National Cancer Institute®
Last Modified: January 1, 2002
UI - 10791373
AU - van der Zee J; Gonzalez Gonzalez D; van Rhoon GC; van Dijk JD; van
TI - Putten WL; Hart AA Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial. Dutch Deep Hyperthermia Group.
SO - Lancet 2000 Apr 1;355(9210):1119-25
AD - Subdivision of Hyperthermia, Academic Medical Centre, Amsterdam, The Netherlands. email@example.com
BACKGROUND: Local-control rates after radiotherapy for locally advanced tumours of the bladder, cervix, and rectum are disappointing. We investigated the effect of adding hyperthermia to standard radiotherapy. METHODS: The study was a prospective, randomised, multicentre trial. 358 patients were enrolled from 1990 to 1996, in cancer centres in the Netherlands, who had bladder cancer stages T2, T3, or T4, NO, MO, cervical cancer stages IIB, IIIB, or IV, or rectal cancer stage M0-1 were assessed. Patients were randomly assigned radiotherapy (median total dose 65 Gy) alone (n=176) or radiotherapy plus hyperthermia (n=182). Our primary endpoints were complete response and duration of local control. We did the analysis by intention to treat. FINDINGS: Complete-response rates were 39% after radiotherapy and 55% after radiotherapy plus hyperthermia (p<0.001). The duration of local control was significantly longer with radiotherapy plus hyperthermia than with radiotherapy alone (p=0.04). Treatment effect did not differ significantly by tumour site, but the addition of hyperthermia seemed to be most important for cervical cancer, for which the complete-response rate with radiotherapy plus hyperthermia was 83% compared with 57% after radiotherapy alone (p=0.003). 3-year overall survival was 27% in the radiotherapy group and 51% in the radiotherapy plus hyperthermia group. For bladder cancer, an initial difference in local control disappeared during follow-up. INTERPRETATION: Hyperthermia in addition to standard radiotherapy may be especially useful in locally advanced cervical tumours. Studies of larger numbers of patients are needed for other pelvic tumour sites before practical recommendations can be made.
UI - 11370497
AU - Brown AL Jr; Zietman AL; Shipley WU; Kaufman DS
TI - An organ-preserving approach to muscle-invading transitional cell cancer of the bladder.
SO - Hematol Oncol Clin North Am 2001 Apr;15(2):345-58, vii
AD - Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Bladder-preserving treatment for muscle-invasive disease is based on the response of the tumor to induction combined modality therapy. In the future, an organ-conserving approach will be widely offered as a safe and reasonable alternative to radical cystectomy.
UI - 11432035
AU - Pieras Ayala E; Palou J; Rodriguez-Villamil L; Millan Rodriguez F;
TI - Salvador Bayarri J; Vicente Rodriguez J [Cytoscopic follow-up of initial G3T1 bladder tumors treated with BCG]
SO - Arch Esp Urol 2001 Apr;54(3):211-7
AD - Servicio de Urologia, Fundacion Puigvert, Barcelona, Espana.
OBJECTIVE: To evaluate the cystoscopic findings during initial follow-up, the anatomopathological correlation of tumor endoscopic features and the results of standard control multiple biopsy performed 6 months after TUR in patients with G3T1 transitional carcinoma treated with BCG. METHODS: 114 patients with G3T1 bladder tumor (52% associated with Cis) were treated with 81 mg Connaught BCG intravesical instillations weekly for 6 consecutive weeks. Follow-up was performed with cystoscopy and cytology at 3 months, and cystoscopy and standard multiple biopsy at 6 months. The endoscopic findings were described as normal bladder, macroscopically tumorous lesion or erythematous lesion. RESULTS: During the first 6 months of follow-up superficial recurrence was found in 16% and 5% showed progression to muscle invasion. Tumor recurrence or progression was found in 61% and 39% at 3 and 6 months, respectively. Most of the macroscopically tumorous lesions resulted in a tumor at 3 and 6 months in 56% and 64%, respectively, and the remaining lesions were mainly inflammatory granulomas produced by BCG therapy. Twenty biopsies of erythematous areas detected only one case of Cis (5%) and 98 standard multiple biopsies of endoscopically normal mucosa detected 10 cases of Cis (overall, 3 at 3 months and 7 at 6 months); all cases were preceded by initial Cis except in one case. CONCLUSIONS: Cystoscopy performed at 3 months is very useful since it detected 61% of the superficial recurrences and 66% of the cases with progression to muscle invasion during the first 6 months. Routine biopsy of erythematous areas detected during cystoscopy is of little value since a large number of these biopsies are unnecessary in view of its diagnostic yield (5%). Since 90% of the Cis detected during the first 6 months of follow-up were patients with Cis in the initial tumor, it would be appropriate to perform standard multiple biopsy for control only in this subgroup of patients if the sensitivity of cytology is low in high grade tumors or Cis.
UI - 11423017
AU - Bulbul MA; Wazzan W; Nasr R; Hemady K
TI - The value of cystoscopy, prostate biopsy and frozen-section urethral biopsy prior to orthotopic neobladder substitution.
SO - Can J Urol 2001 Jun;8(3):1290-2
AD - Department of Surgery, Division of Urology, American University of Beirut, Beirut, Lebanon.
INTRODUCTION: The traditional criteria for selecting suitability of male patients with bladder cancer for othtopic neobladder substitution includes: patient motivation, negative transurethral (TUR) prostate biopsy prior to cystectomy, and/or tumor-free biopsy of the urethral margin at the time of cystectomy. In this report we evaluate the value of these preoperative and intraoperative biopsies in the cystoscopically normal prostatic urethra. METHODS: During a 5-year period, cystectomies were performed on 54 men and 13 women with invasive bladder cancer. Prior to this procedure, all of the men had TUR biopsy of the prostate. Forty men with cystoscopically normal prostatic fossa had negative prostatic biopsies, and. had orthotopic neobladder substitution. RESULTS: Pathological examination showed that 3 out of these 40 men had transitional cell carcinoma (TCC) involving the prostate. In all 40 patients, the prostatic apical resection margin was negative. To date, none of the patients developed urethro-neobladder recurrence. CONCLUSION: TUR biopsy of the prostatic urethra prior to cystectomy, or biopsy of the prostatic urethral margin at the time of cystectomy in patients with cystoscopically normal, tumor free prostatic urethra has limited value in selecting candidates for orthotopic neobladder substitution.
UI - 11455827
AU - Paez Borda A; Lujan Galan M; Romero Cajigal I; Llanes Gonzalez L; Gomez
TI - de Vicente JM; Berenguer Sanchez A [Selective bladder sparing with transrectal resection of muscle-infiltrating tumors]
SO - Actas Urol Esp 2001 Apr;25(4):264-8
AD - Servicio de Urologia, Hospital Universitario de Getafe, Madrid.
OBJECTIVE: To disclose te ability of TUR as monotherapy in muscle invasive bladder cancer. MATERIAL AND METHODS: 27 patients with muscle-invasive bladder cancer recruited throughout 1991-1999 were allocated into a protocol based on TUR. 30-45 days after the first TUR a second procedure was performed. The number of recurrences and progressions was registered. Progression-free survival and survival were analyzed using Kaplan-Meier estimates. RESULTS: Two patients were excluded due to persistence of muscle-invasive disease after the second resection. 8 subjects (32%) were lost in follow-up. 17 were eventually evaluable. 12 patients (70.5%) had recurrences. Eventually, 4 more cystectomies were undertaken for invasive recurrences (4/17, 23.5%). During the study period, 3 deaths were recorder (3/17, 17.6%). The actuarial probability of progression at 93 months was estimated on 60%. CONCLUSIONS: 75% of patients retained their bladders. The proportion of patients lost in follow-up was very high. Patients must commit to a close surveillance.
UI - 11459443
AU - McIntosh J
TI - Analyzing counts, durations, and recurrences in clinical trials.
SO - J Biopharm Stat 2001 Feb-May;11(1-2):65-74
AD - Department of Economics, Concordia University, Montreal, PQ, Canada. firstname.lastname@example.org
In 1985 the (Byar and Blackard, Urology, Vol. X, 556-561, 1978) data set on bladder cancer became available to researchers. Since then, a number of studies have made use of it. However, none of these has fully utilized all of the data nor have they developed a methodology in which it is possible to estimate models of the number of recurrences and durations that are consistent with each other. The purpose of this research is to determine which, if any, of the two drugs used in the trial, pyridoxine and theotepa, were effective and, by example, illustrate procedures that could be useful in the analysis of other clinical trial data sets. First, the number of recurrences is modeled as a count using the Poisson and negative binomial distributions with covariates. Then Poisson models are tested on the durations. Finally, durations and tumor counts per recurrence are fitted to more general autoregressive Wiebull and negative binomial distributions, respectively. Poisson models for durations are rejected in favor of the more general autoregressive models. The data on durations and tumor counts are shown to be more reliable from an inference point of view than the data on the number of recurrences. The data on durations and tumor counts show quite conclusively that both drugs are effective in treating bladder cancer, a result that differs from what others have found.
UI - 11547060
AU - Gomella LG; Mastrangelo MJ; McCue PA; Maguire HC JR; Mulholland SG;
TI - Lattime EC Phase i study of intravesical vaccinia virus as a vector for gene therapy of bladder cancer.
SO - J Urol 2001 Oct;166(4):1291-5
AD - Department of Urology, Jefferson Medical College and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
PURPOSE: Vaccinia virus is a DNA poxvirus previously used as a vaccine to eradicate smallpox. The virus has a high efficiency of infection, replicates in the cytoplasm without chromosomal integration and can transport a large amount of recombinant DNA without losing infectivity. Therefore, it is an excellent choice as a vector for gene delivery in vivo. Large quantities of vaccinia have been injected into dermal, subcutaneous and peripheral lymph node melanoma metastases without significant side effects, and with efficient infection of the tumor cells and recombinant gene transfection. To determine if vaccinia, when given intravesically, can effectively infect bladder mucosa and tumor with acceptable toxicity, we performed a phase I trial of intravesical vaccinia in patients with muscle invasive transitional cell carcinoma before radical cystectomy. MATERIALS AND METHODS: After documenting immune competence and demonstration of a major reaction after revaccination, patients received 3 increasing doses of intravesical Dryvax vaccinia virus (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) that was provided by the Centers for Disease Control. Approximately 24 hours after the third dose, cystectomy was performed and the tissue was examined microscopically. RESULTS: There were 4 patients who were treated. The 3 patients who received the highest doses (100 x 106 plaque forming units) had significant mucosal and submucosal inflammatory infiltration by lymphocytes, eosinophils, and plasma cells into tumor and normal tissue. Dendritic cells were recruited to the site after exposure to the vaccinia. Significant mucosal edema and vascular ectasia were seen. Tumor and normal urothelial cells showed evidence of viral infection, including enlarged vacuolated cells with cytoplasmic inclusions. There were no clinical or laboratory manifestations of vaccinia related toxicity except mild dysuria. Of the 4 patients 3 survived and were free of disease at 4-year followup. CONCLUSIONS: Our study demonstrates that vaccinia virus can be administered safely into the bladder with recruitment of lymphocytes and induction of a brisk local inflammatory response. To our knowledge, this is the first report of direct delivery of live virus into the human bladder. The role of wild type vaccinia as immunotherapy for bladder cancer warrants further study. Furthermore, these data support the exploration of recombinant vaccinia as a putative gene therapy vector for intravesical infection and transfection of bladder tumor cells with cytokine or other genes, an approach that our group pioneered and most recently studied in patients with superficial melanoma.
UI - 11547061
AU - Herr HW; Sogani PC
TI - Does early cystectomy improve the survival of patients with high risk superficial bladder tumors?
SO - J Urol 2001 Oct;166(4):1296-9
AD - Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
PURPOSE: We compared survival after early versus delayed cystectomy in patients with high risk superficial bladder tumors. MATERIALS AND METHODS: Of 307 patients with high risk superficial bladder tumors who were treated initially with transurethral resection and bacillus Calmette-Guerin (BCG) therapy 90 (29%) underwent cystectomy for recurrent tumor during a followup of 15 to 20 years. Disease specific survival distribution of these 90 patients was determined relative to the indications for and time of cystectomy. RESULTS: Of the 90 patients who underwent cystectomy 44 (49%) survived a median of 96 months. Of 35 patients with recurrent superficial bladder tumors 92% and 56% survived who underwent cystectomy less than 2 years after initial BCG therapy and after 2 years of followup, respectively. Of 55 patients with recurrent muscle invasive bladder disease 41% and 18% survived when cystectomy was performed within and after 2 years, respectively. Multivariate analysis showed that survival was improved in patients who underwent earlier rather than delayed cystectomy for nonmuscle invasive tumor relapse. CONCLUSIONS: Earlier cystectomy improves the long-term survival of patients with high risk superficial bladder tumors in whom BCG therapy fails.
UI - 11547062
AU - O'Donnell MA; Krohn J; DeWolf WC
TI - Salvage intravesical therapy with interferon-alpha 2b plus low dose bacillus Calmette-Guerin is effective in patients with superficial bladder cancer in whom bacillus Calmette-Guerin alone previously failed.
SO - J Urol 2001 Oct;166(4):1300-4, discussion 1304-5
AD - Department of Urology, University of Iowa, Iowa City, USA.
PURPOSE: We determined whether combining low dose bacillus Calmette-Guerin (BCG) interferon-alpha 2B would be effective for patients in whom previous BCG failed. MATERIALS AND METHODS: A total of 40 patients in whom 1 (19) or more (21) previous induction courses of BCG failed received 6 to 8 weekly treatments of 1/3 dose (27 mg.) BCG plus 50 million units interferon-alpha 2B. Additional 3 week miniseries of further decreased BCG (1/10, 1/30 or 1/100) titrated to symptoms without changing the interferon-alpha 2B dose were given at 5, 11 and 17 months. In 12 patients a second induction course was given with 1/10 BCG plus 100 million units interferon-alpha 2B. There was multifocal disease in 39 patients, previous BCG had failed within 6 months in 34, disease was aggressive (stage T1, grade 3 or carcinoma in situ in 31, there had been 2 or more previous recurrences in 25 and disease history was greater than 4 years in 13. RESULTS: At a median followup of 30 months 63% and 53% of patients were disease-free at 12 and 24 months, respectively. Patients in whom 2 or more previous BCG courses had failed fared as well as those with 1 failure. Of the 18 failures 14 occurred at the initial cystoscopy evaluation. Of 22 patients initially counseled to undergo cystectomy 12 (55%) are disease-free with a functioning bladder. Combination therapy was well tolerated. CONCLUSIONS: While longer followup and larger multicenter studies are required to validate these encouraging findings, intravesical low dose BCG plus interferon-alpha 2B appears to be effective in many cases of high risk disease previously deemed BCG refractory. However, early failure while on this regimen should be aggressively pursued with more radical treatment options.
UI - 11547071
AU - Smith E; Yoon J; Theodorescu D
TI - Evaluation of urinary continence and voiding function: early results in men with neo-urethral modification of the Hautmann orthotopic neobladder.
SO - J Urol 2001 Oct;166(4):1346-9
AD - Department of Urology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA.
PURPOSE: At our institution we use the Hautmann orthotopic bladder replacement with a chimney and neo-urethral modification. A neo-urethral tube allows tension-free intestino-urethral anastomosis, thus providing application of this procedure for patients who may otherwise not qualify due to the inability of the small bowel to reach the urethra. However, this neo-urethral tube may also enhance continence by providing significant intra-abdominal urethral length. Conversely, such a modification may be associated with a higher degree of urinary retention. Early evaluation and reporting on the results of this and urinary reconstruction with Hautmann repair using chimney and neo-urethral modifications. We performed a retrospective analysis of urinary function and continence with data obtained from patient questionnaires completed preoperatively and at each postoperative office visit. The examining physician chart notes were reviewed for information about urinary retention. The American Urological Association symptom score and voiding bother index were used to assess urinary function and bother, respectively. Urinary continence was defined as the complete absence of any form of urinary leakage protection. RESULTS: Of the 14 patients 12 were completely continent day and night, with a median followup of 17 months. There were 2 patients who wore pads less than 7 months after surgery. Improvement of urinary continence appeared to continue up to 12 months postoperatively. Despite this encouraging effect, when our data were compared to the published literature, we noted a somewhat increased incidence of patients requiring clean intermittent catheterization to manage significant post-void urinary residuals. We had no patients with urethro-intestinal strictures who required clean intermittent catheterization. CONCLUSIONS: The neo-urethral tube modification appears to have a significant and favorable impact on urinary continence while seeming to be associated with a trend towards an increased rate of chronic urinary retention. Longer followup will be required to determine whether this higher rate of chronic urinary retention will remain stable or change with time.
UI - 11547095
AU - John H; Hauri D
TI - Re: Nerve and seminal sparing radical cystectomy with orthotopic urinary diversion for select patients with superficial bladder cancer: an innovative surgical approach.
SO - J Urol 2001 Oct;166(4):1402
UI - 11549484
AU - Luciani LG; Neulander E; Murphy WM; Wajsman Z
TI - Risk of continued intravesical therapy and delayed cystectomy in BCG-refractory superficial bladder cancer: an investigational approach.
SO - Urology 2001 Sep;58(3):376-9
AD - Division of Urology, University of Florida, Gainesville, Florida, USA.
OBJECTIVES: To assess the risk of continued intravesical therapy and delayed cystectomy in the management of superficial bladder cancer refractory to bacillus Calmette-Guerin (BCG) therapy. METHODS: We retrospectively reviewed the medical records of 24 patients who underwent an experimental intravesical treatment with BCG plus interferon alpha-2b or valrubicin for transitional cell carcinoma of the bladder. All patients had Stage Tis and/or T1 transitional cell carcinoma and had failed multiple prior courses of intravesical therapy, including at least one course of BCG. RESULTS: Patients were followed up for a median of 28.5 months (range 6 to 48). One patient died of unrelated disease. All other patients were alive at last follow-up. Fourteen patients with preserved bladder were continuing cystoscopic surveillance: four had no recurrence, five had recurrence limited to the mucosa (Ta or Tis) and became free of disease after an additional course of intravesical therapy, and five had recurrent Ta or Tis or positive cytologic findings. The remaining 9 patients underwent radical cystectomy. All pathologic specimens showed no evidence of progression to muscle-invasive disease. Tis of the resected ureters in 6 and involvement of the prostate in 4 of the 9 patients (three in the urethral ducts and glands and one in the prostatic stroma) were noted. CONCLUSIONS: A select group of patients with BCG-refractory transitional cell carcinoma and a poor surgical risk for cystectomy may benefit from continued intravesical therapy without a significant risk of progression. However, a cautious approach to this treatment modality is recommended, and very close follow-up is necessary to detect bladder recurrences and involvement of the upper tract and prostatic urethra.
UI - 11549485
AU - Zietman AL; Grocela J; Zehr E; Kaufman DS; Young RH; Althausen AF; Heney
TI - NM; Shipley WU Selective bladder conservation using transurethral resection, chemotherapy, and radiation: management and consequences of Ta, T1, and Tis recurrence within the retained bladder.
SO - Urology 2001 Sep;58(3):380-5
AD - Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston Massachusetts 02114, USA.
OBJECTIVES: Although radical cystectomy remains the standard of care for invasive bladder cancer in the United States, many groups are exploring the use of trimodality therapy using transurethral resection of the bladder tumor, radiation, and chemotherapy in an attempt to spare patients the need for cystectomy. As transitional cell carcinoma often arises from a urothelial field change, there is concern that the retained bladder is at risk of subsequent superficial (Ta, T1, Tis) tumors, some of which may have lethal potential. This study reports the outcomes of those patients with superficial relapse of transitional cell carcinoma after trimodality therapy. METHODS: One hundred ninety patients were treated using a series of trimodality therapy protocols between 1986 and 1998. All patients received induction chemotherapy and radiation and were selected for bladder preservation on the basis of a cytologic and histologic complete response. One hundred twenty-one patients had a complete response and formed the subjects of this study. RESULTS: With a median follow-up of 6.7 years for patients still alive, 32 experienced a superficial relapse (26%). The median time to this failure was 2.1 years. Sixty percent of the superficial failures were carcinoma in situ (Tis) and 67% arose at the site of the original invasive tumor. The risk of superficial failure was higher among those who had Tis associated with their original muscle-invasive tumor. Twenty-seven of these 32 cases were managed conservatively with transurethral resection and intravesical therapy. The irradiated bladder tolerated this therapy well and only 3 patients required treatment breaks. The 5 and 8-year survival was comparable for those who experienced superficial failure (68% and 54%, respectively) and those who had no failure at all (n = 74, 69% and 61%, respectively). However, a substantially lower chance of being alive with the native bladder owing to the need for late salvage cystectomies (61% versus 34%) was found. Cystectomy became necessary in 31% (10 of 32) either because of additional superficial recurrence (n = 7) or progression to invasive disease (n = 3). CONCLUSIONS: A trimodality approach to transitional cell bladder cancer mandates lifelong cystoscopic surveillance. Although most completely responding patients retain their bladders free from invasive relapse, one quarter will develop superficial disease. This may be managed in the standard fashion with transurethral resection of the bladder tumor and intravesical therapies but carries an additional risk that late cystectomy will be required.
UI - 11594209
AU - Hautmann RE
TI - [15 years experience with the ileal neobladder. What have we learned?]
SO - Urologe A 2001 Sep;40(5):360-7
During the past 15 years, orthotopic bladder reconstruction has evolved from experimental surgery over "standard of care at larger medical centers" to become the preferred method of urinary diversion in both sexes. The paradigm for choosing a urinary diversion has changed substantially over that time. In 2001, all cystectomy patients are candidates for a neobladder, and we should identify those patients in whom orthotopic reconstruction may be less ideal, noting that the percentage of patients receiving a neobladder today averages 60 to 70 percent. Relative contraindications and comorbidity now play a smaller role in choosing the neobladder option. Patient selection criteria include both patient factors and cancer factors. The primary patient factor being the patient's desire for a neobladder. The psychologically damaging stigma to the patient who enters surgery expecting a neobladder but awakens with a stoma now plays an increasing role. Nevertheless, there are patients who are better served with a conduit. Among that are patients whose main motivation is to "get out of the hospital as soon as possible", and patients who will be happy to resume a normal, relatively sedentary life and who have no concerns about body image. Two important criteria that must be maintained when contemplating a neobladder procedure--the urethral sphincter must remain intact and the cancer operation must not be compromised. However, increasing experience has forced less restrictiveness as far as tumor stage is concerned. A recent study of 435 bladder cancer patients who had bladder replacements after cystectomy, experienced a local recurrence rate of 10 percent. Interference of the local recurrence with the neobladder occurred in just 11 patients--infiltration in six, and obstruction in five. Survival was limited despite multimodality therapy. The option of a neobladder reduced the physician and patient reluctance to perform cystectomy early in the disease process, thereby increasing the survival rate, and patients can anticipate normal neobladder function until time of death. It can be concluded that a neobladder for locally advanced cancer and positive nodes is no more problematic than a conduit. The structural and ultrastructural changes which occur in neobladder mucosa are biphasic. The early phase is inflammatory, showing an infiltration of the lamina propria and a reduction in microvilli. After one year the late regressive phase starts, ending up in a flat mucosa and a stratified epithelium. The structure and response of the implanted ileum change to a detrusor-type: response. The structural and ultrastructural changes an ileal mucosa lead to a primitive surface and glandular epithelium similar to urothelium. This transformation of the ileal mucosa minimizes the risk of metabolic complications. We conclude that mother nature engineers a new bladder almost as good as the one given by God initially. The risk of obstruction of non refluxing techniques is at least twice that following a direct anastomosis. There is no longer a justification of any antireflux mechanism. Ileum seems to be clearly superial to colon when continence rates, metabolic safety and surgeons's issues are considered.
UI - 11594210
AU - Stenzl A; Ninkovic M; Ashammakhi N; Eder IE; Bartsch G
TI - [Reconstruction of the lower urinary tract. Developments at the beginning of a new century]
SO - Urologe A 2001 Sep;40(5):368-75
AD - Urologische Universitats-Klinik Innsbruck/Osterreich. email@example.com
Gastrointestinal segments are currently by far the most popular method to create a bladder substitute. Attempts have been made to further reduce the morbidity and burden for patients by using minimal invasive techniques for both cystectomy and urinary diversion. However, laparoscopy for acceptable forms of urinary diversion is time consuming and costly. A neobladder "off the shelf" would be a better solution. Tissue engineering is an exciting new field which enables the cultivation and expansion of individual bladder cells obtained by transurethral biopsy, the attachment of these cells to a support matrix, and their reimplantation into the body. Advances both in biomaterials as well as in the cultivation and expansion of bladder cells are described. Promising routine clinical applications of tissue engineering may still need several years. Free neurovascular muscle transfer to the bladder demonstrated both experimentally and clinically to be a suitable treatment modality in patients with bladder acontractility. This may therefore be the next logical step towards an improved bladder substitute by combining well vascularized flaps with urothelial cell seeding. Thus a combination of commonly used flap techniques and tissue engineering may soon be possible.
UI - 11594211
AU - Vacha P; Buttner H; Bohle A; Feyerabend T
TI - [Radiotherapy of urothelial carcinomas of the urinary bladder]
SO - Urologe A 2001 Sep;40(5):376-9
AD - Klinik fur Strahlentherapie und Nuklearmedizin, Universitatsklinikum, Ratzeburger Allee 160, 23538 Lubeck.
Radiotherapy of bladder cancer is a locally effective therapeutic approach. It is increasingly becoming part of the multimodal protocols aimed at the preservation of both organ and organ function. In this context, it is an alternative to cystectomy. The addition of chemotherapy to radiotherapy enhances the curative potential of this non-surgical approach and may be useful especially in older, multimorbid patients. If chemotherapy can not be applied, the use of radiotherapy alone is reasonable, although in advanced tumors the results are disappointing. After the transurethral resection of bladder cancer, postoperative radiotherapy should be considered in muscle-invasive cancer as well as when other negative prognostic factors occur. The prerequisites for an effective, minimally toxic, state of the art radiotherapy are a subtle treatment-planning procedure and an accurate delivery of the radiation.
UI - 11594212
AU - Buttner H; Feyerabend T; Bohle A
TI - [Radiochemotherapy of urothelial carcinoma]
SO - Urologe A 2001 Sep;40(5):380-3
AD - Klinik und Poliklinik fur Urologie, Universitatsklinikum Lubeck, Ratzeburger Allee 160, 23538 Lubeck. firstname.lastname@example.org
Radical cystectomy is the current standard therapy for muscle invasive or locally advanced transitional cell carcinoma of the bladder. Organ-preserving monotherapeutic alternatives (e.g. transurethral resection, radiotherapy) do not lead to similar cure rates. In selected cases, a trimodal approach using transurethral resection and combined radio- and chemotherapy can be as efficient as cystectomy.
UI - 11594217
AU - Bohle A; Durek C
TI - [Use of BCG in superficial urinary bladder carcinoma]
SO - Urologe A 2001 Sep;40(5):403-9; quiz 410-1
AD - Klinik fur Urologie, Medizinische Universitat, Ratzeburger Allee 160, 23538 Lubeck. email@example.com
UI - 11597537
AU - Patard J; Moudouni S; Saint F; Rioux-Leclercq N; Manunta A; Guy L;
TI - Ballanger P; Lanson Y; Hajri M; Irani J; Guille F; Beurton D; Lobel B; Bernard Lobel and The members of the Groupe Necker Tumor progression and survival in patients with T1G3 bladder tumors: multicentric retrospective study comparing 94 patients treated during 17 years.
SO - Urology 2001 Oct;58(4):551-6
AD - Department of Urology, Centre Hospitalo-Universitaire Rennes, Rennes, France.
OBJECTIVES: To compare tumor recurrence, progression, and patient survival in T1G3 bladder tumors treated with transurethral resection (TUR) alone, early cystectomy, or TUR with an adjuvant 6-week course of bacille Calmette-Guerin (BCG) and followed up for a minimum of 5 years. METHODS: Between 1979 and 1996, 94 patients with T1G3 bladder tumors (lamina propria invasion) were treated at nine different centers. The time to tumor recurrence, tumor stage and grade progression, number of delayed cystectomies, and patient survival were analyzed retrospectively in relation to the initial treatment. RESULTS: The mean follow-up was 62 months. Thirty patients were treated by TUR alone (32%), 50 patients by TUR plus BCG (53%), and 14 patients by primary cystectomy (15%). The recurrence, progression, and cystectomy rates were significantly different between patients treated by TUR alone and TUR plus BCG (Fisher's exact test, P = 0.0005, P = 0.02, and P = 0.005, respectively). The disease-free survival was also significantly different when comparing TUR plus BCG with TUR alone or primary cystectomy (Kaplan-Meier analysis, log-rank test, P = 0.02). CONCLUSIONS: Endoscopic resection plus BCG treatment of pT1G3 tumors allows an 80% rate of disease-free 5-year survival with bladder preservation. This conservative option has been widely accepted as first-line treatment, offering good cancer control with excellent quality of life. Very accurate surgical and pathologic evaluations before treatment and lifelong follow-up are obviously required.
UI - 11597538
AU - Kim HL; Steinberg GD
TI - Complications of cystectomy in patients with a history of pelvic radiation.
SO - Urology 2001 Oct;58(4):557-60
AD - Department of Surgery, Section of Urology, University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, USA.
OBJECTIVES: To compare the complications occurring during the first year of follow-up after radical cystectomy in two groups, one with and one without a history of pelvic radiation. Radical cystectomy and urinary diversion is the treatment of choice for invasive bladder cancer. METHODS: One hundred ninety-four cystectomies were performed between were identified with a history of external beam radiotherapy to the pelvis (EBRT group), and 23 additional patients without a history of pelvic radiation were randomly selected to serve as the control group. RESULTS: Although the overall risk of having a complication was not statistically different in the EBRT group (48%) than in the control group (30%; P = 0.183), complications directly related to surgery were higher in the EBRT group than in the control group (48% versus 26%; P = 0.045). The patients in the EBRT group were more likely to require an invasive procedure (39% versus 9%; P = 0.018). In addition, 5 (22%) of 23 patients in the EBRT group had a symptomatic fluid collection, which was diagnosed as a urine leak (n = 2) or an abdominal abscess (n = 3). In contrast, no patient in the control group developed a symptomatic fluid collection. CONCLUSIONS: Cystectomy after pelvic radiation is associated with acceptable morbidity; however, compared with cystectomy performed in a nonirradiated pelvis, the risk of complications that will require invasive intervention is increased. A history of prior pelvic radiation significantly increases the risk of a symptomatic fluid collection.
UI - 11600601
AU - Millikan R; Dinney C; Swanson D; Sweeney P; Ro JY; Smith TL; Williams D;
TI - Logothetis C Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC.
SO - J Clin Oncol 2001 Oct 15;19(20):4005-13
AD - Center for Genitourinary Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. firstname.lastname@example.org
PURPOSE: We conducted a phase III trial to investigate the timing of chemotherapy with respect to surgery for patients with resectable but high-risk urothelial cancer. The trial was also designed to evaluate the accuracy of clinical staging in patients with locally advanced cancer and the prognostic significance of chemotherapy-induced downstaging. PATIENTS AND METHODS: A total of 140 uniformly evaluated patients with locally advanced urothelial cancer were studied. Planned treatment was five cycles of chemotherapy (M-VAC: methotrexate, vinblastine, doxorubicin, and cisplatin) plus radical cystectomy and pelvic lymph node dissection. Patients were randomly assigned to receive either two courses of neoadjuvant M-VAC followed by surgery plus three additional cycles of chemotherapy, or, alternatively, to have initial cystectomy followed by five cycles of adjuvant chemotherapy. RESULTS: There were no significant differences in outcome between the two groups. By intent-to-treat, 81 patients (58%) remain disease-free, with median follow-up of 6.8 years. We confirmed a high rate of clinical understaging in this cohort, especially among patients showing lymphovascular invasion on biopsy. Patients with no residual muscle-invasive disease at cystectomy after neoadjuvant chemotherapy were likely to be cured. CONCLUSION: These results lend further support to the impression from small randomized trials that, in a high-risk cohort, there is an improved cure fraction by the combination of multiagent chemotherapy and surgery, although we found no preferred sequence. Importantly, it is possible to select appropriate patients for such therapy on the basis of clinical staging information. These results establish a benchmark of outcome for this cohort.
UI - 11669339
AU - Rotterud R; Skomedal H; Berner A; Danielsen HE; Skovlund E; Fossa SD
TI - TP53 and p21WAF1/CIP1 behave differently in euploid versus aneuploid bladder tumours treated with radiotherapy.
SO - Acta Oncol 2001;40(5):644-52
AD - Department of Pathology, The Norwegian Radium Hospital, Montebello, Oslo.
The aim of this study was to examine any relation between DNA ploidy and previously detected TP53 (p53) or p21WAF1/CIP1 expression in 94 patients with muscle-invasive transitional cell carcinoma of the urinary bladder and to associate these factors with survival. DNA ploidy was determined by image cytometry. In a subgroup of patients, the mutational status of the TP53 gene was assessed by temporal temperature gradient electrophoresis (TTGE) or perpendicular denaturant gradient gel electrophoresis (DGGE) and subsequent sequencing. Significantly more aneuploid than euploid tumours showed TP53 accumulation (p = 0.003). Patients with aneuploid tumours lived longer than patients with euploid tumours (p = 0.003). In the euploid, but not in the aneuploid group, TP53 and p21WAF1/CIP1 were associated with cancer-specific survival (p = 0.002 and 0.02, respectively). Patients with > 50% TP53 expression had the longest survival time. Mutation analyses showed acceptable concordance with TP53 expression. We conclude that DNA aneuploidy may confer increased radiosensitivity in bladder cancer patients and that TP53 accumulation may confer increased radiosensitivity, but its effect is detectable only in euploid tumours.
UI - 11641012
AU - Sandler H; Shipley WU; Gomella L; Pienta K; Bard RH; Bruner D; Clark R;
TI - DeSilvio M; Gaspar L; Gillin M; Grignon D; Hammond E; Hanks G; Heydon KH; Kaufman DS; Lee WR; Michalski J; Mydlo J; Pisansky T; Pollack A; Porterfield H; Rifkin M; Roach M 3rd; Sanda M; True L; Vijayakumar S; Winter KA; Zeitman A; Radiation Therapy Oncology Group Radiation Therapy Oncology Group. Research Plan 2002-2006. Genitourinary Cancer Committee.
SO - Int J Radiat Oncol Biol Phys 2001;51(3 Suppl 2):28-38
UI - 11677109
AU - Bellmunt J; de Wit R; Albanell J; Baselga J
TI - A feasibility study of carboplatin with fixed dose of gemcitabine in "unfit" patients with advanced bladder cancer.
SO - Eur J Cancer 2001 Nov;37(17):2212-5
AD - University Hospital Vall d'Hebron, Barcelona, Spain. email@example.com
For the purpose of a subsequent phase II/III European Organization for Research and Treatment of Cancer (EORTC) trial, a gemcitabine/carboplatin feasibility study in "unfit" patients with advanced urothelial cell cancer was conducted. Gemcitabine was given at 1000 mg/m(2) days 1 and 8 with carboplatin (area under the curve (AUC) 4.5 or 5) day 1 every 21 days. 16 patients were treated, median age 68 years (47-75) years, performance status (PS) 0/1/2 in 3/10/3 patients. Creatinine clearance was >1 ml/s in 3 patients, 0.5-1 ml/s in 9 and <0.5 ml/s in 4 patients. Half of the patients had visceral disease. Median number of cycles given was 4 (range 2-6), for a total of 69 cycles. The first 8 patients received 33 cycles using a carboplatin AUC of 5. World Health Organization (WHO) grade 3-4 toxicity was: haemoglobin 5 patients, platelets 6 patients, neutrophils 5 patients and febrile neutropenia 2 patients. In view of this haematological toxicity in subsequent patients, the carboplatin AUC was decreased to 4.5. At this dose level, 8 patients received 36 cycles. WHO grade 3-4 toxicity was: anaemia 1 patient, platelets 4 patients, neutrophils 4 patients with no febrile neutropenia. Thus, this dose level was regarded to be feasible. For the 16 evaluable patients, overall response rate was 44%, (1 complete response (CR), 6 partial response (PR)). In conclusion, the combination of gemcitabine with carboplatin at an AUC of 4.5 appears to be an active and well tolerated regimen with acceptable toxicity in this unfit patient population. Based on these data, a randomised trial in the framework of the EORTC-Genitourinary (GU) group of gemcitabine/carboplatin versus carboplatin/methotrexate/vinblastine (MCAVI) is ongoing.
UI - 11683967
AU - Sekine H; Ohya K; Kojima SI; Igarashi K; Fukui I
TI - Equivalent efficacy of mitomycin C plus doxorubicin instillation to bacillus Calmette-Guerin therapy for carcinoma in situ of the bladder.
SO - Int J Urol 2001 Sep;8(9):483-6
AD - Department of Urology, University Hospital Mizonokuchi, Teikyo University School of Medicine, Kanagawa, Japan. firstname.lastname@example.org
BACKGROUND: To elucidate the most efficient topical therapy for carcinoma in situ of the bladder, the efficacy of intravesical mitomycin C plus doxorubicin therapy was compared with bacillus Calmette-Guerin (BCG) therapy. The clinical behavior of the tumor was analysed according to the histological grade. METHODS: Forty-two patients with carcinoma in situ of the bladder were randomized to intravesical BCG (21 patients) or mitomycin C plus doxorubicin sequential therapy (21 patients) as first line treatment. The non-responders underwent the subsequent instillation of the other intravesical therapy alternately. Of the patients, 27 had grade 2 and 15 had grade 3 cancer. RESULTS: Both topical therapies were equally effective with initial response rates of 86% (18/21) for BCG and 81% (17/21) for mitomycin C plus doxorubicin, irrespective of the tumor grade. Of seven initial non-responders, five patients achieved a complete response by subsequent instillation, resulting in a total response rate of 95%.