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Mark Schoenberg

Publications and source records attributed to Mark Schoenberg.

11 recordsLinked to original sources
PubMed2006

Nomograms provide improved accuracy for predicting survival after radical cystectomy.

AIMS: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer-specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. METHODS: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. RESULTS: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.663). CONCLUSIONS: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.

Adult↗
PubMed2006

Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection.

BACKGROUND: The noninvasive identification of bladder tumors may improve disease control and prevent disease progression. Aberrant promoter methylation (i.e., hypermethylation) is a major mechanism for silencing tumor suppressor genes and other cancer-associated genes in many human cancers, including bladder cancer. METHODS: A quantitative fluorogenic real-time polymerase chain reaction (PCR) assay was used to examine primary tumor DNA and urine sediment DNA from 15 patients with bladder cancer and 25 control subjects for promoter hypermethylation of nine genes (APC, ARF, CDH1, GSTP1, MGMT, CDKN2A, RARbeta2, RASSF1A, and TIMP3) to identify potential biomarkers for bladder cancer. We then used these markers to examine urine sediment DNA samples from an additional 160 patients with bladder cancers of various stages and grades and from an additional 69 age-matched control subjects. Data were analyzed on the basis of a prediction model and were internally validated using a jacknife procedure. All statistical tests were two-sided. RESULTS: For all 15 patients with paired DNA samples, the promoter methylation pattern in urine matched that in the primary tumors. Four genes displayed 100% specificity. Of the 175 bladder cancer patients, 121 (69%, 95% confidence interval [CI] = 62% to 76%) displayed promoter methylation in at least one of these genes (CDKN2A, ARF, MGMT, and GSTP1), whereas all control subjects were negative for such methylation (100% specificity, 95% CI = 96% to 100%). A logistic prediction model using the methylation levels of all remaining five genes was developed and internally validated for subjects who were negative on the four-gene panel. This combined, two-stage predictor produced an internally validated ROC curve with an overall sensitivity of 82% (95% CI = 75 % to 87%) and specificity of 96% (95% CI = 90% to 99%). CONCLUSION: Testing a small panel of genes with the quantitative methylation-specific PCR assay in urine sediment DNA is a powerful noninvasive approach for the detection of bladder cancer. Larger independent confirmatory cohorts with longitudinal follow-up will be required in future studies to define the impact of this technology on early detection, prognosis, and disease monitoring before clinical application.

Aged↗
PubMed2006

Precystectomy nomogram for prediction of advanced bladder cancer stage.

OBJECTIVE: To evaluate precystectomy prediction of pT and pN stages at cystectomy. METHODS: Multivariate logistic regression analyses modelled variables of 726 evaluable patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. The first set of models predicted pT(3-4) stage at cystectomy, and the second set predicted pN(1-3) stages at cystectomy. Transurethral resection (TUR) predictors consisted of 2002 T stage, 1973 WHO tumour grade, presence of carcinoma in situ, age, gender, and delivery of neo-adjuvant chemotherapy. The area under the ROC curve quantified nomogram accuracy. Two hundred bootstrap resamples were used to reduce overfit bias. RESULTS: At TUR, 11% of patients were staged as pT(3-4) versus 42% at cystectomy. Lymph node metastases were found in 24% of patients at cystectomy (pN(1-3)). The multivariate pT(3-4) nomogram was 75.7% accurate versus 71.4% for TUR T stage. The multivariate pN(1-3) nomogram was 63.1% accurate versus 61.0% for TUR T stage. CONCLUSION: Multivariate nomograms are not perfect, but they do predict more accurately than TUR T stage alone.

Adult↗
PubMed2006

Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder.

PURPOSE: American Joint Committee on Cancer staging represents the gold standard for prediction of recurrence after radical cystectomy in patients with invasive bladder cancer. We tested the hypothesis that American Joint Committee on Cancer stage based predictions may be improved when pathological tumor and node stage information is combined with additional clinical and pathological variables within a prognostic nomogram. MATERIALS AND METHODS: We used Cox proportional hazards regression analysis to model variables of 728 patients with transitional cell carcinoma of the bladder treated with radical cystectomy and bilateral pelvic lymphadenectomy at 1 of 3 participating institutions. Standard predictors, pT and pN, were complemented by age, gender, tumor grade at cystectomy, presence of lymphovascular invasion, presence of carcinoma in situ in the cystectomy specimen, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy. The concordance index was used to quantify the accuracy of regression coefficient based nomograms. A total of 200 bootstrap resamples were used to reduce overfit bias and for internal validation. Calibration plots were used to graphically explore the performance characteristics of the multivariate nomogram. RESULTS: Followup ranged from 0.1 to 183.4 months (median 24.9, mean 36.4). Recurrence was recorded in 249 (34.2%) patients with a median time to recurrence of 108 months (range 0.8 to 131.9). Actuarial recurrence-free probabilities were 69.6% (95% CI 65.8%-73.0%), 60.2% (55.8%-64.3%) and 52.9% (47.3%-58.1%) at 2, 5 and 8 years after cystectomy, respectively. Two-hundred bootstrap corrected predictive accuracy of American Joint Committee on Cancer stage based predictions was 0.748. Accuracy increased by 3.2% (0.780) when age, lymphovascular invasion, carcinoma in situ, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiotherapy were added to pathological stage information and used within a nomogram. CONCLUSIONS: A nomogram predicting bladder cancer recurrence after cystectomy is 3.2% more accurate than American Joint Committee on Cancer stage based predictions. Moreover, a nomogram approach combines several advantages such as easy and precise estimation of individual recurrence probability at key points after cystectomy, which all patients deserve to know and all treating physicians need to know.

Adult↗
PubMed2006

Primary squamous cell carcinoma in unreconstructed exstrophic bladder.

Bladder exstrophy is associated with an increased incidence of primary adenocarcinoma of the bladder. We report a rare case of squamous cell carcinoma occurring in the unreconstructed, exstrophic bladder of a 53-year-old woman treated with radical cystectomy and radiochemotherapy. This case represents the oldest patient to present with squamous cell carcinoma of an unreconstructed exstrophic bladder. We discuss the potential mechanisms of carcinogenesis in this patient, noting how they may potentially differ from those in a patient with a reconstructed bladder.

Bladder Exstrophy↗
PubMed2005

Dynamic MRI of bladder cancer: evaluation of staging accuracy.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of gadoliniumenhanced MRI in staging bladder cancer in a series of patients with surgically proven bladder cancer. MATERIALS AND METHODS: Seventy-one patients with biopsy-proven bladder cancer underwent MRI on a 1.5-T scanner with a phased-array pelvic coil. Conventional T1-weighted spin-echo, T2-weighted spin-echo, and unenhanced and enhanced (0.1 mmol/kg gadolinium) fast spoiled gradient-echo images with fat suppression were obtained. Two blinded reviewers evaluated the MR images and assigned a stage that was compared with the pathologic stage (n = 67) or with clinical follow-up for at least 2 years after MRI (n = 4). RESULTS: Agreement among the reviewers was good in assigning a radiologic stage for bladder cancer (kappa = 0.80). On a stage-by-stage basis, MRI accuracy was 62%, and overstaging was the most common error (32%). Staging accuracy improved to 85% and 82% in differentiating superficial from invasive tumors and organ-confined from non-organ-confined tumors, respectively. The time interval between MRI and transurethral resection (</= 60 days and >/=61 days) was not a statistically significant factor in differentiating superficial from invasive and organ-confined from non-organ-confined tumors (p > 0.05). MRI accuracy in staging transitional cell carcinoma was not significantly different from that obtained in staging non-transitional cell carcinoma (p > 0.05). CONCLUSION: MRI shows good reproducibility between reviewers for staging bladder cancer. Although overall staging accuracy was only moderate, the accuracy for differentiating superficial versus invasive disease and organ-confined versus non-organ-confined disease was high.

Adult↗
PubMed2004

Assessment of perioperative psychological distress in patients undergoing radical cystectomy for bladder cancer.

PURPOSE: Despite a recent growth in our understanding of the impact of psychosocial factors on the outcome of patients with cancer there is still relatively little known about the effect of these issues on patients with genitourinary malignancies. We determined the prevalence of psychological distress in patients with bladder cancer prior to and following radical cystectomy. MATERIALS AND METHODS: A total of 74 consecutive patients with clinically organ confined bladder cancer were prospectively surveyed preoperatively using the Basic Symptom Inventory-18, a validated instrument that measures the psychological domains of general distress, anxiety, depression and somatization. Of the initial 74 patients 62 were available for postoperative assessment 1 month following cystectomy. Preoperative and postoperative distress scores were evaluated with respect to age, sex, marital status, type of surgical reconstruction and tumor stage. RESULTS: The preoperative prevalence of psychological distress in patients diagnosed with bladder cancer was 45% and it remained somewhat increased at 34% approximately 4 weeks after cystectomy. Demographic factors such as gender, age, and marital status were not significantly associated with the overall prevalence of distress. In the entire study group there was a statistically significant decrease in general distress (p = 0.028), depression (p = 0.034) and anxiety (p = 0.0004) from the preoperative to the postoperative assessments. Pathological stage was significantly associated with post-cystectomy anxiety (p = 0.040) and general distress (p = 0.042). CONCLUSIONS: Our findings indicate that a large proportion of patients with bladder cancer undergoing radical cystectomy experience psychological distress during the perioperative period. The identification of psychological distress in this population has the potential to influence health related quality of life as well as recovery in all individuals with bladder cancer.

Adult↗
PubMed2003

High-throughput molecular analysis of urine sediment for the detection of bladder cancer by high-density single-nucleotide polymorphism array.

The detection of urothelial malignancies remains challenging. The majority of patients diagnosed with bladder cancer require life-long surveillance for disease recurrence. Monitoring strategies rely predominantly on invasive endoscopic techniques, which are inconvenient and uncomfortable. Multiple in vitro diagnostic technologies have been developed to supplant the contemporary standard of care. The U.S. Food and Drug Administration has approved several assays, but [because of inferior performance characteristics (low sensitivity and specificity)] these tests have not made a significant impact on practice, to date. We sought to develop a test for bladder cancer with better performance characterization detection based on a novel molecular approach. Matched urine and peripheral blood lymphocyte samples were obtained before surgery from 31 patients with bladder cancer (10 pTa, 4 pT1, and 17 pT2>or). DNA from these samples was subjected to allelic imbalance analysis using HuSNP chips and was validated in parallel with microsatellite analysis for loss of heterozygosity and microsatellite instability. Peripheral blood lymphocyte and urine DNA obtained from 14 individuals without clinical evidence of genitourinary malignancy served as controls. Thirty-one of 31 (100%) urine DNA samples from patients with bladder tumors were found to have 24 or more single-nucleotide polymorphism (SNP) DNA alterations. In general, SNP alterations were more common in urine samples from pT2>or tumors than pTa or pT1 tumors. SNP alterations were not identified in nine normal control subjects and in four of five patients with hematuria. These data support the noninvasive HuSNP chip assay in urine DNA as a valuable tool for the detection of bladder cancer (on a high-throughput-automated platform).

Adult↗
PubMed2003

Genome-wide genetic characterization of bladder cancer: a comparison of high-density single-nucleotide polymorphism arrays and PCR-based microsatellite analysis.

Most human cancers are characterized by genomic instability, the accumulation of multiple genetic alterations, and allelic imbalance throughout the genome. Loss of heterozygosity (LOH) is a common form of allelic imbalance, and the detection of LOH has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. Global patterns of LOH can be discerned by allelotyping of tumors with polymorphic genetic markers. Microsatellites are reliable genetic markers for studying LOH, but typically only a modest number of microsatellites are tested in LOH studies because the genotyping procedure can be laborious. Here we describe the use of a new alternative approach to comprehensive allelotyping in which samples are genotyped for nearly 1500 single-nucleotide polymorphism (SNP) loci distributed across all human autosomal arms. We examined the pattern of allelic imbalance in human transitional cell carcinomas of the urinary bladder including 36 primary tumors and 1 recurrent tumor with matched normal DNAs. The call rate for all SNPs was 78.5 +/- 1.87% overall samples. Overall, the median number of allelic imbalance was 47.5, ranging from 20 to 118. The mean number of allelic imbalances was 36.58, 51.30, and 67.78 for pT(a), pT(1), and > or =pT(2), respectively, and also increased by grade. The SNP microarray analysis result was validated by comparison with microsatellite allelotype analysis of 118 markers in the same tumors. Overall, the two methods produced consistent loss patterns at informative loci. The SNP assay discovered previously undiscovered allelic imbalances at chromosomal arms 12q, 16p, 1p, and 2q. The detection of LOH and other chromosomal changes using large numbers of SNP markers should enable rapid and accurate identification of allelic imbalance patterns that will facilitate the mapping and identification of important cancer genes. Moreover, SNP analysis raises the possibility of individual tumor genome-wide allelotyping with potential prognostic and diagnostic applications.

Carcinoma, Transitional Cell↗