Faculty Bibliography

BACKGROUND: Among screened populations, it is unknown whether men with prostate cancer (PC) diagnosed at the initial screening (prevalent cases) have a different outcome than men who are diagnosed at subsequent screenings (incident cases) after adjusting for known prognostic factors. METHODS: The current study cohort was comprised of 1923 men from a prospective PC screening study who underwent radical prostatectomy (RP) between September 19, 1989 and May 22, 2002. Cox regression multivariate analysis was used to determine whether having prevalent PC versus incident PC was associated with the time to prostate-specific antigen (PSA) failure after RP after adjusting for PSA level, Gleason score, clinical tumor (T) classification, and year of RP. RESULTS: Men with prevalent PC had higher PSA levels (P < .001) and more advanced clinical T classification (P < .001) than men with incident PC. After a median follow-up of 6.1 years, factors that were associated with a significantly shorter time to PSA failure after RP were prevalent PC (adjusted hazard ratio [AHR], 1.8; 95% confidence interval [95% CI], 1.3-2.6; P = .0005), baseline PSA (AHR, 1.07; 95%CI, 1.04-1.09; P < .001), Gleason 7 disease (AHR, 2.5; 95% CI, 1.9-3.3; P < .001), Gleason 8 to 10 disease (AHR, 2.3; 95%CI, 1.5-3.5; P < .001), and the year of RP (AHR, 0.92; 95%CI, 0.86-0.97; P = .003). Men with prevalent PC also had worse outcomes after adjusting for their more advanced pathologic features. CONCLUSIONS: After adjusting for known prognostic factors, men with prevalent PC had a poorer outcome after RP than men with incident PC. The authors believe that this finding should be taken into consideration when weighing the risk of recurrence and treatment options for men who are diagnosed with PC on their initial screening.

BACKGROUND: Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known about the relative utility of pretreatment PSA doubling time (PSA DT) to predict tumor aggressiveness. OBJECTIVE: To compare the utility of PSAV and PSA DT for the prediction of life-threatening prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: From the Baltimore Longitudinal Study of Aging, we identified 681 men with serial PSA measurements. MEASUREMENTS: Receiver operating characteristic analysis was used to evaluate the relationship between PSAV, PSA DT, and the presence of high-risk disease. RESULTS AND LIMITATIONS: Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among men with high-risk or fatal prostate cancer than men without it. By contrast, PSA DT was not significantly associated with high-risk or fatal disease. On multivariate analysis, including age, date of diagnosis, and PSA, the addition of PSAV significantly improved the concordance index from 0.85 to 0.88 (p<0.001), whereas PSA DT did not. CONCLUSIONS: These data suggest that PSAV is more useful than PSA DT in the pretreatment setting to help identify those men with life-threatening disease.

PURPOSE: Although prostate specific antigen is widely used to detect and manage prostate cancer, many patients and physicians are unaware of which prostate specific antigen assay is being used. Most commercial prostate specific antigen assays are standardized to the WHO 90:10 standard or aligned with the original Hybritech assay with potentially disparate results. MATERIALS AND METHODS: A total of 1,916 men participated in a prostate cancer screening study in 2007. On the day of collection prostate specific antigen was tested from the same serum sample using the Access (Hybritech standard) and ADVIA Centaur (WHO 90:10 prostate specific antigen standard) assays. We examined the differences between the 2 assays and the effect that this might have on clinical decisions. RESULTS: Median prostate specific antigen was 0.9 and 1.05 ng/ml for the Centaur and Access assays, respectively, representing a 17% difference. Mean prostate specific antigen was 3.45 and 4.79 ng/ml, respectively, representing a 38% difference. Using a prostate specific antigen threshold of 2.5 ng/ml 5% of men would have been recommended to undergo biopsy using the Access but not the Centaur assay. Furthermore, prostate specific antigen differed by greater than 0.4 ng/ml in 26%, greater than 0.75 ng/ml in 14.5% and greater than 2 ng/ml in 4.5% of men in the same sample simply by using the different assays. CONCLUSIONS: In our prospective screening population median prostate specific antigen was 17% lower using WHO vs Hybritech based assay standardization. As such, if these assays were instead used on a serial basis in the same patient, this could lead to false acceleration or false deceleration in prostate specific antigen velocity. Thus, the assay may influence the likelihood of prostate biopsy and, thereby, prostate cancer detection.

Approximately 5% of all urothelial tumors in adults arise from the upper tracts. While the gold standard treatment is open nephroureterectomy, laparoscopic nephroureterectomy is becoming increasingly popular. Oncologic principles dictate that complete excision of the transmural ureter and bladder cuff and avoidance of urine spillage are paramount. This can be challenging laparoscopically and multiple techniques have been described. We review described surgical techniques, published oncologic data, as well as advantages and disadvantages for each technique including open excision, cystoscopic detachment and ligation, laparoscopic stapling, ureteral intussusception, transurethral resection of ureteral orifice (TURUO) and modifications of TURUO. To date, no controlled studies have been performed demonstrating one technique's superiority.

OBJECTIVES: Conflicting evidence has been reported on the association of prostate-specific antigen velocity (PSAV) with Gleason score in prostate needle biopsy specimens. The Gleason score is an important prognostic indicator for men with prostate cancer, and, in modern practice, it frequently affects treatment decisions. To our knowledge, the relationship between preoperative PSAV and Gleason score in the radical prostatectomy specimen has not been formally demonstrated. METHODS: A total of 1049 men treated with radical prostatectomy had data on PSAV and Gleason score. Statistical analysis was performed to examine the relationship between the preoperative PSAV and the prostatectomy Gleason score and other adverse tumor features. RESULTS: The median preoperative PSAV was 0.84, 0.97, and 1.39 ng/mL/y in men with a Gleason score of 6, 7, and 8-10, respectively (P = .05). A PSAV greater than 2 ng/mL/y was significantly associated with a prostatectomy Gleason score of 7 or greater on univariate and multivariate analysis. In addition, the preoperative PSAV was significantly lower in men with organ-confined disease (0.82 vs 1.17 ng/mL/y, respectively, P = .002). CONCLUSIONS: Our results have further validated PSAV as a marker for prostate cancer aggressiveness. The preoperative PSAV was a significant independent predictor of the Gleason score and non-organ-confined disease in the radical prostatectomy specimen. Thus, PSAV could be useful in treatment decision-making and in assessing the likelihood of long-term cancer control in men with prostate cancer.

PURPOSE: Although prostate specific antigen velocity was proposed to increase the specificity of prostate specific antigen-based screening, there are little published data on the effect of differential prostate growth on prostate specific antigen velocity. If a patient presents with rising prostate specific antigen over a year or more, it would be useful to know whether such a change in prostate specific antigen could be explained by prostate growth. Thus, we investigated the relationship between changes in prostate size and prostate specific antigen changes in a large cohort of men without prostate cancer. MATERIALS AND METHODS: We identified 242 men without prostate cancer from the Baltimore Longitudinal Study of Aging who had 2 or greater serial pelvic magnetic resonance imaging studies and contemporaneous prostate specific antigen measurements. In this population we used the t test, correlation coefficients, and regression analysis to examine the relationship between prostate specific antigen changes and prostate volume changes, as assessed by magnetic resonance imaging. RESULTS: The mean age was 55 years. During 4.2 years of median followup, the median rate of volume change was 0.6 cc per year (range -9.9 to 11.8), and the median prostate specific antigen change was 0.03 ng/ml per year. There was no correlation between prostate specific antigen changes and prostate growth, as measured in cc per year (r = -0.01, p = 0.9) or the percent change per year (r = 0.07, p = 0.3). On multivariate analysis, there was no significant relationship between changes in prostate volume and prostate specific antigen changes. CONCLUSIONS: Our data suggest that volume increases alone do not cause a high prostate specific antigen velocity. Despite growth rates as high as 10 cc per year, prostate specific antigen velocity was less than 0.1 ng/ml per year in most men without prostate cancer. Thus, differential rates of prostatic growth should not confound the use of prostate specific antigen velocity for prostate cancer detection and prognostication.

OBJECTIVES: With the widespread use of prostate-specific antigen (PSA)-based screening, there is now concern about the overdiagnosis and overtreatment of men with low-risk prostate cancer (PCa). One of the most difficult aspects of PCa management is a balance of the often-competing goals of cancer control with functional outcomes and quality of life. To address this issue, we examined the potency, continence and overall complication rates associated with radical prostatectomy (RP), specifically in potential candidates for active monitoring. METHODS: From a large RP database, we compared potency, continence, and complication rates among men meeting one of the following active monitoring criteria from the literature: clinically localized, Gleason score of 7 or less, and no significant comorbidities; T1b-T2b NOMO, Gleason score of 7 or less, and PSA of 15 ng/mL or less; and T1c PCa. RESULTS: There were 3458, 3533, and 2338 men who met the above criteria, respectively. After 18 months of follow-up, potency was preserved in 70% to 74%. At least 93% of patients were continent, and the rate of surgical complications ranged from 5% to 7%. Increasing age was significantly associated with a greater risk of all complications. CONCLUSIONS: Men with newly diagnosed low-risk PCa must carefully weigh the risks and benefits of treatment. In young men with low-risk PCa, RP was associated with a relatively low complication rate and good long-term functional outcomes. However, with increasing age, RP was associated with significantly higher complication rates. These results can be used to help guide management decisions for men with low-risk disease.