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Urinary Bladder Neoplasms: HELP
Articles by Rian J. Dickstein
Based on 9 articles published since 2010
(Why 9 articles?)
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Between 2010 and 2020, Rian J. Dickstein wrote the following 9 articles about Urinary Bladder Neoplasms.
 
+ Citations + Abstracts
1 Review Contemporary management of locally invasive bladder cancer. 2011

Dickstein, Rian J / Kamat, Ashish M. ·Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ·Oncology (Williston Park) · Pubmed #22329191.

ABSTRACT: Bladder cancer is a heterogeneous disease that carries a significant risk of progression and lethality. Radical cystectomy with pelvic lymph node dissection remains the predominant treatment for patients with muscle-invasive disease and offers the best chance of long-term disease control. However, radical surgery is insufficient in patients with advanced-stage disease. Current staging techniques are limited in their ability to detect extravesical disease and lymph node metastases. Thus, integration of systemic therapy with surgery to potentially eradicate micrometastases provides survival superior to that with surgery alone. Yet, because bladder cancer is typically a disease that affects an elderly population of patients with multiple comorbidities, there is a need for less invasive and bladder-conserving therapies. Some physicians have attempted to minimize morbidity by pursuing minimally invasive surgical techniques; however, the long-term effectiveness of this approach remains unproven. Trimodality therapy could be considered in patients with favorable disease status, and may be offered as a reasonable alternative, but does not replace standard treatments for patients with more aggressive disease. Consequently, further improvements in outcomes will rely on improved patient selection based on clinical and molecular assessments.

2 Clinical Trial Lymph node density for patient counselling about prognosis and for designing clinical trials of adjuvant therapies after radical cystectomy. 2012

Lee, Eugene K / Herr, Harry W / Dickstein, Rian J / Kassouf, Wassim / Munsell, Mark F / Grossman, H Barton / Dinney, Colin P N / Kamat, Ashish M. ·Department of Urology Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ·BJU Int · Pubmed #22758775.

ABSTRACT: OBJECTIVE: • To develop a clinical tool based on lymph node density (LND) for patient counselling after radical cystectomy and for design of clinical trials of adjuvant therapies after radical cystectomy. PATIENTS AND METHODS: • Using pooled data from two comprehensive cancer centres, we identified patients with lymph node metastases after radical cystectomy who received an adequate lymph node dissection according to existing literature (resection of eight or more nodes). • Only patients who had not received neoadjuvant or adjuvant chemotherapy were included to ensure that prediction models were based on the natural course of the disease. • Thresholds for LND ranging from 5% to 35%, in 5% increments, were used to dichotomize the study population. Within each set of two groups, the Kaplan-Meier product-limit estimator was used to estimate disease-specific survival (DSS) for each group, and Cox proportional hazards regression was used to test the significance of differences in DSS between the group with higher LND and the group with lower LND. • Tables and graphs showing the relationship between LND categories and 2-year and 5-year estimated DSS were created to aid in clinical decision-making. RESULTS: • LND was valuable as a tool for stratifying node-positive patients into different risk groups based on expected survival. • At each LND threshold from 10% to 35%, patients with higher LND had significantly worse DSS than patients with lower LND (P ≤ 0.001). • As expected, DSS in the higher-LND group worsened with each 5% increase in LND threshold: patients with LND > 35% had a 5-year DSS rate of 4%. • Using our data as a tool, multiple cut-offs can be employed to categorize patients into various risk groups with different risk. For example, patients with LND ≤ 10% have an estimated 5-year DSS rate of 61.9%, whereas patients with LND > 15% have an estimated 5-year DSS rate of 19.2%. CONCLUSIONS: • Patients with node-positive bladder cancer have poor outcomes, and survival varies widely according to LND. • Categorical LND should be used to risk-stratify patients for counselling regarding prognosis. • Furthermore, categorical LND should be used as a tool for designing and reporting on clinical trials of adjuvant therapies.

3 Clinical Trial Use of fluorescence in situ hybridization to predict response to bacillus Calmette-Guérin therapy for bladder cancer: results of a prospective trial. 2012

Kamat, Ashish M / Dickstein, Rian J / Messetti, Fabrizio / Anderson, Roosevelt / Pretzsch, Shanna M / Gonzalez, Graciela Noguera / Katz, Ruth L / Khanna, Abha / Zaidi, Tanweer / Wu, Xifeng / Grossman, H Barton / Dinney, Colin P. ·Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. akamat@mdanderson.org ·J Urol · Pubmed #22245325.

ABSTRACT: PURPOSE: No reliable methods currently exist to predict patient response to intravesical immunotherapy with bacillus Calmette-Guérin given after transurethral resection for high risk nonmuscle invasive bladder cancer. We initiated a prospective clinical trial to determine whether fluorescence in situ hybridization results during bacillus Calmette-Guérin immunotherapy can predict therapy failure. MATERIALS AND METHODS: Candidates for standard of care bacillus Calmette-Guérin were offered participation in a clinical trial. Fluorescence in situ hybridization was performed before bacillus Calmette-Guérin, and at 6 weeks, 3 months and 6 months during bacillus Calmette-Guérin therapy with maintenance. Cox proportional hazards regression was used to assess the relationship between fluorescence in situ hybridization results and tumor recurrence or progression. The Kaplan-Meier product limit method was used to estimate recurrence-free and progression-free survival. RESULTS: A total of 126 patients participated in the study. At a median followup of 24 months 31% of patients had recurrent tumors and 14% experienced disease progression. Patients who had positive fluorescence in situ hybridization results during bacillus Calmette-Guérin therapy were 3 to 5 times more likely than those who had negative fluorescence in situ hybridization results to experience recurrent tumors and 5 to 13 times more likely to have disease progression (p <0.01). The timing of positive fluorescence in situ hybridization results also affected outcomes. For example, patients with a negative fluorescence in situ hybridization result at baseline, 6 weeks and 3 months demonstrated an 8.3% recurrence rate compared to 48.1% for those with a positive result at all 3 points. CONCLUSIONS: Fluorescence in situ hybridization results can identify patients at risk for tumor recurrence and progression during bacillus Calmette-Guérin immunotherapy. This information may be used to counsel patients about alternative treatment strategies.

4 Article Clinical risk stratification in patients with surgically resectable micropapillary bladder cancer. 2017

Fernández, Mario I / Williams, Stephen B / Willis, Daniel L / Slack, Rebecca S / Dickstein, Rian J / Parikh, Sahil / Chiong, Edmund / Siefker-Radtke, Arlene O / Guo, Charles C / Czerniak, Bogdan A / McConkey, David J / Shah, Jay B / Pisters, Louis L / Grossman, H Barton / Dinney, Colin P N / Kamat, Ashish M. ·Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·BJU Int · Pubmed #27753185.

ABSTRACT: OBJECTIVE: To analyse survival in patients with clinically localised, surgically resectable micropapillary bladder cancer (MPBC) undergoing radical cystectomy (RC) with and without neoadjuvant chemotherapy (NAC) and develop risk strata based on outcome data. PATIENTS AND METHODS: A review of our database identified 103 patients with surgically resectable (≤cT4acN0 cM0) MPBC who underwent RC. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests. Classification and regression tree (CART) analysis was performed to identify risk groups for survival. RESULTS: For the entire cohort, estimated 5-year overall survival and disease-specific survival (DSS) rates were 52% and 58%, respectively. CART analysis identified three risk subgroups: low-risk: cT1, no hydronephrosis; high-risk: ≥cT2, no hydronephrosis; and highest-risk: cTany with tumour-associated hydronephrosis. The 5-year DSS for the low-, high-, and highest-risk groups were 92%, 51%, and 17%, respectively (P < 0.001). Patients down-staged at RC In patients with surgically resectable MPBC, NAC appears to confer benefit to patients with muscle-invasive disease without hydronephrosis, while patients with cT1 disease can proceed to upfront RC. Patients with hydronephrosis do not appear to respond well to NAC and have poor prognosis regardless of treatment paradigm. However, further external validation studies are needed to support the proposed risk stratification before treatment recommendations can be made.

5 Article Novel fluorescence in situ hybridization-based definition of bacille Calmette-Guérin (BCG) failure for use in enhancing recruitment into clinical trials of intravesical therapies. 2016

Kamat, Ashish M / Willis, Daniel L / Dickstein, Rian J / Anderson, Rooselvelt / Nogueras-González, Graciela / Katz, Ruth L / Wu, Xifeng / Barton Grossman, H / Dinney, Colin P. ·Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Cytopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·BJU Int · Pubmed #26032953.

ABSTRACT: OBJECTIVES: To present a molecular definition of bacille Calmette-Guérin (BCG) failure that incorporates fluorescence in situ hybridization (FISH) testing to predict BCG failure before it becomes clinically evident, which can be used to enhance trial designs for patients with non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We used data from 143 patients who were followed prospectively for 2 years during intravesical BCG therapy, during which time FISH assays were collected and correlated to clinical outcomes. RESULTS: Of the 95 patients with no evidence of tumour at 3-month cystoscopy, 23 developed tumour recurrence and 17 developed disease progression by 2 years. Patients with a positive FISH test at both 6 weeks and 3 months were more likely to develop tumour recurrence (17/37 patients [46%] and 16/28 patients [57%], respectively) than patients with a negative FISH test (6/58 patients [10%] and 3/39 patients [8%], respectively; both P < 0.001). Using hazard ratios for recurrence with positive 6-week and 3-month FISH results, we constructed clinical trial scenarios whereby patients with a negative 3-month cystoscopy and positive FISH result could be considered to have 'molecular BCG failure' and could be enrolled in prospective, randomized clinical trials comparing BCG therapy (control) with an experimental intravesical therapy. CONCLUSIONS: Patients with positive early FISH and negative 3-month cystoscopy results can be considered to have molecular BCG failure based on their high rates of recurrence and progression. This definition is intended for use in designing clinical trials, thus potentially allowing continued use of BCG as an ethical comparator arm.

6 Article Clinical outcomes of cT1 micropapillary bladder cancer. 2015

Willis, Daniel L / Fernandez, Mario I / Dickstein, Rian J / Parikh, Sahil / Shah, Jay B / Pisters, Louis L / Guo, Charles C / Henderson, Samuel / Czerniak, Bogdan A / Grossman, H Barton / Dinney, Colin P / Kamat, Ashish M. ·Departments of Urology and Pathology (CCG, SH, BAC), University of Texas M.D. Anderson Cancer Center, Houston, Texas. · Departments of Urology and Pathology (CCG, SH, BAC), University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: akamat@mdanderson.org. ·J Urol · Pubmed #25254936.

ABSTRACT: PURPOSE: While many urologists recommend radical cystectomy for micropapillary bladder cancer invading the lamina propria (cT1), contradictory small reports exist on the efficacy of conservative management with intravesical bacillus Calmette-Guérin for this disease. We report our updated experience in what to our knowledge is the largest series of patients with cT1 micropapillary bladder cancer. MATERIALS AND METHODS: An institutional review board approved review of our cancer database identified 283 patients with micropapillary bladder cancer, including 72 staged with cT1N0M0 disease at diagnosis and initiation of therapy. Survival analysis was performed using the Kaplan-Meier estimator and compared using the log rank test. RESULTS: In this cohort of 72 patients 40 received primary intravesical bacillus Calmette-Guérin and 26 underwent up-front radical cystectomy. Of patients who received bacillus Calmette-Guérin 75%, 45% and 35% experienced disease recurrence, progression and lymph node metastasis, respectively. Patients treated with up-front cystectomy had improved survival compared to patients treated with primary bacillus Calmette-Guérin (5-year disease specific survival 100% vs 60% p = 0.006) and patients who underwent delayed cystectomy after recurrence (5-year disease specific survival 62%, p = 0.015). Prognosis was especially poor in patients who waited for progression before undergoing radical cystectomy with an estimated 5-year disease specific survival of only 24% and a median survival of 35 months. In patients treated with up-front cystectomy pathological up-staging was found in 27%, including 20% with lymph node metastasis. CONCLUSIONS: While certain patients with T1 micropapillary bladder cancer may respond to intravesical bacillus Calmette-Guérin, survival is improved in those who undergo early radical cystectomy. Further molecular studies are needed to identify subsets of patients in whom the bladder can be safely spared.

7 Article Refining patient selection for neoadjuvant chemotherapy before radical cystectomy. 2014

Culp, Stephen H / Dickstein, Rian J / Grossman, H Barton / Pretzsch, Shanna M / Porten, Sima / Daneshmand, Siamak / Cai, Jie / Groshen, Susan / Siefker-Radtke, Arlene / Millikan, Randall E / Czerniak, Bogdan / Navai, Neema / Wszolek, Matthew F / Kamat, Ashish M / Dinney, Colin P N. ·Department of Urology, University of Virginia, Charlottesville, Virginia, California. · Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California. · University of Southern California Institute of Urology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California. · Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California. · Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California. Electronic address: cdinney@mdanderson.org. ·J Urol · Pubmed #23911605.

ABSTRACT: PURPOSE: We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy. MATERIALS AND METHODS: We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings. RESULTS: We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged. CONCLUSIONS: The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity.

8 Article Autophagy limits the cytotoxic effects of the AKT inhibitor AZ7328 in human bladder cancer cells. 2012

Dickstein, Rian J / Nitti, Giovanni / Dinney, Colin P / Davies, Barry R / Kamat, Ashish M / McConkey, David J. ·Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·Cancer Biol Ther · Pubmed #22895070.

ABSTRACT: BACKGROUND: Mutations that activate the PI3K/AKT/mTOR pathway are relatively common in urothelial (bladder) cancers, but how these pathway mutations affect AKT dependency is not known. We characterized the relationship between AKT pathway mutational status and sensitivity to the effects of the selective AKT kinase inhibitor AZ7328 using a panel of 12 well-characterized human bladder cancer cell lines. METHODS: Sequenome DNA sequencing was performed to identify mutations in a panel of 12 urothelial cancer cell lines. Drug-induced proliferative inhibition and apoptosis were quantified using MTT assays and propidium iodide staining with FACS analyses. Protein activation via phosphorylation was measured by immunoblotting. Autophagy was measured by LC3 immunofluorescence and immunoblotting. RESULTS: AZ7328 inhibited proliferation and AKT substrate phosphorylation in a concentration-dependent manner but had minimal effects on apoptosis. Proliferative inhibition correlated loosely with the presence of activating PIK3CA mutations and was strengthened in combination with the mTOR inhibitor rapamycin. AZ7328 induced autophagy in some of the lines, and in the cells exposed to a combination of AZ7328 and chemical autophagy inhibitors apoptosis was induced. CONCLUSIONS: The cytostatic effects of AZ7328 correlate with PIK3CA mutations and are greatly enhanced by dual pathway inhibition using an mTOR inhibitor. Furthermore, AZ7328 can interact with autophagy inhibitors to induce apoptosis in some cell lines. Overall, our results support the further evaluation of combinations of PI3K/AKT/mTOR pathway and autophagy inhibitors in pre-clinical in vivo models and ultimately in patients with PIK3CA mutant bladder cancers.

9 Article Effects of mTOR inhibitor everolimus (RAD001) on bladder cancer cells. 2011

Chiong, Edmund / Lee, I-Ling / Dadbin, Ali / Sabichi, Anita L / Harris, Loleta / Urbauer, Diana / McConkey, David J / Dickstein, Rian J / Cheng, Tiewei / Grossman, H Barton. ·Department of Urology, National University Health System, Singapore. ·Clin Cancer Res · Pubmed #21415218.

ABSTRACT: PURPOSE: We investigated the effect of the mTOR inhibitor RAD001 (everolimus) on human bladder cancer (BC) cells in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of RAD001 on the growth of UM-UC-3, UM-UC-6, UM-UC-9, and UM-UC-14 BC cells were assessed by crystal violet and [(3)H]thymidine incorporation assays. Flow cytometric cell-cycle analyses were done to measure the apoptotic cell fraction. Protein synthesis was measured using tritium-labeled leucine incorporation assays. The effects of RAD001 on the mTOR pathway were analyzed by Western blotting. To test the effects of RAD001 in vivo, UM-UC-3, UM-UC-6, and UM-UC-9 cells were subcutaneously implanted into nude mice. Tumor-bearing mice were treated orally with RAD001 or placebo. Tumors were harvested for immunohistochemical analysis. RESULTS: In vitro, RAD001 transiently inhibited BC cell growth in a dose-dependent manner. This effect was augmented by re-treatment of cells after 3 days. UM-UC-14 cells were the most sensitive to RAD001, whereas UM-UC-9 cells were the least sensitive. After re-treatment with RAD001, only sensitive cell lines showed G(1)-phase arrest, with no evidence of apoptosis. RAD001 significantly inhibited the growth of tumors that were subcutaneously implanted in mice. Inhibition of protein synthesis through the S6K and 4EBP1 pathways seems to be the main mechanism for the RAD001-induced growth inhibition. However, inhibition of angiogenesis was the predominant mechanism of the effect of RAD001 on UM-UC-9 cells. CONCLUSIONS: The mTOR inhibitor RAD001 inhibits growth of BC cells in vitro. RAD001 is effective in treating BC tumors in an in vivo nude mouse model despite the heterogeneity of in vitro responses.