Genomic profiling of muscle invasive bladder cancer to predict response to bladder-sparing trimodality therapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 513-513 ◽  
Author(s):  
David Tomoaki Miyamoto ◽  
Ewan Gibb ◽  
Kent William Mouw ◽  
Yang Liu ◽  
Chin-Lee Wu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Genomic Profiling ◽  
Disease Specific Survival ◽  
Clinical Factors ◽  
Gene Set Enrichment ◽  
Muscle Invasive Bladder Cancer ◽  
Trimodality Therapy ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
Disease Specific

513 Background: Trimodality therapy with TURBT followed by chemoradiation is an acceptable alternative to cystectomy for muscle invasive bladder cancer (MIBC). Genomic profiling has demonstrated MIBC can be divided into molecular subtypes with differing responses to chemotherapy. We explored the utility of genomic data to select patients for bladder-sparing trimodality therapy. Methods: Transcriptome wide gene expression profiles were generated for 189 MIBC TURBT samples from patients treated with trimodality therapy at a single institution. Of these, 103 passed microarray QC. Molecular subtype and expression of bladder cancer genes were assessed for association with overall and disease-specific survival. Transcriptome wide differential expression analysis was used to explore gene set enrichment in trimodality therapy response groups. Results: The chemoradiation cohort (n = 103) had a median followup of 6.9 years for alive patients, and was classified into four subtypes: basal (n = 44), basal claudin-low (n = 12), infiltrated luminal (n = 17) and luminal tumors (n = 30). There was no significant difference in overall or disease-specific survival by subtype. However, higher expression of the luminal-associated PPARG was correlated with increased survival after adjusting for subtype and clinical factors (HR = 0.52, p = 0.002). In contrast, a p53 signature predicted worse survival after adjusting for clinical factors (HR = 1.92, p = 0.022). Elevated mRNA expression of the DNA damage repair gene MRE11 was associated with improved survival in the trimodality cohort (HR = 0.69, P = 0.031), consistent with its potential role as a predictive biomarker for radiation response. Gene set enrichment revealed differential regulation of immune pathways in trimodality therapy responders relative to non-responders, including enrichment of interferon gamma signaling (p = 0.01) and CXCL9 (p = 0.031), suggestive of an interplay between tumor immunologic microenvironment and response to chemoradiation. Conclusions: Transcriptional profiling of MIBC revealed gene signatures correlated with response to chemoradiation, suggesting the potential of genomics to guide use of trimodality therapy.

Subtyping muscle-invasive bladder cancer to assess clinical response to trimodality therapy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 287-287
Author(s):  
Jason A. Efstathiou ◽  
Ewan Gibb ◽  
David Tomoaki Miyamoto ◽  
Chin-Lee Wu ◽  
Michael Drumm ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Gene Set Enrichment ◽  
Muscle Invasive Bladder Cancer ◽  
Trimodality Therapy ◽  
Luminal Subtype ◽  
Gene Set ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
Salvage Cystectomy

287 Background: Trimodality therapy with TURBT followed by chemoradiation is an acceptable alternative to cystectomy for muscle invasive bladder cancer (MIBC). Recently, genomic profiling has demonstrated MIBC can be divided into three or more subtypes with differing responses to chemotherapy, suggesting genomic subtype may impact therapeutic response. Here, we explore the utility of genomic information to better select patients for bladder-sparing trimodality therapy. Methods: Transcriptome-wide gene expression profiles were generated for 189 MIBC TURBT samples from patients undergoing trimodality therapy at the Massachusetts General Hospital. Of these, 108 passed microarray QC and 100 had complete clinical information. The patient tumors were classified as basal, basal claudin-low, infilrated luminal or luminal subtype. The subtype and the expression of a number of bladder cancer genes were assessed for their association with need for salvage cystectomy and for overall survival. Finally, transcriptome-wide differential expression analysis was used to explore gene set enrichment in trimodality therapy response groups. Results: Our chemoradiation cohort (n = 108) was classified into the four subtypes: basal (n = 45), basal claudin low (n = 13), infiltrated luminal (n = 17) and luminal tumors (n = 33). Survival analysis (n = 100) showed that patients of the luminal subtype trended to better overall survival, but did not reach significance (HR = 0.63, p = 0.1). Fewer patients with infiltrated luminal tumors (12%) required a salvage cystectomy compared to all other subtypes (34+/-1.5%, p = 0.08). We found high expression of BLACAT1 and NORAD (a lncRNA with a role in genome stability) correlated with worse (p = 0.01) and better prognosis (p = 0.008), respectively. Likewise, patients with high levels of the luminal-associated PPARG showed a significant increase in overall survival (p = 0.0002). Gene set enrichment revealed differential regulation of immune pathways in the trimodality therapy responders relative to the non-responders (p < 0.05). Conclusions: Preliminary data exploring MIBC subtyping suggests the possibility of using genomics to predict response to trimodality bladder-sparing therapy.

scholarly journals Subtype specific expression and survival prediction of pivotal lncRNAs in muscle invasive bladder cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sebastien Rinaldetti ◽  
Thomas Stefan Worst ◽  
Eugen Rempel ◽  
Maximilian C. Kriegmair ◽  
Arndt Hartmann ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Subtype ◽  
Invasive Bladder Cancer ◽  
Survival Prediction ◽  
Disease Specific Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Specific Expression ◽  
Cancer Subtypes ◽  
Muscle Invasive ◽  
Disease Specific

AbstractComprehensive transcriptome expression analyses of bladder cancer revealed distinct lncRNA clusters with differential molecular and clinical characteristics. In this study, pivotal lncRNAs were assessed for their impact on survival and their differential expression between the molecular bladder cancer subtypes. FFPE samples from chemotherapy-naïve patients with muscle invasive bladder cancer (MIBC) were analyzed on the Nanostring nCounter platform for absolute quantification. An established 36-gene panel was used for molecular subtype classification into basal, luminal and infiltrated MIBC. In a second step, 14 pivotal lncRNAs were assessed for their molecular subtype attribution, and their predictive value in disease-specific survival. In silico validation was performed on a total of 487 MIBC patients (MDA, TGCA and Chungbuk cohort). Several pivotal lncRNAs showed a distinct molecular subtype attribution: e.g. MALAT1 showed a downregulation in the basal subtype (p = 0.009), TUG1 and CBR3AS1 showed an upregulation in the luminal subtype (p ≤ 0.001). High transcript levels of SNHG16, CBR3AS1 and H19 appeared to be predictive for a shorter disease-specific survival. Patients overexpressing putative oncogenes MALAT1 and TUG1 in MIBC tissue presented prolonged survival, suggesting tumor suppressive effects of both lncRNAs. The Nanostring nCounter proved to be a valid platform for the quantification of low-abundance transcripts including lncRNAs.

Transurethral Resection of Muscle-Invasive Bladder Cancer: 10-Year Outcome

2001 ◽  
Vol 19 (1) ◽  
pp. 89-93 ◽  
Author(s):  
Harry W. Herr
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Residual Tumor ◽  
Invasive Bladder Cancer ◽  
Tumor Site ◽  
Disease Specific Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Primary Tumor Site ◽  
Muscle Invasive ◽  
Disease Specific

PURPOSE: To determine the 10-year outcome of patients with muscle-invasive bladder cancer treated by transurethral resection (TUR) alone. PATIENTS AND METHODS: Of 432 newly evaluated patients with muscle-invasive bladder cancer, 151 were treated by standard radical cystectomy or by definitive TUR, if restaging TUR of the primary tumor site showed no (T0) or only non–muscle-invasive (T1) residual tumor. Patients were followed-up every 3 to 6 months thereafter for a minimum of 10 years and up to 20 years. Primary end points of the study were disease-specific survival, survival with a bladder, frequency of recurrent invasive tumors in the bladder, and survival after salvage cystectomy. RESULTS: The 10-year disease-specific survival was 76% of 99 patients who received TUR as definitive therapy (57% with bladder preserved) compared with 71% of 52 patients who had immediate cystectomy (P = .3). Of the 99 patients treated with TUR, 82% of 73 who had T0 on restaging TUR survived versus 57% of the 26 patients who had residual T1 tumor on restaging TUR (P = .003). Thirty-four patients (34%) relapsed in the bladder with a new muscle-invasive tumor, 18 (53%) were successfully treated with salvage therapy via cystectomy, and 16 patients (16%) died of disease. CONCLUSION: Radical TUR for muscle-invasive bladder cancer is a successful bladder-sparing therapeutic strategy in selected patients who have no residual tumor on a repeat vigorous resection of the primary tumor site.

scholarly journals Outcomes of trimodality bladder-sparing therapy for muscle-invasive bladder cancer

2019 ◽  
Vol 14 (4) ◽  
Author(s):  
Eric K. Nguyen ◽  
Hang Yu ◽  
Gregory Pond ◽  
Bobby Shayegan ◽  
Jehonathan H. Pinthus ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Response Rates ◽  
Invasive Bladder Cancer ◽  
Single Institution ◽  
Muscle Invasive Bladder Cancer ◽  
Trimodality Therapy ◽  
Muscle Invasive ◽  
Bladder Sparing

Introduction: Although radical cystectomy is considered the standard of care for muscle-invasive bladder cancer (MIBC), recent data has suggested comparable survival outcomes for bladder-sparing trimodality therapy (TMT). We conducted a retrospective, single-institution analysis of MIBC patients to evaluate the efficacy of TMT as an alternative, curative approach to surgical intervention. Methods: We conducted a retrospective analysis of MIBC patients assessed by a multidisciplinary team at the Juravinski Cancer Centre from 2010–2016. Patients underwent transurethral resection of bladder tumor (TURBT) followed by radiotherapy with or without concurrent chemotherapy. Patients could receive neoadjuvant treatment. Clinical data and response rates were summarized, and overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Results: Our analytic cohort included 115 patients, of whom 53 underwent TMT and 62 who underwent radiotherapy alone following TURBT. Median age at diagnosis was 79 years and median followup was 21 months. Complete response rates in those receiving TMT and radiation without chemotherapy were 84.4% and 66.7%, respectively. For TMT patients, three-year OS and DFS were 68.5% and 49.6%, respectively. Patients who received TMT had reduction in risk of mortality (hazard ratio [HR] 0.49; p=0.026) and disease recurrence (HR 0.55; p=0.017) compared to those who had radiation without chemotherapy. Overall, four patients had grade 3 or higher late toxicity. Conclusions: In this single-institution analysis, TMT appears to be a safe and effective approach in the short-term management of MIBC in appropriately selected patients. Extended followup and analysis are necessary to validate these results.

Clinical outcomes of muscle-invasive bladder cancer patients with hydronephrosis treated with tetra-modality bladder sparing therapy incorporating consolidative partial cystectomy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 430-430
Author(s):  
Toshiki Kijima ◽  
Shohei Fukuda ◽  
Hiroshi Fukushima ◽  
Shingo Moriyama ◽  
Sho Uehara ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Response Rate ◽  
Partial Cystectomy ◽  
Invasive Bladder Cancer ◽  
Recurrence Free Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Trimodality Therapy ◽  
Free Survival ◽  
Muscle Invasive ◽  
Bladder Sparing

430 Background: Trimodality bladder sparing therapy has become an accepted treatment for selected patients with muscle-invasive bladder cancer (MIBC). As the presence of hydronephrosis may reduce complete response rate and survival in trimodality therapy, some investigators deem hydronephrosis as a contraindication for bladder sparing. We have developed a tetra-modality bladder sparing therapy (TeMT) consisting of maximal transurethral resection (TUR), induction chemoradiotherapy (CRT), and partial cystectomy (PC) (Koga et al, BJU Int 2012). TeMT which enables surgical consolidation of the original MIBC site, including uretero-vesical anastomosis if necessary, may provide more chance of bladder sparing for patients with hydronephrosis. Methods: In total, 151 patients with cT2-3N0M0 MIBC (median age 69 years, female/male = 33/118, cT2/3 = 100/51) entered tetra-modality bladder-sparing protocol. After maximal TUR and CRT (40 Gy + cisplatin), response was evaluated via cytology, imaging, and tumor-site rebiopsy. Consolidative PC was performed in complete responders, while radical cystectomy was recommended for others. Extension of ipsilateral intrapelvic ureter in pretreatment computed tomography was graded following the Society for Fetal Urology grading system, then patients with grade 2-3 were classified as with hydronephrosis. Response rate to CRT, MIBC recurrence-free survival, and cancer-specific survival (CSS) were compared between patients with or without hydronephrosis. Results: Hydronephrosis was found in 19 patients (14%), and was associated with lower response rate to CRT (42% in hydronephrosis vs 77% in normal, p = 0.03). On an intent-to-treat basis, patients with hydronephrosis (n = 19) had lower 5-yr CSS than those without it (n = 132) (62% vs 85%, p < 0.01). Among the 106 patients who underwent PC as per protocol, patients with (n = 9) and without hydronephrosis (n = 97) had comparable 5-yr MIBC recurrence-free survival (100% vs 97%, p = 0.11) and CSS (100% vs 93%, p = 0.46). Conclusions: Patients with hydronephrosis should not necessarily be excluded from tetra-modality bladder sparing therapy.

scholarly journals Current Management of Localized Muscle-Invasive Bladder Cancer: A Consensus Guideline from the Genitourinary Medical Oncologists of Canada

2020 ◽  
Vol 6 (3) ◽  
pp. 363-392
Author(s):  
Di Maria Jiang ◽  
Scott A. North ◽  
Christina Canil ◽  
Michael Kolinsky ◽  
Lori A. Wood ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Patient Centered ◽  
Muscle Invasive Bladder Cancer ◽  
Trimodality Therapy ◽  
Majority Opinion ◽  
Definitive Therapy ◽  
Level 3 ◽  
Muscle Invasive ◽  
Bladder Sparing

BACKGROUND: Despite recent advances in the management of muscle-invasive bladder cancer (MIBC), treatment outcomes remain suboptimal, and variability exists across current practice patterns. OBJECTIVE: To promote standardization of care for MIBC in Canada by developing a consensus guidelines using a multidisciplinary, evidence-based, patient-centered approach who specialize in bladder cancer. METHODS: A comprehensive literature search of PubMed, Medline, and Embase was performed; and most recent guidelines from national and international organizations were reviewed. Recommendations were made based on best available evidence, and strength of recommendations were graded based on quality of the evidence. RESULTS: Overall, 17 recommendations were made covering a broad range of topics including pathology review, staging investigations, systemic therapy, local definitive therapy and surveillance. Of these, 10 (59% ) were level 1 or 2, 7 (41% ) were level 3 or 4 recommendations. There were 2 recommendations which did not reach full consensus, and were based on majority opinion. This guideline also provides guidance for the management of cisplatin-ineligible patients, variant histologies, and bladder-sparing trimodality therapy. Potential biomarkers, ongoing clinical trials, and future directions are highlighted. CONCLUSIONS: This guideline embodies the collaborative expertise from all disciplines involved, and provides guidance to further optimize and standardize the management of MIBC.

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