Dataset Information

Risk factors for loco-regional recurrence after radical cystectomy of muscle-invasive bladder cancer: A systematic-review and framework for adjuvant radiotherapy.

ABSTRACT: 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.

SUBMITTER: Sargos P

PROVIDER: S-EPMC7441580 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Risk factors for loco-regional recurrence after radical cystectomy of muscle-invasive bladder cancer: A systematic-review and framework for adjuvant radiotherapy.

Sargos Paul P Baumann Brian C BC Eapen Libni L Christodouleas John J Bahl Amhit A Murthy Vedang V Efstathiou Jason J Fonteyne Valérie V Ballas Leslie L Zaghloul Mohamed M Roubaud Guilhem G Orré Mathieu M Larré Stéphane S

Cancer treatment reviews 20180721

<h4>Background</h4>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.< ...[more]

PMID: 30125800

Similar Datasets

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:Importance:Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can decrease locoregional failure but has not been studied in the chemotherapy era. Objective:To investigate if adjuvant sequential RT plus chemotherapy can improve locoregional recurrence-free survival (LRFS) compared with adjuvant chemotherapy alone. Design, Setting, and Participants:A randomized phase 3 trial was opened to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but a third arm was added later as a randomized phase 2 trial to compare chemotherapy plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat phase 2 trial reported herein enrolled patients from December 2002 to July 2008. Data were analyzed from August 3, 2015, to January 6, 2016. Routine follow-up and surveillance pelvic computed tomographic (CT) scans every 6 months during the first 2 years were performed. The setting was an academic center. Patients with bladder cancer 70 years or younger having 1 or more risk factors (≥pT3b, grade 3, or positive nodes) with negative margins after radical cystectomy plus pelvic lymph node dissection were eligible. Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, no evidence of distant metastases on CT scan of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and hematologic function. Ninety-one percent (109 of 120) had ≥ pT3 disease. Interventions:Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day 2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of gemcitabine and cisplatin. Main Outcome and Measure:Locoregional recurrence-free survival. Results:The chemotherapy plus RT arm accrued 75 patients, and the chemotherapy-alone arm accrued 45 patients, with a weighted randomization to speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and 46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced except for age (median, 52 vs 55 years; P = .04) and tumor size (mean, 4.9 vs 5.8 cm; P < .01), both favoring chemotherapy plus RT. Two-year outcomes and overall adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were 96% vs 69% (HR, 0.08; 95% CI, 0.02-0.39; P < .01) for LRFS, 68% vs 56% (HR, 0.53; 95% CI, 0.27-1.06; P = .07) for disease-free survival, and 71% vs 60% (HR, 0.61; 95% CI, 0.33-1.11; P = .11) for overall survival (OS). Five patients (7%) had RT-associated late grade 3 gastrointestinal tract adverse effects in the chemotherapy plus RT arm. Conclusions and Relevance:Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC. The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials. Trial Registration:clinicaltrials.gov Identifier: NCT01734798.

Dataset Information

Risk factors for loco-regional recurrence after radical cystectomy of muscle-invasive bladder cancer: A systematic-review and framework for adjuvant radiotherapy.

Publications

Risk factors for loco-regional recurrence after radical cystectomy of muscle-invasive bladder cancer: A systematic-review and framework for adjuvant radiotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets