H Barton Grossman

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (236)1217.15 Total impact

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    ABSTRACT: To evaluate the influence of intravesical tumor location on nodal metastasis and mortality after cystectomy. The microvascular anatomy of the urinary bladder is variable in distinct regions of the bladder and thus tumor location may influence the tumors' ability to access lymphatic and vascular structures.
    Urology 08/2014; · 2.42 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
    Human Molecular Genetics 07/2014; · 7.69 Impact Factor
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    Urology 04/2014; · 2.42 Impact Factor
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    ABSTRACT: To compare the rate of parastomal hernia in patients undergoing anterior fascial fixation of the ileal conduit with that in patients without fascial fixation. Limited data exist on whether anterior fascial fixation of the ileal conduit impacts the rate of parastomal hernia. A total of 496 consecutive patients undergoing radical cystectomy and ileal conduit reconstruction from 1995 to 2012 were retrospectively evaluated for parastomal hernia. All patients had a 2-fingerbreadth aperture and the ileal conduit brought through the rectus muscle and sheath. Patients were divided into 1 of 3 groups based on stoma fixation and/or reinforcement: anterior fascial fixation, posterior reinforcement, or no fascial fixation. A parastomal hernia was defined as a palpable bulge at the stoma site. Multivariate logistic regression was conducted for the primary end point of parastomal hernia, controlling for other patient- and treatment-related factors that might affect the rate of parastomal hernia. Median follow-up was 16 months (range, 1-189 months). The parastomal hernia rate was significantly greater in the anterior fascial suture group (43 of 281; 15.3%) than the no fascial suture group (12 of 164; 7.3%; P = .02). Multivariate logistic regression analysis modeled for the occurrence of a parastomal hernia demonstrated that anterior fascial fixation was an independent predictor of the development of parastomal hernia (odds ratio, 2.3; 95% confidence interval, 1.03-5.14; P = .04). Anterior fascial fixation of the ileal conduit does not reduce the risk of parastomal hernia formation compared with the patients treated without fascial fixation. Surgeons should consider avoiding anterior suture fixation during ileal conduit creation.
    Urology 04/2014; · 2.42 Impact Factor
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    ABSTRACT: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience. Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed. In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% and 58% of the patients had at least 1 adverse event (AE), although predominantly mild to moderate. The majority was considered as not related to HAL-BLC and reported in the urinary tract. No serious adverse events (SAEs) were considered definitely related to HAL-BLC, but in 6 patients serious AEs were of an uncertain relationship. Four possibly related hypersensitivity reactions have been reported. Repeated use did not reveal additional toxicity, also supported by data from 3 European centers. This combined and detailed analysis of patients from 6 HAL-BLC studies with very comparable criteria shows that HAL-BLC is safe and poses very little additional risks other than expected for WL cystoscopy for bladder tumor resection in this specific patient population. This is supported by 9 years of postmarketing experience. Repeated use also seems safe.
    Urology 04/2014; · 2.42 Impact Factor
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    ABSTRACT: Many molecular assays for bladder cancer diagnosis and surveillance have been developed over the past several decades. However, none of these markers have been routinely implemented into clinical decision making. Beyond their potential for screening high-risk populations, urine markers likely have the greatest potential in the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). Here, we discuss the current options and limitations of the use of urine markers for patient surveillance, focusing on patients with low-/intermediate-risk NMIBC. As these patients have a very low risk of tumor progression, the primary goal of surveillance is detection of recurrent disease. Although urine cytology seems to be limited to detection of few patients who would develop high-grade tumors, we conclude that the use of markers with high sensitivity for low-grade disease for patient follow-up has the potential to decrease the frequency of urethrocystoscopy without compromising patient prognosis. Because a single marker may not have sufficient sensitivity for detection of low-grade tumors, different scenarios, e.g., multitesting and reflex or sequential approaches, are discussed. There is consensus that currently available markers have the potential to support clinical decision making in follow-up of patients with low-/intermediate-risk NMIBC. In light of our analysis, further additional randomized controlled studies to effectively assess the clinical usefulness of modern urine markers are required.
    Urologic Oncology 01/2014; · 3.65 Impact Factor
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    ABSTRACT: Objectives: To evaluate the pathologic findings and outcomes after distal ureterectomy for a retained ureteral segment following incomplete nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter. Materials and Methods: After IRB approval, an institutional database identified patients who underwent distal ureterectomy for a retained ureteral segment after assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis. Clinical and pathologic variables were analyzed. Results: From January 1993 to July 2007, 12 patients were identified with median age at the time of ureterectomy of 60.5 years (41-85 years). Initial approach to surgery was open in 9 patients and laparoscopic in 3 patients. The median time from nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66). At the time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4 patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6 patients and grade 3 in six patients. Pathology from the subsequent surgery demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients, dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local recurrence in 2 patients was present in a segment of ureter discontinuous with the bladder after laparoscopic nephroureterectomy. Three patients (25%), all with initial grade 3 renal pelvis lesions, developed metastatic disease. Conclusions: Tumor recurrence in a retained ureteral segment after incomplete nephroureterectomy is a significant problem and may contribute to intravesical recurrence or metastatic disease. Complete, en bloc resection is imperative to minimize these risks.
    International braz j urol: official journal of the Brazilian Society of Urology 12/2013; 39(6):817-22.
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    ABSTRACT: Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2,422 bladder cancer cases and 5,751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6,911 cases and 11,814 controls of European descent. TaqMan genotyping of 13 promising SNPs with P< 1x10(-5) was pursued in a follow-up set of 801 cases and 1,307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P=4.53×10(-9)) and rs907611 on 11p15.5 (P=4.11×10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P=7.13×10(-7)) and rs4510656 on 6p22.3 (P=6.98×10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
    Human Molecular Genetics 10/2013; · 7.69 Impact Factor
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    ABSTRACT: We evaluated 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. We identified patients with muscle-invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were deemed high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histologic evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease-specific, progression-free, and overall) and rate of pathological upstaging. An independent cohort of patients from a separate institution was used to confirm our findings. We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased five-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 were upstaged. Five-year disease-specific survival of low risk patients was above 80%, supporting the distinction of high 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 who are low risk can undergo upfront surgery with good expectations and avoid chemotherapy-associated toxicity.
    The Journal of urology 07/2013; · 4.02 Impact Factor
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    ABSTRACT: ● Pathologic examination of ureteral margins during radical cystectomy (RC) occasionally reveals lesions present in proximal but not in distal ureteral sections ("skip lesions"). ● We assessed the incidence and clinical significance of these lesions. ● We identified 660 patients who underwent a RC and had at least 2 permanent margins for a given ureter. ● Overall, 1173 ureters were analyzed and classified as the followings: "normal" (no tumor, reactive atypia, mild or moderate dysplasia) or "abnormal" (severe dysplasia, carcinoma in situ (CIS), or tumor). ● Transitions from "normal" distal pathology to "abnormal" on proximal section(s) determined frequency of skip lesions. ● Fisher's exact test and log-rank test were used to study correlations. ● Ureteral skip lesions were found in 4.8% patients (2.9% ureters). ● Pathology of skip lesions was CIS: 55.9%, TCC: 23.5% and severe dysplasia in 20.6%. ● Skip lesions were associated with lymphovascular invasion (34.4% vs. 13.7%, p=0.0035) and advanced pT stage (p=0.0068). ● On multivariate analysis, skip lesions correlated with lower median overall survival (OS) (inestimable vs. 8.2 years, p=0.014) in patients with pT0 or pTa disease and a trend towards lower OS (2.7 years vs. 8.8 years, p=0.066) in pTis disease. ● Concordance between frozen distal margin and permanent proximal margin varied; sensitivity was 80% in those without and 20% in those with skip lesions. ● The presence of a ureteral skip lesion may be associated with lower survival in patients with pT0, pTa or pTis urothelial carcinoma. ● Thus, while uncommon, ureteral skip lesions should be reported in pathologic findings.
    BJU International 07/2013; · 3.05 Impact Factor
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    J Wang, X Wu, A Kamat, H Barton Grossman, C P Dinney, J Lin
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    ABSTRACT: Background:Results of studies of fluid consumption and its association with bladder cancer have been inconsistent. Few studies have considered modification effects from genetic variants that may interact with the type of consumed fluids. UDP-glucuronosyltransferases (UGTs), which are membrane-bound conjugating enzymes, catalyse the transformation of hydrophobic substrates to more water-soluble glucuronides to facilitate renal or biliary excretion. Whether genetic variants in UGTs could modulate the association between fluid intake and bladder cancer has not been studied.Methods:We conducted a case-control study with 1007 patients with histopathologically confirmed bladder cancer and 1299 healthy matched controls. Fluid intake and epidemiologic data were collected via in-person interview. Multivariate unconditional logistic regression was used to estimate odds ratios (ORs) and the 95% confidence intervals (95% CI).Results:After adjustment for potential confounders, high quantity of total fluid intake (2789 vs <1696 ml per day) conferred a 41% increased risk of bladder cancer (OR=1.41; 95% CI=1.10-1.81). Specific fluids such as regular soft drinks and decaffeinated coffee were also associated with increased risks, whereas tea, wine, and liquor were associated with decreased risks. Among 83 single-nucleotide polymorphisms in the UGT gene family, 18 were significantly associated with bladder cancer risk. The most significant one was rs7571337, with the variant genotype conferring a 29% reduction in risk (OR=0.71; 95% CI=0.56-0.90).Conclusions:Total and specific fluid intakes are associated with bladder cancer risk in the study population and that genetic variants of UGT genes could modulate the effects. These results facilitate identification of high-risk individuals and have important implications in bladder cancer prevention.British Journal of Cancer advance online publication, 30 April 2013;doi:10.1038/bjc.2013.190 www.bjcancer.com.
    British Journal of Cancer 04/2013; · 5.08 Impact Factor
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    ABSTRACT: BACKGROUND: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.
    European Urology 04/2013; · 10.48 Impact Factor
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    ABSTRACT: PURPOSE: A Phase l trial of intravesical recombinant adenovirus-mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with non-muscle invasive bladder cancer (NMIBC) who recurred after Bacillus Calmette-Guerin (BCG). The primary objective was to determine the safety of rAd-IFNα/Syn3; secondary endpoints were to demonstrate effective rAd-IFNα gene expression and preliminary evidence of clinical activity at three months. PATIENTS AND METHODS: Seventeen patients with recurrent NMIBC after BCG were enrolled. A single treatment of rAd-IFNα (3x10(9) to 3x10(11) particles/mL) formulated with the excipient Syn3 was administered. Patient safety was evaluated for ≥12 weeks. Efficacy of gene transfer was determined by urine IFNα protein concentrations. Preliminary drug efficacy was determined at 3 months. RESULTS: Intravesical rAd-IFNα/Syn3 was well tolerated as no dose limiting toxicity (DLT) was encountered. Urgency was the most common adverse event and all were grade 1 or 2. rAd-IFNα DNA was not detected in the blood, however, transient low serum IFNα and Syn3 levels were measured. High and prolonged dose-related urine IFNα levels were achieved with the initial treatment. Of the 14 patients treated at doses ≥ 10(10) particles/mL with detectable urine IFNα, 6 (43%) experienced a complete response at 3 months and 2 remained disease free at 29.0 and 39.2 months respectively. CONCLUSION: Intravesical rAd-IFNα/Syn3 was well tolerated with no DLT encountered. Dose dependent urinary IFNα concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNα/Syn3 demonstrated clinical activity in NMIBC recurring after BCG.
    The Journal of urology 03/2013; · 4.02 Impact Factor
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    ABSTRACT: CONTEXT: Bladder cancer (BCa) is the fourth most common cancer in men. Survival from the disease has not improved in the last 25 yr. Population-based screening theoretically provides the best opportunity to improve the outcomes of aggressive BCa. OBJECTIVE: To review the current literature regarding the usefulness and feasibility of screening for bladder cancer. EVIDENCE ACQUISITION: We conducted a nonsystematic review restricted to English using the keywords urinary bladder neoplasms, mass screening, mandatory testing, and early detection of cancer. We retrieved 184 articles and selected 22. EVIDENCE SYNTHESIS: There was no level 1 evidence (obtained from a randomised controlled trial [RCT]) addressing the impact of screening on BCa survival or tumour downstaging. No study assessed the diagnostic performance of urinary markers in the context of screening. Two case-control series suggested a benefit of screening on survival, and a third found a nonsignificant beneficial trend in favour of screening. Two studies suggested downstaging of BCa at diagnosis. Other reports concluded that most cancers detected with screening were of low grade and that current urinary testing cannot detect all tumours. Screening is likely to be of benefit in high-risk populations using cost-efficient high-performing urinary biomarkers. There was insufficient evidence to define an efficient screening protocol. CONCLUSIONS: Although BCa screening is theoretically feasible in a high-risk population, there is currently insufficient evidence to recommend it. This is due to insufficient data to define an efficient screening protocol with selection of an appropriate population and the lack of accurate and cost-effective urinary markers able to discriminate low-risk from high-risk cancers. Major improvements are needed in the evaluation of urinary biomarkers before evaluation in a RCT can be achieved.
    European Urology 01/2013; · 10.48 Impact Factor
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    ABSTRACT: At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of 'suboptimal' chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multimodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection.
    Urologic Oncology 11/2012; 30(6):772-780. · 3.65 Impact Factor
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    ABSTRACT: BACKGROUND: Neoadjuvant chemotherapy improves the survival of patients with high-risk urothelial cancer. However, the lack of curative alternatives to cisplatin-based chemotherapy is limiting for patients with neuropathy or hearing loss. Sequential chemotherapy also has not been well studied in the neoadjuvant setting. The authors explored sequential neoadjuvant ifosfamide-based chemotherapy in a patient cohort at high risk of noncurative cystectomy. METHODS: Patients with muscle-invasive cancer and lymphovascular invasion, hydronephrosis, clinical T3b and T4a (cT3b-4a) disease (defined as a 3-dimensional mass on examination under anesthetic or invasion into local organs), micropapillary tumors, or upper tract disease received 3 cycles of combined ifosfamide, doxorubicin, and gemcitabine followed by 4 cycles of combined cisplatin, gemcitabine, and ifosfamide. The primary endpoint was downstaging to pT1N0M0 disease or lower. RESULTS: At a median follow-up of 85.3 months, the 5-year overall survival (OS) and disease-specific survival (DSS) rates for all 65 patients were 63% and 68%, respectively (95% confidence interval: 5-year OS rate, 0.52%-0.76%; 5-year DSS rate, 0.58%-0.81%). Pathologic downstaging to pT1N0 disease or lower occurred in 50% of patients who underwent cystectomy and in 60% of patients who underwent nephroureterectomy and was correlated with the 5-year OS rate (pT1N0 disease or lower, 87%; pT2-pT3aN0 disease, 67%; and pT3b disease or higher or lymph node-negative disease, 27%; P ≤ .001 for pT1 or lower vs pT2 or higher). Variant histology was associated with an inferior 5-year DSS rate (50% vs 83% in pure transitional cell carcinoma; P = .02). The most frequent grade 3 toxicities were infection (38%), febrile neutropenia (22%), and mucositis (18%). There were 3 grade 4 toxicities (myocardial infarction, thrombocytopenia, and vomiting) and 1 grade 5 toxicity in a patient who refused antibiotics for pneumonia. CONCLUSIONS: Sequential therapy was active and maintained the historic expectation of achieving a cure. The current results strongly reinforced previous experience suggesting that pathologic downstaging to pT1N0 disease or less is a useful surrogate for eventual cure in patients with urothelial cancer. Cancer 2012. © 2012 American Cancer Society.
    Cancer 08/2012; · 5.20 Impact Factor
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    ABSTRACT: CONTEXT: Urothelial bladder cancer (UBC) is a disease of significant morbidity and mortality. It is important to understand the risk factors of this disease. OBJECTIVE: To describe the incidence, prevalence, and mortality of UBC and to review and interpret the current evidence on and impact of the related risk factors. EVIDENCE ACQUISITION: A literature search in English was performed using PubMed. Relevant papers on the epidemiology of UBC were selected. EVIDENCE SYNTHESIS: UBC is the 7th most common cancer worldwide in men and the 17th most common cancer worldwide in women. Approximately 75% of newly diagnosed UBCs are noninvasive. Each year, approximately 110 500 men and 70 000 women are diagnosed with new cases and 38 200 patients in the European Union and 17 000 US patients die from UBC. Smoking is the most common risk factor and accounts for approximately half of all UBCs. Occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons are other important risk factors. The impact of diet and environmental pollution is less evident. Increasing evidence suggests a significant influence of genetic predisposition on incidence. CONCLUSIONS: UBC is a frequently occurring malignancy with a significant impact on public health and will remain so because of the high prevalence of smoking. The importance of primary prevention must be stressed, and smoking cessation programs need to be encouraged and supported.
    European Urology 07/2012; · 10.48 Impact Factor
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    ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Patients with positive lymph nodes at radical cystectomy have a poor prognosis. The actual outcome of patients varies based on many factors, among which lymph node density has emerged as being more informative than nodal status of TNM staging. We combined clinical data from two major cancer centres in the USA and identified patients with an adequate lymphadenectomy and no perioperative chemotherapy to understand the natural history of the disease. Using this information, we created prognostic tools incorporating lymph node density that can be used for risk stratification, patient counselling and clinical trial design. 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.
    BJU International 07/2012; · 3.05 Impact Factor
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    ABSTRACT: We assessed the impact of hexaminolevulinate fluorescence cystoscopic detection of papillary, nonmuscle invasive bladder cancer on the long-term recurrence rate. Long-term followup was assessed in 551 participants enrolled in a prospective, randomized study of fluorescence cystoscopy for Ta or T1 urothelial bladder cancer. In the original study 280 patients in the white light cystoscopy group and 271 in the fluorescence cystoscopy group were followed with cystoscopy for 3, 6 and 9 months after initial resection or until recurrence. A study extension protocol was done for long-term followup of these patients. Followup information was obtained for 261 of the 280 patients (93%) in the white light group and 255 of the 271 (94%) in the fluorescence group. Median followup in the white light and fluorescence groups was 53.0 and 55.1 months, and 83 (31.8%) and 97 patients (38%) remained tumor free, respectively. Median time to recurrence was 9.4 months in the white light group and 16.4 months in the fluorescence group (p = 0.04). The intravesical therapy rate was similar in the 2 groups (46% and 45%, respectively). Cystectomy was done in 22 of 280 cases (7.9%) in the white light group and in 13 of the 271 (4.8%) in the fluorescence group (p = 0.16). Hexaminolevulinate fluorescence cystoscopy significantly improves long-term bladder cancer time to recurrence with a trend toward improved bladder preservation.
    The Journal of urology 05/2012; 188(1):58-62. · 4.02 Impact Factor
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    ABSTRACT: BACKGROUND: Small cell urothelial carcinoma (SCUC) is a rare, aggressive malignancy with a propensity for early microscopic metastases. Data suggest that neoadjuvant chemotherapy may lead to improved survival compared with initial surgery. OBJECTIVE: To determine the influence of neoadjuvant chemotherapy on survival of SCUC patients in a large single-institution cohort. DESIGN, SETTING, AND PARTICIPANTS: Between 1985 and 2010, 172 patients were treated for SCUC at MD Anderson Cancer Center (MDACC). Clinical, pathologic, and surgical data were collected and analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the effects of neoadjuvant chemotherapy on survival. RESULTS AND LIMITATIONS: Of 125 patients with resectable disease (≤cT4aN0M0), 95 were surgical candidates. Forty-eight received neoadjuvant chemotherapy, and 47 underwent initial surgery. Neoadjuvant treatment was associated with improved OS and DSS compared with initial cystectomy (median OS: 159.5 mo vs 18.3 mo, p<0.001; 5-yr DSS: 79% vs 20%, p<0.001). Neoadjuvant chemotherapy resulted in pathologic downstaging to ≤pT1N0 in 62% of tumors compared with only 9% treated with initial surgery (odds ratio: 44.55; 95% confidence interval, 10.39-191). Eight patients with clinically node-positive disease had surgical consolidation with cystectomy and extended lymph node dissection after clinical complete response to chemotherapy. Median OS and DSS in this group of patients were 23.3 mo and 21.8 mo, respectively, with 5-yr OS and DSS of 38%. CONCLUSIONS: Neoadjuvant chemotherapy is associated with a high rate of pathologic downstaging and correlates with significantly higher survival compared with historical expectations. Although limited by a small sample size and retrospective analysis, in the context of a rare disease, this experience suggests neoadjuvant chemotherapy as a standard approach in treating SCUC.
    European Urology 04/2012; · 10.48 Impact Factor

Publication Stats

6k Citations
1,217.15 Total Impact Points


  • 1997–2014
    • University of Texas MD Anderson Cancer Center
      • • Department of Urology
      • • Department of Pathology
      • • Department of Epidemiology
      Houston, Texas, United States
  • 2013
    • National Institutes of Health
      • Branch of Urologic Oncology
      Bethesda, MD, United States
    • Centre Hospitalier Universitaire de Reims
      Rheims, Champagne-Ardenne, France
  • 2011–2012
    • National Cancer Institute (USA)
      • • Medical Oncology Branch and Affiliates
      • • Division of Cancer Epidemiology and Genetics
      Maryland, United States
    • National University Health System
  • 2004–2012
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 2010
    • Universitätsklinikum Tübingen
      • Department of Urology
      Tübingen, Baden-Württemberg, Germany
    • University of Texas Southwestern Medical Center
      • Department of Urology
      Dallas, TX, United States
  • 1996–2010
    • University of Michigan
      • • Department of Urology
      • • Department of Surgery
      Ann Arbor, MI, United States
  • 2009
    • Baylor College of Medicine
      • Department of Medicine
      Houston, TX, United States
  • 2008
    • Texas Southern University
      • Department of Pharmaceutical Sciences
      Houston, TX, United States
    • Karolinska University Hospital
      • Department of Oncology
      Stockholm, Stockholm, Sweden
  • 2007–2008
    • McGill University
      • Division of Urology
      Montréal, Quebec, Canada
    • Centre Hospitalier Universitaire de Québec (CHUQ)
      Québec, Quebec, Canada
  • 2006
    • University of Miami
      • Department of Urology
      Coral Gables, FL, United States
  • 2005–2006
    • The University of Arizona
      • Department of Obstetrics and Gynecology
      Tucson, AZ, United States
  • 2001
    • Wayne State University
      Detroit, Michigan, United States
  • 1996–2000
    • University of California, Davis
      Davis, California, United States
  • 1983
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States