Management Of Superficial Bladder Cancer Research Articles

Recurrence rate of superficial bladder cancer with intravesical BCG and mitomycin.

Objective: To compare the recurrence rate of superficial transitional cell carcinoma of urinary bladder using intravesical BCG and Mitomycin-C. Study Design: Randomized Controlled Trial. Setting: Urology Department, Teaching DHQ Hospital, Gujranwala. Period: November 2018, to Sep, 2019. Material & Methods: Was carried out on total 270 patients, admitted with suspicion of urothelial tumors. They were grouped in Group A and B, comprising 135 in each group. Group A received BCG and Group B received Mtiomycin-C intravesically following TUR-BT. Results: Out of 270 patients male to female ratio was 3:1. Age range of patients was between 30 to 70 years with mean of 50.0± 13.1 and 552.3 ± 12.9 years in Group A and B respectively. Recurrence was noted in 05.38% and 15.38% patients in Group A and B respectively. Regarding side effects pyrexia was associated with BCG in 27.40% patients which were self-limited in 26.66% cases however required anti-tuberculosis therapy for six months in 0.74%. Whereas only 06.67% patients receiving Mitomycin had pyrexia. Dysuria occurred in 74% and frequency in 68% patients who received BCG. Whereas Dysuria occurred in 20% and frequency in 36.29% patients who received Mitomycin-C. However genital skin rash was more common (08.14%) in Mitomycin group than BCG. Conclusion: Keeping in mind less recurrence rate and bearable toxicity, it is concluded that BCG is superior to Mitomycin. This study suggests long term follow up is required to establish recurrence in the management of superficial bladder cancer.

Our experience with the management of superficial bladder cancer (Transitional Cell Ca), the role of adjuvant intravesical BCG therapy

We present our experience of 52 patients with bladder cancer. 47 patients (90%) were having superficial bladder disease (Ta, T1) who underwent TURBT followed by intravesical BCG postoperatively, 35 patients (67.3%) completed 6 weeks. Course of intravesical BCG with 10 patients (19.3%) showed recurrence of disease after` six month of follow-up. 4 patients (7.6%) left after 2 weeks of intravesical BCG and 3 patients (5.76%) did not take BCG therapy. These patients hade invasive disease and underwent radical cystectomy and two patients had metastatic bladder cancer disease which were advised systemic palliative treatment. We found intravesical BCG as effective and successful adjuvant therapy for superficial bladder cancer.

A comparative study between full-dose and half-dose intravesical immune bacille Calmette–Guérin injection in the management of superficial bladder cancer

ObjectivesTo determine whether a half-dose of bacille Calmette–Guérin (BCG) can reduce toxicity without affecting its efficacy in the management of non-muscle-invasive bladder cancer. Patients and methodsFrom January 2012 to January 2014, 80 patients with superficial bladder cancer and in the intermediate-risk group were simply randomised to receive two different doses of BCG, i.e., a full dose of 90mg (group A) or a half-dose of 45mg (group B). There were no significant differences in clinical and pathological characteristics between the groups. At completion of the study, 40 patients could be evaluated in each group. ResultsAll patients were evaluated for a follow-up of 12months after treatment. There was no significant difference in recurrence rate (15 patients, 38%, in group A and 16, 40%, in group B) in the two groups, and no difference in progression rate of the disease, at eight patients (20%) in each group. There were significant differences between groups A and B in toxicity (grade 1 adverse events, 70% vs. 60%; grade 2, 18% vs. 7.5%, respectively). Grade 3 adverse events were only reported in group A (2.5%). ConclusionThe half dose of intravesical BCG instillation can reduce the toxicity and side-effects that are associated with the treatment of superficial bladder cancer, without affecting the efficacy of therapy.

Probiotics, dendritic cells and bladder cancer

What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette-Guérin).

Intravesical immunotherapy of superficial bladder cancer with chitosan/interleukin-12.

Intravesical BCG has been used successfully to treat superficial bladder cancer for three decades. However, 20% to 30% of patients will fail initial BCG therapy and 30% to 50% of patients will develop recurrent tumors within 5 years. Alternative or complementary strategies for the management of superficial bladder cancer are needed. Interleukin-12 (IL-12) is a potent T(H)1 cytokine with robust antitumor activity and the ability to potentiate immunologic memory. Unfortunately, intravesical IL-12 did not show antitumor efficacy in a recent clinical study of patients with recurrent superficial bladder cancer. We hypothesized that coformulation of IL-12 with chitosan, a biocompatible, mucoadhesive polysaccharide, could improve intravesical IL-12 delivery and provide an effective and durable alternative for the treatment of superficial bladder cancer. In antitumor studies, 88% to 100% of mice bearing orthotopic bladder tumors were cured after four intravesical treatments with chitosan/IL-12. In contrast, only 38% to 60% of mice treated with IL-12 alone and 0% treated with BCG were cured. Antitumor responses following chitosan/IL-12 treatments were durable and provided complete protection from intravesical tumor rechallenge. Urinary cytokine analysis showed that chitosan/IL-12 induced multiple T(H)1 cytokines at levels significantly higher than either IL-12 alone or BCG. Immunohistochemistry revealed moderate to intense tumor infiltration by T cells and macrophages following chitosan/IL-12 treatments. Bladder submucosa from cured mice contained residual populations of immune cells that returned to baseline levels after several months. Intravesical chitosan/IL-12 is a well-tolerated, effective immunotherapy that deserves further consideration for testing in humans for the management of superficial bladder cancer.

Efficacy of bacillus Calmette‐Guérin in the treatment of superficial bladder cancer: The impact of previous intravesical treatment

To clinically evaluate the role of intravesical bacillus Calmette-Guérin (BCG) in the management of superficial bladder cancer, focusing on dose, age, high grade/stage, and pretreatment episodes with other therapies in long-term follow-up patients. A total of 213 patients with superficial (Ta-T1) transitional cell carcinoma of the bladder received 6-8 weekly instillations of 40, 60 or 80 mg of Tokyo strain BCG. Further 6-8 monthly applications were given in some cases. Recurrence-free and progression-free survival rates were compared with reference to dose, age, previous treatment, grade, stage, and high risk categories. Overall recurrence-free rates for 3, 5, and 10 years were 70.8%, 67.1%, and 57.6%, with progression-free survival rates of 94.5%, 93.6%, 90.6%, respectively. In univariate analyses, younger cases demonstrated higher recurrence-free survival rates, but without statistical significance (P = 0.1229). Recurrence-free rates were significantly higher for cases without previous intravesical treatment (P = 0.0010). There was no significant BCG dose-dependence. High grade and high stage patients were confirmed as having higher recurrence and progression rates. Intravesical instillation of BCG is the most effective in the long term when chosen as the initial prophylactic therapy for the prevention of recurrence in superficial bladder cancer.

Clinical Value of PTEN in Patients with Superficial Bladder Cancer

Introduction: Frequent mutations or deletions of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are reported in bladder cancer, while there are few studies which evaluated PTEN as a clinical prognostic parameter of superficial bladder cancer. We prospectively evaluated PTEN expression in patients with superficial bladder cancer by immunohistochemical staining and defined the value of PTEN mutations in predicting tumor behavior of superficial bladder cancer. Materials and Methods: A total of 190 patients were enrolled in this study. All of the patients underwent transurethral resection of bladder tumor and had superficial tumors. All pathologic materials used in this study were obtained from transurethral resection of bladder tumor. Immunohistochemical stainings were performed. The immunohistochemical staining intensity was judged to be either normal or reduced compared with the PTEN protein expression of positive and negative controls. Disappearance of more than 50% stained cytoplasmic granules was defined as reduced PTEN expression. Results: The alteration of PTEN expression was significantly different according to tumor stage and grade (p = 0.03, p = 0.048), especially high in carcinoma in situ. However, PTEN expression was not significantly correlated with disease recurrence, progression and recurrence- or progression-free survival. Conclusions: Reduced PTEN expression relates to aggressiveness of bladder tumors but seems not to have enough specificity for clinical use in the management of superficial bladder cancer.

Bacillus Calmette-Guerin in the management of superficial bladder cancer

Intravesical Bacillus Calmette-Guérin (BCG) is the mainstay of superficial bladder cancer treatment. We performed a literature search through Medline/Pubmed using key words ‘Bacillus Calmette-Guérin’, ‘intravesical’, ‘bladder neoplasm’ and ‘immunotherapy’ for published data in the English language from 1970 to 2007 to review the current status of intravesical therapy and practice recommendations. The exact mechanism of action of intravesical BCG is yet to be elucidated. However, it appears that it is mediated by the local immune response, mainly through T-helper cell response. It reduces the recurrence rate by an average of 40% and progression by more than 20% in papillary tumors over the patients without BCG therapy. However, progression prevention is seen only in series which have used maintenance therapy at least for one year. It is effective in CIS of bladder with a response rate of more than 40% and prevention of progression in one-fourth patients. Most acceptable dose, induction treatment and maintenance therapy protocols are discussed. However, these are yet to be confirmed in large randomized trials. Intravesical BCG is well tolerated in most of the patients with mild to moderate side-effects in induction therapy; however, most patients do not complete maintenance therapy due to side-effects which is the most common concern at the present time.

Innovations in superficial bladder cancer treatments. Review

Bladder cancer treatment is a challenge for both urologists and oncologists. Particularly during these last years many changes have been made in the management of superficial bladder cancer. In the case of superficial bladder cancer, intravesical instillation of chemo/immunotherapeutic agents after transurethral resection is the standard. The treatment goals include: complete removal of the initial tumor, prevention of recurrences and inhibition of disease progression. This work aims at reviewing the new developments in the therapeutic field of superficial bladder cancer. A growing trend involves the use of multimodality treatment to obtain the activation of the host immunity against the tumor, and to enhance the cytotoxic effects of chemotherapeutic agents. The new therapeutic modalities, which are under preclinical and clinical investigations, are showing promising results.

The management of superficial bladder cancer

From review of the currently available trial evidence, several clinical recommendations for bladder tumor management become apparent. Transurethral resection should be done, but this procedure is prone to both overestimating and underestimating staging. Restaging transurethral resection for patients with T1 tumors should, therefore, be performed. Data support the immediate postoperative instillation of a chemotherapeutic agent for patients with solitary, low-grade papillary tumors, whereas patients with multiple lesions might benefit from a more intensive adjuvant regimen. Although the use of intravesical immunotherapy for reducing tumor progression or as maintenance therapy is controversial, bacillus Calmette-Guérin has demonstrated significant benefit for tumor prophylaxis when no obvious residual disease is present. Early radical cystectomy can be beneficial and should be performed in patients with refractory T1 tumors or carcinoma in situ before progression to muscle invasion. In this Review I present an overview of the management of nonmuscle invasive bladder cancer. The most common intravesical chemotherapeutic agents are described as well as the impact of chemotherapy on the recurrence and progression of tumors. The effect of intravesical immunotherapy in bladder cancer is explored as well as the role of early cystectomy.

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.

Innovations in superficial bladder cancer treatments.

Bladder cancer treatment is a challenge for both urologists and oncologists. Particularly during these last years many changes have been made in the management of superficial bladder cancer. In the case of superficial bladder cancer, intravesical instillation of chemo/immunotherapeutic agents after transurethral resection is the standard. The treatment goals include: complete removal of the initial tumor, prevention of recurrences and inhibition of disease progression. This work aims at reviewing the new developments in the therapeutic field of superficial bladder cancer. A growing trend involves the use of multimodality treatment to obtain the activation of the host immunity against the tumor, and to enhance the cytotoxic effects of chemotherapeutic agents. The new therapeutic modalities, which are under preclinical and clinical investigations, are showing promising results.

Superficial bladder cancer: part 1. Update on etiology, classification and natural history

Superficial ‘nonmuscle-invasive’ bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.

UP-03.32: A prospective study into the tolerability of side effects of intravesical BCG in the management of superficial bladder cancer

UP-03.32: A prospective study into the tolerability of side effects of intravesical BCG in the management of superficial bladder cancer

Fluorescence cystoscopy: is it ready for use in routine clinical practice?

To review the recent literature on the use of fluorescence cystoscopy in the diagnosis and management of bladder cancer. Recent advances have been made in fluorescence cystoscopy with the use of newer fluorescence agents (hexylester aminolevulinate and hypericin) and their application to flexible cystoscopy. Within several hours of intravesical administration of these agents, bladder tumors can be detected using fluorescence cystoscopy resulting in improved cancer detection and lower short-term recurrence rates than white light cystoscopy. Preliminary results with flexible fluorescence cystoscopy suggest that this technique can be used for office-based cystoscopy. Significant advances have been made in the field of fluorescence cystoscopy. The currently available fluorescence agents in recent phase II and III trials outperform white light cystoscopy in terms of cancer detection and recurrence-free survival. Fluorescence cystoscopy should be considered as an adjunctive tool for the diagnosis and management of superficial bladder cancer.

Vitamin D Receptor Agonists, Cancer and the Immune System: An Intricate Relationship

Vitamin D receptor (VDR) agonists can inhibit cell growth, promote apoptosis, and induce differentiation of many cell types, in addition to inhibiting metastasis and angiogenesis, all desirable properties for a drug to control cancer. However, from an immunological perspective, the immunomodulatory properties of VDR agonists are apparently just opposite to the main aims of cancer immunotherapy: boosting the immune response and breaking tumor-related tolerance. While it may be possible to identify VDR agonists with enhanced anti-proliferative/pro-differentiative and reduced immunomodulatory activities as anti-cancer agents, a complementary approach could rely on identifying clinical indications where their systemic immunomodulatory properties could be minimized. Superficial bladder cancer, where treatments are usually administered by vesical instillation, may represent such an indication. We have observed a strong synergism in vitro between calcitriol and doxorubicin or epirubicin in the inhibition of bladder cancer cell proliferation. Thus, calcitriol and doxorubicin or epirubicin in combination may have clinical value in the management of superficial bladder cancer.

Bladder cancer

This article will review the diagnosis and management of bladder cancer at each stage, from superficial to metastatic disease with an emphasis on recent developments over the last year. Bacille Calmette-Guerin is the most effective therapy for carcinoma in situ. All patients who receive intravesical therapy with bacille Calmette-Guerin should be considered for ongoing maintenance therapy. The management of muscle invasive disease in the United States centers on radical cystectomy with bilateral pelvic lymphadenectomy. Areas of research include the optimal role for bladder preservation therapy, a growing experience in centers with laparoscopy, the effect of urinary diversion on quality of life, and the optimal standard for pelvic lymphadenectomy at surgery. The role of combination chemotherapy for advanced bladder cancer continues to evolve. Many questions remain unanswered including the relative value of neoadjuvant versus adjuvant chemotherapy for locally advanced disease and optimal chemotherapy regimen. The detection of bladder cancer continues to rely on direct visualization with cystoscopy. Efforts are underway to improve the utility of urinary markers and cystoscopy through fluorescence endoscopy. The management of superficial bladder cancer is based on transurethral resection of the tumor with perioperative intravesical instillation of chemotherapy strongly suggested for most patients. Risk stratifying patients with high-risk superficial bladder cancer remain a challenge and area of future research.

New treatments for superficial bladder cancer

The successful treatment of bladder cancer remains a challenge for urologists and oncologists. Substantial changes have been made in the therapeutic options for the management of superficial bladder cancer in the past 5 years. We review the preclinical and clinical developments over the past year in bladder cancer therapeutics. A growing trend involves the use of multimodality treatments for all bladder cancers. For superficial disease, intravesical instillation of chemotherapeutic agents after transurethral resection is quickly becoming the standard of care. Novel therapeutic modalities under investigation include DNA vaccines, magnetically targeted carriers, bioadhesive microspheres, and antisense oligodeoxynucleotides. Treatment goals for superficial bladder cancer are complete removal of the initial tumor, prevention of disease recurrence, and inhibition of progression to invasive disease. The myriad novel therapeutic modalities under exploration suggest that these goals may be achievable within our lifetime.

S14-2 Risk factors and prediction of recurrence in superficial bladder cancer(Symposium 14「Management of Superficial Bladder Cancer」)

S14-2 Risk factors and prediction of recurrence in superficial bladder cancer(Symposium 14「Management of Superficial Bladder Cancer」)

Current Practice in the Management of Superficial Bladder Cancer in the Netherlands and Belgian Flanders: A Survey

ObjectiveBecause there is no national guideline for the diagnosis, therapy and follow up of (superficial) bladder cancer in the Netherlands and Belgium, the actual patient management may differ between urologists. The purpose of this study is to get insight in the current way urologists diagnose, treat and follow patients with superficial bladder cancer. MethodsAll practising urologists in the Netherlands (n=293) and Flemish speaking Belgium (Flanders, n=223) received a questionnaire with regard to the current management of patients with superficial bladder cancer. The results were compared with the guidelines provided by the European Association of Urology (EAU). Also a comparison was made between the two countries and between university and community hospitals. ResultsThe results show a wide variation in current practice for superficial bladder cancer. Although the majority of urologists do not follow the EAU guidelines, current practice roughly matches these guidelines. There are no major differences between the two countries or between different types of hospitals. Discrepancies between current practice and guidelines are mostly too frequent use of techniques for the diagnosis, treatment and follow-up. ConclusionIn all, there is a need for clear guidelines in superficial bladder cancer and an effective implementation of such guidelines into everyday practice.