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Urinary Bladder Neoplasms: HELP
Articles by Donald G. Skinner
Based on 14 articles published since 2010
(Why 14 articles?)

Between 2010 and 2020, Donald Skinner wrote the following 14 articles about Urinary Bladder Neoplasms.
+ Citations + Abstracts
1 Clinical Trial Variability in surgical quality in a phase III clinical trial of radical cystectomy in patients with organ-confined, node-negative urothelial carcinoma of the bladder. 2015

Mata, Douglas A / Groshen, Susan / Von Rundstedt, Friedrich-Carl / Skinner, Donald G / Stadler, Walter M / Cote, Richard J / Stein, John P / Lerner, Seth P. ·Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. ·J Surg Oncol · Pubmed #25873574.

ABSTRACT: BACKGROUND AND OBJECTIVES: Previous studies have shown that variability in surgical technique can affect the outcomes of cooperative group trials. We analyzed measures of surgical quality and clinical outcomes in patients enrolled in the p53-MVAC trial. METHODS: We performed a post-hoc analysis of patients with pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC) and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical quality were examined for associations with time to recurrence (TTR) and overall survival (OS). RESULTS: We reviewed operative and/or pathology reports for 440 patients from 35 sites. We found that only 31% of patients met all suggested trial eligibility criteria of having ≥15 lymph nodes identified in the pathologic specimen (LN#) and having undergone both extended and presacral LND. There was no association between extent of LND, LN#, or presacral LND and TTR or OS after adjustment for confounders and multiple testing. CONCLUSIONS: We demonstrated that there was substantial variability in surgical technique within a cooperative group trial. Despite explicit entry criteria, many patients did not undergo per-protocol LNDs. While outcomes were not apparently affected, it is nonetheless evident that careful attention to study design and quality monitoring will be critical to successful future trials.

2 Clinical Trial Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer. 2015

Skinner, Eila C / Fairey, Adrian S / Groshen, Susan / Daneshmand, Siamak / Cai, Jie / Miranda, Gus / Skinner, Donald G. ·Department of Urology, Stanford University, Stanford, California. Electronic address: skinnere@stanford.edu. · Department of Urology, University of Alberta, Edmonton, Canada. · USC Institute of Urology, Keck Medical Center of USC, Los Angeles, California. ·J Urol · Pubmed #25823791.

ABSTRACT: PURPOSE: The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. MATERIALS AND METHODS: This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. RESULTS: Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. CONCLUSIONS: T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures.

3 Clinical Trial Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. 2011

Stadler, Walter M / Lerner, Seth P / Groshen, Susan / Stein, John P / Shi, Shan-Rong / Raghavan, Derek / Esrig, David / Steinberg, Gary / Wood, David / Klotz, Laurence / Hall, Craig / Skinner, Donald G / Cote, Richard J. ·University of Chicago, Chicago, IL, USA. ·J Clin Oncol · Pubmed #21810677.

ABSTRACT: INTRODUCTION: Retrospective studies suggest that p53 alteration is prognostic for recurrence in patients with urothelial bladder cancer and predictive for benefit from combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) adjuvant chemotherapy. PATIENTS AND METHODS: Patients with pT1/T2N0M0 disease whose tumors demonstrated ≥ 10% nuclear reactivity on centrally performed immunohistochemistry for p53 were offered random assignment to three cycles of adjuvant MVAC versus observation; p53-negative patients were observed. By using a log-rank test with one-sided α = .05 and β = .10, 190 p53-positive patients were planned to be randomly assigned to detect an absolute improvement in probability of recurring by 3 years from 0.50 to 0.30. RESULTS: A total of 521 patients were registered, 499 underwent p53 assessment, 272 (55%) were positive, and 114 (42%) were randomly assigned. Accrual was halted on the basis of the data and safety monitoring board review of a futility analysis. Overall 5-year probability of recurring was 0.20 (95% CI, 0.16 to 0.24) with no difference on the basis of p53 status. Only 67% of patients randomly assigned to MVAC received all three cycles with 12 patients receiving no treatment. There was no difference in recurrence in the randomly assigned patients (hazard ratio, 0.78; 95% CI, 0.29 to 2.08; P = .62). CONCLUSION: Neither the prognostic value of p53 nor the benefit of MVAC chemotherapy in patients with p53-positive tumors was confirmed, but the high patient refusal rate, lower than expected event rate, and failures to receive assigned therapy severely compromised study power.

4 Article Use of Artificial Intelligence and Machine Learning Algorithms with Gene Expression Profiling to Predict Recurrent Nonmuscle Invasive Urothelial Carcinoma of the Bladder. 2016

Bartsch, Georg / Mitra, Anirban P / Mitra, Sheetal A / Almal, Arpit A / Steven, Kenneth E / Skinner, Donald G / Fry, David W / Lenehan, Peter F / Worzel, William P / Cote, Richard J. ·University of Southern California, Los Angeles, California; Goethe University Frankfurt, Frankfurt, Germany. · University of Southern California, Los Angeles, California. · Everist Genomics, Ann Arbor, Michigan. · University of Copenhagen, Copenhagen, Denmark. · University of Miami, Miami, Florida. Electronic address: RCote@med.miami.edu. ·J Urol · Pubmed #26459038.

ABSTRACT: PURPOSE: Due to the high recurrence risk of nonmuscle invasive urothelial carcinoma it is crucial to distinguish patients at high risk from those with indolent disease. In this study we used a machine learning algorithm to identify the genes in patients with nonmuscle invasive urothelial carcinoma at initial presentation that were most predictive of recurrence. We used the genes in a molecular signature to predict recurrence risk within 5 years after transurethral resection of bladder tumor. MATERIALS AND METHODS: Whole genome profiling was performed on 112 frozen nonmuscle invasive urothelial carcinoma specimens obtained at first presentation on Human WG-6 BeadChips (Illumina®). A genetic programming algorithm was applied to evolve classifier mathematical models for outcome prediction. Cross-validation based resampling and gene use frequencies were used to identify the most prognostic genes, which were combined into rules used in a voting algorithm to predict the sample target class. Key genes were validated by quantitative polymerase chain reaction. RESULTS: The classifier set included 21 genes that predicted recurrence. Quantitative polymerase chain reaction was done for these genes in a subset of 100 patients. A 5-gene combined rule incorporating a voting algorithm yielded 77% sensitivity and 85% specificity to predict recurrence in the training set, and 69% and 62%, respectively, in the test set. A singular 3-gene rule was constructed that predicted recurrence with 80% sensitivity and 90% specificity in the training set, and 71% and 67%, respectively, in the test set. CONCLUSIONS: Using primary nonmuscle invasive urothelial carcinoma from initial occurrences genetic programming identified transcripts in reproducible fashion, which were predictive of recurrence. These findings could potentially impact nonmuscle invasive urothelial carcinoma management.

5 Article Ureteroenteric Strictures After Open Radical Cystectomy and Urinary Diversion: The University of Southern California Experience. 2015

Shah, Swar H / Movassaghi, Kamran / Skinner, Donald / Dalag, Leonard / Miranda, Gus / Cai, Jie / Schuckman, Anne / Daneshmand, Siamak / Djaladat, Hooman. ·USC Institute of Urology, USC/Norris Comprehensive Cancer Center, Los Angeles, CA. · USC Institute of Urology, USC/Norris Comprehensive Cancer Center, Los Angeles, CA. Electronic address: djaladat@med.usc.edu. ·Urology · Pubmed #25987494.

ABSTRACT: OBJECTIVE: To evaluate the risk factors, management, and outcomes of benign ureteroenteric strictures (UES) in patients undergoing open radical cystectomy (RC) and urinary diversion for urothelial bladder carcinoma. MATERIALS AND METHODS: Using our institutional review board-approved institutional bladder cancer database, we identified 1964 patients who underwent RC for urothelial bladder carcinoma between 1971 and 2008. Patients underwent a uniform refluxing ureteroenteric anastomosis technique to ileum. In patients with UES, we reviewed clinicopathologic, management, and outcome variables. A multivariate logistic regression model was used to identify independent UES predictors. RESULTS: Forty-nine patients and 51 renal units were retrospectively identified with benign UES (2.6%). Median follow-up was 12.4 years (0.2-27.3 years) and median time from RC to UES diagnosis was 10 months (2 months-10 years). Although one-third were asymptomatic, common presentations included flank pain (22%) and urinary tract infection (9%). Thirty-one patients underwent primary endoscopic treatments, including dilatation and stenting, of whom, 13 patients (42%) underwent secondary endoscopic treatment and 9 patients (29%) underwent open revision. Three patients underwent primary open management. Median glomerular filtration rate did not change after management (49-48 mL/min); however, imaging showed improvement in 50% of cases. A multivariate logistic regression model revealed no association with age, body mass index, Charlson comorbidity index, perioperative radiation or chemotherapy, or preoperative serum albumin in predicting UES. CONCLUSION: Benign UES are uncommon after RC and urinary diversion using a consistent meticulous surgical approach. More commonly on the left, UES generally present a few months after RC. Although no specific predisposing factor was determined, surgical technique plays an important role.

6 Article Significance of lymphovascular invasion in organ-confined, node-negative urothelial cancer of the bladder: data from the prospective p53-MVAC trial. 2015

von Rundstedt, Friedrich-Carl / Mata, Douglas A / Groshen, Susan / Stein, John P / Skinner, Donald G / Stadler, Walter M / Cote, Richard J / Kryvenko, Oleksandr N / Godoy, Guilherme / Lerner, Seth P. ·Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA. · Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA. · Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. · Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA. · Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA. · Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA. · Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA. ·BJU Int · Pubmed #25413313.

ABSTRACT: OBJECTIVES: To investigate the association between lymphovascular invasion (LVI) and clinical outcome in organ-confined, node-negative urothelial cancer of the bladder (UCB) in a post hoc analysis of a prospective clinical trial. To explore the effect of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) on outcome in the subset of patients whose tumours exhibited LVI. PATIENTS AND METHODS: Surgical and tumour factors were extracted from the operative and pathology reports of 499 patients who had undergone radical cystectomy (RC) for pT1-T2 N0 UCB in the p53-MVAC trial (Southwest Oncology Group 4B951/NCT00005047). The presence or absence of LVI was determined by pathological examination of transurethral resection or RC specimens. Variables were examined in univariate and multivariate Cox proportional hazards models for associations with time to recurrence (TTR) and overall survival (OS). RESULTS: Among 499 patients with a median follow-up of 4.9 years, a subset of 102 (20%) had LVI-positive tumours. Of these, 34 patients had pT1 and 68 had pT2 disease. LVI was significantly associated with TTR with a hazard ratio (HR) of 1.78 [95% confidence interval (CI) 1.15-2.77; number of events (EV) 95; P = 0.01) and with OS with a HR of 2.02 (95% CI 1.31-3.11; EV 98; P = 0.001) after adjustment for pathological stage. Among 27 patients with LVI-positive tumours who were randomised to receive adjuvant chemotherapy, receiving MVAC was not significantly associated with TTR (HR 0.70, 95% CI 0.16-3.17; EV 7; P = 0.65) or with OS (HR 0.45, 95% CI 0.11-1.83; EV 9; P = 0.26). CONCLUSIONS: Our post hoc analysis of the p53-MVAC trial revealed an association between LVI and shorter TTR and OS in patients with pT1-T2N0 disease. The analysis did not show a statistically significant benefit of adjuvant MVAC chemotherapy in patients with LVI, although a possible benefit was not excluded.

7 Article Urinary functional outcomes in female neobladder patients. 2014

Bartsch, Georg / Daneshmand, Siamak / Skinner, Eila C / Syan, Sumeet / Skinner, Donald G / Penson, David F. ·Institute of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Los Angeles, CA, 90089, USA, georg.bartsch@kgu.de. ·World J Urol · Pubmed #24317553.

ABSTRACT: PURPOSE: The ratio between orthotopic and non-orthotopic diversions in women is far lower than in male patients. Data on urinary function in female patients with neobladders are therefore sparse. METHODS: We investigated the urinary function of female neobladder patients utilizing the Bladder Cancer Index, a validated and reliable health-related quality-of-life (HRQOL) questionnaire. Furthermore, we tried to identify preoperative factors that may influence functional results. All living female patients with an orthotopic neobladder (N = 82) from the University of Southern California Bladder Cancer Database were sent a questionnaire including the University of Michigan Bladder Cancer Index. Univariate analyses were performed using the Kruskal-Wallis test followed by a multivariate stepwise regression model. RESULTS: Fifty-six patients (68.3%) responded and were included in the analysis. Thirty-five (62.5%) of these patients had to catheterize their neobladder to a certain amount, while 25 patients (44.6%) depend on catheterization to empty their neobladder. Univariate analyses showed that patient age (>65 years) was the only variable associated with a statistically significant lower rate of neobladder catheterization. Better urinary bother scores were associated with organ-confined disease (p = 0.038) and education level (p = 0.01). However, these variables were not significant in a multivariate stepwise linear regression model. CONCLUSION: Considerably more women require urinary catheterization to void than previously reported. In this study, representing the largest investigated cohort in this topic, we were unable to identify any predictors of this outcome or any other urinary HRQOL in this cohort.

8 Article Outcomes of radical cystectomy with extended lymphadenectomy alone in patients with lymph node-positive bladder cancer who are unfit for or who decline adjuvant chemotherapy. 2014

Zehnder, Pascal / Studer, Urs E / Daneshmand, Siamak / Birkhäuser, Frédéric D / Skinner, Eila C / Roth, Beat / Miranda, Gus / Burkhard, Fiona C / Cai, Jie / Skinner, Donald G / Thalmann, George N / Gill, Inderbir S. ·USC Institute of Urology, Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Urology, University of Bern, Bern, Switzerland. ·BJU Int · Pubmed #24131453.

ABSTRACT: OBJECTIVE: To analyse the long-term outcomes of patients with lymph node (LN)-positive bladder cancer, who did not receive any adjuvant therapy after radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND). PATIENTS AND METHODS: We conducted a retrospective, combined cohort analysis based on two prospectively maintained cystectomy databases from the University of Southern California and the University of Bern. Eligible patients underwent RC with ePLND for cN0M0 disease but were found to have LN-positive disease. No patient had neoadjuvant therapy, and all had negative surgical margins. Kaplan-Meier plots were used to estimate recurrence-free survival (RFS) and overall survival (OS). Subgroup comparisons were performed using log-rank tests, and multivariable analysis was based on Cox proportional hazard models. RESULTS: Of 521 patients with LN-positive disease, 251 (48%) never received adjuvant therapy. Although the pathological stage distribution was similar, the 251 patients who did not receive adjuvant therapy were older and had both fewer total and positive LNs than those who underwent adjuvant therapy. The median RFS for patients treated with RC alone was 1.6 years. Recurrences mainly occurred <2 years after RC, resulting in 5- and 10-year RFS rates of 32 and 26%, respectively. Pathological T stage, the total number of LNs and the number of positive LNs detected were independent predictors of RFS and OS. CONCLUSIONS: In this study, 25% of patients with documented LN metastases who did not receive adjuvant therapy were cured with RC and ePLND; however, a few relapses may occur later than 3 years. Predictors of survival were pathological T stage, the number of total LNs and the number of positive LNs identified.

9 Article Outcome in patients with exclusive carcinoma in situ (CIS) after radical cystectomy. 2014

Zehnder, Pascal / Moltzahn, Felix / Daneshmand, Siamak / Leahy, Marya / Cai, Jie / Miranda, Gus / Bartsch, Georg / Mitra, Anirban P / Skinner, Donald G / Skinner, Eila C / Gill, Inderbir S. ·Catherine & Joseph Aresty Department of Urology, USC Institute of Urology, Los Angeles, CA, USA; Department of Urology, University of Bern, Bern, Switzerland. ·BJU Int · Pubmed #23937628.

ABSTRACT: OBJECTIVE: To evaluate oncological outcomes of patients with carcinoma in situ (CIS) exclusively at radical cystectomy (RC) and no previous history of ≥T1 disease. PATIENTS AND METHODS: Patients undergoing RC with curative intent for CIS between 1971 and 2008 at the University of Southern California were included if they met all the following criteria: (i) pathological CIS-only disease at RC, (ii) preoperative clinical stage cCIS and/or cCIS + cTa, and (iii) no previous history of lamina propria invasion (≥pT1). Kaplan-Meier plots were used to estimate the probabilities of recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of the 1964 consented patients 52 met the inclusion criteria with a median (range) follow-up of 8.5 (0.008-34) years. A median (range) of 36 (10-95) lymph nodes were identified per patient but no metastases found. Estimated 5- and 10-year RFS rates were 94% and 90%, respectively and estimated 5- and 10-year OS rates were 85% and 66%, respectively. Different mechanisms of recurrence were found in four (8%) patients after a median (range) interval of 2.4 (0.6-7.1) years. While two patients had metachronous recurrence within the urinary tract, the first of the other two had early systemic recurrence and the second late local recurrence. CONCLUSIONS: We noticed excellent outcomes after RC for CIS-only disease. However, patients may have synchronous and/or develop metachronous tumours, as well as local and/or distant/systemic recurrence that can be cured but may also lead to fatal outcomes.

10 Article A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine. 2013

Birkhahn, Marc / Mitra, Anirban P / Williams, Anthony J / Barr, Nancy J / Skinner, Eila C / Stein, John P / Skinner, Donald G / Tai, Yu-Chong / Datar, Ram H / Cote, Richard J. ·Urologie am Ring, Kaiser Wilhelm Ring 36, Cologne, Germany. ·Eur J Cancer · Pubmed #23849827.

ABSTRACT: BACKGROUND: Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells. OBJECTIVE: Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection. METHODS: A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies. RESULTS: Five samples were paucicellular by standard cytology; no samples processed by microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p<0.001). Microfilter cytology was more concordant (κ=50.4%) than standard cytology (κ=33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by microfilter cytology compared to 5.5 min by standard cytology. Median microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively. CONCLUSIONS: The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.

11 Article Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades. 2013

Zehnder, Pascal / Studer, Urs E / Skinner, Eila C / Thalmann, George N / Miranda, Gus / Roth, Beat / Cai, Jie / Birkhäuser, Frédéric D / Mitra, Anirban P / Burkhard, Fiona C / Dorin, Ryan P / Daneshmand, Siamak / Skinner, Donald G / Gill, Inderbir S. ·University of Southern California (USC) Institute of Urology, Catherine & Joseph Aresty Department of Urology, Keck School of Medicine, USC, Los Angeles, CA, USA; Department of Urology, University of Bern (UB), Bern, Switzerland. ·BJU Int · Pubmed #23795798.

ABSTRACT: OBJECTIVE: To evaluate oncological outcome trends over the last three decades in patients after radical cystectomy (RC) and extended pelvic lymph node (LN) dissection. PATIENTS AND METHODS: Retrospective analysis of the University of Southern California (USC) RC cohort of patients (1488 patients) operated with intent to cure from 1980 to 2005 for biopsy confirmed muscle-invasive urothelial bladder cancer. To focus on outcomes of unexpected (cN0M0) LN-positive patients, the USC subset was extended with unexpected LN-positive patients from the University of Berne (UB) (combined subgroup 521 patients). Patients were grouped and compared according to decade of surgery (1980-1989/1990-1999/≥2000). Survival probabilities were calculated with Kaplan-Meier plots, log-rank tests compared outcomes according to decade of surgery, followed by multivariable verification. RESULTS: The 10-year recurrence-free survival was 78-80% in patients with organ-confined, LN-negative disease, 53-60% in patients with extravesical, yet LN-negative disease and ≈30% in LN-positive patients. Although the number of patients receiving systemic chemotherapy increased, no survival improvement was noted in either the entire USC cohort, or in the combined LN-positive USC-UB cohort. In contrast, patient age at surgery increased progressively, suggesting a relative survival benefit. CONCLUSIONS: Radical surgery remains the mainstay of therapy for muscle-invasive bladder cancer. Yet, our study reveals predictable outcomes but no survival improvement in patients undergoing RC over the last three decades. Any future survival improvements are likely to result from more effective systemic treatments and/or earlier detection of the disease.

12 Article Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program. 2013

Mitra, Anirban P / Castelao, Jose E / Hawes, Debra / Tsao-Wei, Denice D / Jiang, Xuejuan / Shi, Shan-Rong / Datar, Ram H / Skinner, Eila C / Stein, John P / Groshen, Susan / Yu, Mimi C / Ross, Ronald K / Skinner, Donald G / Cortessis, Victoria K / Cote, Richard J. ·Department of Pathology, University of Southern California, Los Angeles, California, USA. ·Cancer · Pubmed #23319010.

ABSTRACT: BACKGROUND: Traditional single-marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population-based cohort. METHODS: Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking. RESULTS: Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively). CONCLUSIONS: Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone.

13 Article Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. 2011

Zehnder, Pascal / Studer, Urs E / Skinner, Eila C / Dorin, Ryan P / Cai, Jie / Roth, Beat / Miranda, Gus / Birkhäuser, Frédéric / Stein, John / Burkhard, Fiona C / Daneshmand, Sia / Thalmann, George N / Gill, Inderbir S / Skinner, Donald G. ·University of Southern California Institute of Urology, Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. pascal.zehnder@insel.ch ·J Urol · Pubmed #21849183.

ABSTRACT: PURPOSE: There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage. MATERIALS AND METHODS: Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed. RESULTS: Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%). CONCLUSIONS: Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

14 Article Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study. 2011

Dorin, Ryan P / Daneshmand, Siamak / Eisenberg, Manuel S / Chandrasoma, Shahin / Cai, Jie / Miranda, Gus / Nichols, Peter W / Skinner, Donald G / Skinner, Eila C. ·USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-9178, USA. ·Eur Urol · Pubmed #21802833.

ABSTRACT: BACKGROUND: The value of lymph node dissection (LND) in the treatment of bladder urothelial carcinoma is well established. However, standards for the quality of LND remain controversial. OBJECTIVE: We compared the distribution of lymph node (LN) metastases in a two-institution cohort of patients undergoing radical cystectomy (RC) using a uniformly applied extended LND template. DESIGN, SETTING, AND PARTICIPANTS: Patients undergoing RC at the University of Southern California (USC) Institute of Urology and at Oregon Health Sciences University (OHSU) were included if they met the following criteria: (1) no prior pelvic radiotherapy or LND; (2) lymphatic tissue submitted from all nine predesignated regions, including the paracaval and para-aortic LNs; (3) bladder primary; and (4) category M0 disease. The number and location of LN metastases were prospectively entered into corresponding databases. MEASUREMENTS: LN maps were constructed and correlated with preoperative and pathologic characteristics. Kaplan-Meier curves were constructed to estimate overall survival (OS) and recurrence free survival (RFS) among LN-positive (LN+) patients. RESULTS AND LIMITATIONS: Inclusion criteria were met by 646 patients (439 USC, 207 OHSU), and 23% had LN metastases at time of cystectomy. Although there was a difference in the median per-patient LN count between institutions, there were no significant interinstitutional differences in the incidence or distribution of positive LNs, which were found in 11% of patients with ≤pT2b and in 44% of patients with ≥pT3a tumors. Among LN+ patients, 41% had positive LNs above the common iliac bifurcation. Estimated 5-yr RFS and OS rates for LN+ patients were 45% and 33%, respectively, and did not differ significantly between institutions. CONCLUSIONS: LN metastases in regions outside the boundaries of standard LND are common. Adherence to meticulous dissection technique within an extended template is likely more important than total LN count for achieving optimal oncologic outcomes.