Dataset Information

Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions?

ABSTRACT:

Objectives

To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy.

Materials and methods

MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB).

Results

The literature search identified 12 eligible studies. Three (all rated as "moderate RoB") out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03-1.88). Four (mainly rated as "serious RoB") out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20-1.59).

Conclusion

Pooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches.

SUBMITTER: Wettstein MS

PROVIDER: S-EPMC6488073 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions?

Wettstein Marian S MS Rooprai Jasjit K JK Pazhepurackel Clinsy C Wallis Christopher J D CJD Klaassen Zachary Z Uleryk Elizabeth M EM Hermanns Thomas T Fleshner Neil E NE Zlotta Alexandre R AR Kulkarni Girish S GS

PloS one 20190429 4

<h4>Objectives</h4>To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy.<h4>Materials and methods</h4>MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on ad ...[more]

PMID: 31034504

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Project description:BackgroundMuscle-invasive bladder cancer (MIBC) remains undertreated despite multiple potentially curative options. Both radical cystectomy (RC) with or without neoadjuvant chemotherapy and trimodal therapy (TMT), including transurethral resection of bladder tumor followed by chemoradiotherapy, are standard treatments.ObjectiveTo evaluate real-world clinical outcomes of RC with neoadjuvant chemotherapy (RC-NAC), RC without NAC, TMT with National Comprehensive Cancer Network guideline-preferred radiosensitizing chemotherapy including cisplatin or mitomycin-C and 5-fluorouracil (pTMT), and TMT with nonpreferred chemotherapy (npTMT).Design setting and participantsUS veterans with nonmetastatic MIBC (T2-4aN0-3M0) were studied.Outcome measurements and statistical analysisOverall mortality (OM) was evaluated with multivariable Cox proportional hazard model. Bladder cancer-specific mortality (BCSM) was evaluated with multivariable Fine-Gray regression. Salvage cystectomy rates were obtained by chart review.Results and limitationsOverall 2306 patients were included: 1472 (64%) with RC without NAC, 506 (22%) with RC-NAC, 163 (7%) with pTMT, and 165 (7%) with npTMT. On multivariable analysis, pTMT was associated with similar OM (hazard ratio [HR] 1.19; 95% confidence interval [CI] 0.94-1.50; p = 0.15) and BCSM (HR 1.34; 95% CI 0.99-1.83; p = 0.06) to RC-NAC; npTMT was associated with worse OM (HR 1.30; 95% CI 1.04-1.61; p = 0.02) and BCSM (HR 1.45; 95% CI 1.09-1.94; p = 0.01). RC without NAC was associated with similar OM (HR 1.08; 95% CI 0.95-1.24; p = 0.24) and BCSM (HR 1.02; 95% CI 0.86-1.21; p = 0.79). When stratified by age, among patients ≥65 yr of age, treatment with pTMT was associated with similar OM (HR 1.14; 95% CI 0.87-1.50; p = 0.35) and BCSM (HR 1.11; 95% CI 0.76-1.62; p = 0.60). Among patients <65 yr of age, pTMT was associated with worse OM (HR 1.82; 95% CI 1.14-2.91; p = 0.01) and BCSM (HR 2.51; 95% CI 1.52-4.13; p < 0.01). The 5-yr cumulative incidence of salvage cystectomy in the TMT group was 3.6%.ConclusionsIn MIBC, patients receiving pTMT have comparable survival in RC-NAC patients ≥65 yr and inferior survival in RC-NAC patients <65 yr. Salvage cystectomy rates were low.Patient summaryManagement of muscle-invasive bladder cancer is a multidisciplinary effort requiring thoughtful discussions with patients about treatment options, including trimodal therapy, which is an effective treatment option.

Project description:ImportanceEarlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days.ObjectiveTo compare the 1-year costs associated with trimodal therapy vs radical cystectomy, accounting for survival and intensity effects on total costs.Design, setting, and participantsThis population-based cohort study used the US Surveillance, Epidemiology, and End Results-Medicare database and included 2963 patients aged 66 to 85 years who had received a diagnosis of clinical stage T2 to T4a muscle-invasive bladder cancer from January 1, 2002, through December 31, 2011. The data analysis was performed from March 5, 2018, through December 4, 2018.Main outcomes and measuresTotal Medicare costs within 1 year of diagnosis following radical cystectomy vs trimodal therapy were compared using inverse probability of treatment-weighted propensity score models that included a 2-part estimator to account for intrinsic selection bias.ResultsOf 2963 participants, 1030 (34.8%) were women, 2591 (87.4%) were white, 129 (4.4%) were African American, and 98 (3.3%) were Hispanic. Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83 754 vs $68 692; median difference, $11 805; 95% CI, $7745-$15 864), 180 days ($187 162 vs $109 078; median difference, $62 370; 95% CI, $55 581-$69 160), and 365 days ($289 142 vs $148 757; median difference, $109 027; 95% CI, $98 692-$119 363), respectively. Outpatient care, radiology, medication expenses, and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On inverse probability of treatment-weighted adjusted analyses, patients undergoing trimodal therapy had $136 935 (95% CI, $122 131-$152 115) higher mean costs compared with radical cystectomy 1 year after diagnosis.Conclusions and relevanceCompared with radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. The differences in costs were largely attributed to medication and radiology expenses associated with trimodal therapy. Extrapolating cost figures resulted in a nationwide excess spending of $468 million for trimodal therapy compared with radical cystectomy for patients who received a diagnosis of bladder cancer in 2017.

Project description:ImportanceRadical cystectomy is the guidelines-recommended treatment of muscle-invasive bladder cancer, but a resurgence of trimodal therapy has occurred. Limited comparative data are available on outcomes and costs attributable to these 2 treatments.ObjectiveTo compare the survival outcomes and costs between trimodal therapy and radical cystectomy in older adults with muscle-invasive bladder cancer.Design, setting, and participantsThis population-based cohort study used data from the Surveillance, Epidemiology, and End Results-Medicare linked database. A total of 3200 older adults (aged ≥66 years) with clinical stage T2 to T4a bladder cancer diagnosed from January 1, 2002, to December 31, 2011, and with claims data available through December 31, 2013, were included in the analysis. Patients who received radical cystectomy underwent either only surgery or surgery in combination with radiotherapy or chemotherapy. Patients who received trimodal therapy underwent transurethral resection of the bladder followed by radiotherapy and chemotherapy. Propensity score matching by sociodemographic and clinical characteristics was used. Data analysis was performed from August 1, 2017, to March 11, 2018.Main outcomes and measuresOverall survival and cancer-specific survival were evaluated using the Cox proportional hazards regression model and the Fine and Gray competing risk model. All Medicare health care costs for inpatient, outpatient, and physician services within 30, 90, and 180 days of treatment were compared. The total amount spent nationwide was estimated, using 180-day medical costs between treatments, by the total number of new cases of muscle-invasive bladder cancer in the United States in 2011.ResultsOf the 3200 patients who met the inclusion criteria, 2048 (64.0%) were men and 1152 (36.0%) were women, with a mean (SD) age of 75.8 (6.0) years. After propensity score matching, 687 patients (21.5%) underwent trimodal therapy and 687 patients (21.5%) underwent radical cystectomy. Patients who underwent trimodal therapy had significantly decreased overall survival (hazard ratio [HR], 1.49; 95% CI, 1.31-1.69) and cancer-specific survival (HR, 1.55; 95% CI, 1.32-1.83). No differences in costs at 30 days were observed between trimodal therapy ($15 233 in 2002 vs $18 743 in 2011) and radical cystectomy ($17 990 in 2002 vs $21 738 in 2011). However, median total costs were significantly higher with trimodal therapy than with radical cystectomy at 90 days ($80 174 vs $69 181; median difference, $8964; Hodges-Lehmann 95% CI, $3848-$14 079) and at 180 days ($179 891 vs $107 017; median difference, $63 771; Hodges-Lehmann 95% CI, $55 512-$72 029). Extrapolating these figures to the total US population revealed $335 million in excess spending for trimodal therapy compared with the less costly radical cystectomy ($492 million) for patients who received a muscle-invasive bladder cancer diagnosis in 2011.Conclusions and relevanceTrimodal therapy was associated with significantly decreased overall survival and cancer-specific survival as well as $335 million in excess spending in 2011. These findings have important health policy implications regarding the appropriate use of high value-based care among older adults with invasive bladder cancer who are candidates for either radical cystectomy or trimodal therapy.

Project description:BackgroundNeo-adjuvant chemotherapy followed by radical cystectomy with extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with ≥pT3 tumors develop a pelvic recurrence. We hypothesize that postoperative adjuvant external beam radiotherapy (EBRT) might prevent local and lymph node recurrence and improve disease free- and overall survival as loco-regional recurrence is linked to the development of distant metastasis.MethodsWe plan to perform a multicentric prospective phase two study including 76 patients. Eligible patients are patients with MIBC, treated with radical cystectomy and presenting with ≥1 of the following characteristics: Pathological (p)T3 stage + presence of lymphovascular invasion on pathological examination pT4 stage <10 lymph nodes removed positive lymph nodes positive surgical margins Patients will have a 18F-FDG PET-CT to rule out the presence of distant metastasis prior to EBRT. A median dose of 50 Gy in 25 fractions is prescribed to the pelvic lymph node regions with inclusion of the operative bladder bed in case of a positive surgical margin. Patients with suspected lymph nodes on PET- CT can still be included in the trial, but a simultaneous integrated boost to 74Gy to the positive lymph nodes will be delivered. Blood and urine samples will be collected on day-1 and last day of EBRT for evaluation of biomarkers. The primary endpoint is evaluation of acute ≥Grade 3 intestinal or grade 4 urinary toxicity, in case of a neo-bladder reconstruction, within 12 weeks after EBRT. Secondary endpoints are: assessment of QOL, late RTOG toxicity, local control, disease free survival and overall survival. Biomarkers in urine and blood will be correlated with secondary survival endpoints.DiscussionThis is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC.Trial registrationThe Ethics committee of the Ghent University Hospital (EC2014/0630) approved this study on 31/07/2014. Trial registration on Clinicaltrials.gov ( NCT02397434 ) on November 19, 2014.

Dataset Information

Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions?

Objectives

Materials and methods

Results

Conclusion

Publications

Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions?

Similar Datasets

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