Stacy J. Childs

A Quantitatively Controlled Method to Study Prospectively Interstitial Cystitis and Demonstrate the Efficacy of Pentosanpolysulfate

A randomized, prospective, double-blind, placebo-controlled study was conducted at 7 clinical centers on 148 patients. Patients received orally either 100 mg. pentosanpolysulfate (a synthetic polysaccharide) 3 times per day or a placebo. Of the patients on drug therapy 32% showed significant improvement compared to 16% of those on placebo (p = 0.01). This study provides a model to assess this disease quantitatively in a prospective manner using a method whereby the patients globally assess their symptoms as either worse or improved by 0, 25, 50, 75 or 100%. Patients on drug therapy also experienced a significant decrease in pain and urgency (p = 0.04 and 0.01) on analogue scales when compared to placebo and also more drug patients showed an average increase of more than 20 ml. in voided volume than did placebo patients (p = 0.02). All adverse effects were minor, with 7 in the drug group and 10 in the placebo group. The results support the concept that some patients with the interstitial cystitis syndrome may have abnormal bladder surface glycosaminoglycans.

A prospective randomized comparison of transurethral resection to visual laser ablation of the prostate for the treatment of benign prostatic hyperplasia

OBJECTIVES Transurethral resection of the prostate (TURP) represents the accepted standard of surgical therapy for the management of symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH). However, this is a major operative procedure associated with significant perioperative morbidity. Visual laser ablation of the prostate (VLAP) utilizing a neodymium:yttrium-aluminum-garnet laser represents a new technologic approach to the surgical management of BPH. We compared the relative safety and efficacy of these two surgical approaches in a prospective, randomized trial. METHODS At 6 investigational sites in the United States, 115 men with symptomatic BPH more than 50 years of age and not in retention, were randomly assigned to undergo either TURP (59 patients) of VLAP (56 patients). VLAP patients received a mean of 10,200 J of energy delivered in a mean of 5.5 intraprostate laser applications. At preoperative baseline, 3 months, 6 months, and 1 year postoperatively, all patients underwent clinical evaluations, including ultrasonic prostatic volume determination, standardized American Urological Association (AUA)-6 symptom score, peak urine flow, postvoid residual urine volume, and quality-of-life assessment. RESULTS Compared to TURP, the VLAP procedure required less time (23.4 versus 45.2 minutes; P < 0.01) and shorter hospitalization (1.8 versus 3.1 days, P < 0.01). VLAP was associated with a significantly lower rate of serious treatment-related complications compared to TURP (10.7% versus 35.6%; P < 0.01). Only One (2.2%) patient undergoing VLAP experienced a greater than 2.2 g/dL decrease in hemoglobin compared to 40% of TURP patients (P = 0.01). No patient in the VLAP group required blood transfusion compared with 3.4% of those undergoing TURP. Of the 115 patients, clinical outcomes measured at 1 year showed a mean improvement in AUA-6 symptom scores of -9.0 for VLAP compared with -13.3 for TURP (P < 0.04), mean increase in peak urinary flow rate of 5.3 cc/s for VLAP compared with 7.0 cc/s for TURP (P = 0.27), and mean decrease in postvoid residual urine volume of -55.4 cc for VLAP compared with -138.8 cc for TURP (P < 0.01). At 1 year, 78.2% of patients undergoing VLAP indicated that their quality of life was improved compared with 93.0% of patients undergoing TURP (P = 0.03). When compared with TURP, treatment of BPH with VLAP is associated with less hemoglobin decrease, a lower likelihood of serious complication, and requires less procedure time and a shorter hospital stay. Through a 1-year follow-up, VLAP produced significant improvement over baseline in objective and subjective outcome measures. However, for 1-year improvement in AUA-6 symptom score, postvoid residual urine volume, and quality of life, VLAP was less effective than TURP. CONCLUSIONS In this initial study in the United States, with relatively low-energy laser applications, VLAP did not result in as complete a removal of prostatic tissue as did TURP. Considering the lower morbidity, shorter procedure and hospitalization times, and the degree of effectiveness that was achieved even at the low-energy doses used in this study, VLAP appears to be a viable and safe alternative to standard TURP.

Complexed prostate-specific antigen for early detection of prostate cancer in men with serum prostate-specific antigen levels of 2 to 4 nanograms per milliliter

Complexed PSA (cPSA) has been shown to improve specificity in the detection of prostate cancer over that of total PSA (tPSA) testing in men with tPSA values greater than the cutoff value of 4.0 ng/mL. However, recent studies have reported a 25% incidence of prostate cancer in men with tPSA values in the 2.5- to 4.0-ng/mL range. We performed a multicenter study of cPSA in a population of men who underwent prostate biopsies because of elevated PSA levels or abnormal digital rectal examination (DRE). As part of this study, we sought to assess the clinical value of cPSA in comparison to tPSA, the free/tPSA ratio (f/tPSA) and the complexed/tPSA ratio (c/tPSA) in early detection of prostate cancer in men with tPSA values in the range of 2 to 4 ng/mL. The study was performed at 7 centers. Sera were drawn from men who underwent biopsy procedures consisting of >10 prostate tissue cores. Receiver operating characteristic (ROC) analysis was performed from the results of patients with tPSA values in the range of 2 to 4 ng/mL, including men with suspicious as well as unremarkable findings on DRE. Sera were collected and tested with the Bayer tPSA and cPSA assay and the Beckman free PSA and tPSA assays. ROC analysis was performed for all samples in the 2- to 4-ng/mL PSA range. At biopsy, 158 men had no evidence of malignancy and 57 (26.5%) were diagnosed with prostate cancer. ROC analysis indicated that the area under the curve (AUC) for cPSA was 0.64, which was statistically significantly greater than that achieved for tPSA (AUC, 0.57; P <0.0001). The AUC for f/tPSA and c/tPSA were 0.60 and 0.63, respectively, which was not statistically significantly different from that of tPSA or cPSA (P >or=0.252). A cutpoint of 2.5 ng/mL for tPSA and 2.1 ng/mL for cPSA provided a specificity of 20.3% and 34.2%, respectively, and sensitivity levels of 86%. Using cutpoints of 25% for f/tPSA and 74% for c/tPSA provided a specificity of 11.0% and 21.5%, respectively, and sensitivity levels of 97%. In all, >92% of the cancers treated with radical prostatectomy were organ confined, and the histologic grading of the tumors ranged from moderately to poorly differentiated with Gleason scores from 5 to 9. These data confirm that there is a high incidence of clinically significant prostate cancer in men with tPSA levels <4.0 ng/mL. Measurement of cPSA proved useful in stratifying men with tPSA values in the 2- to 4-ng/mL range into high- and low-risk groups for prostate cancer. The use of cPSA as a single test was found to enhance detection of prostate cancer over that of testing with tPSA and PSA ratios in men with tPSA values in the range of 2 to 4 ng/mL.

Initial report on intraves1cal administration of N-trifluoroacetyladriamycin-14-valerate (AD 32) to patients with refractory superficial transitional cell carcinoma of the urinary bladder

Abstract Objectives This study was designed to assess the pharmacokinetics, safety, and antitumor activity of intravesically administered AD 32, a novel anthracycline, in patients with transitional cell carcinoma (TCC) of the bladder. Methods Six weekly doses of AD 32 (200 to 900 mg) were administered to 32 patients with superficial TCC who were candidates for intravesical treatment. Serum drug levels were measured during the 6-hour period after administration of the first, third, and sixth doses. Patients underwent bladder evaluations at 3-month intervals to determine responses to treatment. Results Very low levels of unmetabolized AD 32 and its two primary metabolites were measured in serum. The lack of systemic exposure was confirmed by the finding of only a few minor systemic adverse events. Local bladder irritation, the main toxicity associated with intravesical administration of AD 32, persisted for several days after each instillation. The maximum tolerated dose was 800 mg. Thirteen patients had complete responses to treatment, including 8 who remained disease free for 12.1 to 38.5 months. Conclusions AD 32 is an active drug for the treatment of superficial bladder cancer. Further studies of intravesical administration of AD 32 are warranted.

Predicting the outcome of prostate biopsy: comparison of a novel logistic regression-based model, the prostate cancer risk calculator, and prostate-specific antigen level alone.

To develop a logistic regression‐based model to predict prostate cancer biopsy at, and compare its performance to the risk calculator developed by the Prostate Cancer Prevention Trial (PCPT), which was based on age, race, prostate‐specific antigen (PSA) level, a digital rectal examination (DRE), family history, and history of a previous negative biopsy, and to PSA level alone.

Antibiotic prophylaxis for genitourinary surgery in community hospitals.

For 92 patients who had undergone transurethral and open urologic surgery a prospective, randomized, double-blind study was done that compared the effects of ceftriaxone, a third generation cephalosporin, to placebo. The 2 groups were similar in respect to demographic characteristics. Ceftriaxone reduced significantly the incidence of postoperative infection (p less than 0.01). Of 43 patients who received ceftriaxone 2 (5 per cent) became infected compared to 15 of 49 (30 per cent) who received placebo. Patients in the placebo group who had positive postoperative urine cultures did so approximately 2 days earlier than those in the ceftriaxone group, even though the day of catheter removal averaged about 1 1/2 days later in the ceftriaxone group. There was no correlation between the incidence of fever and infection, and there was no difference between groups with regard to postoperative bleeding, or the incidence of recatheterization or rehospitalization. Average operating time, highest temperature postoperatively and number of hospital days were approximately the same in both groups. Two patients in the placebo group had serious complications and incurred approximately

COMPLEXED PROSTATE-SPECIFIC ANTIGEN AS A STAGING TOOL: RESULTS BASED ON A MULTICENTER PROSPECTIVE EVALUATION OF COMPLEXED PROSTATE-SPECIFIC ANTIGEN IN CANCER DIAGNOSIS

11,600 in additional expenses as a result of those complications. Of these patients 1 became septic, and 1 had urinary tract and wound infections postoperatively. These data suggest that this method of antibiotic prophylaxis will not only reduce the incidence of postoperative infection in such patients, thereby reducing morbidity, mortality and hospital costs, but also may provide an additional 1 to 2 days of protection from infection for patients who require postoperative catheterization.

Appropriate surgical prophylaxis in transurethral genitourinary surgery and potential reduction in nosocomial infections

Within a 7-site prospective evaluation of the Bayer complexed prostate-specific antigen PSA (cPSA) assay, we analyzed the ability of cPSA to predict extracapsular extension (ECE) before radical prostatectomy. Included in this analysis were 152 men diagnosed with cancer, who subsequently underwent radical prostatectomy. Sera were tested with the Bayer total PSA (tPSA) and cPSA assays, and the Beckman free PSA (fPSA) and tPSA assays. Treating surgical pathology result as a binary variable (organ confined vs ECE), mean tPSA, cPSA, fPSA/tPSA (f/tPSA) ratios, tPSA density (tPSAD), and cPSA density (cPSAD) were compared by receiver operating characteristic (ROC) curves and univariate analysis. In all, 28 men (18.4%) had pathologically identified ECE. Between those with and without ECE, significant differences were observed for tPSA (P = 0.0127), cPSA (P = 0.0120), tPSAD (P = 0.0001), and cPSAD (P = 0.0002), but not f/tPSA (P = 0.3774) or c/tPSA (P = 0.2882). All tested parameters except f/tPSA (P = 0.376) and c/tPSA (P = 0.288) predicted ECE (P <0.05) by logistic regression. The ROC area under the curve (AUC) was identical for tPSA and cPSA (0.621) and for tPSAD (0.692) and cPSAD (0.691). Kendall-tau correlation coefficients also demonstrated the strongest correlation with ECE for cPSAD and tPSAD. Either alone or as a tPSAD calculation, cPSA carries equivalent staging ability to tPSA. The use of f/tPSA appears to be less effective in staging than either cPSA or tPSA, whereas the use of either cPSAD or tPSAD provides maximal staging accuracy. Therefore, cPSA could be applied as an accurate predictor of ECE independently or in a nomogram along with other predictive variables.

The appropriate lower limit for the percent free prostate-specific antigen reflex range

Despite the high rate of urinary tract infections seen in hospitals, until recently many surgeons did not advise antibiotic prophylaxis for transurethral genitourinary surgery. This situation has changed with the realization that older trials with questionable results were poorly designed. Several recent well-controlled clinical studies show that appropriate antibiotic prophylaxis greatly reduces the high incidence of infections following transurethral genitourinary surgery. Effective antibiotic prophylaxis for transurethral operations may be a major route to substantial reduction in nosocomial urinary tract infections and bacteremia. To achieve effective prophylaxis, the surgeon must choose a correct antibiotic and use it according to proved principles.

Can volume measurement of the prostate enhance the performance of complexed prostate-specific antigen?

OBJECTIVES The ability of percent free prostate-specific antigen (PSA) to distinguish benign from malignant prostate disease has been established within the 4.0 to 20.0 ng/mL total PSA range, but its utility within the less than 4.0 ng/mL total PSA range has not been clearly defined. We undertook this study to determine the lower limit for the percent free PSA reflex range. METHODS Four hundred seventy-nine men (mean age [+/-SD] 63.2 +/- 9.68 years) met the following criteria: (1) a measurable total serum PSA level of 4.0 ng/mL or less (mean 2.64 +/- 0.050); (2) concurrently measured free PSA and percent free PSA calculated (mean 19.3% +/- 0.59%); (3) a sextant biopsy diagnosed benign (B) (n = 376) or malignant (M) (n = 103), at one institution, within 90 days of serum collection; and (4) no prior history of prostate cancer. We defined the lower limit to be the lowest total PSA value at which (1) percent free PSA distributions differed between benign and malignant cases; and (2) percent free PSA could predict malignant disease. We compared age, total PSA, and percent free PSA differences with the Mann-Whitney U test and analysis of variance, and used univariate logistic regression to determine each variables predictive value. Other statistical analysis was performed with contingency tables, Fishers exact test, and linear regression. RESULTS The lowest total PSA value at which percent free PSA both differed between benign and malignant cases and predicted prostate cancer was 4.0 ng/mL. CONCLUSIONS The lower limit for the percent free PSA reflex range should be 4.0 ng/mL.