Can digital rectal examination or transrectal ultrasonography biopsy findings predict the side of nodal metastasis in prostate cancer?

PURPOSE: To assess the use of several preoperative parameters in predicting the side of pelvic lymph node metastasis in patients with prostate cancer. MATERIALS AND METHODS: A retrospective chart review (January 1982 to February 2004) identified 106 men with pathology proven lymph node positive prostate cancer for whom complete medical records were available. RESULTS: The median serum prostate-specific antigen at diagnosis was 11 ng/ml with the clinical stage T1C in 9 patients, T2 in 68, and T3 in 29. The Gleason score on transrectal ultrasonography (TRUS) biopsy was < or =6 in 13, 7 in 41, and > or =8 in 52. A total of 93 patients had documented pretreatment digital rectal examination (DRE) findings: 54 had a unilaterally suspicious DRE, and 31 had a bilaterally suspicious DRE. Of patients with a unilaterally positive DRE, 30 had ipsilateral lymph node metastasis, 16 contralateral, and 8 bilateral. DRE showed a 71% sensitivity and 29% false-negative rate in predicting the side of nodal metastasis. A total of 98 patients had documented TRUS biopsy findings: 37 had unilaterally positive TRUS biopsies and 61 bilaterally positive biopsies. Of patients with unilaterally positive TRUS biopsies, 20 had ipsilateral lymph node metastasis, 11 contralateral, and 6 bilateral. TRUS biopsies showed an 86% sensitivity and 14% false-negative rate in predicting the side of nodal metastasis. CONCLUSIONS: DRE and TRUS biopsies do not accurately predict the side of pelvic lymph node metastasis and should not determine the extent of the pelvic lymphadenectomy.

Review of the M.D. Anderson experience in the treatment of bladder sarcoma.

OBJECTIVE: To assess the histologic subtypes, clinical presentations, treatment approaches, and treatment-related outcomes of patients with bladder sarcoma. METHODS: Between January 1985 and July 2004, 19 patients (12 men and 7 women) with primary bladder sarcoma were evaluated at the University of Texas M.D. Anderson Cancer Center. Median follow-up duration was 72 months (range 3-141). RESULTS: The median age of patients at presentation was 57 years (range 22-94). The histologic subtypes of bladder sarcoma were leiomyosarcoma (N = 14), angiosarcoma (N = 3), and unclassified sarcoma (N = 2). The clinical presentation consisted of gross, painless hematuria in 79% of patients, lower urinary tract symptoms in 16%, and microhematuria in 5%. The primary treatment modalities used were surgery in 16 (84%) patients, chemotherapy in 2 (11%), and palliation in 1 (5%). The rate of local and distal recurrence was 16% and 53%, respectively. The most common sites of distant metastases were the lungs, bone, brain, and liver. The 5-year disease-specific survival rate was 59%, with a median survival duration of 6 years. There was no statistically significant difference in disease-specific survival between patients with bladder leiomyosarcoma compared to other sarcoma subtypes (P = 0.149). Lymphovascular invasion (P = 0.03) and lymphatic metastasis (P = 0.03) were associated with disease-specific survival, and surgical margin status was associated with recurrence-free (P = 0.04), disease-specific (P = 0.03), and overall survival (P = 0.005). CONCLUSIONS: Bladder sarcoma is a highly aggressive malignancy, regardless of its histologic subtype. Surgical margin status is an important determinant of survival.

Biomarkers for detection and surveillance of bladder cancer.

INTRODUCTION: Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women in Canada. Early detection of tumours is essential for improved prognosis and long-term survival. The standard method for detection and surveillance is cystoscopy together with urine cytology. Cystoscopy is relatively sensitive but is expensive and invasive. Urinary cytology is a noninvasive method that has poor sensitivity but high specificity; it is relied on for the detection of carcinoma in situ. Currently, several urinary-based bladder tumour biomarkers with USFDA/Health Canada approval are available commercially, but none have been widely adopted by urologists despite their offering high sensitivity and/or specificity. We present here a review of recent studies evaluating 7 commercial biomarker assays for the detection and/or surveillance of bladder cancer. RESULTS: SENSITIVITY AND SPECIFICITY RANGES, RESPECTIVELY, FOR EACH MARKER WERE REPORTED AS FOLLOWS: BTA Stat (Polymedco), 52.5%-78.0% and 69.0%-87.1%; BTA Trak (Polymedco), 51%-100% and 73%-92.5%; cytology, 12.1%-84.6% and 78.0%-100%; hematuria dipstick, 47.0%-92.6% and 51.0%-84.0%; NMP22 Bladder Cancer Test (Matritech), 34.6%-100% and 60.0%-95.0%; NMP22 BladderChek (Matritech), 49.5%-65.0% and 40.0%-89.8%; ImmunoCyt/uCyt+ (DiagnoCure), 63.3%-84.9% and 62.0%-78.1%; ImmunoCyt/uCyt+ and cytology, 81.0%-89.3% and 61.0%-77.7%; and UroVysion (Abbott Molecular)/florescence in situ hybridization, 68.6%-100% and 65.0%-96.0%. CONCLUSION: We find that no currently available bladder cancer urinary marker is sensitive enough to eliminate the need for cystoscopy. In addition, cytology remains integral to the detection of occult cancer. However, owing to their relatively high sensitivities, these markers may be used to extend the period between cystoscopies in the surveillance of patients with transitional cell carcinoma. Further study is required to determine which markers, alone or in panel, would best accomplish this.

Contemporary management of muscle-invasive bladder cancer.

Over the past decade, there have been a number of substantial changes in the treatment of invasive bladder cancer. Muscle-invasive bladder cancer is an aggressive disease that often presents at an advanced stage with or without distant metastases. The potential for cure is highest when the disease is confined to the bladder. Optimal management depends on our understanding of disease biology, refinements to our clinical staging, and improvements in the quality of treatment. This review will focus on the contemporary management of muscle-invasive urothelial carcinoma of the bladder and will discuss the role of radical cystectomy, extended lymphadenectomy, neoadjuvant/ adjuvant chemotherapy, and various forms of bladder-preservation strategies.

Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection.

BACKGROUND: Chromosome missegregation and the resulting aneuploidy is a common change in neoplasia. The Aurora kinase A (AURKA) gene, which encodes a key regulator of mitosis, is frequently amplified and/or overexpressed in cancer cells, and the level of AURKA amplification is associated with the level of aneuploidy. We examined whether AURKA gene amplification is a biomarker for the detection of bladder cancer. METHODS: The effect of ectopic expression of Aurora kinase A (AURKA) using an adenoviral vector in simian virus 40-immortalized urothelial cells (SV-HUC) on centrosome multiplication and chromosome copy number was measured in vitro by immunofluorescence and fluorescence in situ hybridization (FISH), respectively. The FISH test was also used to examine AURKA gene copy number in exfoliated cells in voided urine samples from 23 patients with bladder cancer and 7 healthy control subjects (training set), generating a model for bladder cancer detection that was subsequently validated in an independent set of voided urine samples from 100 bladder cancer patients and 148 control subjects (92 healthy individuals and 56 patients with benign urologic disorders). An AURKA gene score (the proportion of cells with three or more AURKA signals) was used to produce receiver operating characteristic (ROC) curves and to calculate the specificity and sensitivity of the AURKA FISH test. Differences between mean AURKA scores in different pathogenetic groups of bladder cancer stratified according to histological grade and stage were tested by unpaired Mann-Whitney t tests or one-way Wilcoxon tests. All statistical tests were two-sided. RESULTS: Forced overexpression of AURKA in urothelial cells induced amplification of centrosomes, chromosome missegregation, and aneuploidy, and natural overexpression was detectable in in situ lesions from patients with bladder cancer. The FISH test for the AURKA gene copy number performed on the validation set yielded a specificity of 96.6% (95% confidence interval [CI] = 92.3% to 98.5%) and sensitivity of 87% (95% CI = 79.0% to 92.2%) and an area under the ROC curve of 0.939 (95% CI = 0.906 to 0.971; P < .001). CONCLUSION: Overexpression of AURKA can cause aneuploidy in urothelial cells, and the AURKA gene copy number is a promising biomarker for detection of bladder cancer.

Evaluation of the intact specimen after laparoscopic radical nephrectomy for clinically localized renal cell carcinoma identifies a subset of patients at increased risk for recurrence.

PURPOSE: Laparoscopic radical nephrectomy (LRN) is emerging as a standard approach for low stage renal cell carcinoma (RCC). Some suggest that specimen morcellation for extraction results in less morbidity and a faster recovery. However, morcellation may preclude accurate pathological staging and may hinder precise pathological grading. With pathological evaluation of an intact specimen we identified patients harboring high risk disease that was not anticipated preoperatively, defined as pT2 high grade (G3-4) or lesions greater than pT2. MATERIALS AND METHODS: We retrospectively reviewed the records of 192 patients who underwent LRN for renal lesions at The University of Texas M. D. Anderson Cancer Center between April 2002 and April 2004. RESULTS: A total of 192 patients underwent LRN for presumed RCC. In all cases specimens were removed intact. Of these cases 137 were cT1/T2 N0 M0 and had a final pathological diagnosis of RCC. All surgical margins were negative. Of the 137 patients 40 (29.2%) were at increased risk for recurrence based on high risk features. Specifically up staging from cT1-2 to pT3 disease occurred in 30 patients (21.9%) while 12 patients (8.8%) were found to have pT2 G3-4 disease. All 40 patients with high risk disease underwent more intensive surveillance and 17 (43%) participated in adjuvant systemic therapy trials. CONCLUSIONS: In our study 21.9% of patients with clinical T1-2 disease were pathologically up staged and 29.2% were identified as being at high risk for recurrence after intact specimen extraction for localized RCC. These patients are candidates for more intensive followup treatment and may benefit from enrollment in adjuvant therapy protocols.

Laparoscopic radical nephroureterectomy: dilemma of the distal ureter.

PURPOSE OF REVIEW: Laparoscopic nephroureterectomy has recently emerged as a safe, minimally invasive approach to upper tract urothelial cancers. The most controversial and challenging feature of laparoscopic nephroureterectomy is the management of the distal ureter. We review the most common methods of managing the distal ureter, with emphasis on contemporary oncologic outcomes, indications, advantages, and disadvantages. RECENT FINDINGS: There are currently in excess of five different approaches to the lower ureter. These techniques often combine features of endoscopic, laparoscopic, or open management. They include open excision, a transvesical laparoscopic detachment and ligation technique, laparoscopic stapling of the distal ureter and bladder cuff, the "pluck" technique, and ureteral intussusception. Each technique has distinct advantages and disadvantages, differing not only in technical approach, but oncological principles as well. While the existing published data do not overwhelmingly support one approach over the others, the open approach remains one of the most reliable and oncologically sound procedures. SUMMARY: The principles of surgical oncology dictate that a complete, en-bloc resection, with avoidance of tumor seeding, remains the preferred treatment of all urothelial cancers. The classical open technique of securing the distal ureter and bladder cuff achieves this principle and has withstood the test of time. Transvesical laparoscopic detachment and ligation is an oncologically valid approach in patients without bladder tumors, but is limited by technical considerations. The laparoscopic stapling technique maintains a closed system but risks leaving behind ureteral and bladder cuff segments. Both transurethral resection of the ureteral orifice (pluck) and intussusception techniques should be approached with caution, as the potential for tumor seeding exists. Additional long-term comparative outcomes are needed to solve the dilemma of the distal ureter.

Normal variation and influence of stress, caffeine intake, and sexual activity on uroflowmetry parameters of a middle-aged asymptomatic cohort of volunteer male urologists.

AIMS: To assess normal variations of uroflowmetry in middle-aged asymptomatic male urologists and to analyse the influence of stress, caffeine intake, and sexual activity. METHODS: Thirty-one male urologists from Quebec and Ontario were recruited for this study. All were healthy, not taking any current medications known to interfere with lower urinary tract function, and symptom-free (International Prostate Symptom Score less than 5). Each received two identical flowmeters to keep over a period of 2 weeks, one at home and one in his busiest office. Ten uroflow tracings, with a volume greater than 150 mL, were requested from each of them; five at home and five in the office. A total of 310 flows were analysed. The subjective level of stress, coffee intake, and sexual activity, in the hour before each uroflowmetrogram, was recorded, through a short self-administered questionnaire and stress visual scale. RESULTS: are presented as an average per individual. The voided volume was 331.9 mL, with an SD of 94.8 mL. The voiding time was 32.7 seconds (SD=15.5). The peak flow rate was 20.5 mL/sec (SD=3.9), the mean flow rate was 14.3 mL/sec (SD=3.0), and the time to maximum flow was 7.2 sec (SD=4.0). Subjective levels of stress did not significantly change these parameters. Uroflows were obtained with and without coffee drinking. The voided volume was 337.4 mL (SD=109.2) vs. 290.8 mL (SD=77.3) (P=0.03), and peak flow rate 19.4 mL/sec (SD=4.1) vs. 18.9 mL/sec (SD=3.1) (P=0.49), respectively. CONCLUSIONS: Uroflowmetry parameters and voided volume are highly variable in a normal asymptomatic population. Subjective stress level does not seem to have an influence on these parameters. Coffee intake significantly increases the voided volume but does not change the peak flow rate. These conclusions should be considered when using uroflowmetry parameters as an outcome measure.

Complications of tension-free vaginal tape surgery: a multi-institutional review.

OBJECTIVE: To analyse the complications of tension-free vaginal tape (TVT) surgery, a minimally invasive alternative for treating patients with stress urinary incontinence (SUI), at six institutions, and to review the management of these complications and their effect on patient outcome. PATIENTS AND METHODS: In all, 241 patients who had a TVT procedure by six urologists at six hospitals (two university and four community) were reviewed retrospectively by the same urologist. Complications during and after surgery, and their management, were analysed. RESULTS: Complications during surgery included bladder perforation in 48 patients (5.8%) and blood loss > 500 mL in 16 (2.5%). Immediate complications after surgery were urinary retention (>24 h after) in 47 patients (19.7%), pelvic haematoma in four (1.9%) and suprapubic wound infection in one (0.4%). Of the 47 patients in retention, 32 were in retention for <48 h and treated with an indwelling catheter. The 15 remaining patients were treated with an indwelling catheter (one) or clean intermittent catheterization for a mean of 22 days. To correct the retention the TVT was released in seven patients and the tape sectioned in three. Late complications were de novo urgency, persistent suprapubic discomfort and intravaginal tape erosion in 36 (15%), 18 (7.5%) and one (0.4%) patient, respectively. Most of these complications resolved with observation and medical management, but intravaginal tape erosion required partial resection of the tape with closure and repair of the vaginal mucosa. CONCLUSIONS: The present TVT complication rates were slightly higher than reported previously. This multi-institutional review in both academic and community hospitals may better reflect the morbidity of TVT insertion in clinical practice. TVT is a highly effective, minimally invasive method for treating SUI. A stricter definition of each complication and a better understanding of the mechanism of these complications may further improve the surgical outcome and decrease patient morbidity.