Faculty Bibliography

OBJECTIVES: Prior studies have reported that men with a PSA density (PSAD) less than 0.15, less than 3 positive biopsy cores, 50% or less of any core involved, and a Gleason score 6 or lower are likely to have "insignificant" prostate cancer (CaP) in their radical prostatectomy (RRP) specimen. In this study, we examined the ability of PSAD and biopsy features to predict pathologic outcomes in a contemporary RRP population. METHODS: From 1999 to 2005, 274 men underwent RRP and had the required data for our analysis. As our database does not record the percentage or length of cancer in each biopsy core, we examined the relative importance of PSAD, the number of positive biopsy cores, and Gleason grade to predict "insignificant" cancer, defined as organ-confined with a tumor volume less than 0.5 mL and no Gleason pattern 4 or 5. RESULTS: Overall, by these criteria, 24.5% of patients were considered to have potentially "insignificant" cancer preoperatively; whereas, only 2.6% had a so-called "insignificant" tumor in the RRP specimen. Without the percentage of biopsy core involvement, the preoperative model to predict "insignificant" cancer was associated with 57% sensitivity, 76% specificity, 6% positive predictive value, and 99% negative predictive value. CONCLUSIONS: A model including Gleason grade, PSAD, and number of positive biopsy cores did not provide an accurate means of selecting patients for active monitoring in our patient cohort. However, it was helpful in identifying men with a high likelihood of "clinically significant" CaP. Knowledge of the percentage of biopsy core involvement with cancer may be a critical prognostic factor.

OBJECTIVE: To assess the biochemical outcome after radical prostatectomy (RP) specifically for men aged 30-39 years, as previous studies suggest that prostate cancer in young men might be more aggressive. PATIENTS AND METHODS: From a large (15 899) database of RPs (1975-2007) we identified 42 men aged 30-39, 893 aged 40-49, 4085 aged 50-59, 3766 aged 60-69, and 182 men aged > or =70 years old. The clinical characteristics and treatment outcomes were compared between men aged 30-39 years and older men. RESULTS: Among the men in their thirties, 81% had organ-confined disease in the RP specimen, vs 62% of men aged > or =40 years. At a mean follow-up of 5 years, there was biochemical progression in 4.8% of men in their thirties and 16.1% of men age > or =40 years (P = 0.055). The corresponding 5-year biochemical progression-free survival estimates were 95% for men in their thirties and 83% for men aged > or =40 years (P = 0.045). On multivariate analysis, increasing age was a significant independent predictor of biochemical progression. CONCLUSION: Contrary to earlier reports, in the present study men in their thirties did not have more aggressive disease. Instead, they had more favourable pathological features and progression-free survival rates than their older counterparts. After controlling for other prognostic variables on multivariate analysis, being in the fourth decade was independently associated with a lower risk of biochemical progression. These results suggest that early aggressive treatment for these patients with a long life-expectancy is associated with favourable long-term biochemical outcomes.

PURPOSE: In collaboration with deCODE Genetics Inc. we previously reported on the association between genetic variants on chromosome 8q24 and prostate cancer susceptibility. Several prior studies have examined the relationship between these 8q24 alleles and clinical tumor features. In this study we examine the differences in clinical and pathological tumor features between carriers and noncarriers of these 8q24 alleles in patients with prostate cancer. MATERIALS AND METHODS: We genotyped 551 white men who underwent radical prostatectomy or radiation therapy for clinically localized prostate cancer at single institution between 2002 and 2005. Of these men 177 (32.1%) were carriers of the -8 allele of the microsatellite marker DG8S737, the A allele of the single nucleotide polymorphism rs1447295 and/or the A allele of the rs16901979 (a surrogate single nucleotide polymorphism of HapC) 8q24 alleles. We used statistical analyses to compare the distribution of clinical characteristics and pathological outcomes between carriers and noncarriers. RESULTS: The -8, A and HapC surrogate single nucleotide polymorphism alleles were present in 77 (14%), 128 (23%) and 61 (14%) patients with prostate cancer, respectively. Carriers of the -8 or multiple 8q24 alleles were significantly more likely to have a Gleason score of 7 or greater and lymph node metastases. Among men with a family history of prostate cancer, carriers of the -8 allele had a significantly greater risk of high grade disease (64% vs 39%, p = 0.04). CONCLUSIONS: In our predominantly surgically treated population there was a significant association between 8q24 prostate cancer susceptibility alleles, particularly the -8 allele, and high grade disease. In men with a family history of prostate cancer the presence of 1 or more of these alleles also conferred a greater risk of some adverse pathological features.

OBJECTIVES: For prostate cancer screening, the role of prostate-specific antigen (PSA) velocity (PSAV) in conjunction with total PSA is controversial. We evaluated the relationship of PSAV to histologic findings on biopsy and assessed whether PSAV provides independent predictive information. METHODS: From a community-based cohort of 25,276 men screened from 1991 to 2001, 1851 underwent a first biopsy for an elevated PSA and nonsuspicious digital rectal examination with a PSAV available from the year before biopsy. We analyzed the association between PSAV and biopsy histology. RESULTS: The histologic findings on biopsy were cancer in 468 (25%), prostatic inflammation in 135 (7%), and benign prostate tissue in 1248 (68%). The cancer detection rate was associated with PSAV and, depending on PSAV, ranged from 13% to 36% (P <0.001). Among men with a PSAV less than 0.5 ng/mL per year, the cancer rate ranged from 27% to 36%, at a PSAV of 0.5 to 3.0 ng/mL per year was 24% to 28%, and at a PSAV greater than 3.0 ng/mL per year was 13% to 18%. On multivariable analysis adjusting for age and PSA, PSAV was independently associated with risk of cancer on biopsy (P <0.0005). The rate of prostatic inflammation was directly associated with PSAV (PSAV of 3.0 ng/mL per year or less: 5% to 9%; PSAV greater than 3.0 ng/mL per year: 11% to 13%, P = 0.01). CONCLUSIONS: In screened men with an elevated PSA undergoing biopsy, PSAV provides independent predictive information for estimating prostate cancer risk. Modest increases in PSA are associated with an increased risk of cancer, whereas more dramatic PSA rises are associated with a diminishing risk of cancer and higher rate of inflammation.

OBJECTIVE: To determine whether prostate-specific antigen velocity (PSAV) is useful for prostate cancer detection in men from different age groups, and whether the same PSAV thresholds can reasonably be applied to all men aged >or=40 years. PATIENTS AND METHODS: From a large prostate cancer screening study, 13,615 men had data on age and a calculable PSAV. We used statistical analysis to examine the ability of PSAV to predict prostate cancer risk in each age decade. RESULTS: For men of all ages, the median PSAV was 0.6-0.7 ng/mL/year in men with prostate cancer, and 0-0.1 ng/mL/year in men with no prostate cancer (P < 0.005 for all). On receiver operating characteristic (ROC) analysis, the area under the curve was 0.800, 0.697, 0.693, and 0.668 for predicting prostate cancer risk using PSAV for men aged 40-49, 50-59, 60-69 and >or=70 years, respectively. In the multivariate model controlling for race, family history, and the total PSA level, both PSA and PSAV were significant independent predictors of prostate cancer risk in men of all ages. CONCLUSIONS: The PSAV is significantly higher in men of all ages with prostate cancer compared with men with no prostate cancer; although on ROC analysis it performed the best in young men. Interestingly, the median PSAV in men with prostate cancer was <0.75 ng/mL/year regardless of age, suggesting that this threshold may be too high. Overall, this data confirms that PSAV is a useful tool for prostate cancer detection for men aged >or=40 years.

BACKGROUND AND PURPOSE: The usefulness of plain film chest radiography (CXR) in evaluation for thoracic complications after laparoscopic urologic procedures is uncertain. Our objectives were to examine the association between radiographic findings and clinical manifestations of thoracic complications after laparoscopic urologic procedures and to determine the prevalence of postoperative CXR at our institution. PATIENTS AND METHODS: We performed a retrospective review of 195 patients who underwent laparoscopic renal/adrenal urologic procedures at our institution from 1998 to 2005. Chi-square analysis was used to compare the rate of radiographic abnormalities and thoracic complications between different types of laparoscopic procedures. RESULTS: A total of 96 patients (96/195, 49%) had postoperative CXR, and abnormalities were noted in 75 (75/96, 78%). The abnormalities seen on CXR included atelectasis, pleural effusions, pneumomediastinum, pneumothorax, subcutaneous emphysema, and pneumonia. Retroperitoneal laparoscopy had significantly more incidental subclinical pneumothoraces (P = 0.000469) and subcutaneous emphysema (P = 0.043) identified by CXR than either transperitoneal, hand-assisted, or cryosurgery. Overall, eight patients (8.3%) had clinical manifestations of a thoracic complication but only five (5.2%) were clinically significant complications detected by CXR. Thus, while 75 CXRs were noted as abnormal, 70 (93%) documented incidental findings that did not affect patient care. CONCLUSIONS: Thoracic complications after laparoscopic urologic procedures are uncommon events. Although the majority of CXRs after such procedures do contain abnormalities, most abnormalities are subclinical and do not affect postoperative management. Patients with significant radiographic findings demonstrated significant clinical symptoms. Thus, routine CXR after urologic laparoscopy does not appear to be necessary to identify thoracic complications and may be overused.

PURPOSE: Despite the tremendous stage migration associated with prostate cancer screening to our knowledge it remains unproven whether prostate specific antigen based screening decreases prostate cancer specific mortality. Recent studies have shown that prostate specific antigen velocity more than 2 ng/ml per year in the year before diagnosis is associated with a significantly greater risk of prostate cancer specific mortality after treatment. This may serve as a surrogate marker for prostate cancer outcomes. We compared the prostate specific antigen velocity profile between patients with prostate cancer in whom the tumor was detected in a formal screening study and those who were referred for treatment. MATERIALS AND METHODS: We evaluated prostate specific antigen velocity in 1,101 men from a prostate cancer screening study and in 368 not enrolled in a screening study who were referred for treatment. All patients underwent radical prostatectomy for clinically localized disease and had multiple preoperative prostate specific antigen measurements to calculate prostate specific antigen velocity. RESULTS: Median prostate specific antigen velocity before diagnosis was significantly higher in referred vs screened men (1.35 vs 0.68 ng/ml per year, p <0.0001). In addition, a significantly greater proportion of referred patients had prostate specific antigen velocity more than 2 ng/ml per year (38% vs 17%, p <0.0001). On multivariate analysis using prostate specific antigen, clinical stage and biopsy Gleason score screened vs referred status was a significant independent predictor of prostate specific antigen velocity more than 2 ng/ml per year (p <0.0004). CONCLUSIONS: Prostate specific antigen velocity more than 2 ng/ml per year has been linked to a significantly greater risk of prostate cancer specific mortality. Patients who underwent serial screening had a more favorable prostate specific antigen velocity profile at diagnosis, suggesting that screen detected prostate cancer may be more likely to be cured with definitive therapy.

For more than a decade, prostate-specific antigen (PSA) has been used for prostate cancer screening. Over the years, this screening has been continually refined, including investigation into the use of lower total PSA thresholds, PSA isoforms, and PSA kinetics. This review describes the evolution of prostate cancer screening and provides clinical insights into the informed use of PSA and its adjunctive measurements.

Despite a lack of data, many patients receive primary androgen-deprivation therapy (PADT) for the treatment of localized prostate cancer. To evaluate the association between PADT and survival, a population-based cohort study was conducted in 19,271 men with clinical stage T1-T2 prostate cancer. The primary outcome measures were prostate cancer-specific and overall survival. Comparing 7867 patients who received PADT with 11,404 patients who underwent conservative management, the 10-year cancer-specific survival was lower with the PADT group and overall survival was found to be similar between the groups. However, in the subset with poorly differentiated cancer, PADT was associated with improved cancer-specific, but not overall, survival. This suggests that PADT is not associated with improved survival in the majority of elderly men compared with conservative management. 2008 Future Medicine Ltd