Dataset Information

Development of a Prediction Tool for Exclusive Locoregional Recurrence After Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.

ABSTRACT: BACKGROUND:Limited information is available about the pattern of relapse after perioperative chemotherapy with radical cystectomy (RC) vs. RC alone in muscle-invasive bladder cancer. PATIENTS AND METHODS:Data from 1082 patients of the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium database, treated from February 1990 to December 2013 at 27 centers in the United States, Europe, Israel, and Canada, were collected. Locoregional relapse was defined as any pelvic lymph node or soft tissue-only recurrences. Cumulative incidence methods were used to estimate time to locoregional relapse (TTRL). Cox regression analyses were performed and a nomogram for 12-month locoregional relapse-free survival (RFS) was developed. The nomogram was applied to an external data set (n = 1021). RESULTS:A total of 517 patients (47.8%) developed a relapse: 177 (16.4%) exclusive locoregional relapse. In multivariable analyses, perioperative chemotherapy was associated with longer TTRL (P < .001). Other factors were nonurothelial histology (P = .013), pT-stage (P < .001), and surgical margins (P < .001). The concordance index of the model was 0.681 (95% bootstrapped confidence interval, 0.666-0.716). Risk group categories were obtained according to nomogram tertiles. Despite, overall, observed locoregional RFS in the validation cohort exceeding predicted results, for high-risk patients (80 points or less, lowest nomogram tertile) observed 12-month RFS was similar between development and validation cohorts (60.1% and 66.6%). The study is limited by its retrospective nature. CONCLUSION:In the largest study, to our knowledge, that analyzed locoregional recurrences after RC, we propose a risk prediction tool for exclusive locoregional failures that might be suitable for clinical studies. Patients best suited for adjuvant radiotherapy might be those within the lowest nomogram tertile. Prospective trials are needed to validate findings.

SUBMITTER: Necchi A

PROVIDER: S-EPMC6857172 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Development of a Prediction Tool for Exclusive Locoregional Recurrence After Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.

Necchi Andrea A Pond Gregory R GR Moschini Marco M Plimack Elizabeth R ER Niegisch Gunter G Yu Evan Y EY Bamias Aristotelis A Agarwal Neeraj N Vaishampayan Ulka U Theodore Christine C Sridhar Srikala S SS Rosenberg Jonathan E JE Bellmunt Joaquim J Gallina Andrea A Colombo Renzo R Montorsi Francesco F Briganti Alberto A Galsky Matthew D MD

Clinical genitourinary cancer 20180913 1

<h4>Background</h4>Limited information is available about the pattern of relapse after perioperative chemotherapy with radical cystectomy (RC) vs. RC alone in muscle-invasive bladder cancer.<h4>Patients and methods</h4>Data from 1082 patients of the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium database, treated from February 1990 to December 2013 at 27 centers in the United States, Europe, Israel, and Canada, were collected. Locoregional relapse was defined as ...[more]

PMID: 30292628

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Project description:BACKGROUND:Radical cystectomy (RC) associated with pelvic lymph node dissection (PLND) is the most common local therapy in the management of non-metastatic muscle invasive bladder cancer (MIBC). Loco-regional recurrence (LRR), however, remains a common and important therapeutic challenge associated with poor oncologic outcomes. We aimed to systematically review evidence regarding factors associated with LRR and to propose a framework for adjuvant radiotherapy (RT) in patients with MIBC. METHODS:We performed this systematic review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We searched the PubMed database for articles related to MIBC and associated treatments, published between January 1980 and June 2015. Articles identified by searching references from candidate articles were also included. We retrieved 1383 publications from PubMed and 34 from other sources. After an initial screening, a review of titles and abstracts, and a final comprehensive full text analysis of papers assessed for eligibility, a final consensus on 32 studies was obtained. RESULTS:LRR is associated with specific patient-, tumor-, center- or treatment-related variables. LRR varies widely, occurring in as many as 43% of the cases and is strongly related to survival outcomes. While perioperative treatment does not impact on LRR, pathological factors such as pT, pN, positive margins status, extent of PLND, number of lymph nodes removed and/or invaded are correlated with LRR. Patients with pT3-T4a and/or positive lymph-nodes and/or limited pelvic lymph-node dissection and/or positive surgical margins have been distributed in LRR risk groups with accuracy. CONCLUSIONS:LRR patterns are well-known and for selected patients, adjuvant treatments could target this event. Intrinsic tumor subtype may guide future criteria to define a personalized treatment strategy. Prospective trials evaluating safety and efficacy of adjuvant RT are ongoing in several countries.

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: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.

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.

Dataset Information

Development of a Prediction Tool for Exclusive Locoregional Recurrence After Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.

Publications

Development of a Prediction Tool for Exclusive Locoregional Recurrence After Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.

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