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European Urology May 2015Urothelial carcinoma in situ (CIS) has a high propensity for progression. It is usually reported within the heterogeneous context of non-muscle-invasive bladder cancer... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Urothelial carcinoma in situ (CIS) has a high propensity for progression. It is usually reported within the heterogeneous context of non-muscle-invasive bladder cancer (NMIBC) but warrants special consideration.
OBJECTIVE
To review the contemporary literature on the diagnosis and management of CIS.
EVIDENCE ACQUISITION
A systematic search using broad terms to capture the diagnosis and treatment of CIS was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. Full-text original articles, reviews, and editorials from 1966 to 2014 in English were included. References from selected articles, relevant guidelines, and conference abstracts were searched. Abstracts were excluded.
EVIDENCE SYNTHESIS
A total of 1887 articles were identified, of which 120 were used in this review. Most reports were retrospective and heterogeneous in caseload. There is a lack of standardised classification of CIS. Many studies consider CIS in the context of NMIBC without a clear separation of the subset with CIS. Recent prospective phase 2 and 3 studies have improved the evidence base.
CONCLUSIONS
We are beginning to understand that CIS has a spectrum of biologic potential. Bacillus Calmette-Guérin immunotherapy appears superior to other intravesical agents and may alter the natural history of CIS. New imaging modalities, agents, and treatment strategies have emerged in recent years with the aim of better identification of CIS, more bladder-preserving treatments, and prevention of surgical overtreatment.
PATIENT SUMMARY
Improvements in imaging techniques combined with new bladder-preserving treatments will continue to have an impact on the outcomes of bladder carcinoma in situ.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Carcinoma in Situ; Carcinoma, Transitional Cell; Humans; Multimodal Imaging; Treatment Outcome; Urinary Tract; Urologic Neoplasms
PubMed: 25466937
DOI: 10.1016/j.eururo.2014.10.040 -
The Journal of Urology May 2017We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer.
MATERIALS AND METHODS
Systematic literature searches were performed of Ovid MEDLINE (January 1990 through February 2016), the Cochrane databases and reference lists. Randomized and quasi-randomized trials of intravesical bacillus Calmette-Guérin, mitomycin C, gemcitabine, thiotepa, valrubicin, doxorubicin, epirubicin and interferon vs transurethral bladder tumor resection alone, and head-to-head trials of intravesical therapies were selected. Data were pooled using a random effects model.
RESULTS
Overall 39 trials evaluated adjuvant intravesical therapy vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin was associated with a decreased risk of bladder cancer recurrence (3 trials, RR 0.56, 95% CI 0.43-0.71) and progression (4 trials, RR 0.39, 95% CI 0.24-0.64) (strength of evidence low). Mitomycin C, doxorubicin, epirubicin and thiotepa were also associated with a decreased risk of recurrence, with no difference in risk of progression (strength of evidence low). There were 55 trials that compared one intravesical therapy agent against another. There were no differences between bacillus Calmette-Guérin vs mitomycin C in recurrence risk (RR 0.95, 95% CI 0.81-1.11), but bacillus Calmette-Guérin was associated with a decreased risk of recurrence in the subgroup of trials of maintenance regimens (RR 0.79, 95% CI 0.71-0.87, strength of evidence low). Bacillus Calmette-Guérin was associated with a lower recurrence risk vs doxorubicin, epirubicin, interferon alpha-2a, bacillus Calmette-Guérin plus interferon alpha-2b, and thiotepa (strength of evidence low to moderate). Bacillus Calmette-Guérin was associated with higher rates of local and systemic adverse events than other intravesical agents (strength of evidence low). Head-to-head trials showed no clear differences between standard and lower doses of bacillus Calmette-Guérin in recurrence, progression or mortality risk (strength of evidence low). Limited evidence suggested that bacillus Calmette-Guérin maintenance regimens are associated with reduced recurrence risk vs no further intravesical therapy in responders to induction therapy (strength of evidence low).
CONCLUSIONS
For nonmuscle invasive bladder cancer several intravesical therapies are associated with a decreased risk of recurrence vs transurethral bladder tumor resection alone. Bacillus Calmette-Guérin is the only agent associated with a decreased progression risk vs transurethral bladder tumor resection alone, but may be associated with a higher risk of adverse events than other intravesical therapies, indicating trade-offs between potential benefits and harms.
Topics: Administration, Intravesical; Antineoplastic Agents; BCG Vaccine; Chemotherapy, Adjuvant; Clinical Trials as Topic; Cystectomy; Disease Progression; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 28027868
DOI: 10.1016/j.juro.2016.12.090 -
Aktuelle Urologie Aug 2017Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer...
Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure. We performed a systematic search in the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, including all randomised controlled trials (RCTs), quasi-RCTs and single-arm studies, in which patients with NMIBC were treated with second-line intravesical or systemic therapy after BCG failure. A minimum of eight patients were included in each treatment arm. Full papers were restricted to English language. Literature research and data analysis were assessed independently by two reviewers. Data on treatment response, recurrence, time to recurrence, progression and rate of cystectomy were collected and analysed. This systematic review included 42 publications with a total of 3521 patients (2371 BCG failures). Valrubicin, taxanes, gemcitabine, combination chemotherapy, thermochemotherapy, photodynamic therapy, combination of BCG and interferon and immunotherapies or targeted therapies were identified as conservative treatment options. For taxanes, gemcitabine and thermochemotherapy there is the highest evidence for a clinical meaningful response with minor toxicities. Despite some promising response rates for taxanes, gemcitabine or thermochemotherapy, an evidence-based recommendation for treatment options superior to RC in patients failing BCG therapy cannot be made. The definition of BCG failure is still inconsistent and heterogeneous outcomes in patients with BCG failure have been reported. In order to identify effective conservative therapy options in patients failing BCG therapy, prospective trials with a standardised trial design are needed.
Topics: Adjuvants, Immunologic; Antimetabolites, Antineoplastic; BCG Vaccine; Conservative Treatment; Deoxycytidine; Drug Resistance, Viral; Humans; Immunotherapy; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 28609792
DOI: 10.1055/s-0043-108944