Trials In Bladder Cancer Research Articles

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

BackgroundIn Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.MethodThe SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.DesignThe SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.DiscussionThis is the first report on a selenium randomized trial in bladder cancer patients.Trial registrationClinicalTrials.gov identifier: NCT00729287

1050 Bacillus Calmette-Guerin: One third dose versus full dose and one year versus three years of maintenance. Final results of an EORTC GU Cancers Group randomized trial in non muscle invasive bladder cancer

1050 Bacillus Calmette-Guerin: One third dose versus full dose and one year versus three years of maintenance. Final results of an EORTC GU Cancers Group randomized trial in non muscle invasive bladder cancer

Molecular signatures that predict nodal metastasis in bladder cancer: does the primary tumor tell tales?

Evaluation of: Smith SC, Baras AS, Dancik G et al. A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol. 12, 137–143 (2011).Accurate identification of nodal status in patients with bladder cancer is important in determining their prognosis and administration of perioperative chemotherapy. In this article, we review the study by Smith and colleagues, documenting the identification of a 20-gene model that can predict nodal stage in patients with bladder cancer based on the profiles of their primary tumors. The gene-expression model generated in this study was able to identify node-positive disease based on tumor tissues obtained from patients in a Phase III bladder cancer trial cohort. The model was able to predict nodal status independent of standard clinicopathologic prognostic criteria. This study adds the agnostic profiling dimension to prior investigations that have attempted to define molecular signatures that predict nodal metastasis in bladder cancer patients based on the primary tumors’ gene-expression profiles.

Abstract A106: Efficacy of EGFr inhibitors gefitinib on development of OH-BBN-induced rat bladder tumors: Dose dependency and modulation of biomarkers

Abstract The preventive effects of the EGFr inhibitor Iressa on the induction of urinary bladder cancers induced by OH-BBN was determined. Treatment of rats with Iressa (10 mg/kg BW/day) beginning two weeks after the last dose of OH-BBN decreased the incidence of large palpable bladder cancer lesions by 95% at an 8-month observation period. Treatment with lower doses of Iressa (4 and 1.33 mg/kg BW/day) decreased the incidence of large tumors by 80 and 65%, respectively. This preventive efficacy was similarly observed when one examined an incidence curve; i.e., a large increase in tumor latency. At 3 1/2 months after the last OH-BBN dose, 75% of the rats had already developed microscopic cancers. Iressa treatment beginning at this time period also lowered the incidence of large tumors; implying that most of the effects of Iressa were during the latter periods of tumor progression. We also examined potential biomarkers modulated by short-term exposure to Iressa (10 mg/kg BW/day) in urinary bladder cancers. Three approaches were taken to identify biomarkers: (1) Alterations in EGFr related proteins directly associated with the efficacy of Iressa by immunohistochemistry. Levels of various biomarkers (phosphorylated EGFr, phosphorylated AKT, but not phosphorylated ERK levels were significantly decreased in the bladder tumors of treated rats. (2) Alterations in protein expression when comparing control and Iressa treated tumors. Employing two-dimensional gel electrophoresis and tandem mass spectrometry, it was found that proteins associated with the angiogenic effects of VEGF were decreased in tumors from treated animals. These included cytoskletal proteins nucleolin, annexin A1 and the MAP kinase (MAPKK). (3) Alterations in gene expression employing array gene technology. Numerous metabolic and cellular pathways were markedly altered by Iressa treatment, most particularly cell cycle related genes; i.e., there were strong inhibition of expression of CDC20 and both of the aurora kinases. Thus, we have identified biomarkers that might be relevant as pharmacodynamic or efficacy biomarkers in clinical prevention trials of urinary bladder cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A106.

Utility‐Based Optimization of Combination Therapy Using Ordinal Toxicity and Efficacy in Phase I/II Trials

An outcome-adaptive Bayesian design is proposed for choosing the optimal dose pair of a chemotherapeutic agent and a biological agent used in combination in a phase I/II clinical trial. Patient outcome is characterized as a vector of two ordinal variables accounting for toxicity and treatment efficacy. A generalization of the Aranda-Ordaz model (1981, Biometrika 68, 357-363) is used for the marginal outcome probabilities as functions of a dose pair, and a Gaussian copula is assumed to obtain joint distributions. Numerical utilities of all elementary patient outcomes, allowing the possibility that efficacy is inevaluable due to severe toxicity, are obtained using an elicitation method aimed to establish consensus among the physicians planning the trial. For each successive patient cohort, a dose pair is chosen to maximize the posterior mean utility. The method is illustrated by a trial in bladder cancer, including simulation studies of the method's sensitivity to prior parameters, the numerical utilities, correlation between the outcomes, sample size, cohort size, and starting dose pair.

Abstract 2693: MDR1 and ERCC1 expression predict outcome in patients with locally advanced bladder cancer and adjuvant chemotherapy

Abstract Aims: Patients with locally advanced bladder cancer show a poor prognosis and can benefit from adjuvant chemotherapy. It was previously shown that expression of MDR1 and ERCC1 is linked to resistance against platinum-based chemotherapy in several cancer types. The aim of the present study was to evaluate the impact of classical histological, new immunohistochemical and molecular markers on prognosis of patients with locally advanced bladder cancer undergoing cystectomy (pT3a-4a and/or pN+) and response to chemotherapy within a randomized, multicenter, phase III trial (AUO-AB 05/95). Methods: Clinico-pathological parameters were assessed retrospectively after histopathological review in 204 patients randomized to adjuvant systemic chemotherapy with cisplatin and methotrexate (CM) vs. methotrexate, vinblastine, epirubicin, and cisplatin (M-VEC) after radical cystectomy. Tissue microarrays were constructed to study the immunohistochemical expression of ERCC1, BSG (Emmprin/CD147) CAV1, phospho-CAV1 (Y14), RRM1, BRCA1, BRCA2, BIRC5 (Survivin), and KISS1. Tumor samples from 108 patients were analyzed for MDR1 and ERCC1 mRNA expression by quantitative real-time RT-PCR using formalin-fixed and paraffin embedded tumor tissue. Results: Expression of MDR1 and ERCC1 were independently associated with overall and progression-free survival (p=0.001, 2.9 exp[b]; p=0.01, 2.24 exp[b]). In contrast to ERCC1 expression, MDR1 separated patients receiving M-VEC with higher sensitivity and specificity than those receiving CM (ROC Analysis p=0.008; [AUC]=0.71). These results could be partially confirmed by immunohistochemical analysis of 204 patients. ERCC1 and RRM1 expression correlated significantly with shorter overall survival in both therapy arms by univariate analysis. Multivariate analysis showed that ERCC1 expression was an independent prognostic factor for shorter overall survival (HR=2.3, 95%CI=1.18-4.43, p=0.014). Positive nodal status (pN1-3), histologic blood vessel invasion (V1), and positive BIRC5 immunoreactivity were significant as well. Conclusion: Our results suggest a predictive value of ERCC1 and MDR1 expression levels for therapy response and outcome in patients with locally advanced bladder cancer which allows the identification of patients who are likely to benefit from adjuvant platinum-based chemotherapy. The qPCR analysis is feasible in studying paraffin-embedded material from clinical bladder cancer trials. In addition, standard histopathological variables in combination with immunohistochemical and molecular prognostic markers can be used to predict therapy outcome in bladder cancer, irrespective of the mode of chemotherapy. Prospective studies are warranted to define a role for MDR1, ERCC1 and RRM1 in individualizing multimodality treatment in locally advanced bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2693.

Emerging apoptosis agonists for bladder cancer

Bladder cancer is a very common and aggressive tumor entity. Unfortunately, common chemotherapy is not able to cure advanced bladder cancer. Therefore, several attempts have been made to improve the response to chemotherapy. Because changes in apoptotic pathways are frequent events in the development of chemoresistance of malignancies, pro-apoptotic treatment seems promising for the improvement of bladder cancer prognosis. Preclinical data show potential ways for a successful combination of apoptosis agonists with conventional chemotherapy. None of these principles has so far successfully been translated into clinical trials for bladder cancer. This review describes actual studies and future perspectives for apoptotic agonists in bladder cancer.

Ras-MAPK Pathway as a Therapeutic Target in Cancer - Emphasis on Bladder Cancer

The Ras-MAPK pathway is important to orchestrating a cell's response to external and internal stimuli. This pathway is commonly dysregulated in cancer, including bladder cancer. Multiple components of this complex pathway have been identified as potential targets for drug development. After initial preclinical studies many drugs targeting the Ras-MAPK pathway are being studied in phase II clinical trials for advanced bladder cancer either alone or in combination with other chemotherapeutic agents. Drugs presently in clinical trials inhibit the tyrosine kinases, including FGFR, EGFR, ERBB2, and PDGF, either through small molecule tyrosine kinase, dual kinase or farnesyltransferase inhibitors. Recent drug patents targeting the Ras-MAPK pathway in cancer are becoming more selective with the potential for improved therapeutic response and better toxicity as compared to the more universal MAPK pathway inhibitors. In the present review we summarize the importance of the Ras-MAPK pathway in cancer with a focus on bladder cancer and discuss current drugs and recent patents (2004-2008) that target this important pathway in bladder cancer.

The MRC superficial bladder cancer trial of intravesical mytomicin-c after complete surgical resection. Sequential statistical methods applied to survival data from a randomised clinical trial

Reduction in the duration of a study and in the number of patients required can be obtained when we adopt a sequential design. In this paper we re-analyse a trial completed by the British Medical Research Council on the effects of chemotherapy to prevent the recurrence of surgically removed superficial bladder cancer as if it had been monitored sequentially. The aim is to illustrate the use and benefits of sequential designs (stopping rules) and to highlight how to handle some potential problems when the assumptions of the statistical model are not satisfied. These problems are not exclusive to the sequential design, but are also present when a conventional design is used.

Advanced bladder cancer: So many drugs, so little progress

Accrual to bladder cancer trials in the US has hampered the ability to advance beyond cisplatin‐based chemotherapy for advanced disease. Progress in the management of advanced disease will require new agents and new approaches.

Moving Forward in Advanced Bladder Cancer

strated an increased number of metastases compared with HER-2/ neu–negative patients (two v one; P .014), a greater probability of having two or more metastatic sites (51%v 31%;P .051), and a trend toward more liver and bone metastases. Perhaps, then, the group treated in the TPCG trial represents a cohort of patients with an especially poor prognosis. Previously, Bajorin et al 8 reported that Karnofsky performance status less than 80% and the presence of visceral sites of metastases (liver, lung, or bone) had independent poor prognostic significance for patients with advanced urothelial cancer treated with cisplatin-based chemotherapy. Patients with zero, one, and two risk factors had median survivals of 33, 13.4, and 9.3 months, respectively (P .0001). An important message of the Bajorin study is that advanced bladder cancer trials should report the proportion of patients with zero, one, and two risk factors to allow more meaningful interpretation of the results. Does the choice of the platinum analog matter in bladder cancer? From the toxicity point of view, carboplatin certainly offers some advantages, especially in a group of patients in which a significant proportion may present with impaired renal function. Small randomized phase II trials comparing regimens that differ mainly in the choice of the platinum compound favor the cisplatin arms. 9,10 Phase II trials of carboplatin plus either gemcitabine or paclitaxel doublets generally result in median survivals consistently less than those seen with the M-VAC and GC regimens. Although the evidence is indirect, cisplatin is probably the better agent. The effectiveness of the carboplatin-containing PCG triplet may be accounted for by the addition of a third cytotoxic agent. Certainly,

576: Patient Randomization Factors in the P53 Targeted Therapy Trial in Bladder Cancer (SWOG 4B951)

You have accessJournal of UrologyPodium 18, Sunday, May 20, 2007, 3:30 - 5:30 pm1 Apr 2007576: Patient Randomization Factors in the P53 Targeted Therapy Trial in Bladder Cancer (SWOG 4B951) Ellenie D. Tuazon, Susan G. Groshen, Seth P. Lerner, Walter Stadler, John P. Stein, and Richard J. Cote Ellenie D. TuazonEllenie D. Tuazon More articles by this author , Susan G. GroshenSusan G. Groshen More articles by this author , Seth P. LernerSeth P. Lerner More articles by this author , Walter StadlerWalter Stadler More articles by this author , John P. SteinJohn P. Stein More articles by this author , and Richard J. CoteRichard J. Cote More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)30816-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "576: Patient Randomization Factors in the P53 Targeted Therapy Trial in Bladder Cancer (SWOG 4B951)." The Journal of Urology, 177(4S), p. 192 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 192 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Ellenie D. Tuazon More articles by this author Susan G. Groshen More articles by this author Seth P. Lerner More articles by this author Walter Stadler More articles by this author John P. Stein More articles by this author Richard J. Cote More articles by this author Expand All Advertisement PDF downloadLoading ...

Review pathology in a diagnostic bladder cancer trial: Effect of patient risk category

Objectives Bladder cancer pathologic features are a continuous spectrum from benign to invasive lesions, causing diagnostic difficulties. Review pathology might be an answer, but appears to be of limited value. We studied the effect of patients’ risk profile on the value of review pathology. Methods We used three Phase III multicenter studies that assessed the value of hexaminolevulinate fluorescence cystoscopy on diagnosis and management. Two studies (Europe and United States) included patients at high risk of carcinoma in situ (CIS), the third study (Europe) included all patients at risk of bladder cancer. Tumors and biopsies were examined by a local and review pathologist. Results The percentage of patients with CIS was high in the first two studies (20.6% and 15.9%) compared with the epidemiologic data (7.9%) and the third study (7.8%). The numbers of patients (specimens) in the three studies were 209 (927), 277 (986), and 142 (553). Overall conformity for both grade and stage was between 50.5% and 56.6%, comparable to published data. Although conformity was best in the high-risk study, this was predominantly because of the better conformity in low-risk tumors. Conformity in Stage T1, CIS, and invasive tumors was low. The results from Europe and the United States were comparable, although the local pathologist in the United States tended to overstage or overgrade. Conclusions Although histologic conformity was greater in the high-risk patient population, this was mainly a result of pTa tumors. The diagnosis of pT1, CIS, and invasiveness appears difficult. Because these tumors significantly influence therapy, review pathology in patients at high risk or suspicious for high risk should be considered.

Current status of establishing standards for lymphadenectomy in the treatment of bladder cancer

Pelvic lymph node dissection at the time of radical cystectomy is a crucial component of the surgical management of invasive bladder cancer. No established therapeutic or diagnostic guidelines regarding pelvic lymph node dissection are, however, currently available. We reviewed the past and contemporary literature to clarify the current role of pelvic lymph node dissection both as a staging modality as well as potential therapeutic intervention. The role of pelvic lymph node dissection has evolved over the past 60 years. Although the added benefits of radical cystectomy over simple cystectomy alone are accepted, an optimal template for pelvic lymph node dissection has not been established. Increasing evidence suggesting therapeutic and diagnostic benefits by extending the boundaries of lymphadenectomy or by increasing the number of nodes excised has been reported. Much of the recent literature, however, is based on retrospective studies, and is influenced by factors such as node count variability, inconsistencies in the quality of the surgery, and the biases in patient selection. Currently, the optimal boundaries of pelvic lymph node dissection and the minimum number of nodes to be pathologically examined remain undetermined. The diagnostic and therapeutic benefits obtained by extending the limits of lymphadenectomy are compelling but inconclusive. Establishing standards for pelvic lymph node dissection will not only increase the consistency of staging and improve the design and interpretation of clinical trials in invasive bladder cancer but also help to identify and optimize the therapeutic benefits of lymphadenectomy. Prospective, randomized trials will be needed to properly establish the extent of lymphadenectomy required to obtain such benefits.

Principles, technology and indication of hyperthermia and part body hyperthermia

Clinical hyperthermia with controlled alteration of temperature (40 to 44 degrees C) in the target area is used in interdisciplinary treatment concepts for tumor treatment in combination with radiation and/or radiotherapy. Besides the direct cytotoxic power of hyperthermia there is an immunomodulatory effect and a radiation and chemotherapy sensitizing effect in the heated tissue. Clinical hyperthermia is an invasive or non-invasive supply of energy to the body of the patient, which leads to an artificial heating of the tumor and the surrounded tissue. The clinical hyperthermic procedures should take into account the oncologic disease and its pattern of organ involvement. There are three different types of hyperthermia: local hyperthermia (LHT), regional hyperthermia (RHT) and part body hyperthermia (PBH). PBH is used to heat regions of the body in case of metastatic disease, e. g. to the abdomen. I and phase II trials could show that the effects of radiation and chemotherapy can be altered by the simultaneous addition of hyperthermia. Data of trials involving skin metastasis in malignant melanoma, local relapse in breast cancer, tumors of the head and neck with regional lymph node metastasis, as well as trials in colorectal tumors, bladder cancer, pancreatic cancer, cervical cancer and sarcoma are presented. The results shows, that response to treatment can be improved by hyperthermia.

Overview of bladder cancer trials in the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy.

Overview of bladder cancer trials in the European Organization for Research and Treatment.

In the 1990s, the European Organization for Research and Treatment of Cancer Genito-Urinary (EORTC GU) Group focused on dose-intensity concepts of the methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimen for patents with bladder cancer. In a randomized trial in patients with advanced urothelial cell cancer, standard MVAC was compared with 2-weekly intensified MVAC plus granulocyte-colony stimulating factor (G-CSF) support. Although the dose-intensified therapy resulted in a higher overall and complete response rates, it did not result in a better median survival. In parallel, the Spanish Oncology Genitourinary Group (SOGUG), in collaboration with the EORTC GU Group, conducted Phase I and II trials to investigate the feasibility and efficacy of the incorporation of two new active agents, gemcitabine and paclitaxel, into two-drug or three-drug cisplatin-based or carboplatin-based regimens. The EORTC GU Group currently is conducting randomized studies of combined paclitaxel, cisplatin, and gemcitabine compared with combined gemcitabine plus cisplatin in patients with good performance status and good renal function and studies of combined gemcitabine plus carboplatin compared with combined carboplatin, methotrexate, and vinblastine in patients who are unsuited for cisplatin. In the 1990s, the EORTC coordinated a large Intergroup study of neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy versus no chemotherapy before definitive treatment. That study included 976 patients and was based on a design to detect at least a 10% absolute improvement in survival. The final results showed a 5.5% survival difference at 3 years in the chemotherapy arm. The EORTC GU Group currently is coordinating an Intergroup study that was designed to detect an improvement of 7% in absolute survival in the adjuvant setting. Cancer 2003;97(8 Suppl):2120-6.

Overview of bladder cancer trials in the Radiation Therapy Oncology Group.

In the United States, radical cystectomy is viewed as the gold standard and, with few exceptions, is the only treatment recommended for patients with invasive bladder cancer. In many areas of cancer treatment, however, the trend in the 1990s has been toward organ conservation using combined chemotherapy and radiation with or without conservative local surgery. For patients with breast, esophageal, anal, and laryngeal cancers as well as limb sarcomas, conservative therapy often is recommended. However, invasive bladder cancer has not been viewed generally as a condition that allows for conservative management. In the past 15 years, the Radiation Therapy Oncology Group (RTOG) has completed six prospective protocols of combined-modality therapy for patients with muscle-invasive cancer who were candidates for cystectomy. Bladder preservation with intravesical surgery, chemotherapy, and radiation therapy were combined as initial treatment, with radical cystectomy recommended for incomplete responders. Five of the RTOG protocols were Phase I-II trials of concurrent chemotherapy and radiation therapy, and one protocol was a Phase III trial that tested the efficacy of adjuvant chemotherapy with methotrexate, cisplatin, and vinblastine. A total of 415 patients were entered on these trials. The 5-year overall survival rate was approximately 50%, with three-quarters of those patients achieving a cure for their bladder cancer while maintaining a functioning bladder. The current RTOG protocol and its successor are directed toward better tolerated and potentially more effective chemotherapy regimens that may result in a high protocol compliance rate and, possibly, a higher overall survival rate. The trimodality therapeutic approach used in all of these RTOG protocols was more effective compared with the radiation monotherapy offered in the 1970s and with protocols that used only chemotherapy. Trimodality therapy with selective bladder preservation is not designed to take the place of radical cystectomy; however, it may be offered as a reasonable alternative to patients with invasive bladder cancer who are not willing to undergo radical cystectomy and urinary diversion. A bladder-sparing strategy may be offered appropriately to highly selected patients with the understanding that radical cystectomy is an available option in those who fail combined radiation and chemotherapy with no diminution in survival related to the delay in cystectomy.

Frequency of Positive Biopsies after Visual Disappearance of Superficial Bladder Cancer Marker Lesions

Introduction and Objectives: In phase II trials in superficial bladder cancer, marker lesions have been used to test the ablative activity of intravesical chemo– or immunotherapy. These studies provide important knowledge about drug activity and toxicity without exposing hundreds of patients in phase III trials to drugs which ultimately may not be successful in preventing tumour recurrence or progression. After treatment a deep biopsy was necessary at the site of the marker lesion even in the absence of any visual tumour. The question is if this biopsy, in the absence of any visual tumour, should be done. Material and Methods: The ablative effect of MMC, epirubicin, and quarter dose BCG instillations was evaluated in three different studies on a papillary marker lesion. Patients with multiple, primary or recurrent superficial bladder tumours were included. All visible Ta–T1 lesions were resected except for one marker lesion not exceeding 1 cm. TIS was excluded. In the last study, patients with T1 G3 tumours or multiple tumours >10 were also excluded. If the marker lesion disappeared completely, a deep biopsy was performed at the scar in order to prove histological disappearance of the tumour. Results: 185 patients were evaluated. No visual tumours were seen in 110 patients and a TUR was performed in 101 of them. It revealed only 3 Ta lesions. In the 9 others no biopsy was performed but follow–up cystoscopy revealed no lesions. Conclusions: In the absence of any visual tumors, TUR and deep biopsy at the site of the scar of the marker lesion only rarely revealed (3 out of 110) the histological presence of a tumour. Therefore, this biopsy can be omitted in new marker lesion protocols in patient with Ta–T1, G1 G2 papillary superficial bladder tumours at intermediate risk for recurrence and low risk for progression.

Recent clinical trials in superficial bladder cancer.

The present review addresses literature regarding the management of superficial bladder cancer published since March 2000. There is no definitive winner among urinary markers of bladder cancer, because they lack specificity or are insufficiently tested. Pathologists continue in their efforts to improve prediction of evolution of superficial bladder cancer to recurrent or infiltrative disease. A few studies have confirmed the value of previously described prognostic factors for recurrence and progression, and have added some refinements. Transurethral resection is not as complete as was believed. Fluorescence detection of flat bladder carcinoma has been demonstrated to improve diagnosis and treatment. The necessity to perform a repeat transurethral resection in high-grade superficial bladder cancer became evident. Identification of the working mechanisms of bacille Calmette-Guérin on superficial bladder cancer remains an important objective, and may help to improve treatment schedules and avoid the morbidity associated with bacille Calmette-Guérin administration. Patients who are at high risk may benefit from long-term maintenance bacille Calmette-Guérin therapy. Valrubicin and keyhole limpet haemocyanin appear to be promising agents in the treatment of superficial bladder cancer.