Faculty Bibliography

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.

BACKGROUND: A prostate-specific antigen (PSA) velocity (PSAV) >2 ng/mL during the year before diagnosis has been associated with an increased risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP) or radiation therapy. The objective of the current study was to examine whether the proportion of men with a PSAV >2 ng/mL per year has changed significantly during the PSA era. METHODS: The authors evaluated 1095 men from a prospective prostate cancer screening study who underwent RP between 1989 and 2002. For the purposes of this analysis, clinicopathologic features were compared between men who were treated during the following 3 periods: before 1995, from 1995 to 1998, and after 1998. Logistic regression analysis was used to evaluate for an association between the year of diagnosis and the proportion of men with a PSAV >2 ng/mL per year. RESULTS: Two hundred sixty-two of 1095 men (24%) had a PSAV >2 ng/mL per year. There was a statistically significant reduction in the proportion of men presenting with a PSAV >2 ng/mL per year over the study period. Specifically, 35% of men presented with a PSAV >2 ng/mL per year in the early period compared with only 22% and 12% in the middle and late periods, respectively (P < .001). Over the studied periods, there also was a significantly greater proportion of men with >2 PSA values obtained before diagnosis (P < .001). CONCLUSIONS: Men who were screened serially with PSA were less likely to present with a PSAV >2 ng/mL per year. This association lends support to the hypothesis that serial PSA-based screening may lead to a decrease in PCSM.

BACKGROUND: Randomized trials have shown an improvement in progression-free survival rates with adjuvant radiation therapy (ART) after radical prostatectomy for patients with a high risk of cancer recurrence. Less is known about the relative advantages and disadvantages of initial observation with delayed salvage radiation therapy (SRT). OBJECTIVE: To examine the results of SRT in a large single-surgeon radical prostatectomy series. DESIGN, SETTING, AND PARTICIPANTS: From a radical prostatectomy database, we identified 859 men with positive surgical margins (SM+), extracapsular tumor extension (ECE), or seminal vesicle invasion (SVI) who chose to defer ART. Following a period of initial observation, 192 ultimately received SRT for prostate-specific antigen (PSA) progression. MEASUREMENTS: Survival analysis was performed to examine the outcomes of initial observation followed by SRT. RESULTS AND LIMITATIONS: In patients with SM+/ECE and SVI, the 7-yr PSA progression-free survival rates with observation were 62% and 32%, respectively. Among those who had PSA progression, 56% and 26%, respectively, maintained an undetectable PSA for 5 yr after SRT. The long-term rates of undetectable PSA associated with an SRT strategy were 83% and 50% for men with SM+/ECE and SVI, respectively. In the subset of 716 men who did not receive any hormonal therapy, the corresponding long-term rates of undetectable PSA were 91% and 75%, respectively. CONCLUSIONS: Following radical prostatectomy, initial observation followed by delayed SRT at the time of PSA recurrence is an effective strategy for selected patients with SM+/ECE. Some patients with SVI may also benefit from this strategy. However, additional prospective studies are necessary to further examine the survival outcomes following SRT.

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.