Bladder-sparing Treatment Research Articles

PD51-07 ONCOLOGIC AND FUNCTIONAL EFFECTIVENESS OF NEOADJUVANT CHEMOTHERAPY FOLLOWED BY EITHER BLADDER-SPARING SURGERY PLUS CONCURRENT CHEMORADIOTHERAPY OR CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVE: Previous researches indicated Neoadjuvant Chemotherapy (NAC) achieved optimistic tumor degrading and bladder preservation rates in muscle-invasive bladder cancer (MIBC). However, maximum Transurethral Resection of Bladder Tumor (TURBT) was mostly performed before NAC which might impact oncologic effect of NAC. Our aim was to assess the real effect of NAC for MIBC before TURBT, then bladder preservation rate and quality of life. METHODS: Patients with clinical T2-4N0M0 bladder cancer confirmed by imagings and biopsy, were enrolled from September 2015 to September 2018. 3 or 4 courses of NAC were performed with Gemcitabine/Cisplatin (GC) regimen. Imagings, urine cytology and TURBT were underwent to assess NAC effect. Responders received bladder-sparing treatments including chemoradiotherapy or partial cystectomy followed by Bacillus Calmette-Guerin (BCG) instillation, but salvage cystectomy if recurrence. Others received radical cystectomy. The endpoints included overall survival (OS), bladder preservation rates and life quality. RESULTS: 59 patients (53 men & 6 women) were enrolled with a median age of 63 years. Numbers of patients at each clinical stage were: cT2 15, cT3 39, cT4 5. All pathologies of biopsy were urothelial carcinoma. The complete response (CR) rate of NAC was 10.2% (6/59) and an additional 52.5% (31/59) experienced a partial response (PR), for an overall response rate (ORR) of 62.7%. Of these 37 cases, 94.6% received combined-modality treatments of bladder preservation including TURBT plus chemoradiotherapy (42.4%), TURBT plus BCG (6.8%), TURBT (3.4%), and partial cystectomy plus pelvic lymphadenectomy (6.8%). With a median follow-up of 28.3 months, the 3-year OS was 71.2%. 59.3% (35/59) successfully preserved bladder and the OS was 88.0%, besides relapse-free survival (RFS) was 70.5%. In SF-36 questionnaires, patients had favorable scores of total physical (59 ± 6.11) and tmental (55 ± 5.44) health. As for preserved bladder function, the results of OABSS were satisfied. CONCLUSIONS: NAC had a good efficacy in MIBC. Responders can choose combined-modality treatments for bladder preservation, resulting in satisfied bladder-sparing rate, fair prognosis and quality of life. Source of Funding: 2015 Beijing Hope Run Special Fund of China Cancer Research Foundation

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.

Patient-reported Quality of Life Outcomes in Patients Treated for Muscle-invasive Bladder Cancer with Radiotherapy ± Chemotherapy in the BC2001 Phase III Randomised Controlled Trial

BackgroundBC2001, the largest randomised trial of bladder-sparing treatment for muscle-invasive bladder cancer, demonstrated improvement of local control and bladder cancer–specific survival from the addition of concomitant 5-fluorouracil and mitomycin C to radiotherapy. ObjectiveTo determine the impact of treatment on the health-related quality of life (HRQoL) of BC2001 participants. Design, setting, and participants458 UK patients with T2-T4a N0 M0 transitional cell carcinoma of the bladder. InterventionPatients were randomised to the chemotherapy comparison (radiotherapy, 178, or chemoradiotherapy, 182); and/or to the radiotherapy comparison (standard, 108, or reduced high-dose volume radiotherapy, 111). Outcome measurements and statistical analysisPatients completed Functional Assessment of Cancer Therapy—Bladder (FACT-BL) questionnaires at baseline, end of treatment (EoT), and 6, 12, 24, 36, 48, and 60 months after radiotherapy. The primary endpoint was change from baseline in the bladder cancer subscale (BLCS) at 12 months. Results and limitationsData were available for 331 (92%) and 204 (93%) participants at baseline and for 192 (54%) and 114 (52%) at 12 months for the chemotherapy and radiotherapy comparisons, respectively. HRQoL declined at EoT (BLCS –5.06 [99% confidence interval: –6.12 to –4.00, p< 0.001]; overall FACT-B TOTAL score –8.22 [–10.76 to –5.68, p< 0.01]), recovering to baseline at 6 months and remaining similar to baseline subsequently. There was no significant difference between randomised groups at any time point. ConclusionsImmediately following (chemo)radiotherapy, a significant proportion of patients report declines in HRQoL, which improve to baseline after 6 months. Two-thirds of patients report stable or improved HRQoL on long-term follow-up. There is no evidence of impairment in HRQoL resulting from the addition of chemotherapy. Patient summaryQuality of life of bladder cancer patients treated with radiotherapy±chemotherapy deteriorates during treatment, but improves to at least pretreatment levels within 6 months. Addition of chemotherapy to radiotherapy does not affect patient-reported quality of life.

Imaging in Localized Bladder Cancer: Can Current Diagnostic Modalities Provide Accurate Local Tumor Staging?

Local tumor staging is paramount in the evaluation and management of bladder cancer. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy and urinary diversion remains the gold standard for management of muscle-invasive bladder cancer, bladder-sparing regimens involving systemic chemotherapy and pelvic radiotherapy remain a viable option for select patients. Moreover, pre-cystectomy identification of patients with a complete response to NAC may obviate the need for radical cystectomy, but accurate post-therapy staging can be difficult to achieve. Contemporary imaging techniques may provide additional benefit in local tumor staging beyond standard imaging and cystoscopic biopsy. Our purpose is to summarize the ability of different imaging modalities to accurately stage bladder cancer patients in the treatment-naïve and post-chemotherapy settings. Contemporary investigations have been studying multiparametric magnetic resonance imaging (mp-MRI) in the evaluation of bladder cancer. Its recent incorporation into bladder cancer staging is mainly being assessed in treatment-naïve patients; however, different sequences are being studied to assess their accuracy after the introduction of chemotherapy and possibly radiation. Multiple recent studies incorporating cystoscopy and biopsy are proving to be less accurate than originally predicted. Imaging has generally had a very limited role in guiding therapy in localized bladder cancer, but with the incorporation of newer sequences and techniques, imaging is poised to become vital in decision-making strategies of this cancer. Reliable local tumor staging through improved imaging may help better select patients for bladder-sparing treatments while maintaining optimized oncologic outcomes and allow this paradigm to become more acceptable in the urologic oncology community.

Long-term survival and complications following bladder-preserving brachytherapy in patients with cT1-T2 bladder cancer

Background and purposeRadical cystectomy (RC) is considered standard treatment for muscle-invasive bladder cancer (BC) and high-risk non-muscle invasive BC. In selected cases, bladder-sparing treatment using brachytherapy can be offered. We examined the outcome after brachytherapy in comparison to RC in terms of survival, complications and bladder preservation in patients with cT1G3-T2N0M0 BC. Materials and methodsBetween 1988 and 2016, 301 patients underwent brachytherapy in two centres. Overall survival (OS) and disease specific survival (DSS) after brachytherapy and RC were assessed using Kaplan-Meier curves. Cox proportional hazards modelling was used to determine variables associated with OS and DSS. Local recurrences, bladder preservation and salvage cystectomy (SC) after brachytherapy were reported. Complications after brachytherapy, RC and SC were compared using CTCAE criteria. ResultsMedian follow-up was 9.6 years (95% confidence interval (CI): 8.8–10.4) after brachytherapy and 10.6 years (95% CI: 10.0–11.2) after RC. Five/10-year OS was 66%/49% after brachytherapy and 68%/53% after RC (p = 0.4). Five/10-year DSS was 73%/67% after brachytherapy and 75%/65% after RC (p = 0.8). Intravesical recurrence occurred in 58/259 brachytherapy patients after which salvage cystectomy was performed in 32 patients. In total, 84% of brachytherapy-treated patients preserved their bladder. The brachytherapy cohort experienced less high grade complications than the RC cohort (p = 0.02). ConclusionIn selected patients with solitary, ≤5 cm cT1G3-T2N0M0 bladder tumours brachytherapy is a bladder-sparing therapy with good survival outcome and with a favourable complication rate compared to RC.

Bladder-sparing treatment in MIBC: where do we stand?

The gold-standard treatment of muscle-invasive bladder cancer is radical cystectomy (RC), but this can be associated with morbidity and perioperative risks. Patients may not be fit for RC or choose to preserve their bladders. There are evolving bladder-sparing treatments that are often delivered in a multimodal approach. Here, we aim to review recent advances in bladder-sparing treatments. We undertook a narrative review informed by a Medline/PubMed literature search using a combination of terms for recent (5 years) articles in English. Relevant studies from authors' bibliographies were retrieved. Bladder-sparing treatment consists of transurethral resection of bladder tumour (TURBT), radiotherapy and chemotherapy. Experimental approaches with immunotherapy and using gene signatures for radiation therapy and chemotherapy response are being explored. Bladder-sparing treatment is an option for patients with bladder cancer. Those who may benefit most are those with solitary invasive cancers, those with good bladder capacity and compliance, those who choose to preserve their bladder and sexual function and who are not fit for RC. Multimodal bladder-sparing approaches may have comparable oncological outcomes to RC and so appear an attractive alternative in suitable patients.

Intravesical BCG: where do we stand? Past, present and future

High and intermediate risk non-muscle invasive bladder cancer poses a real challenge for treatment. Approximately 70% of bladder cancer presents as non-muscle invasive and 20–25% will progress to muscle invasive disease. Recurrences occur in up to 70% but treatment options are limited. Intravesical bacillus Calmette–Guérin is still considered the bladder sparing treatment of choice despite its well documented pitfalls. This review considers how bacillus Calmette–Guérin has become the recommended treatment, its benefits and risks and the alternative options for treatment. Level of evidence: Not applicable for this multicentre audit.

Urothelial Carcinoma in Bladder Diverticula: A Multicenter Analysis of Characteristics and Clinical Outcomes

BackgroundUrothelial carcinoma arising in a bladder diverticulum (UCBD) is uncommon, and data on treatment and outcome are sparse. ObjectiveTo analyze clinicopathological characteristics of UCBD and to compare outcome after radical cystectomy (RC) and partial cystectomy (PC). Design, setting, and participantsData of 115 UCBD patients treated with RC (n=81) or PC (n=34) between 2000 and 2016 were collected from 11 institutional databases and were analyzed retrospectively. Median follow-up was 5.0yr (95% confidence interval [CI]: 4.0–6.2). Outcome measurements and statistical analysisUpstaging of tumor stage at diagnostic transurethral resection (TUR) to the RC/PC specimen was investigated. Overall survival (OS) and metastasis-free survival (MFS) after RC and PC were analyzed using Kaplan-Meier estimates, and compared using the log-rank test. Intravesical recurrences after PC were reported. A multivariable Cox proportional-hazard model was used to identify factors associated with OS. Results and limitationsThere were no statistically significant differences in clinicopathological characteristics between RC and PC groups. Fifty-five percent of patients with cTa/is/1 at diagnostic TUR had ≥pT2 tumors at RC/PC. Five-year OS and MFS were, respectively, 62% and 66% for RC and 66% and 55% for PC (p=0.9 and p=0.6). Intravesical tumor recurrence was seen in six of 34 (18%) PC patients. In multivariable analysis, positive surgical margins and extravesical disease (≥pT2) were associated with worse OS, whereas treatment modality was not (RC: reference; PC: hazard ratio 0.94, [95% CI: 0.47–1.90], p=0.9). ConclusionsUpstaging of UCBD was frequent, indicating an inaccuracy in clinical staging. We found no differences in OS or MFS between PC and RC groups; therefore, PC may represent a feasible surgical alternative to RC in selected UCBD patients. Patient summaryIn this report, we looked at the treatment of urothelial carcinoma arising in a bladder diverticulum (UCBD). We found that bladder-sparing treatment by partial cystectomy may be an alternative to radical cystectomy in carefully selected UCBD patients.

Long-term Outcomes and Patterns of Failure Following Trimodality Treatment With Bladder Preservation for Invasive Bladder Cancer

To report long-term results on survival, toxicity, and patterns of failure of 3 different organ-sparing strategies for patients with muscle invasive bladder cancer. This is a monoinstitutional prospective analysis of 3 consecutive bladder-sparing protocols combining maximal transurethral resection of bladder tumor (mTURBT), radiotherapy (RT), and cisplatin-based chemotherapy. Protocol 1 consisted of neoadjuvant methotrexate-cisplatin-vinblastine followed by endoscopic re-evaluation and consolidative RT 60 Gy in complete responders. Protocol 2 involved altered-fractionation RT 64.8 Gy and concurrent weekly cisplatin with re-evaluation after 40.8 Gy. Protocol 3 consisted of RT 64.8 Gy with concomitant weekly cisplatin. Nonresponders underwent radical cystectomy. Probabilities for overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier product limited estimates. A Cox regression multivariate analysis was performed to detect potential risk factors for OS, CSS, and MFS. The 10-year bladder preservation rate was 79%. The 10-year OS, CSS, and MFS rates were 43.2%, 76.3% and 79.2%, respectively. There was no statistically significant difference in OS between the different treatment protocols. On multivariate analysis, mTURBT of the bladder and the complete response after induction therapy were independent correlates of improved OS and of MFS. The development of invasive bladder recurrence was independently associated with worse CSS and MFS. Ten-year results indicate that bladder-sparing treatment is a successful approach for muscle invasive bladder cancer in selected patients. The mTURBT of the bladder tumor and complete response after induction therapy remain the most relevant predictive factors.

The effect of tri-modality therapy on the treatment of muscle-invasive bladder cancer

Objective: To explore the effect of radical TURBT combing with concomitant chemo-radiotherapy for muscle-invasive bladder cancer (MIBC). Methods: From 2010 to 2015, 73 patients were diagnosed as MIBC, in which 28 patients (TMT Group) received tri-modality bladder sparing treatment, including 21 males and 7 females, mean age (68.9±8.9) yr. There were 16 cases of T(2), 12 cases of T(3). 45 patients (RC Group) received radical cystectomy (RC), including 32 males and 13 females, mean age (66.3±9.6) yr. There were 25 cases of T(2), 18 cases of T(3) and 2 cases of T(4a). The effect of two treatment modality and influence for patient's life quality were retrospective analysis. Results: The overall survival (OS) rate of TMT group was 64.3%, cancer specific survival (CSS) rate was 78.6%. And the OS rate of RC group was 66.7%, CSS rate was 82.2%. There was no statistical difference between two groups. The life quality of TMT group was better than that of RC group. Conclusion: In strict control of indication criterion, rigorous postoperative follow-up and timely salvage radical cystectomy, tri-modality therapy can be used as a new option of muscle-invasive bladder cancer.

Intravesical recurrence after bladder sparing treatment of small cell carcinoma of the bladder: Characteristics, treatment, and outcome

IntroductionSmall cell carcinoma of the bladder (SCCB) is a rare and lethal disease. Previously, we and others have reported a bladder sparing strategy with platinum-etoposide-based chemotherapy followed by radiotherapy of the bladder. Little is known on frequency and treatment of intravesical recurrence following this approach. The objective of this study is to describe the incidence of intravesical recurrences and their management. Materials and methodsRetrospective study including all patients with SCCB treated at a single institution from 1993 until 2016. All patients with limited disease (LD) SCCB who had a bladder sparing approach with sequential chemotherapy and radiotherapy were identified. Intravesical and overall recurrence rate, overall and disease specific survival, salvage treatment options and their results were retrieved. ResultsOf the 110 patients with SCCB (82% male) with a mean age of 65 years and a median follow up of 48 months, 89 patients (81%) had LD-SCCB. Of these, 65 were treated with chemotherapy and radiotherapy, with a median overall recurrence free survival of 22 months (CI: 14–30). Of 65 patients, 23 (35%) progressed to distant metastasis without intravesical recurrence after a median of 9 months (CI: 8–11), whereas 14 patients (22%) developed isolated intravesical recurrence at a median of 24 months (CI: 14–34). Local recurrence contained SCCB, urothelial carcinoma, and carcinoma in situ and was treated with various local salvage treatments including TURB, cystectomy, neoadjuvant chemotherapy, and BCG. Following salvage treatment a complete response was seen in 64%. Median overall survival for intravesical vs. systemic recurrence was different, with 28 (CI: 9–47) and 8 (CI: 5–11) months, respectively (P<0.001). ConclusionSCCB is a serious potentially lethal disease. Even in patients with LD-SCCB a high percentage rapidly develops systemic disease. This suggests that systemic therapy is more important than the type of local treatment to control the disease but small sample sizes limit the ability to distinguish between different treatment options in this study. A bladder sparing approach can be a reasonable alternative to major surgery. However, in those surviving long enough isolated intravesical recurrence occurs even after many years. Our results indicate that long term follow up is required because salvage therapy can be successful in the majority of patients.

Systematic Review and Meta-Analysis on the Efficacy of Chemotherapy with Transurethral Resection of Bladder Tumors as Definitive Therapy for Muscle Invasive Bladder Cancer.

Background:Bladder-sparing treatment of muscle invasive bladder cancer (MIBC) with systemic chemotherapy plus transurethral resection of bladder tumors (TURBT) is increasingly seen in the literature –both in case series and subanalyses of patients who opt out of or are unfit for radical cystectomy (RC). Survival outcomes among these patients are often impressive, but these are typically small retrospective studies from single institutions and therefore of limited clinical value.Objectives:Our aim is to summarize the literature regarding definitive treatment of MIBC with systemic chemotherapy plus TURBT and provide a meta-analysis of survival outcomes for patients who received this treatment.Methods:A systematic literature search was performed consistent with the Prisma statement to identify publications reporting the outcomes of patients treated with TURBT and systemic chemotherapy as definitive treatment for locally confined MIBC. Identified studies were screened in a two-stage process: first by title and abstract; then by full-text reading. 18 publications (518 patients) were included in the qualitative systematic review and 10 publications (266 patients) were included in the meta-analysis. The primary objective was overall survival (OS).Results:Overall survival ranged from 20% to 87.5% across studies at median follow-up ranging 4 to 120 months. 5-year survival rate for all patients included in the meta-analysis was estimated to be 72% [95% CI: 64%, 82%].Conclusions:Definitive treatment with systemic chemotherapy plus TURBT can lead to favorable survival outcomes in select patients. Further study to improve patient selection for this method of treatment is needed.

AB007. Bladder-sparing treatments for muscle-invasive bladder cancer

Radical cystectomy (RC) with pelvic lymph node dissection remains the gold-standard treatment for muscle-invasive bladder cancer (MIBC). Growing evidence suggests that bladder-sparing treatments may lead to acceptable oncologic outcomes in carefully selected patients and can offer improved quality of life through preservation of a functioning bladder. We summarize our clinical experience of bladder-sparing treatments for MIBC and review articles. MIBC patients with cT2 stage, unifocal tumor, absence of CIS or hydronephrosis are eligible for selective bladder preservation if they refuse or unfit for RC.

GEC-ESTRO/ACROP recommendations for performing bladder-sparing treatment with brachytherapy for muscle-invasive bladder carcinoma

The standard treatment for muscle-invasive bladder cancer (MIBC) is a radical cystectomy with pelvic lymph node dissection with or without neoadjuvant chemotherapy. In selected cases a bladder sparing approach is possible, for example a limited surgical excision combined with external beam radiotherapy and brachytherapy. To perform brachytherapy flexible catheters have to be implanted in the bladder wall. The implantation is done either by the open retropubic approach or the endoscopic surgical approach. The largest experience for brachytherapy is with low-dose rate and pulsed-dose rate, although some short-term experience with high-dose rate is also reported.The main advantage for this technique is the conservation of bladder function, with comparable local control rates as for cystectomy series in selected cases.The GEC-ESTRO/ACROP (Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology / Advisory Committee on Radiation Oncology Practice) recommendations to perform bladder implantations and brachytherapy as a treatment option for MIBC are described.

Renal Function Preserved in Bladder-sparing Treatment for Muscle-Invasive Cancer

Renal Function Preserved in Bladder-sparing Treatment for Muscle-Invasive Cancer

The Timing of Radical Cystectomy for bacillus Calmette-Guérin Failure: Comparison of Outcomes and Risk Factors for Prognosis

We compared the pathological and survival outcomes of patients who underwent radical cystectomy soon after bacillus Calmette-Guérin failure with those of patients who received additional salvage intravesical chemotherapy before cystectomy for nonmuscle invasive bladder cancer. We also identified predictors of prognosis in the entire cohort. We retrospectively analyzed the records of 117 patients who underwent radical cystectomy for recurrent nonmuscle invasive bladder cancer at our institution from 1990 to 2012. The cohort was divided into group 1 of 61 patients treated only with bacillus Calmette-Guérin with or without interferon-α and group 2 of 56 who received at least 1 additional salvage intravesical chemotherapy after bacillus Calmette-Guérin. Final pathology and survival outcomes did not differ significantly between the groups. Five-year overall and cancer specific survival was similar ingroups 1 and 2 at 80% and 85%, respectively, at approximately equivalent followups. Median bladder retention was 1.7 years longer in group 2 (p <0.001). On multivariate Cox regression analysis delayed cystectomy in group 2 did notconvey a significant hazard for all cause mortality after cystectomy (HR 1.08, p = 0.808). Only up-staging to cT1 (HR 1.88, p = 0.045), lymph node invasion (HR 2.58, p = 0.023) and prostatic urethra involvement (HR 1.95, p = 0.029) achieved significance. With appropriate selection for salvage intravesical chemotherapy patients who elect bladder sparing treatment instead of earlier radical cystectomy after bacillus Calmette-Guérin fails do not sacrifice positive pathological or oncologic outcomes while retaining bladder function for a significantly longer duration.

Anamnese, pathologische Originalbefunde, Therapie bezogene Parameter und Krankheitsverlauf: retrospektive Analyse von klinisch basierten Faktoren für die Prognose des tumorspezifischen Überlebens von 378 Patienten mit pT1-Harnblasenkarzinom

Urothelial carcinoma of the bladder (UBC) at stage pT1 is a heterogenous disease. Established criteria for prognosis prediction are not suitable for every patient. Choosing the right therapeutic strategy for the individual patient thus remains a challenge. The aim of the present study was to identify clinical parameters regarding cancer-specific survival (CSS) in patients with pT1 UBC. A retrospective analysis of clinical parameters of all patients with a pT1 UBC between 1989 and 2012 from a single centre was performed. Treatment consisted of transurethral resection, second resection followed by initially bladder sparing treatment. Anamnestic data, histopathological reports and clinical course were assessed with CSS being defined as primary endpoint. Kaplan-Meier analysis, uni- and multivariate analysis were performed using SPSS (Version 22, IBM). 378 patients (78% male, median age 72 years) were included, median follow-up was 35 months. Pathological stage pT1G3 (66 vs. 91%, p<0.001), lack of instillation therapy (66 vs. 83%, p<0.001), presence of a second malignoma (41 vs. 77%, p=0,004), diagnosis after 2000 (75 vs. 76%, p=0,018) and tumour progress (42 vs. 85%, p<0.001) were associated with a worse CSS in univariate and Kaplan-Meier analysis. Multivariate analysis revealed the presence of a second malignoma (HR 2.267; CI 95% 1.143-4.497, p=0.019), pathological stage pT1G3 at initial diagnosis (HR 4.567; CI 95% 2.040-10.22, p<0.001) and tumour progress (HR 3.742; CI 95% 1.544-9.069, p=0.003) as independent negative predictors of CSS. Instillation therapy was a prognostic factor for improved CSS (HR 0.368; CI 95% 0.212-0.638, p<0.001). The present study identified the presence of a second malignoma, pathological stage pT1G3 and tumour progress as negative predictive factors for CSS. Maintenance instillation therapy after reresection was associated with an improved CSS.

736 Radical cystectomy versus bladder-sparing treatment for patients with muscle-invasive urothelial carcinoma of the urinary bladder: A comparative effectiveness population-based study

INTRODUCTION AND OBJECTIVES: Muscle-invasive urothelial carcinoma of the urinary bladder (UCUB) is an aggressive disease. The standard treatment of care is radical cystectomy (RC). Trimodal bladder-preserving treatment (BPT), including transurethral resection of the bladder tumor, radiation, and chemotherapy has gained considerable interest. We sought to perform a comparative effectiveness assessment of RC vs. BPT in a stage-for-stage analysis. METHODS: We performed a retrospective cohort study of Medicare beneficiaries with non-metastatic muscle-invasive (T2eT4a, N0) UCUB treated with RC or BPT from 1991 to 2009. Following instrumental variable analysis that accounts for both measured and unmeasured confounders, multivariable Coxand competing-risks regression two-stage residual inclusions models were fitted. All analyses were stratified according to disease stage (organ-confined vs. non-organ confined). Our primary outcomes were overall survival (OS) and cancer-specific mortality (CSM). RESULTS: Overall 4168 patients with muscle-invasive UCUB were identified, where 3488 (84%) underwent RC and 680 (16%) received BPT, respectively. During the entire study span, the 5-year OS rates for RC and BPT were 42.9% (95% confidence interval [CI]1⁄441 to 45%) and 21.8% (95% CI1⁄419 to 26%), respectively. Five-year CSM rates were 34.0% (95% CI1⁄432 to 36) and 47.6% (95% CI1⁄444 to 52) for the same groups, respectively. In patients with organ-confined UCUB (T2N0), BPTtreated individuals had significantly increased risks of mortality (hazard ratio [HR]: 1.49, 95% CI1⁄41.04e2.13, P1⁄40.031) and CSM (HR: 1.66, 95% CI1⁄41.03e2.67, P1⁄40.036) compared to RC patients. Among those with non-organ confinedUCUB ( T3N0), no differencewas noted with respect to OS (HR: 1.22, 95%CI1⁄40.62e2.40, P1⁄40.571) and CSM (HR: 1.13, 95% CI1⁄40.48e2.64, P1⁄40.780) between the two groups. CONCLUSIONS: RC was associated with improved cancer control outcomes compared to BPT in organ-confined UCUB. However, no difference between the two treatment modalities was observed with respect to survival amongst patients with more advanced disease stage.

BCG-refractory vs. BCG-relapsing non–muscle-invasive bladder cancer: A prospective cohort outcomes study

PurposePatients with recurrent or persistent high-grade non–muscle-invasive bladder cancer after bacille Calmette-Guérin (BCG) therapy are termed “BCG failures.” We hypothesize that BCG-refractory patients who fail to respond to BCG have worse outcomes after bladder-sparing treatments compared with BCG-relapsing patients whose tumors recur after at least a 6-month disease-free interval. Materials and methodsWe screened 32 patients who had failed BCG therapy for eligibility in a multicenter investigational trial. BCG-refractory patients received instillations of a mycobacterial cell wall–DNA complex extract. BCG-relapsing patients were treated with additional BCG or other intravesical agents. Both groups of patients were followed prospectively with transurethral biopsy after 6 months, and cystoscopy every 3 to 6 months for more than 2 years. Median follow-up time for all patients was 53 months (range: 24–72mo). ResultsSeventeen patients were classified as BCG refractory and 15 patients defined BCG relapsing. Recurrence-free median survival time was 10 months for BCG-refractory patients receiving mycobacterial cell wall–DNA complex vs. 23 months for BCG-relapsing patients who received another induction course of BCG therapy (P = 0.002). Progression-free survival time was 18 months for BCG-refractory vs. 52 months for BCG-relapsing patients (P = 0.001). Of the 17 BCG-refractory patients, 8 (47%) have died vs. 3 (20%) of the 15 BCG-relapsing patients. ConclusionsBCG-refractory and BCG-relapsing categories differentiate BCG-failed patients into high-and lower-risk prognostic groups that may be useful in guiding treatment strategies.

How to predict the risk of complication or death after radical cystectomy?

Radical cystectomy represents nowadays the gold standard in the treatment of localized muscle-invasive bladder cancer and high risk non-muscle-invasive bladder cancer. On the other hand, the rate of morbidity and mortality remains significant despite the advances in perioperative management and postoperative care in recent years [1]. This is even more expressed with the fact that firstly, we talk about a disease affecting eldery people and secondly, the population is aging. Comorbities, and thus the risk of a complication or death, come with age that implies consideration of bladder sparing treatment like radiochemotherapy or partial cystectomy in these patients [2]. EAU guidelines recommend using the Charleson Comorbidity Index as an independent prognostic factor for perioperative mortality [2]. POSSUM and P-POSSUM provide tools for risk adjustment to predict morbidity and mortality which were developed and validated within the general surgical population. A retrospective multicenter study from Japan [3] validated both predictors on 280 patients operated on within a period of 9 years. The authors came to somewhat non-convincing results. POSSUM significantly underestimated morbidity and overestimated mortality. Only P-POSSUM correctly predicted mortality, though the AUC was not that impressive (0.518). Nontheless, the authors concluded that POSSUM underestimated mortality in low-risk patients. This was explained, besides other things, by the fact that most of the low-risk patiens had diversion different to ureterocutaneostomy, which led to longer operative times and consequently to more complications and deaths. The main limitations of the study are the retrospective data collection, short follow-up of 30 days, and obvious selection bias (a strikingly high number of ureterocutaneostomies implicating a co-morbid population with signifiant risk of morbidity and mortality). However, in order to choose the right treatment for an individual patient with advanced bladder cancer, validation of existing predictors or the investigation of new tools becomes more and more important. To get a global view on the matter, not only refferal centers with multiple operations done within a year must take part. The most important factors are a prospective standardized approach to data collection, developing appropriate patient databases and registers and adequate follow-up [4].