Intravesical Chemo Research Articles

Intravesical Therapy of Superficial Urothelial Bladder Cancer with BCG and Epirubicin 50 Mg - Comparative Analysis

Summary Bladder cancer is a heterogeneous disease in molecular, histological and clinical aspects. Treatment should also be considered from different angles - surgery, intravesical chemo- or immunotherapy, radiation therapy and lifestyle changes. Intravesical treatment of superficial bladder cancer with Еpirubicin or Bacillus Calmette-Guérin (BCG) is a continuation of surgical treatment to reduce or eliminate further recurrence.

Recurrence and progression of non-muscle invasive bladder cancer following trans-urethral resection of bladder tumour with adjuvant intravesical chemo-immunotherapy

Background: Trans-urethral resection of bladder tumor is an essential diagnostic tool as well as effective treatment modality for non-muscle invasive bladder cancer. We aimed to evaluate the recurrence and progression of the non-muscle invasive bladder cancer in Nepalese patients.
 Methods: This was a retrospective study of 43 patients with non-muscle invasive bladder cancer, who underwent trans-urethral resection of bladder tumour followed by adjuvant intravesical instilla­tion of chemo or immunotherapy between January, 2013 to December, 2018. Patients were divided into low, intermediate and high-risk groups according to the clinical and pathological factors used by the European Organization for Research and Treatment of Cancer scoring system. Outcomes were calculated in terms of recurrence and progression in each group.
 Results: Out of 43 patients, 11 (25.58%) patients had low risk, 18 (41.86%) patients had intermediate risk and 14 (32.56%) patients had high risk of recurrence categories. No recurrence and progression of the disease noted in low risk group. In the intermediate risk group, out of 18 patients, 4 (22.2%) patients developed recurrence and 2 (11.1%) patients had progression of disease. In high risk group, out of 14 patients, 4 (26.8%) patients developed recurrence and 2 (14%) patients developed progres­sion of the disease.
 Conclusions: Even in a low volume centre of bladder cancer, effective treatment for non-muscle inva­sive bladder cancer with trans-urethral resection of bladder tumour followed by adjuvant intravesical chemo or immunotherapy can be given safely to reduce recurrence and progression of the disease.

RECURRENCE AND PROGRESSION OF NON-MUSCLE INVASIVE BLADDER CANCER FOLLOWING TRANS-URETHRAL RESECTION OF BLADDER TUMOUR WITH ADJUVANT INTRAVESICAL CHEMO-IMMUNOTHERAPY

Background: Trans-urethral resection of bladder tumor is an essential diagnostic tool as well as effective treatment modality for non-muscle invasive bladder cancer. We aimed to evaluate the recurrence and progression of the non-muscle invasive bladder cancer in Nepalese patients. Methods: This was a retrospective study of 43 patients with non-muscle invasive bladder cancer, who underwent trans-urethral resection of bladder tumour followed by adjuvant intravesical instilla­tion of chemo or immunotherapy between January, 2013 to December, 2018. Patients were divided into low, intermediate and high-risk groups according to the clinical and pathological factors used by the European Organization for Research and Treatment of Cancer scoring system. Outcomes were calculated in terms of recurrence and progression in each group. Results: Out of 43 patients, 11 (25.58%) patients had low risk, 18 (41.86%) patients had intermediate risk and 14 (32.56%) patients had high risk of recurrence categories. No recurrence and progression of the disease noted in low risk group. In the intermediate risk group, out of 18 patients, 4 (22.2%) patients developed recurrence and 2 (11.1%) patients had progression of disease. In high risk group, out of 14 patients, 4 (26.8%) patients developed recurrence and 2 (14%) patients developed progres­sion of the disease. Conclusions: Even in a low volume centre of bladder cancer, effective treatment for non-muscle inva­sive bladder cancer with trans-urethral resection of bladder tumour followed by adjuvant intravesical chemo or immunotherapy can be given safely to reduce recurrence and progression of the disease.

Current and innovative approaches in the treatment of non-muscle invasive bladder cancer: the role of transurethral resection of bladder tumor and organoids.

BackgroundBladder cancer is the 7th most common cancer in men. About 75% of all bladder cancer are non-muscle invasive (NMIBC). The golden standard for definite diagnosis and first-line treatment of NMIBC is transurethral resection of bladder tumour (TURB). Historically, the monopolar current was used first, today bipolar current is preferred by most urologists. Following TURB, depending on the tumour grade, additional intravesical chemo- or/and immunotherapy is indicated, in order to prevent recurrence and need for surgical resection. Development of new technologies, molecular and cell biology, enabled scientists to develop organoids – systems of human cells that are cultivated in the laboratory and have characteristics of the tissue from which they were harvested. In the field of urologic cancers, the organoids are used mainly for studying the course of different diseases, however, in the field of bladder cancer the data are scarce.ConclusionsDifferent currents - monopolar and bipolar, have different effect on urothelium, that is important for oncological results and pathohistological interpretation. Specimens of bladder cancer can be used for preparation of organoids that are further used for studying carcinogenesis. Bladder organoids are step towards personalised medicine, especially for testing effectiveness of chemo-/immunotherapeutics.

Emerging intravesical therapies for the management of bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer: Charting a path forward.

Management of patients with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk, non-muscle-invasive bladder cancer (NMIBC) presents a formidable clinical challenge that requires urologists to weigh the competing risks of progression during further intravesical therapy vs. the morbidity of radical cystectomy. The prognosis of high-risk NMIBC recurring after BCG depends on the adequacy of prior BCG, timing of recurrence, and tumor histology. The standard of care is currently radical cystectomy, as effective salvage intravesical therapy has not been established. The development of bladder-sparing treatments has been hampered to date by inconsistent definitions of BCG failure and difficulties in identifying appropriate control treatments in clinical trials. Despite these limitations, the spectrum of salvage therapy is expanding to include enhanced intravesical chemo-, gene, and immuno-therapies. In this review, we provide an overview of these emerging agents in the context of our current understanding of BCG failure and the unique considerations for clinical trial design in this disease state.

Minimally invasive cystectomy approaches in the treatment of bladder cancer

Bladder cancer is the most frequently occurring tumor of the urinary system, with over 10,000 new diagnoses each year in the UK. Approximately 70% of these are non-muscle-invasive and limited to the mucosa (Ta) or submucosa (T1). These tumors are generally managed with transurethral resection followed by adjuvant intravesical chemo- or immuno-therapy and regular cystoscopic surveillance. The principal end points in the management of these tumors are prevention of recurrence and progression. Muscle-invasive bladder cancer is a life-threatening disease with overall 5-year mortality of 50%. Neoadjuvant chemotherapy, where possible followed by radical surgery, is currently considered the best standard of care. Open radical cystectomy is the gold-standard treatment for muscle-invasive or high-risk non-muscle-invasive (multifocal or recurrence after intravesical therapy) bladder cancer. Historically, this procedure has carried significant morbidity, although mortality of open radical cystectomy has reduced to 1–2% owing to improvements in anesthesia and intensive care facilities. Over the last 15 years, minimally invasive techniques in radical cystectomy have evolved, with the aim of reducing morbidity. In this article, we review the development of laparoscopic radical cystectomy and robot-assisted radical cystectomy, along with current evidence on perioperative morbidity and medium-term oncological outcomes.

Current and Emerging Strategies in Bladder Cancer

Urothelial cell carcinoma is one of the most common malignancies of the urinary tract. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. Muscle invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors, been few in number and largely unsuccessful. Hence, bladder cancer represents a considerable opportunity and challenge for alternative therapies. In this review, we will focus on promising global or pathway-based approaches (epigenetic modulators, kinase inhibitors, angiogenesis blockage, peroxisome proliferator-activated receptor γ agonists, apoptosis inductors, virus therapy) supported by a deeper understanding of molecular biology of urothelial carcinoma, which have been recently tested in clinical trials.

Reported use of intravesical therapy for non‐muscle‐invasive bladder cancer (NMIBC): results from the Bladder Cancer Advocacy Network (BCAN) survey

Study Type - Therapy (patterns of practice) Level of Evidence 2b. What's known on the subject? and What does the study add? Claims-based analyses suggest unexplained and potentially problematic variation in treatment intensity adherence to guidelines-recommended care in NMIBC. Previous physician surveys prior to the contemporary Clinical Practice Guidelines (CPGs) reported associations between variation in NMIBC care and practice type, years in practice, and other physician-related factors. In the largest physician survey addressing the management of NMIBC, and the first to examine these questions after the promulgation of contemporary CPGs, US urologists report grade-specific utilization consistent with CPG recommendations, at rates higher than suggested by recent claims-based analyses. As with prior studies, practice type and years in practice were significantly associated with variation in practices. Further research is needed to reconcile these findings with administrative claims data. To determine self-reported practices of use of intravesical chemo- and immunotherapy for patients with non-muscle-invasive bladder cancer (NMIBC) • To evaluate the extent to which respondent characteristics were associated with any observed variation. Guidelines recommend intravesical therapy (IVT) in the management of NMIBC, but recent claims-based analyses suggest exceedingly low rates of use of some of these therapies. An electronic survey was developed by members of the Bladder Cancer Advocacy Network (BCAN) to elicit self-reported use of management strategies for NMIBC. • The survey was circulated to urologists via the American Urological Association, Society for Urologic Oncology and Large Urology Group Practice Association distribution lists. • In all, 512 respondents completed the survey. In all, 63% reported routine perioperative mitomycin-c (MMC) after transurethral resection of bladder tumour (80% academic vs 54% private practice, P < 0.001). • Whereas 5% of respondents reported routine induction therapy with all new low-grade (LG) diagnoses, 99% reported routinely doing so in new high-grade (HG) cases; most commonly with single-agent bacille Calmette-Guérin (BCG) (94% vs 9% BCG/interferon and 5% MMC). • Reported induction therapy was higher in the setting of high-volume (77%) or frequently recurrent (44%) LG disease. • In all, 89% reported routinely using maintenance therapy for HG vs 29% for LG disease. • Routine biopsy after BCG, even with normal cystoscopy, was endorsed by 28% (39% academic vs 22% private practice, P < 0.001). Urologists report grade-specific use of IVT for NMIBC, at rates higher than suggested in some claims-based analyses. • Further study is needed to corroborate these self-reported patterns of care with lower rates of use suggested by claims-based analyses.

870 A NEW MOLECULAR CHEMOSENSITIVITY TEST TO IMPROVE AND PREDICT EFFICACY OF INTRAVESICAL ADJUVANT THERAPY IN NMIBC (NON MUSCLE INVASIVE BLADDER CANCER)

You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 2011870 A NEW MOLECULAR CHEMOSENSITIVITY TEST TO IMPROVE AND PREDICT EFFICACY OF INTRAVESICAL ADJUVANT THERAPY IN NMIBC (NON MUSCLE INVASIVE BLADDER CANCER) Ettore De Berardinis, Gian Maria Busetto, Gabriele Antonini, Chiara Nicolazzo, Arianna Petracca, Paola Gazzaniga, and Vincenzo Gentile Ettore De BerardinisEttore De Berardinis Roma, Italy More articles by this author , Gian Maria BusettoGian Maria Busetto Roma, Italy More articles by this author , Gabriele AntoniniGabriele Antonini Roma, Italy More articles by this author , Chiara NicolazzoChiara Nicolazzo Roma, Italy More articles by this author , Arianna PetraccaArianna Petracca Roma, Italy More articles by this author , Paola GazzanigaPaola Gazzaniga Roma, Italy More articles by this author , and Vincenzo GentileVincenzo Gentile Roma, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.694AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The treatment choice for high risk NMIBC is still controversial, and no markers are still available to guide the urologist in the individualization of therapy. Although intravesical chemo and immuno treatments represent the gold standard in adjuvant setting after TURB the percentage of recurrence and progression under treatment is still high. We here describe the design of a chemosensitivity assay based on the expression of genes involved in the resistance to standard intravesical regimens. METHODS 128 patients with high risk NMIBC have been enrolled, all candidates for TUR-B followed by intravesical treatment. All patients have been evaluated by cystoscopy 3 and 6 months after TUR-B. One mg of tumoral tissue from each patient was kept for molecular assay subjected to RNA extraction and RT-PCR amplifications with primers specific for MRP1, MRP2, hENT1, dCK, à5â1 integrin, used to trace a specific chemosensitivity profile to drugs commonly used in intravesical regimen: anthracyclines, mitomycin-c, gemcitabine and BCG. On the basis of densitometric analysis of the amplification bands obtained by normalisation with the GAPDH internal controls, we obtained for each patient a chemosensitivity molecular profile. We considered high, intermediate and low sensitivity to mitomycin c, epirubicin, and doxorubicin a ratio MRP/GAPDH <1, =1, >1 respectively. For gemcitabine resistance, we considered sensitivity, intermediate sensitivity and resistance a ratio hENT-dCK/GAPDH >1, =1 and <1 respectively. Sensitivity to BCG was evaluated as follows: high, intermediate, low sensitivity in the presence of à5â1/GAPDH >1; =1; <1 respectively. We then compared both the molecular profiles of chemosensitivity to the clinical response to the intravesical regimen adopted in the first 6 months of follow up. RESULTS This chemosensitivity test was able to predict response to treatment in 93% of patients. The assay is easy to perform with low costs and rapid time of execution. CONCLUSIONS Our results are encouraging in the view of an individualised therapeutic approach, to provide a higher treatment success rate while sparing patients unnecessary toxicity from drugs that are not suited for their tumors. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e348-e349 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ettore De Berardinis Roma, Italy More articles by this author Gian Maria Busetto Roma, Italy More articles by this author Gabriele Antonini Roma, Italy More articles by this author Chiara Nicolazzo Roma, Italy More articles by this author Arianna Petracca Roma, Italy More articles by this author Paola Gazzaniga Roma, Italy More articles by this author Vincenzo Gentile Roma, Italy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Reported patterns of utilization of intravesical therapy in non-muscle-invasive bladder cancer: Results from the BCAN/SUO/AUA/LUGPA electronic survey.

267 Background: Guidelines recommend intravesical chemotherapy and immunotherapy in the management of non-muscle-invasive bladder cancer (NMIBC) to reduce the risks of recurrence and potentially progression. Nevertheless, recent claims-based analyses have suggested exceedingly low rates of utilization of some of these therapies in practice. In general, there is a paucity of data to inform our understanding of current patterns of care. Methods: An electronic survey was developed by the Bladder Cancer Advocacy Network (BCAN) to elicit self-reported practices of utilization of intravesical chemo- and immuno-therapy for patients with NMIBC. The survey was circulated to urologists via the AUA, SUO and LUGPA distribution lists. 512 respondents completed the survey. Results: Overall, 63% of respondents reported routine administration of perioperative mitomycin-c (MMC) after TURBT [80% of SUO respondents vs. 55% of AUA/LUGPA respondents (p&lt;0.001)]. Whereas 5% of respondents reported routine induction therapy with all new low-grade (LG) diagnoses, 99% reported routinely doing so in new high-grade (HG) cases; most commonly with single- agent BCG (94%; vs. 9% BCG/IFN and 5% MMC). Reported induction therapy was higher in the setting of high-volume (77%) or frequently recurrent LG (44%) disease. 89% reported routinely using maintenance therapy for HG, vs. 29% for LG. Reduced strength BCG was most commonly endorsed only in the settings of poor tolerance of full strength (84%) or maintenance (11%), with only 3% endorsing routine use. Routine post-BCG biopsy, even with normal cystoscopy, was endorsed by 28% of respondents, and 64% of respondents used urine-based markers to assess response to intravesical therapy. Conclusions: Urologists report grade-specific patterns of utilization of intravesical therapy for NMIBC, at rates higher than suggested in some claims-based analyses. Variation exists in post-treatment followup practices. Further study is needed to rectify these self-reported patterns of care with results from claims-based analyses. No significant financial relationships to disclose.

Emerging targeted therapies for bladder cancer: a disease waiting for a drug

Urothelial cell carcinoma is the fifth most common cancer and the costliest to treat. This is largely because of all new cases, about 70% present as superficial disease and this while rarely fatal, tends to recur, requiring long-term follow-up and repeat interventions. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. Muscle-invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors such as lung, breast and prostate, been few in number and largely unsuccessful, with no new agents being registered in the last 20 years. Hence, bladder cancer represents a considerable opportunity and challenge for molecularly targeted therapy.

Advances in the Management of Superficial Bladder Cancer

Given its high tendency to recur, coupled with an ever-present possibility to progress to potentially life-threatening muscle-invasive disease, superficial bladder cancer remains a challenging clinical problem. Optimal management begins with early detection and accurate risk assessment through careful attention to clinical features, aided by an emerging array of urinary markers and molecular characterizations. Prevention of recurrence requires the sequential application of tools to completely remove all visible disease, avert reimplantation during surgical resection, ablate microscopic foci, and prevent the emergence of new primary tumors amidst a field of carcinogen-exposed urothelium. Previously standard adjunctive intravesical chemo- and immunotherapies are enjoying new vitality as optimization strategies, new drugs, and rational drug combinations provide the potential for improved efficacy with reduced toxicity. New technological advances such as fluorescence-aided cystoscopy, microwave chemothermotherapy, and electromotive chemotherapeutic drug delivery offer further hope for better outcomes even for disease previously refractory to conservative measures. Yet despite these advances, aggressive surgical management involving bladder removal continues to be an indispensable life-saving maneuver that must be considered in all high-risk cases that fail to promptly respond to other measures.

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.

Intravesical therapy of superficial bladder cancer.

Transurethral resection (TUR) of the superficial transitional cell carcinoma (TCC) of the bladder is known to be insufficient in controlling the disease because of the unacceptable rates of recurrence, progression and ultimate cystectomy. Adjuvant intravesical chemo-and/or immunotherapy is administered in an effort to enhance the efficacy of surgery alone. The initial tumor stage and grade, the multifocality of this cancer and the history of previous recurrences remain the determinant factors in survival. It is important to decide exactly which patients are at risk, and, therefore, do need treatment. Knowledge of the natural history of the disease will facilitate this decision making, although the natural history of TCC is largely unpredictable owing to tumor heterogeneity. Several cytotoxic and immune modifying agents have been used intravesically in different treatment schedules. However, despite their effectiveness, no consensus exists about the optimal antineoplastic regimen. The selection of the latter is a subject of continuous investigation. Intravesical treatment with cytotoxic drugs has been demonstrated to achieve an acceptable reduction in short- and intermediate-term recurrence rates, but has no proven ability in preventing disease progression to muscle-invasive cancer or prolonging survival. On the other hand, bacillus Calmette-Guerin (BCG) currently appears to be the most effective agent for intravesical use, especially in patients with high grade and stage neoplasms but the optimum strain, dosage and duration schedule have not been determined. Clinical trials have shown that BCG provides long-term protection from tumor recurrence, while there is evidence that it may favorably alter the progression rate of the disease with prolongation of survival. Toxicity of intravesical chemo- and immunotherapy still remains a major problem and attempts at reducing the dosage, and, thus, toxicity without affecting efficacy are underway. This review endeavors to present updated information on intravesical chemotherapy in treating superficial bladder cancer, the expanding role of intravesical immunotherapy, the recent work comparing various immunotherapeutic regimens with chemotherapeutic intravesical therapies, and the progress made towards achieving optimal treatment regimens.

Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long-term experience.

Photodynamic therapy (PDT) combines a photosensitizer such as Photofrin with red laser light (630 nm) to destroy cancer cells. Investigators have reported effectiveness of PDT in the management of patients with recurrent superficial bladder cancer. We retrospectively reviewed our experience in 58 patients to assess the long-term role of PDT in the management of resistant superficial transitional cell carcinoma (TCC) including Ta, T1, and refractory carcinoma in situ (CIS) of the urinary bladder. All 58 patients had failed at least one course of standard intravesical therapy or had contraindication for intravesical chemo- or immunotherapy. Patients with malignancy present (Ta-T1/Grade I-III, CIS) were accepted for ablative PDT. Patients undergoing prophylactic PDT after complete resection were confirmed to be tumor-free by cystoscopy and bladder was cytology before PDT. Post-PDT evaluations included weekly telephone contact to assess acute adverse reactions and assessment of efficacy and bladder toxicity at three months and quarterly thereafter. These 58 patients underwent a single PDT treatment with 2.0 or 1.5 mg/kg of Photofrin and 10-60 J/cm2 light (630 nm). At three months, complete response rates were 84% and 75% for residual resistant papillary TCC and refractory CIS respectively; and 90% of patients treated prophylactically had not had recurrences. At a median followup of 50 months (range 9-110), 59% (34/58) of the responders are alive, with 31/34 still disease-free. PDT using 1.5 mg/kg of Photofrin and 15 J/cm2 of light (630 nm) should be considered a safe and effective treatment for refractory CIS or recurrent papillary TCC.

Radical cystectomy for high risk patients with superficial bladder cancer in the era of orthotopic urinary reconstruction.

Many patients with aggressive clinically superficial bladder cancer ultimately die of their cancer, due in part to resistance to undergo radical cystectomy. Radical cystectomy is usually curative for patients with pathologic superficial tumors. Orthotopic urinary reconstruction has lessened the morbidity and lifestyle changes in patients after cystectomy, and may increase patient acceptance of cystectomy as therapy for high risk superficial tumors. A retrospective analysis was performed on 182 patients with clinically superficial bladder cancer (Ta, Tis, T1) who had radical cystectomy between 1971 and 1989, to determine the incidence of pathologic upstaging and to assess overall survival, cause-specific survival, and recurrence free survival. Indications for cystectomy included failure of intravesical chemo- or immunotherapy, high grade lamina propria invasive tumors, presence of bladder diverticulae, spread of superficial tumors into the prostatic urethra, and endoscopically uncontrollable tumors. Pathologic upstaging to muscle-invasive or metastatic tumors occurred in 34% of patients, and of these, only half remained organ confined. Metastases were present in 8% of patients at the time of cystectomy. Mucosa-confined tumors were upstaged only 19% of the time, whereas tumors demonstrating lamina propria invasion (T1) were upstaged 40% of the time. Pathologic upstaging to muscle-invasive or metastatic disease was significantly associated with a decreased probability of survival (P = 0.042). With a median follow-up of 7.2 years, overall survival was estimated to be 86%, 72%, and 47%, and recurrence free survival 90%, 83%, and 77% at 2, 5, and 10 years, respectively. Pathologic upstaging to muscle-invasive or metastatic tumors occurs in one third of highly selected patients with clinically superficial bladder cancer who have had radical cystectomy, half of whom have extravesical disease. Survival is significantly decreased in this group of upstaged patients. With the alternative of orthotopic urinary diversion available to most men and women requiring cystectomy, radical cystectomy should be considered a viable alternative to continued conservative measures for selected patients with aggressive superficial bladder tumors.

Treatment of superficial bladder tumors with alpha 2b Interferon and Epirubicin

The relapse of superficial bladder tumours can be prevented, after endoscopic treatment, by intravesical chemo and immunoprophylaxis. In the first 6 months of 1991, 14 patients (13 males, 1 female, average age 58.3) were treated endoscopically for superficial bladder tumours, which had been detected on average 3.5 years earlier. Intravesical treatment was with 50 mg Epirubicin and, after 3 hours, alpha-2b Interferon once a week for 8 weeks. The patients had a hematological and cystoscopic control every 3 months for one year. A decrease in tumour recurrence was noted at the first endoscopic control, then only slow growth of superficial bladder tumour recurrence was observed.