer-specific survival in patients with nonmetastatic transitional cell carcinoma of the upper urinary tract (UUT-TCC). METHODS: Clinical and pathologic data from 269 patients who underwent nephroureterectomy for UUT-TCC from 1989 to 2005 in 3 urologic European centers were collected retrospectively. Log-rank tests and Cox proportional-hazards regression models were used for univariate and multivariate analyses. RESULTS: Two hundred fifty patients underwent nephroureterectomy, and 19 patients underwent concomitant cystectomy for synchronous muscle-invasive bladder cancer. The median follow-up of the whole cohort was 34 months, and the median follow-up of the patients who remained alive and disease-free was 52 months. At follow-up, 57 cancer-related deaths (21.2%) were censored, and 169 patients (62.8%) were alive and disease-free. On univariate analysis, a history of previous bladder cancer, pathologic stage of the primary tumor and lymph nodes, tumor grade, the presence of lymphovascular invasion, tumor site, synchronous muscle-invasive bladder TCC, and tumor multifocality were associated with cancer-specific survival probabilities. On multivariate analysis, pathologic stage of the primary tumor and lymph nodes, tumor multifocality within the UUT, synchronous muscle-invasive bladder TCC, and a history of bladder TCC before the diagnosis of UUT-TCC were independent predictors of cancer-specific survival probabilities. CONCLUSIONS: In a multi-institutional dataset of patients who had undergone nephroureterectomy for UUT-TCC, the current results indicated that pathologic stage of the primary tumor and lymph nodes, a history of prior bladder TCC, the presence of synchronous muscle-invasive bladder cancer, and tumor multifocality within the UUT were independent predictors of cancer-specific survival probabilities.     

Prognostic factors,pattern of recurrence and survival in a Danish bladder cancer cohort treated with radical cystectomy

A cohort of 248 consecutive patients with bladder cancer undergoing radical cystectomy between 1992 and 98 was retrospectively followed from diagnosis until death. Prognostic factors, pattern of recurrence and survival were analysed. Pathological T and N, angiolymphatic and perineural invasion had an independent prognostic influence on survival. Patients without muscle-invasive tumour (Ta, T1) had a good prognosis, whereas patients with primarily superficial tumour progressing to muscle-invasive tumour had a significantly poorer outcome. Forty-six percent of these patients developed recurrences in the follow-up period, with a median time from recurrence to death of 5 months. The 5-year disease-specific survival for all 248 patients was 57%. Patients with pT4b or N + all died within 3 years. Patients with positive lymph nodes or T4b were not curable with cystectomy alone. Patients with advanced T or with perineural/vessel invasion are in need of improved treatment options. Patients with superficial tumours at high risk of progression should be offered early cystectomy.