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PubMed2004

Expression of Maspin in non-muscle invasive bladder carcinoma: correlation with tumor angiogenesis and prognosis.

OBJECTIVES: Maspin is a member of the serpin (serine protease inhibitor) family and has been shown to be a suppressor of tumor growth and an inhibitor of angiogenesis as well as metastasis in several types of tumors. We studied expression patterns of Maspin in pTa/pT1 urothelial carcinoma of the bladder and compared them with microvessel density (MVD) for two vascular markers (CD34 and CD105) and correlated the findings with clinical outcome. MATERIAL AND METHODS: We investigated tumor samples of 110 patients undergoing transurethral resection for pTa/pT1 bladder carcinoma (pTa, n=84; pT1, n=26; grade 1, n= 22; grade 2, n= 81; grade 3, n=7). Immunohistochemical studies were performed using the monoclonal antibodies, anti-human Maspin (NCL Maspin), anti-CD34 Class II and anti-CD105. Maspin expression level was classified according to the staining intensity (- to +++). The blood vessels (CD34) and specifically proliferating blood vessels (CD105) were counted as vessels per field (microvessel density, MVD). RESULTS: Of the 110 tumors, 27 showed a negative immunostaining for Maspin, 46 tumors stained +, 29 stained ++, and 8 stained +++. Maspin expression correlated inversely with CD34 reactivity. In tumors with loss of or only weak Maspin expression, the MVD for CD34 was 21.7 vessels per field, and 4.2 vessels per field for proliferating vessels (CD105), whereas Maspin-positive tumors had an MVD of 17.7 vessels per field (CD34), and of 6.0 vessels per field (CD105). Complete follow-up data are available in 92 patients. After a median follow-up of 25 months, 18 of the 92 patients (19.6%) had tumor recurrences. Tumors with decreased Maspin expression (-/+) had a shorter disease-free interval (23 months) than patients with stronger Maspin (++/+++) expression (29 months), whereas a Kaplan-Meier analysis and the log-rank test showed no significant difference in disease-free survival between the patients. CONCLUSION: The clinical importance of Maspin has been mainly investigated regarding tumor progression or metastasis. We found a decreased Maspin expression in a large portion of pTa/pT1 bladder tumors. Even if patients with decreased Maspin expression have a slightly shorter disease-free survival Maspin does not appear to be a promising prognostic marker.

Adult↗
PubMed2005

Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder: case report.

BACKGROUND: The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. CASE PRESENTATION: The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. CONCLUSION: This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms.

Aged↗
PubMed1993

[Two cases of bladder cancer in patients with chronic renal failure].

We report here two cases of bladder cancer in patients with chronic renal failure who had been treated with hemodialysis. Case 1: A 58-year-old male on hemodialysis for 3 years visited with a complaint of gross hematuria. Transurethral resection of the bladder tumor (TUR-Bt) was performed and histopathological examination showed grade 1, stage pTa transitional cell carcinoma (TCC). The patient was followed for 4 years postoperatively without recurrence. Case 2: A 64-year-old male with hemodialysis for 1 week was referred to our department with a gross hematuria. TUR-Bt was conducted and histopathological findings showed grade 2, stage pT1b TCC. In April, 1992, he revisited our hospital with bladder tamponade due to massive hematuria, and TUR-Bt was performed. Histopathologically, the tumors were grade 2, stage pT2 TCC. He was followed for 1 year without recurrence.

Carcinoma, Transitional Cell↗
PubMed1983

[Chemotherapy of bladder tumors. Indications and value of loco-regional and systemic application].

Systemic chemotherapy of advanced and metastatic bladder carcinomas leads to tumor regression and shows a palliative effect on symptomatic lesions in some of the cases, but the duration of the effect is limited. The value of an adjuvant chemotherapy following radical surgery or radiotherapy is not evaluated in clinical studies. Local chemotherapy induces complete regression of multifocal superficial bladder tumors in many cases. Of special interest are the results of treatment of carcinoma in situ by doxorubicin. Furthermore the intravesical chemotherapy has become widely used with a prophylactic goal in mind after complete transurethral resection of superficial bladder tumors. Aims and preliminary results of randomized clinical EORTC trials are reported.

Antineoplastic Agents↗
PubMed2006

Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial.

BACKGROUND: The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer. METHODS: After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website . FINDINGS: Median follow-up was 88 months (IQR 63-110). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (69 months [95% CI 55-86] vs 21 months [15-54]; difference between groups 48 months [42-54], log-rank p=0.0012). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (41.9% [32.7-51.5] vs 57.9% [48.7-67.5]; difference between groups 16.0% [2.7-29.3], log-rank p=0.0012); progression (9.3% [3.8-14.8] vs 21.9% [17.9-25.9]; difference between groups 12.6% [3.0-22.2], log-rank p=0.004); overall mortality (21.5% [13.5-29.5] vs 32.4% [23.4-41.4], difference between groups 10.9% [0.6-21.2], log-rank p=0.045); and disease-specific mortality (5.6% [1.2-10.0] vs 16.2% [6.1-23.3], difference between groups 10.6% [2.5-18.7], log-rank p=0.01). Side-effects were mainly localised to the bladder. INTERPRETATION: BCG-induced inflammation might increase the permeability of the bladder mucosa such that mitomycin can reach the target tissue more easily and exert its anticancer effect.

Aged↗
PubMed1987

Preoperative doxorubicin instillation in recurrent superficial bladder cancer.

Further recurrence of superficial bladder cancer after transurethral resection is frequent in patients who have already experienced recurrence. In an attempt to prevent or delay further recurrences in such patients, the effect of preoperative doxorubicin instillation was investigated. A total of 51 patients with recurrent superficial bladder cancer were randomized to receive either TUR alone or TUR with preoperative doxorubicin instillation. Doxorubicin was administered twice a week for 3 weeks before TUR surgery. An objective response (CR + PR) of the tumors was observed at operation in 12 of 25 (48%) evaluable doxorubicin-treated patients. Chemical cystitis was seen in 32% of the patients. Further recurrence after TUR was observed in 13 of 25 (52%) patients in the doxorubicin group, as against 15 of 23 (65%) evaluable patients in the control group. The mean disease-free interval was significantly longer (11.8 as against 7.1 months) in the doxorubicin group. These preliminary results suggest that preoperative doxorubicin instillation might be effective for prolongation of the disease-free interval in patients with recurrent bladder cancer.

Administration, Intravesical↗
PubMed2000

Numerical aberrations of chromosome 8 and allelic loss at 8p in non-muscle-invasive urothelial carcinomas of the urinary bladder.

OBJECTIVES: Cytogenetic and molecular studies indicate that the development and progression of bladder cancer involves multiple and complex genetic events. We screened 39 primary T(a )and T(1) transitional cell carcinomas of the urinary bladder for numerical changes of chromosome 8 and for the presence of relative allelic loss at 8p. The results were compared with the histopathologic stage and grade and with tumour recurrence. METHODS: Thirty-nine paraffin-embedded transurethral resection specimens containing bladder cancer were examined by interphase cytogenetics with a probe specific for chromosome 8. DNA from tumour cells and normal tissue was prepared after microdissection. Allelic loss was assessed by PCR-based microsatellite analysis. RESULTS: Numerical aberrations of chromosome 8 were present in 20 of the 39 cases (51.3%) and were significantly associated with a higher tumour grade and stage. Ten cases (25.6%) displayed allelic losses at 8p. Sixteen patients (41%) suffered from tumour recurrence, but Kaplan-Meier analysis and the log-rank test did not show any statistically significant correlation between tumour grade, stage, numerical aberrations of chromosome 8, allelic losses of 8p and freedom from disease recurrence. CONCLUSIONS: In this group of patients with non-muscle-invasive bladder cancers, numerical and structural aberrations at chromosome 8 are associated with a higher tumour grade and stage, but not with tumour recurrence.

Aged↗
PubMed1993

Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for infiltrating transitional cell carcinoma of the bladder.

BACKGROUND: Based on the excellent results with combination chemotherapy such as M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in patients with advanced disease, neoadjuvant chemotherapy has been advocated to improve survival and in some cases to permit bladder conservation. METHODS: A Phase II study of neoadjuvant M-VAC chemotherapy was performed in patients with T2-T4N0M0 bladder tumors. After clinical staging, three cycles of M-VAC were given. After patients underwent postchemotherapy clinical restaging, pathologic restaging (partial or radical cystectomy) was planned. RESULTS: Forty-six patients are evaluable. A clinical response was attained in 78%. Six patients (13%) had stable disease, and four (9%) had progression. After chemotherapy, 17 patients underwent radical cystectomy, none of whom were pTO. In this group, 10 of the 17 (59%) are alive at a median follow-up of 37+ months (range, 8-62+ months). Eleven patients had a partial cystectomy; 7 of the 11 (64%) are alive, 6 (55%) with a preserved bladder. Eighteen patients had clinical restaging only, and did not have pathologic staging. Median follow-up for this group is 36+ months (11-65+ months). Twenty-one of the 29 (72%) patients managed with conservative surgery or transurethral resection of the bladder alone are alive with a functional bladder. Median survival for all patients has not yet been reached. Two-year survival is 82%, and 3-year survival is 70%. CONCLUSIONS: The current study is of interest in terms of bladder conservation. Assessment of the true success of any bladder-preserving treatment will require longer follow-up.

Aged↗
PubMed2025

Biomarker-Based Nomogram to Predict Neoadjuvant Chemotherapy Response in Muscle-Invasive Bladder Cancer.

Background/Objectives: The aim of this study was to identify response prediction and prognostic biomarkers in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). Methods: A retrospective multicentre study including 191 patients with MIBC who received NAC previous to radical cystectomy (RC) between 1996 and 2013. Gene expression patterns were analysed in 34 samples from transurethral resection of the bladder (TURB) using Illumina microarrays. The expression levels of 45 selected differentially expressed genes between responders and non-responders to NAC were validated by quantitative PCR in an independent cohort of 157 patients. Regression analysis was used to identify predictors of downstaging and relapse. A nomogram for predicting downstaging and relapse-including clinicopathological and gene expression variables-was developed. Results: The expression levels of 1352 transcripts differed between responders and non-responders to NAC. A nomogram based on the most predictive clinical variables (age, Tis (in situ), gender, history of NMIBC, and lymphadenopathy) and genes selected following the Akaike information criterion (AIC) (CBTB16, CHMP6, DDX54, CASP8, LOR, and PLEC) was then created. In addition, a three-gene expression prognostic model to predict tumour relapse was generated. This model was able to discriminate between two groups of patients with a significantly different probability of tumour relapse (HR: 2.11; CI: 1.16-3.83, p = 0.01). Conclusions: Our nomogram based on gene expression and clinical data is a useful tool to predict downstaging and tumour relapse after NAC in MIBC patients. Further validation is warranted.

bladder cancer↗
PubMed1996

Müllerianosis of the urinary bladder.

Three women, 37, 44, and 46 years of age, had masses up to 4 cm in maximal size, which involved the posterior wall of the urinary bladder, treated by transurethral resection. Microscopic examination showed prominent involvement of the lamina propria and muscularis propria by tubules and cysts lined by müllerian-type epithelium; in two cases, the latter also focally replaced the urothelium and formed polypoid projections into the bladder lumen. The tubules and cysts were usually round to oval but occasionally exhibited prominent branching. In all three cases, the glands were predominantly lined by tubal-type epithelium (including ciliated cells, intercalated, and peg cells), that represented endosalpingiosis. Each case also contained a minor component of glands lined by columnar mucinous cells (endocervicosis). In one case, there was a minor component of typical endometriosis, and, in another, endometrioid epithelium was associated with prominent pseudoxanthoma cells in the adjacent stroma. On the basis of these three cases, striking endosalpingiosis of the urinary bladder, which has not been previously documented, is usually associated with endocervicosis, endometriosis, or both, and, in such cases, the designation "müllerianosis" is appropriate. Müllerianosis can be distinguished from adenocarcinoma and various non-neoplastic glandular lesions of the urinary bladder on the basis of a variety of architectural and cytologic features.

Adult↗
PubMed1998

Recurrent bilateral renal calculi in a tetraplegic patient.

An 18-year-old male developed C-5 complete tetraplegia following a motor-cycle accident in May 1975. The neuropathic bladder was managed by an indwelling urethral catheter. He developed recurrent episodes of urinary infection with Proteus species. In September 1975, an X-ray of the abdomen revealed small calculi in both the kidneys. In July 1976, he underwent transurethral resection of the bladder neck and division of the external urethral sphincter; subsequently, he was put on a penile sheath drainage. He continued to suffer from repeated episodes of urinary tract infection with Proteus, Providencia, and Pseudomonas species, and he was treated with antibiotics. In 1980, intravenous urography (IVU) showed two large stones in the left kidney with marked caliectasis. The IVU performed in 1984 showed an increase in the size of the calculi in the left kidney which was grossly hydronephrotic. There were clusters of small calculi in the right kidney. The left renal calculi were treated by percutaneous lithotripsy in two sessions. In 1988, an X-ray of the abdomen revealed staghorn calculus in the right kidney and recurrence of stones in the left kidney. The staghorn calculus in the right kidney was treated by percutaneous nephrostolithotomy in two sessions. In 1991, he was admitted with acute urinary infection. IVU showed a stone in the pelviureteric junction with no excretion of contrast in the left kidney. Percutaneous nephrostomy drainage was established followed by left percutaneous nephrostolithotomy. In 1992, he was found to retain large amount of urine in the bladder; subsequently, his mother was taught to perform regular intermittent catheterisations. In 1995, he was admitted with acute urine infection. Abdominal X-ray revealed recurrence of large stones in both kidneys. With multiple sessions of Extracorporeal Shockwave Lithotripsy (ESWL), about 80% clearance was achieved on the left side. Right staghorn renal stone awaits treatment. This case shows that recurrent urinary infection in spinal cord injury patients is a predisposing factor for renal lithiasis. These patients require annual urological evaluation. Urinary tract calculi, if detected, should be dealt with promptly to prevent renal damage due to urinary obstruction and urosepsis. Renal calculi can be treated effectively and safely by ESWL in spinal cord injury patients, thus avoiding the need for an invasive procedure. It is essential to achieve low-pressure, adequate emptying of the urinary bladder in patients with spinal cord injury in order to prevent recurrent urinary infection and its sequelae. Social issues involved in the care of a tetraplegic patient play a vital role in the implementation of ideal medical treatment and need to be addressed promptly to avoid any compromise in the quality of medical care.

Adolescent↗
PubMed2001

Gene therapy for bladder cancer using adenoviral vector.

BACKGROUND AND PURPOSE: Bladder cancer is common. Current treatment for patients with superficial bladder cancer involves transurethral resection followed by adjuvant bacillus Calmette-Guérin (BCG) administration. Adjuvant BCG has been reported to be effective in 38% to 68% of patients; however, more than 30% of patients do not respond. Because p53 mutations are common among superficial bladder cancers, we tested the feasibility of using p53 as a gene therapy agent for targeting superficial tumors, which are easily accessible using an intravesical approach. MATERIALS AND METHODS: Wild-type p53 was transduced into various human and murine bladder cancer cell lines (HTB9, KU-1, and MBT-2) using a recombinant adenoviral vector (Ad5CMV-p53) in vitro. Also, subcutaneous tumors were established and then treated with intratumoral injection of Ad5CMV-p53 or control viruses. RESULTS: In vitro assays revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV-PA vector or untreated control cells. In vivo studies using subcutaneous bladder tumor models established in syngeneic mice demonstrated that the rate of tumor growth and volume was reduced to a greater extent by 14 days of intratumoral injection of Ad5CMV-p53 rather than Ad5CMV-PA. Furthermore, the survival of host animals bearing tumors that were infected with Ad5CMV-p53 was significantly longer than that of the control group treated with Ad5CMV-PA (P < 0.01). CONCLUSION: Our data suggest that Ad5CMV-p53 is effective in suppressing bladder cancer growth and improving host survival.

Adenoviridae↗
PubMed2001

Cytokeratin-20 reverse-transcriptase polymerase chain reaction as a new tool for the detection of circulating tumor cells in peripheral blood and bone marrow of bladder cancer patients.

OBJECTIVES: Systemic progression is the prevalent form of bladder tumor recurrence after radical cystectomy. The ability to detect circulating tumor cells in peripheral blood or bone marrow could be of prognostic value for the disease with the consequence of early adjuvant chemotherapy. We established a sensitive and specific method using a double cytokeratin-20 (CK-20) reverse-transcriptase polymerase chain reaction (RT-PCR) to detect circulating bladder cancer cells in venous blood and bone marrow MATERIAL AND METHODS: The sensitivity of the detection method was determined by a serial dilution of bladder cancer cells from the cell line HT1376 in whole blood. Bone marrow from 20 bladder cancer patients was drawn prior to radical cystectomy and CK-20 cDNA was amplified by RT-PCR. Additionally, pre- and postoperative venous blood samples from 11 of these patients with bone marrow aspirates and 9 patients undergoing only transurethral resection of the bladder as well as blood samples of 25 healthy volunteers were investigated by CK-20 RT-PCR. RESULTS: The detection limit of the method was 2 bladder cancer cells/ml whole blood containing one million peripheral blood mononuclear cells. The positive detection rate in bone marrow was 7 of 20 (35%) for bladder cancer patients of all stages. However, investigation of the preoperatively collected venous blood samples from 20 patients revealed onyl 2 positive findings, belonging to advanced tumor stages pT4pN0M0 and pT3pN2M0. In contrast, CK-20 was detected in 3 of 20 postoperatively collected venous blood samples from patients with low tumor stages (pTaNXM0 and pT1NXM0) as well as from 1 patient with pelvic lymph node metastases (pT3apN2M0). All venous blood samples of the control group (n = 25) were negative for CK-20. CONCLUSION: The detection of circulating bladder tumor cells in venous blood and bone marrow by the CK-20 RT-PCR is a promising approach that could improve risk assessment and the identification of bladder cancer patients who would benefit from adjuvant chemotherapy.

Adult↗
PubMed2003

Is there a role for bladder preserving strategies in the treatment of muscle-invasive bladder cancer?

Single modality bladder sparing therapy for muscle-invasive bladder cancer, including transurethral resection, systemic chemotherapy or radiotherapy have been demonstrated to result in insufficient local control of the primary tumor as well as decreased long-term survival of the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitize tumor tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder preserving approaches are costly, and require close co-operation between different clinical specialists as well as very close follow-up. The good long-term results obtained after cystectomy and creation of an orthotopic neobladder make the possible advantage of a bladder preservation strategy questionable in consideration of quality of life issues. Additionally, side effects related to bladder sparing therapy may result in an increased morbidity and mortality in those patients who in fact need to undergo surgery due to recurrent or progressive disease. Multimodality bladder sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder tumors.

Adult↗
PubMed2006

A case of TURBT after penile prosthesis implantation.

The patient was a 66-year-old man who had undergone implantation of a penile prosthesis for organic erectile dysfunction 7 years prior to consulting our hospital with a complaint of gross hematuria. Since a pedunculated, superficial tumor 1 cm in diameter was noted lateral to the left ureteral orifice, transurethral resection of the bladder tumor (TURBT) was performed. In this patient, we were able to insert the sheath with no difficulty, and the surgical procedure was done smoothly, resulting in complete resection of the tumor. However, the location of the tumor in the anterior or posterior wall of the bladder predicted difficulty of the tumor resection. Therefore, we consider it important to sufficiently evaluate the feasibility of complete TURBT before surgery and to thoroughly examine the patient for benign prostatic hyperplasia and bladder cancer, which can cause difficulty with post-implantation ransurethral procedures, and to perform transurethral surgery before implantation, if prosthesis implantation is planned.

Aged↗
PubMed2005

Recurrence and progression of T1G3 transitional cell carcinoma of the bladder treated with intravesical bacillus Calmette-Guérin.

OBJECTIVE: To examine the incidence of recurrence and progression in patients with stage T1, grade-3 carcinoma of the bladder treated with endovesical bacillus Calmette-Guérin (BCG) after complete transurethral resection. MATERIAL AND METHODS: From May 1995 to June 2002, 937 patients with superficial bladder cancer underwent transurethral resection. 46 patients (4.9%) had T1G3 tumors. All patients received endovesical BCG therapy 2-3 weeks after transurethral resection, given in 6 sessions as weekly instillations of 120 ml Pasteur strain BCG in 50 ml saline. Success was defined by normal cytology and cystoscopy, and normal bladder biopsies. Recurrent tumors were resected and a second or third cycle of therapy was given according to pathological status. Progressive tumors were managed by radical cystectomy, radiotherapy and/or chemotherapy depending on the nature of the tumor or clinical status of the patient. RESULTS: During follow-up 60.7% of the patients (28 of 46) remained tumor free after only 1 BCG cycle and 73.9% (34 of 46) after the third BCG cycle, and the bladder was preserved in all. Muscle-invasive progression was noted in 10 (21.7%) patients at the end of the BCG cycles. Radical cystectomy was done in 10 patients. The tumor-free survival rate of all patients including those who underwent cystectomy is 84.8% (39 of 46) with a median follow-up of 61 (range 39-118) months. CONCLUSION: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective treatment for bladder preservation in stage pT1, grade-3 carcinoma of the bladder. pT1G3 tumors with early high-grade recurrence after failed immunotherapy should be regarded as candidates for early radical cystectomy.

Adjuvants, Immunologic↗
PubMed1990

Can chemo-radiotherapy plus transurethral tumor resection make cystectomy unnecessary for invasive bladder cancer?

The standard treatment for muscle-invading bladder tumors is, in the US, radical cystectomy +/- radiation; in Europe, it is radical radiotherapy. Neither of these therapies alone is wholly satisfactory. Suggested improvements in the complete response rates of the primary tumor have been reported with combination chemotherapy and with chemo-radiotherapy. Selecting for full chemo-radiotherapy only patients having a biopsy-proven CR to initial chemotherapy and/or to 4,000-4,500 cGy of radiation may further increase the success of bladder-preserving programs and not compromise survival (relative to immediate cystectomy), but this has not yet been proven. Randomized trials of neoadjuvant chemotherapy must be finished before its efficacy in subclinical systemic disease will be known. Likewise, proof of the efficacy of neoadjuvant chemotherapy in improving bladder preservation by chemo-radiotherapy must await completion of randomized trials. Three to five years of follow-up will be necessary before chemo-radiotherapy can be recommended as curing the bladder of cancer.

Combined Modality Therapy↗