Faculty Bibliography

OBJECTIVES: To determine the effect of prostate volume on the specificity of prostate-specific antigen density (PSAD) and PSAD of the transition zone (PSA-TZ) in the detection of prostate cancer. METHODS: Between February 1994 and April 1998, transrectal ultrasound-guided prostate needle biopsies were performed in 235 men with serum prostate-specific antigen (PSA) levels between 4.0 and 10.0 ng/mL. The PSAD and PSA-TZ specificities were calculated at 95% sensitivity cutoff levels generated from the whole group, as well as from cohorts stratified by transition zone index or prostate volume. RESULTS: Statistical significance was noted between the benign (n = 176) and prostate cancer (n = 59) groups for all tested PSA parameters. At 95% sensitivity, PSA-TZ carried a specificity of 37.5% compared with 29.6% for PSAD. When applying a single 95% sensitivity cutoff derived from the entire group to individual volume-stratified cohorts, the specificity decreased to 0% in glands less than 30 g in size. A 95% sensitivity PSA-TZ cutoff generated individually for volume-stratified cohorts of glands less than 30, 30 to 40, and 40 to 60 g resulted in more consistent specificity of 28.2%, 35.2%, and 45.7% for each cohort, respectively. CONCLUSIONS: Unlike whole group-derived cutoffs, the use of volume-specific PSA-TZ cutoffs allows consistently high specificity in all volume-stratified cohorts. The discrepancies in the PSA-TZ and PSAD specificities in published reports are likely due to the application of published cutoffs to populations of differing prostate volumes. The use of volume-specific cutoffs results in reproducible specificity in populations with differing prostate volume distribution, and thereby definitively resolves the differences in PSA-TZ specificity reported in published reports

PURPOSE: We determine the use of information gained with intraoperative biopsy and frozen section analysis of the apical soft tissue margin during nerve sparing radical retropubic prostatectomy. MATERIALS AND METHODS: A separate 2 to 3 mm. circumferential biopsy was obtained from the apical soft tissue margin, and was sent for frozen and permanent section analysis during radical retropubic prostatectomy in 95 men with clinically localized adenocarcinoma of the prostate. A single pathologist examined the surgical and apical soft tissue margin specimens for evidence and extent of benign or malignant prostate tissue. Urinary continence was evaluated at catheter removal and 3 months postoperatively. RESULTS: Of the patients 26% had positive surgical margins, of which 64% were positive apical margins. Permanent section of the apical soft tissue biopsy revealed no prostate in 39%, benign prostate in 54% and prostate cancer in 7% of patients. Because of the frozen section finding of adenocarcinoma in 3 patients, the apical soft tissue margin was further resected until the specimen was negative for malignancy. The apical soft tissue margin was the only positive margin site in 2 of these 3 patients. Positive surgical and apical margins, and percent tumor volumes greater than 26% on prostatectomy specimen had a significantly higher likelihood for positive apical soft tissue margins. The pathological finding of a positive apical margin on the surgical specimen had sensitivity, specificity, and positive and negative predictive values of 57%, 86%, 25% and 96%, respectively, for detecting prostate cancer on the apical soft tissue biopsy. Of the apical soft tissue biopsies 54% contained an element of benign prostatic tissue, although 92% of them contained benign tissue in less than 25% of the total specimen. Mean continence score in the men with and those without benign prostate tissue on apical soft tissue biopsy was 15.6 and 14.4, respectively (p = 0.15). The percent of men who required no protective pads for urinary continence at 3 months was 53% and 65% for those who had no prostate and those who had benign prostate tissue, respectively, in the apical soft tissue margin. CONCLUSIONS: Excising and submitting an additional 2 to 3 mm. of apical soft tissue margin for permanent section analysis after prostate removal during radical prostatectomy represent an effective method for decreasing residual prostate tissue. Attempts at maximizing urethral length when dividing the prostato-urethral junction likely increases the chance of leaving residual prostate without improving continence

Stress urinary incontinence is a recognized complication following radical prostatectomy. Fortunately, in the hands of experienced surgeons, the overwhelming majority of men ultimately regain urinary continence following the procedure. Most men regain urinary continence 3 to 12 months after the prostatectomy. We have developed and validated a continence index that is administered at the time of catheter removal after radical prostatectomy. This index identifies those men who rapidly regain continence and men who will have permanent incontinence after prostatectomy. The study population was stratified into tertile groups based on the continence scores. At 3 months, 96%, 82%, and 68% of men in the highest, mid, and lowest tertile groups reported using no pads or one small pad. Based on these observations, we recommend initiating biofeedback immediately postoperatively in men with continence scores of 14 or less. At 1 year, 100%, 98%, and 87% of the men in the highest, mid, and lowest tertile group reported using no pads or only one small pad. Men who have continence scores greater than 14 can be assured that they will regain urinary continence within 1 year. To our knowledge, this index is the only validated instrument that predicts the return of urinary continence after radical prostatectomy

This article discusses the basic elements of chemoprevention trial designs using cohorts of men following radical prostatectomy who either have prostate-specific antigen (PSA) failure indicative of recurrence or are at high risk for recurrence (positive surgical margins, extracapsular extension, seminal vesicle invasion, positive lymph nodes, Gleason score of greater than or equal to 8, preoperative serum PSA less than 20 ng/mL). Two ongoing randomized, double-blind, placebo-controlled clinical trials with soy protein as intervention in these 2 populations are described. In the trial with men at high risk for recurrence, participants started intervention within 4 months after surgery and were followed for up to 2 years; primary endpoints were PSA failure rate and time-to-PSA failure. In the trial with men with PSA failure (PSA 0.1 to 2.0 ng/mL), participants received treatment for 8 months and the primary endpoint is rise in PSA over time. The strengths and limitations of these designs are discussed and interim experience using studies with soy protein as the intervention agent are summarized

OBJECTIVES: To examine the incidence, effectiveness of intervention, effect on continence, and factors predisposing to the occurrence of anastomotic strictures following radical retropubic prostatectomy. METHODS: Between January 1994 and June 1999, 753 radical retropubic prostatectomies were performed by a single surgeon. Anastomotic strictures were managed by dilatation followed by a self-catheterization regimen. Dilatations were repeated unless more than three dilatations were required over a 9-month interval. A control group representing a randomly selected group of men who did not develop anastomotic strictures was identified. The largest width of the midline vertical abdominal scar was measured. RESULTS: Of the 753 radical retropubic prostatectomies, 36 (4.8%) developed an anastomotic stricture. The mean time interval between the surgical procedure and diagnosis of the stricture was 4.22 months. Of the 26 cases of anastomotic strictures with at least 1-year follow-up, 24 (92.3%) were managed successfully by dilatations alone. No baseline characteristics before surgery were associated with the development of a stricture. The maximal scar width was the only factor that was associated with the development of a stricture in this study. Men with a maximal scar of greater than 10 mm were eight times more likely to develop strictures than men with smaller scars. The percentage of men who required protective pads 1 year following radical retropubic prostatectomy in the control and stricture groups was 12.5% and 46.2%, respectively. CONCLUSIONS: Anastomotic strictures are relatively rare following radical prostatectomy and have a negative effect on the development of continence. Most men are successfully managed with dilatations alone. The development of anastomotic strictures in some men appears to be related to a generalized hypertrophic wound-healing mechanism

OBJECTIVES: To determine whether the response to recombinant erythropoietin is dose dependent in men undergoing radical prostatectomy and to elucidate the relative cost-effectiveness of two dosing regimens. METHODS: A prospective, open-label study comparing the effectiveness, cost, and safety of two different doses of recombinant erythropoietin was performed in men undergoing radical retropubic prostatectomy. The first 100 men received 600 IU/kg (high dose) of epoetin alfa. A second group of 100 men received 300 IU/kg (low dose). All men received two doses of erythropoietin on preoperative days 14 and 7, provided their baseline hematocrit levels were less than 48%. Hematocrit levels were measured at baseline (more than 14 days before surgery), at the time of anesthesia induction, in the recovery room postoperatively, on the first postoperative day, and on the morning of discharge. RESULTS: The mean increase in hematocrit from baseline to induction for the high and low-dose groups was 4.50 and 4.69, respectively (P = 0.7225). Six men (6%) in the high-dose group and seven (7%) in the low-dose group required allogenic blood transfusions. The mean cost of high and low-dose epoetin alfa was $1218 and $656, respectively. The cost per percentage point increase in hematocrit in the low-dose group was significantly less than in the high-dose group. No thromboembolic events occurred in the high or low-dose group. CONCLUSIONS: In men undergoing radical retropubic prostatectomy, the administration of epoetin alfa on preoperative days 14 and 7 was a safe and effective treatment strategy for reducing the risk of allogenic blood transfusions. The 300 IU/kg dosing regimen was significantly more cost effective than the 600 IU/kg dosing regimen