Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the National Cancer Data Base

PURPOSE: Studies of perioperative chemotherapy for muscle invasive bladder cancer have shown a survival benefit with combined modality therapy. We reviewed chemotherapy use in patients with stage III transitional cell carcinoma of the bladder from 1998 to 2003 to evaluate perioperative chemotherapy treatment patterns. MATERIALS AND METHODS: The National Cancer Data Base collected data on approximately 60% of all newly diagnosed bladder cancer cases in the United States from 1998 to 2003. We queried the National Cancer Data Base for all treatment of male and female patients 18 years old or older with bladder transitional cell carcinoma diagnosed between 1998 and 2003. A total of 224,060 bladder transitional cell carcinoma records were reviewed. Perioperative chemotherapy was defined as chemotherapy given within 4 months before and 4 months after surgery. Of 11,339 cases of stage III bladder cancer treatment, analysis was possible for 7,161. RESULTS: Treatment patterns were analyzed in 7,161 patients with stage III bladder transitional cell carcinoma. Perioperative chemotherapy was administered to 11.6% of patients with stage III bladder transitional cell carcinoma with 10.4% receiving adjuvant chemotherapy and 1.2% receiving neoadjuvant chemotherapy. When comparing perioperative chemotherapy use by diagnosis year in 1998 and 2003, a small statistically significant increase was observed using the Pearson's chi-square test with Bonferroni correction (p <0.05) at 11.3% of patients in 1998 vs 16.8% in 2003. CONCLUSIONS: Perioperative chemotherapy is underused in the management of surgically resectable stage III transitional cell carcinoma of the bladder. This finding may reflect a delay in implementing the results of recently reported randomized trials, a low incidence of referrals by urologists for chemotherapy and/or confidence in salvage chemotherapy as an equivalent alternative. Further followup will determine if this treatment pattern changes in the future.     

Micropapillary urothelial carcinoma of the bladder: case report and review of the literature

Micropapillary urothelial carcinoma (MCP) of the urinary bladder is an rare anatomopathology variant of aggressive behaviour. It is usually found as a high grade and stage carcinoma, and doesn't differ clinically from normal cell carcinoma of the bladder. Treatment should be early and aggressive, because radiotherapy and chemotherapy have shown limited results the therapy is surgically based. The diagnosis of this disease is required because its metastasic capacity is associate with a significantly increased mortality risk. In this study we report the case of a 64 years old man with a long development hematuria diagnosed of Micropapillary carcinoma infiltrating the bladder involving the ureter.     

Prophylactic intravesical chemotherapy in bladder tumors after surgery of upper tract urothelial carcinoma

Sixteen patients with upper tract urothelial carcinoma underwent intravesical chemotherapy usually at 2 week intervals in the first year and at 4 week intervals in the second year after nephrouretectomy. For bladder instillation 10 mg mitomycin C in 20 ml saline was used on 7 patients, 5 mg carboquone and 100 mg cytosine arabinoside in 40 ml saline on 5 patients and 30 mg adriamycin in 40 ml saline on 4 patients. Two (12.5%) of the 16 patients developed bladder tumors within 2 years after surgery, but 11 (42.3%) of the 26 patients with upper tract urothelial carcinoma who did not receive intravesical chemotherapy suffered from bladder tumor within 2 years after surgery. Prophylactic intravesical chemotherapy reduced significantly (p less than 0.1) the incidence of bladder tumor after the surgery of renal pelvic and ureteral tumors.     

Three cases of small cell carcinoma of the urinary bladder: a case report

We report three cases of small cell carcinoma of the urinary bladder. Case 1: A 69-year-old man showed microscopic hematuria during follow up of prostate cancer of stage D2. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0. Complete remission was achieved by three courses of chemotherapy consisting of irinotecan and carboplatin. The patient was died by prostate cancer 16 months after the chemotherapy. Case 2: An 83-year-old woman presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0 and partial cystectomy was performed. The patient has been alive without any evidence of tumor recurrence at 6 months after surgery. Case 3: An 84-year-old man presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage ofcT3bN0M1 with multiple liver metastases. Complete remission was achieved by three courses of chemotherapy consisting of etoposide and carboplatin.     

A young patient with invasive small cell carcinoma of the urinary bladder: a case report

A 29-year-old woman with gross hematuria was referred to our hospital. Cystoscopy revealed a nonpapillary broad-based tumor on the right lateral wall of the urinary bladder, which a transurethral biopsy identified as transitional cell carcinoma (G2). CT and MRI suggested that the carcinoma invaded beyond the bladder wall. We performed a radical cystectomy with hysterectomy and the construction of an ileal neobladder. Pathological examination of the specimen indicated that it was small-cell undifferentiated carcinoma at the stage of pT2bpN0. For adjuvant chemotherapy, four cycles of CPT-11 and CDDP chemotherapy were performed, which is currently the usual chemotherapy for small-cell lung carcinoma in Japan. The patient is alive without any evidence of tumor recurrence at 12 months after surgery.     

A case of squamous cell carcinoma of the urinary bladder effectively responsive to combination chemotherapy]

A case of invasive pure squamous cell carcinoma of the urinary bladder effectively responsive to combination chemotherapy in a 79-year-old female is reported. Clinical staging of the tumor was T3b. We used combination chemotherapy with methotrexate, peplomycin and cis-platinum (MBD regimen) before radical cystectomy. Remarkable regression of the tumor was identified by computed tomographic scan after one course of chemotherapy and the surgical specimen revealed no viable tumors. The patient has been very active in her daily life without evidence of local recurrence or metastasis for more than one year. Squamous cell carcinoma of the bladder generally is regarded as having a poor prognosis with 5-year survival rates ranging from 7.4 to 26% and effective chemotherapy has not yet been established. Our experience suggests that the cure rate of pure squamous cell carcinoma may be improved markedly by the use of MBD regimen.     

Brain metastases from transitional cell carcinoma of the bladder

We present our experience with 4 patients with transitional cell carcinoma of the bladder and brain metastases. In all 4 cases a solitary intracranial metastasis occurred. In 3 patients this represented the first site of recurrent disease following systemic chemotherapy. Aggressive therapy of the brain metastases was instituted in 3 patients, including external beam radiation and in 2 cases surgical resection. Although all patients died only 3 died as a result of metastatic transitional cell carcinoma, including 2 who died as a direct result of intracranial disease. A review of the literature suggests an increasing incidence of brain metastases from transitional cell carcinoma of the bladder with the advent of more aggressive therapy for bladder cancer, which includes radical surgery for high stage disease and combination chemotherapy. Aggressive intervention for solitary brain metastases from transitional cell carcinoma can relieve neurological dysfunction and may prolong survival.     

Primary signet-ring cell carcinoma of the urinary bladder inducing renal failure

A case of primary signet-ring cell carcinoma of the urinary bladder that was found to have induced renal failure is the second such case reported in the world. Primary signet-ring cell carcinoma of the urinary bladder is a rare histologic variant of adenocarcinoma. The patient died of distant metastasis 8 months after undergoing total cystectomy. The neoplasm had a high stage at diagnosis, so the prognosis was very poor. To improve the prognosis, earlier diagnosis and establishing a regimen of chemotherapy is necessary.     

Primary small cell carcinoma of the bladder in which the bladder preservation was achieved by chemotherapy and transurethral resection

A 78-year-old man was referred to our hospital for asymptomatic gross hematuria on April 16, 2007. Cystoscopy and abdominal computed tomography revealed a nonpapillary tumor at the upper area of the bladder. Abdominal and thoracic computed tomography showed no lymph nodes and no metastasis to other organs. Transurethral resection of bladder tumor (TURBT) was performed, and a pathological diagnosis of small cell carcinoma of the bladder at stage pT2N0M0 was made. Considering the patient's age and the location of the tumor, we administered chemotherapy using carboplatin and etoposide after resection of the tumor. After 2 courses of chemotherapy, a second-look TURBT was performed, and pathological examination showed no viable tumor cells. Cystoscopy performed after 3 months revealed recurrence of a nonpapillary tumor at a different area of the bladder. We performed TURBT and made a pathological diagnosis of small cell carcinoma of the bladder at stage pT1N0M0. The patient was free from disease in January 2011.     

Urachal carcinoma treated with neoadjuvant intra-arterial chemotherapy: a case report

A 43-year-old man visited our clinic with gross hematuria. Ultrasonography and computed tomography demonstrated a tumor at the bladder dome. Cold punch biopsy revealed well-differentiated adenocarcinoma and stage III A urachal carcinoma was diagnosed. Neoadjuvant intra-arterial chemotherapy with cisplatin, adriamycin and angiotensin II was performed and 40% reduction of tumor size was noted 3 weeks after this therapy. En bloc segmental resection was performed. Augmentation ilealcystoplasty was subsequently performed to secure bladder capacity. Adjuvant chemotherapy (UFT) was given for 1 year. Cystolithotomy and closure of ventral hernia were required 10 years after radical surgery for postoperative complications. The patient has survived 12 years with no evidence of local recurrence or distant metastasis.     

脐尿管癌的诊断和治疗(附9例报告)

目的探讨脐尿管癌的诊断和治疗方法及其疗效。方法回顾性分析广西医科大学附属肿瘤医院1999年7月至2009年12月收治的9例脐尿管癌患者的临床资料和随访结果,其中黏液腺癌6例、肠型腺癌1例、尿路上皮癌2例。结果本组患者最常见的临床症状为血尿和膀胱刺激症状,膀胱镜检查主要表现为膀胱顶部宽基底肿物,影像学检查常见膀胱顶前壁与腹壁之间软组织肿块影,多浸润膀胱壁。2例(Ⅲ期)膀胱部分切除者分别于术后7、9个月局部复发,并于1年内死亡。1例(Ⅳ期)晚期未切除者行化疗,无进展生存6个月,化疗后13个月死亡。6例行扩大性膀胱部分切除术,患者中1例(Ⅳ期)术后18个月因肺转移死亡,2例(Ⅲ期)术后32个月及41个月死亡,3例(Ⅲ期)分别为术后22、58和62个月,仍在随访中。结论脐尿管癌发病位置隐匿,术前诊断较为困难。治疗方法主要是行扩大性膀胱部分切除术,首次手术彻底切除肿瘤及对晚期及术后复发转移患者积极的综合治疗是提高脐尿管癌疗效的关键。本病的预后很差,临床分期与预后密切相关。     

原发性膀胱小细胞癌诊治体会

目的 探讨膀胱小细胞癌的临床及病理特点.方法 回顾性分析9例膀胱小细胞癌的基本资料.男6例,女3例.年龄45～79岁,平均62岁.临床表现为肉眼血尿7例,排尿困难及下腹部疼痛2例.肿瘤直径0.5～7.0 cm,平均2.0 cm;多发2例,单发5例,全膀胱弥漫性生长2例.7例行尿脱落细胞学检查,阳性4例.9例均行手术治疗,其中4例术前诊断为浅表性者行TURBt,术后均定期行吡柔比星膀胱灌注,1例化疗3个周期;膀胱部分切除2例,均定期行吡柔比星膀胱灌注,1例化疗2个周期;根治性膀胱全切3例,静脉化疗2例.结果 术后病理检查:肿瘤细胞体积小,呈圆形,胞质稀少,核浓染,缺乏巢状结构.免疫组化染色:嗜铬素A(+)、神经元特异性烯醇化酶(+).诊断为小细胞癌,其中1例含移行细胞癌成分,1例合并前列腺癌.1例术前检查显示高血钙(3.15 mmol/L)和低血磷(0.61 mmol/L),术后1个月血钙及血磷恢复正常.保留膀胱者随访4例,3例分别于术后4、9、25个月死于转移,1例术后化疗者随访24个月未见复发及转移.膀胱全切3例中2例分别于术后2、28个月死亡,1例术后随访32个月未见肿瘤复发及转移.结论膀胱小细胞癌恶性程度高,预后差,根治性膀胱全切加全身化疗是主要的治疗方法,保留膀胱的手术应配合全身化疗.决定预后的是肿瘤的临床分期及治疗方法.

Abstract：

Objective To investigate the clinical and pathological features of small cell carcinoma of the urinary bladder. Methods The pathological and clinical data of 9 cases of small cell carcinoma were analyzed retrospectively. There were 6 males and 3 females, ages 45 to 79 years (mean age, 62 years). Clinical manifestations of 7 cases included gross hematuria and dysuria, the other 2 cases experienced lower abdominal pain. The mean tumor size was 2.0 cm (ranged, 0.5 to 7.0 cm). Two cases had multiple tumors and 5 cases had single tumors. The growth pattern in 2 cases was diffuse growth in the whole bladder. In 4 cases tumor cells were found in urine cytology. All 9 patients underwent surgical treatment, including TURBt. Four patients were diagnosed as superficial tumors before operation. All the patients underwent regular theprubicine irrigation in the bladder. One case underwent additional intravenous chemotherapy for 3 cycles. Partial cystectomy was performed in 2 cases, with regular theprubicine irrigation in bladder and 1 case underwent intravenous chemotherapy for 2 cycles. Radical cystectomy was performed in 3 cases, with 2 cases undergoing intravenous chemotherapy after operation. Results Pathological findings showed that tumor cells were small and round in shape. These hyperchromatic nuclei showed limited cytoplasm with lack of nesting characters. CgA and NSE were positive in immunohistochemistry. The final diagnosis was small cell carcinoma, with 1 case accompanied with transitional cell carcinoma and 1 case accompanied with prostate cancer. One case showed high preoperative serum calcium (3.15 mmol/L) and low serum phosphate (0.61 mmol/L), which returned to normal 1 month after operation. Four cases who′s bladder was preserved were followed up, 3 cases were alive for 4, 9 and 25 months after operation. The 1 case who underwent intravenous chemotherapy was followed up for 24 months and there was no sign of relapse or metastasis. In all the 3 cases with radical cystectomy, 2 cases died 2 and 28 months postoperativly. Another case with adjuvant chemotherapy was followed up for 24 months without recurrence or metastasis. Conclusions Small cell carcinoma of the urinary bladder is highly malignant with poor prognosis. Radical cystectomy in combination with systemic chemotherapy has better efficacy. Retained bladder surgery with systemic chemotherapy is an alternative choice. The most important factors which influence the prognosis of the tumor are clinical stage and therapeutic methods.     

Preliminary European results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder

INTRODUCTION: Superficial bladder cancer can be treated by transurethral resection (TUR) and adjuvant intravesical therapy. Intravesical bacillus Calmette-Guérin (BCG) has been proven to be more efficacious with respect to recurrence prevention than intravesical chemotherapy, although at the cost of more severe side effects. There is a need for a new treatment modality with higher efficacy and less toxicity. The subject of this study is the efficacy of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Ninety eligible patients received adjuvant treatment with a combination of mitomycin-C (MMC) and local microwave hyperthermia. All patients had multiple or recurrent Ta or T1 TCC of the bladder and were classified as intermediate or high risk according to EAU criteria. In total, 41 patients were BCG failures. The treatment regimen included 6 to 8 weekly sessions followed by 4 to 6 monthly sessions. Follow-up consisted of video-cystoscopy and urine cytology every 3 months. All patients were observed for 2 years. RESULTS: Kaplan-Meier analyses of the total group (N = 90) indicated that 1 year after treatment only 14.3% (SE 4.5%) of all patients experienced a recurrence. After 2 years of follow-up the risk of recurrence was 24.6% (SE 5.9%). No progression in stage and grade was observed. CONCLUSION: Microwave induced hyperthermia combined with MMC has promising value in intermediate or high risk superficial bladder cancer patients compared to literature data of BCG and/or intravesical chemotherapy, particularly where other treatments, i.e. BCG, have failed.     

A case of successful preoperative chemotherapy with cisplatin and irinotecan followed by curative-intent surgery for locally advanced thymic carcinoma

The optimal chemotherapy for thymic carcinoma has yet to be determined based on clinical evidence because of the rarity of this pathological entity. We report the case of a patient with locally advanced thymic carcinoma in whom radical excision was achieved with intensive preoperative chemotherapy followed by curative-intent surgery. A 59-year-old woman was diagnosed with Masaoka-Koga stage III thymic cancer showing squamous cell carcinoma histology. Invasion to the ascending aorta and left brachiocephalic vein was suspected from imaging, so preoperative chemotherapy with three cycles of cisplatin and irinotecan was administered. Partial response to chemotherapy was achieved and the residual tumor was completely resected with subsequent surgery. Histopathological examination of the resected specimen demonstrated stage II thymic carcinoma. The patient has shown no evidence of recurrence or surgical complications as of 46 months after completing preoperative chemotherapy.     

Intravesical suramin: a novel agent for the treatment of superficial transitional-cell carcinoma of the bladder

Summary Patients with recurrent or high-grade superficial transitional-cell carcinoma of the bladder that has recurred after intravesical chemotherapy are at increased risk for tumor invasion and metastases. Intravesical chemotherapy is a minimally invasive technique that allows high doses of therapeutic agents to be delivered directly to the malignancy, doses that would not be tolerated systemically. In vitro studies demonstrate suramin's significant efficacy against transitional-cell carcinoma cell lines at relatively low doses. Humans treated with similar doses delivered in a systemic fashion have experienced no bladder toxicity. Suramin has been shown to block the binding of epidermal growth factor (EGF) to its receptors, which are found in large amounts in bladder cancers. Because a significant association has been found between the number of EGF receptors on a bladder-cancer cell and its sensitivity to suramin, transitional-cell carcinoma could potentially be very responsive to such therapy. On the basis of these findings, a phase I escalating-suramin-dose study is currently being conducted.     

Small cell carcinoma of the bladder: a case report

A 61-year-old man was referred to our hospital with a complaint of gross hematuria and lower abdominal discomfort. Ultrasonography, magnetic resonance imaging and cystoscopy revealed a nodular invasive tumor in urinary bladder. The histopathological findings of transurethral-biopsy specimen was the small cell carcinoma and transitional cell carcinoma of the bladder infiltrating into smooth muscle layer. Total cystectomy with ileal conduit was performed following 1 course of neoadjuvant chemotherapy (M-VAC). Computed tomography (CT) before adjuvant chemotherapy revealed tiny lung metastasis in left peripheral lung area. As postoperative adjuvant therapy, 4 courses of chemotherapy (etoposide and calboplatin) were performed with 50 Gy of extra beam radiotherapy to the lung metastasis. Follow up CT revealed disapperance of lung metastasis, and the patient has been free from disease for one year after chemotherapy.     

Primary signet ring cell adenocarcinoma of the bladder

Primary signet ring cell adenocarcinoma of the bladder accounts for less than 1 per cent of all primary bladder neoplasms. This tumor is insidious because of its subepithelial infiltrative nature, which makes diagnosis possible only late in the course of the disease. Survival is poor; greater than 50 per cent of the patients are dead within a year after diagnosis. Exenterative procedures offer the only hope of palliation; irradiation and chemotherapy have not been effective. We add 5 cases of primary signet ring cell adenocarcinoma of the bladder and 1 case of high grade transitional cell carcinoma of the bladder with signet ring cell foci to the 14 cases reported in the literature. Pathological correlation supports the origin of this neoplasm from totipotential transitional epithelium.     

保留膀胱髂内动脉化疗治疗膀胱癌(附38例报告)

目的：提高膀胱癌的治疗效果,尽可能保留有功能的膀胱。方法总结38例不同分期、分级膀胱癌患者的临床资料,分3组,T1 12例为第1组,行经尿道膀胱肿瘤切除术（TURBt)和髂内动脉化疗及膀胱灌注化疗;T2 14例为第2组,行膀胱部分切除,髂内动脉化疗及膀胱灌注化疗;T312例为第3组,行姑息性TURBt和髂内动脉化疗,化疗后行内动脉栓塞。结果38例中33例保留了膀胱。38例术后随访2－15。第1组中10例保留膀胱且存活至;4例多次复发者反复行TURBt,其中2例最终行全膀胱切除加淋巴清扫未发现浸润加深和转移。第2组中1例2年后死于淋巴转移,1例疗后出现肾衰行血透治疗,共13例保留膀胱,均存活至今。第3组中8例为高危病淋巴转移,1例化疗后出现肾衰行血,人13例保留膀胱,均存活至今。第3组中8组为危危病淋巴转移。1例化疗后出现肾衰行血透治疗;共13例保留膀胱,均存活至今。第3组中8例为高危病人,其中2例末坚持治疗者于2－3年内死亡;3例肿瘤消失。多次随机活检均未找到肿瘤细胞;7例肿缩小,其中3例行膀胱部分切除术,病理分期有所好转,余4例血尿控制,膀胱容量增加,一般情况改善;共10例保留膀胱,平均存活58个月,结论：保留有功能性的膀胱手术加髂内动脉藻注化疗为治疗膀胱癌有效方法之一。     

The limits of bacillus Calmette-Guerin for carcinoma in situ of the bladder

PURPOSE: Historically carcinoma in situ of the bladder has been treated with radical cystectomy based on the aggressive and potentially invasive nature of this disease. The introduction in the late 1970s of intravesical bacillus Calmette-Guerin (BCG) has made this therapy the gold standard in the management of carcinoma in situ. Cases that are refractory or resistant to BCG therapy are a management dilemma with various available treatment options. MATERIALS AND METHODS: A comprehensive literature review of the current management of carcinoma in situ of the bladder was performed using MEDLINE, a review of current urology journals and abstracts from recent urology meetings. Data focused on BCG resistant carcinoma in situ of the bladder and current approaches in use for refractory disease. RESULTS: Complete and durable response rates have been reported in more than 70% of patients with carcinoma in situ who are treated with intravesical BCG. To our knowledge the optimal therapeutic regimen has not been established, although extended periods of treatment beyond the originally described 6-week course have not been shown to improve complete response rates. Prolonged administration of BCG is associated with adverse side effects. Various prognostic indicators of recurrence and progression exist that may identify a subset of cases unlikely to respond favorably to a conservative approach, including carcinoma in situ with associated stage T1 bladder lesions, diffuse and multifocal carcinoma in situ, multiple recurrences with intravesical therapy and extravesical involvement. Current molecular markers may also predict the response of carcinoma in situ to therapy. Treatment options available for BCG refractory carcinoma in situ of the bladder include intravesical chemotherapy, combined immuno-chemotherapy and radical cystectomy. Intravesical valrubicin and oral bropirimine have been shown to induce a complete response rate of 21% to 50%, although data on long-term followup are forthcoming. Radical cystectomy remains effective therapy for aggressive carcinoma in situ of the bladder. CONCLUSIONS: The current management of carcinoma in situ of the bladder is ill defined due to the variable natural history and unpredictable response of this disease to therapy. Controversy exists as to the optimal treatment of carcinoma in situ of the bladder since different forms of carcinoma in situ may exist that complicate therapeutic decisions for appropriate therapy. Some tumor characteristics are associated with more aggressive behavior and may be predictive of treatment outcome.     

Current developments in the diagnostics and therapy of bladder carcinoma

Considerable progress has been made in nearly all clinical scenarios of bladder carcinoma. Nevertheless early detection of bladder carcinoma using urine markers is still difficult so that none of the available tests can be recommended as a screening test. Photodynamic diagnostics and resection has now been shown for the first time to improve recurrence-free survival of patients but this impact on survival has to be confirmed in a phase III clinical trial before being regarded as standard of care. In pT1G3 tumors early cystectomy seems to improve the prognosis compared to organ preserving strategies. The value of adjuvant chemotherapy is becoming more and more evident, as, apart from several retrospective analyses it has been shown to improve survival in a clinical phase III trial. Furthermore, molecular markers are gaining importance and in the future can be used for identifying patients who may benefit from systemic chemotherapy of bladder carcinoma.