Biomedical subjects

Kimberly A Roehl

Publications and source records attributed to Kimberly A Roehl.

At least 19 recordsLinked to original sources

PubMed2007

Does body mass index affect preoperative prostate specific antigen velocity or pathological outcomes after radical prostatectomy?

PURPOSE: Several studies suggest that obesity may be associated with more aggressive prostate cancer. Similarly the rate of serum prostate specific antigen change is associated with adverse tumor features and prostate cancer specific mortality rates after radical prostatectomy and radiation therapy. We examined the associations among obesity, prostate specific antigen velocity and adverse tumor features in men treated with radical prostatectomy. MATERIALS AND METHODS: A total of 587 men with documented preoperative height and weight measurements underwent radical prostatectomy. Prostate specific antigen velocity and other clinicopathological features were compared among men with a body mass index of less than 25, 25 to 29.9 and 30 or greater. RESULTS: Although Gleason score and prostate volume were similar among groups, there was a significantly lower proportion with organ confined disease and fewer low volume tumors as body mass index increased. Of patients with a body mass index of 30 or greater 52% had a preoperative prostate specific antigen velocity of more than 2 ng/ml yearly compared to 34% with a body mass index of 25 to 29.9 and 26% with a body mass index of less than 25 (p = 0.04). Although on univariate analysis body mass index was associated with adverse clinical and pathological tumor features, on multivariate analysis with other preoperative variables body mass index did not add significant independent predictive information concerning pathological stage (OR 1.02, 95% CI 0.96-1.08). CONCLUSIONS: Obesity was significantly associated with several adverse pathological features. However, it did not provide independent predictive information concerning final pathological tumor stage. Nevertheless, obesity was significantly associated with increased preoperative prostate specific antigen velocity. Additional studies are needed to further clarify the links between body mass index, prostate specific antigen velocity and prostate cancer progression, and determine whether weight reduction could lead to improved outcomes.

Adult↗

PubMed2007

Prostate specific antigen density correlates with features of prostate cancer aggressiveness.

PURPOSE: An increased prostate specific antigen density (serum prostate specific antigen divided by prostate volume) is an established parameter to help determine the need to perform prostate biopsies. A man with a high prostate specific antigen and a normal size prostate gland is more likely to have cancer than a man with the same prostate specific antigen and a large gland. Prostate specific antigen in relation to prostate size should also reflect the volume of cancer in the gland. One group defined clinically unimportant prostate cancer as tumor volume less than 0.5 cc, organ confined disease and Gleason less than 7. Another group noted that at the time of biopsy, a prostate specific antigen density less than 0.15 ng/ml/cc combined with low risk clinical tumor features predicted insignificant cancer. There are limited published validating data on the association of prostate specific antigen density with the criteria for prostate cancer aggressiveness. We tested the association of prostate specific antigen density with features of tumor aggressiveness in a screened and in a nonscreened cohort of patients with clinically localized prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: The screened patient cohort included 1,280 patients with screen detected prostate cancer treated from 1990 to 2002 at Washington University, and the nonscreened cohort included 382 patients treated from 2003 to 2004 at Northwestern University. We recorded the clinical and pathological tumor parameters in a prospective database. Parameters evaluated were pathological tumor stage, Gleason sum, tumor volume, biochemical progression and the previously mentioned 2 criteria for clinically unimportant cancers. We grouped patients into 4 prostate specific antigen density categories of less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc. RESULTS: There was a significant trend for worsening clinicopathological prognostic features as prostate specific antigen density increased. There were 357 (82%), 283 (75%), 171 (75%) and 192 (55%) men with organ confined disease with clear surgical margins if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). There were 86 (20%), 102 (27%), 64 (28%) and 157 (45%) men with a Gleason sum greater than 7 when grouped into each increasing PSA density category, respectively (p <0.001). There were 91 (21%), 91 (25%), 74 (33%) and 157 (46%) men with a total cancer volume greater than 0.5 cc when grouped into each increasing PSA density category, respectively (p <0.001). Prostate specific antigen velocity was greater than 2 ng/ml per year in 11%, 30%, 27% and 46% of men if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively (p <0.001). CONCLUSIONS: Prostate specific antigen density measurements are useful in helping to determine the aggressiveness of clinically localized prostate cancer, and can be used as an adjunct in predicting insignificant cancer and outcomes after local therapy.

Aged↗

PubMed2006

Pooled genome linkage scan of aggressive prostate cancer: results from the International Consortium for Prostate Cancer Genetics.

While it is widely appreciated that prostate cancers vary substantially in their propensity to progress to a life-threatening stage, the molecular events responsible for this progression have not been identified. Understanding these molecular mechanisms could provide important prognostic information relevant to more effective clinical management of this heterogeneous cancer. Hence, through genetic linkage analyses, we examined the hypothesis that the tendency to develop aggressive prostate cancer may have an important genetic component. Starting with 1,233 familial prostate cancer families with genome scan data available from the International Consortium for Prostate Cancer Genetics, we selected those that had at least three members with the phenotype of clinically aggressive prostate cancer, as defined by either high tumor grade and/or stage, resulting in 166 pedigrees (13%). Genome-wide linkage data were then pooled to perform a combined linkage analysis for these families. Linkage signals reaching a suggestive level of significance were found on chromosomes 6p22.3 (LOD = 3.0), 11q14.1-14.3 (LOD = 2.4), and 20p11.21-q11.21 (LOD = 2.5). For chromosome 11, stronger evidence of linkage (LOD = 3.3) was observed among pedigrees with an average at diagnosis of 65 years or younger. Other chromosomes that showed evidence for heterogeneity in linkage across strata were chromosome 7, with the strongest linkage signal among pedigrees without male-to-male disease transmission (7q21.11, LOD = 4.1), and chromosome 21, with the strongest linkage signal among pedigrees that had African American ancestry (21q22.13-22.3; LOD = 3.2). Our findings suggest several regions that may contain genes which, when mutated, predispose men to develop a more aggressive prostate cancer phenotype. This provides a basis for attempts to identify these genes, with potential clinical utility for men with aggressive prostate cancer and their relatives.

Black or African American↗

PubMed2006

Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer.

BACKGROUND: The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS: The study population consisted of 67 patients who had a PSA doubling time (DT) < or =6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS: : A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score < or =7 versus > or =8, respectively. CONCLUSIONS: : Among men with a PSA DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or =8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer.

Aged↗

PubMed2006

Lymphovascular invasion in radical prostatectomy specimens: prediction of adverse pathologic features and biochemical progression.

OBJECTIVES: Patients and referring physicians often ask about the significance of lymphovascular invasion (LVI) on pathology reports from radical prostatectomy specimens. However, limited data are available concerning the relationship between LVI and preoperative screening characteristics, pathologic tumor features, and patient prognosis. METHODS: LVI was evaluated for its ability to predict elevated prostate-specific antigen velocity, adverse pathologic features, and biochemical progression in 1709 men who underwent radical prostatectomy for clinically localized disease. RESULTS: LVI was present in 118 (7%) of the 1709 men. On univariate analysis, LVI was significantly associated with tumor grade, tumor volume, and other adverse pathologic features. Prostate-specific antigen velocity was not significantly associated with the presence of LVI. Biochemical progression occurred in 34% of those with LVI compared with 10% of those without LVI (P <0.0001). However, on multivariate analysis with other pathologic tumor features, LVI was not an independent predictor of progression. CONCLUSIONS: LVI is a relatively uncommon finding in radical prostatectomy specimens for clinically localized disease. Although LVI was seen primarily in large-volume, high-grade tumors, it was not an independent predictor of progression in the multivariate model.

Disease Progression↗

PubMed2006

Impact of age, benign prostatic hyperplasia, and cancer on prostate-specific antigen level.

BACKGROUND: The distribution of prostate-specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification bias. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios. METHODS: Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification bias in a screening population, were used to estimate the mean and variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a suspicious digital rectal exam (nodular) were excluded from analysis. RESULTS: Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/mL for younger (<60 yr) and older (> or =60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL in the presence of benign prostatic hyperplasia for younger and older men, respectively. For men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for younger and older men, respectively, among those with benign prostatic hyperplasia. CONCLUSIONS: Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL should not be applied indiscriminately.

Age Factors↗

PubMed2006

Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old.

OBJECTIVES: Limited data are available concerning the extent to which the initial prostate-specific antigen (PSA) measurement in men younger than age 60 predicts for the risk of prostate cancer (CaP) and how this compares to other known risk factors. METHODS: From 1991 to 2001, 13,943 men younger than 60 years old participated in a CaP screening study. Men aged 40 to 49 years were eligible for the study if they had a positive family history or African-American heritage, and men older than 50 years were screened without respect to risk factors. The CaP detection rate, PSA velocity, pathologic features, and treatment outcomes were evaluated as a function of the baseline PSA level. RESULTS: The median PSA level was 0.7 ng/mL for men aged 40 to 49 years and 0.9 ng/mL for men aged 50 to 59. A baseline PSA level between the median and 2.5 ng/mL was associated with a 14.6-fold and 7.6-fold increased risk of CaP in men aged 40 to 49 and 50 to 59 years, respectively. A greater baseline PSA value was also associated with a significantly greater PSA velocity, more aggressive tumor features, a greater biochemical progression rate, and a trend toward a greater cancer-specific mortality rate. CONCLUSIONS: In men younger than 60, a baseline PSA value between the age-specific median and 2.5 ng/mL was a significant predictor of later CaP and was associated with a significantly greater PSA velocity. A young man's baseline PSA value was a stronger predictor of CaP than family history, race, or suspicious digital rectal examination findings. A greater baseline PSA level was associated with significantly more adverse pathologic features and biochemical progression.

Adult↗

PubMed2006

More favorable tumor features and progression-free survival rates in a longitudinal prostate cancer screening study: PSA era and threshold-specific effects.

OBJECTIVES: To describe the changes in pathologic outcomes and progression-free survival (PFS) rates after radical retropubic prostatectomy for clinically localized prostate cancer in men whose cancers were detected in a 12-year longitudinal prostate cancer screening study. METHODS: Between 1989 and 2001, more than 36,000 men participated in a digital rectal examination-based and prostate-specific antigen (PSA)-based screening program. In 1995, the PSA cutoff for biopsy recommendation was lowered from 4.0 ng/mL to 2.6 ng/mL, and the biopsy protocol was changed from four to at least six-sector biopsies. From the screening study, 2952 men were diagnosed with cancer and 2241 of these men underwent radical retropubic prostatectomy. We analyzed the differences in clinical and pathologic stage and PFS after surgery, according to the greater PSA cutoff era (1989 to 1995) and lower PSA cutoff era (1996 to 2001). RESULTS: A significant downward clinical and pathological stage migration was found toward T1c and organ-confined disease, respectively, in men whose cancer was detected in the lower PSA cutoff era. Furthermore, men with cancer diagnosed in the lower PSA cutoff era had improved PFS rates 5 and 8 years after radical retropubic prostatectomy (P = 0.007). These changes occurred without a significant increase in the proportion of unimportant tumors (organ confined, smaller than 0.5 cm3 without a Gleason pattern of 4 or 5). CONCLUSIONS: These findings support the enhanced detection of favorable cancer and improved PFS rates with lower PSA cutoffs and more intensive biopsy regimens, although the follow-up and lead-time and length-time biases, as well as improvements in surgical technique, might also have affected these results.

Adult↗

PubMed2006

Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma.

BACKGROUND: ELAC2, MSR1, and RNASEL are candidate genes for hereditary prostate carcinoma (HPC). While, studies have demonstrated that single nucleotide polymorphisms (SNPs) in these genes are associated with sporadic disease as well as HPC, these results are often not replicated in follow-up studies. Given that the majority of patients studied had localized disease and up to 50% of localized prostate cancer is clinically insignificant, the inability to replicate the initial findings may reflect that some subjects had indolent tumors. Herein, we examine patients with metastatic disease to determine if an association exists between HPC SNPs and unambiguously significant prostate cancer. METHODS: We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays. RESULTS: Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented. Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk. Patients with both genotypes were of particularly high-risk (OR 2.66: 95% CI=1.36-5.19). CONCLUSIONS: These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease. ELAC2 and RNASEL SNP analysis may prove useful in determining which patients are at risk for developing clinically significant prostate carcinoma.

Base Sequence↗

PubMed2006

Prediagnosis prostate specific antigen velocity is associated with risk of prostate cancer progression following brachytherapy and external beam radiation therapy.

PURPOSE: Prostate specific antigen velocity 2.0 ng/ml per year or greater in the year before prostate cancer diagnosis is associated with cancer specific survival following radical prostatectomy and radiation therapy. We evaluated the relationship between prediagnosis prostate specific antigen velocity and cancer progression following primary radiation therapy. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study and identified 237 with clinically localized prostate cancer who elected primary radiation therapy. Our final cohort consisted of 130 men, including 83 treated with external beam radiation and 47 treated with brachytherapy. Patient specific variables at diagnosis were analyzed for their value in predicting biochemical progression using American Society for Therapeutic and Radiation Oncology criteria. RESULTS: Mean followup +/- SD was 64 +/- 35 months. Prostate specific antigen at diagnosis, family history of prostate cancer and prediagnosis prostate specific antigen velocity 2.0 ng/ml per year or greater were associated with cancer progression following brachytherapy or external beam radiation. Of men with prostate specific antigen velocity 2.0 ng/ml per year or greater 38% had cancer progression compared to 12% with prostate specific antigen velocity less than 2.0 ng/ml per year (OR 4.3, p = 0.003). The 6-year progression-free survival estimate was 57% in men with prostate specific antigen velocity 2.0 ng/ml per year or greater and 82% in men with prostate specific antigen velocity less than 2.0 ng/ml per year (p < 0.001). On multivariate analysis absolute prostate specific antigen at diagnosis and prostate specific antigen velocity 2.0 ng/ml per year or greater were independently associated with cancer progression in men treated with external beam radiation therapy or brachytherapy. CONCLUSIONS: Men with a prediagnosis prostate specific antigen velocity of 2.0 ng/ml per year or greater are at increased risk for cancer progression following brachytherapy or external beam radiation compared to men with a prostate specific antigen velocity of less than 2.0 ng/ml per year.

Adult↗

PubMed2006

Identifying men diagnosed with clinically localized prostate cancer who are at high risk for death from prostate cancer.

PURPOSE: We identified factors at diagnosis that are significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. MATERIALS AND METHODS: The study cohort included 1,453 men treated with radical prostatectomy (1,095) or external beam radiation therapy (358) for localized prostate cancer between 1989 and 2002. Cox regression multivariate analysis was used to evaluate whether prostate specific antigen, prostate specific antigen velocity, biopsy Gleason score and clinical tumor category at diagnosis were significantly associated with time to prostate cancer specific mortality following radical prostatectomy or external beam radiation therapy. RESULTS: In addition to increasing prostate specific antigen (p < or =0.04) and biopsy Gleason score 8 to 10 disease (p < or =0.02), prostate specific antigen velocity more than 2 ng/ml yearly was significantly associated with shorter time to prostate cancer specific mortality in patients treated with radical prostatectomy (adjusted HR 12, 95% CI 3 to 54) and external beam radiation therapy (adjusted HR 12, 95% CI 3 to 54) compared with that in men with prostate specific antigen velocity 2 ng/ml yearly or less (p < or =0.001). Despite low risk disease 7-year estimates of prostate cancer specific mortality were 5% to 19% in patients in whom prostate specific antigen increased by more than 2 ng/ml during the year before diagnosis compared with less than 1% in those with a prostate specific antigen increase of 2 ng/ml or less. CONCLUSIONS: Despite prostate specific antigen level less than 10 ng/ml and Gleason score 6 cancer a prostate specific antigen increase of more than 2 ng/ml during the year before diagnosis places a man at high risk for prostate cancer death following radical prostatectomy or external beam radiation therapy.

Aged↗

PubMed2006

Characteristics of patients with familial versus sporadic prostate cancer.

PURPOSE: There are conflicting reports concerning whether prostate cancer in families with multiple affected members has different clinical and pathological features than sporadic cases. In our study we compared the clinical characteristics, pathological outcomes and the 7-year biochemical progression-free rate in patients with apparent sporadic prostate cancer, affected sibling pairs, families with multiple affected members and families meeting the Johns Hopkins criteria for hereditary prostate cancer. MATERIALS AND METHODS: From 1983 to 2003, 3,478 men underwent radical retropubic prostatectomy by a single surgeon (WJC). Of these men 1,186 reported family history status. We compared age at surgery, prostate specific antigen at diagnosis, pathological tumor stage, Gleason score, tumor characteristics and 7-year biochemical progression-free survival rates in the groups using chi-square, 1-way ANOVA or Cox proportional hazards regression analysis. RESULTS: The 7-year biochemical progression-free survival rates were 81% for sporadic cases, 71% for sibling pairs, 72% for hereditary cases and 81% for high density family members (p = 0.3). Of the clinical and pathological features examined only age (p <0.0001) and positive surgical margin rate (p = 0.03) were significantly different among groups. CONCLUSIONS: In our study population clinicopathological features and progression-free survival are similar between sporadic and familial prostate cancer cases. The sibling pairs had a trend toward less favorable tumor features and progression-free survival, but the difference was not statistically significant.

Aged↗

PubMed2006

Comparison of methods for calculating prostate specific antigen velocity.

PURPOSE: Prostate specific antigen velocity is frequently calculated using regression analysis of multiple prostate specific antigen measurements during an interval of 18 to 24 months. It has been reported that the prostate specific antigen velocity in the year before prostate cancer diagnosis is associated with the cancer specific mortality rate following radical prostatectomy and radiation therapy. There are limited data comparing alternate methods of calculating prostate specific antigen velocity. In this study we compared simple arithmetic prostate specific antigen velocity calculations to the more complicated regression analysis using prostate specific antigen measurements from varying intervals to determine whether the methods were interchangeable. MATERIALS AND METHODS: From 2003 to 2005 a total of 540 men underwent radical retropubic prostatectomy for localized prostate cancer. Preoperative prostate specific antigen velocity was calculated using arithmetic and linear regression methods during 12 and 18-month intervals. The correlation, mean and median prostate specific antigen velocity were compared among methods. RESULTS: Prostate specific antigen velocity calculations using simple arithmetic and linear regression had a strong correlation when restricted to prostate specific antigen values from 12 months before diagnosis (r = 0.92). When prostate specific antigen measurements beyond 1 year were included in the calculation, prostate specific antigen velocity was significantly lower than in the 12 months before cancer diagnosis. CONCLUSIONS: Using a simple arithmetic prostate specific antigen velocity calculation yields results comparable to those of the more complicated regression analysis when restricted to prostate specific antigen values from within the year before diagnosis in patients with clinically localized prostate cancer. In this manner arithmetic prostate specific antigen velocity calculations may be used in daily clinical practice to help predict the outcome following definitive therapy. Prostate specific antigen velocity is significantly lower when calculated during a longer interval before prostate cancer diagnosis.

Disease Progression↗

PubMed2006

Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality.

OBJECTIVES: To compare the preoperative characteristics, postoperative prostate-specific antigen (PSA) doubling time (DT), and prostate cancer-specific mortality (PCSM) estimates after PSA failure in men diagnosed during a screening study versus a community referral population. A PSA-DT of less than 3 months is a surrogate endpoint for PCSM. METHODS: From 1988 to 2002, 1492 of 9637 patients with clinically localized prostate cancer underwent radical prostatectomy and experienced PSA failure. They were either participating in a screening study (n = 841) or attended 1 of 44 community-based practices (n = 611). The distributions of PSA, Gleason score, tumor stage, and PSA-DT were compared using chi-square metric. The estimates of PCSM after PSA failure were compared using Gray's P value. RESULTS: Compared with the community population, the annually screened men experiencing PSA failure had a lower PSA level at diagnosis (5.1 versus 9.5 ng/mL, P <0.0001), were less likely to have Gleason score 7 to 10 cancer (25.1% versus 42.1%, P <0.0001), and were more likely to have low-risk disease (64.5% versus 23.8%, P <0.0001). Furthermore, the screened cohort had a reduction (P <0.0001) in the proportion with a PSA-DT of less than 3, 3 to 5.99, and 6 to 11.99 months and a significant increase in the proportion with a PSA-DT of 12 months or longer. After a median follow-up of 4.5 and 4.1 years after PSA failure in the screened and community cohorts, respectively, the PCSM estimates were lower (P = 0.0002) in the screened cohort (10-year estimate 3.6% [95% confidence interval 1.3 to 5.8] versus 11.3% [95% confidence interval 5.9 to 17.4]). CONCLUSIONS: Patients diagnosed by annual prostate cancer screening appeared more likely to experience an indolent PSA recurrence and less likely to die of prostate cancer after PSA recurrence compared with patients referred from the community.

Adult↗

PubMed2006

Pathological characteristics of prostate cancer detected through prostate specific antigen based screening.

PURPOSE: Since the introduction of PSA testing for CaP, there has been an increase in CaP detection. However, it is uncertain to what extent clinically insignificant tumors are being diagnosed and treated. In a large, community based population we determined the pathological characteristics of screening detected cancers. MATERIALS AND METHODS: From 1989 to 2001, 35,661 men were enrolled in a longitudinal prostate cancer screening study. Data were available on 3,492 of the 3,568 men (98%) diagnosed with CaP during this study period. Radical prostatectomy was performed in 2,254 men (63%). Clinical stage, Gleason score and pathological analysis were recorded and analyzed in the context of preoperative PSA, digital rectal examination findings, PSA velocity and the year of cancer detection. RESULTS: CaP was detected in 10% of men. Virtually all cases were clinically localized (99.8%) and approximately 70% treated with radical prostatectomy were pathologically organ confined disease. Fewer than 10% of tumors would be considered clinically insignificant based on 2 previously published pathological criteria. CONCLUSIONS: Compared to the high prevalence of CaP found in autopsy studies there is a lower detection rate using current screening protocols. Although the outcomes are unknown if these tumors had been left untreated, the majority met pathological criteria for significant cancer.

Adult↗

PubMed2006

Evidence to support a continued stage migration and decrease in prostate cancer specific mortality.

PURPOSE: We evaluated whether the proportion of patients with a postoperative PSA-DT less than 3 months, a surrogate for PCSM, decreased significantly during the PSA era. MATERIALS AND METHODS: Between July 1988 and July 2002, 3,719 men with clinically localized prostate cancer treated with RP comprised the study cohort. A chi-square metric was used to compare the preoperative and postoperative characteristics, 5-year actual PSA failure rates, and PSA-DTs for patients treated during the 2 equally divided eras of the early PSA era, July 1988 to July 1995 and the late PSA era, August 1995 to July 2002. RESULTS: Patients presenting in the more recent PSA era were of younger age (p < 0.0001), with earlier stage (p < 0.0001) and lower grade disease (p = 0.01). Similarly, patients had lower grade (p < 0.001), stage (p < 0.0001), and positive margin (p < 0.0001) and lymph node rates (p = 0.0002) at RP. The 5-year actual PSA failure rates decreased from 14.3% in the early PSA era to 2.5% in the later PSA era (p < 0.0001). There was a 37% reduction in the proportion of patients with a PSA-DT less than 3 months, corresponding to a decrease in absolute magnitude from 9% to 5.7% between the 2 eras. Absolute reductions of 3.1% and 9% were also noted for the proportion of PSA-DTs of 3 to 5.99 months and 6 to 11.99 months, respectively, whereas PSA-DTs of 12 months or greater increased by 15.3%. CONCLUSIONS: During the recent PSA era, postoperative PSA failure has significantly decreased and PSA-DTs have increased, suggesting that PCSM will continue to decrease.

Aged↗

PubMed2005

Identifying patients at risk for significant versus clinically insignificant postoperative prostate-specific antigen failure.

PURPOSE: We evaluated whether men at risk for significant versus clinically insignificant prostate-specific antigen (PSA) failure after radical prostatectomy could be identified using information available at diagnosis. PATIENTS AND METHODS: A prospective prostate cancer screening study that enrolled, diagnosed, and treated 1,011 men with radical prostatectomy at Barnes-Jewish Hospital (St Louis, MO) from January 1, 1989, to June 1, 2002, for localized prostate cancer formed the study cohort. Preoperative predictors of a postoperative PSA doubling time (DT) of less than 3 months and more than 12 months or no PSA failure were identified using logistic regression. RESULTS: A preoperative PSA velocity more than 2.0 ng/mL/yr (P = .001) and biopsy Gleason score 7 (P = .006) or 8 to 10 (P = .003) were significantly associated with having a postoperative PSA DT less than 3 months. A PSA level less than 10 ng/mL (P = .005), a nonpalpable cancer (P = .001) with a Gleason score < or = 6 (P = .0002), and a preoperative PSA increase that did not exceed 0.5 ng/mL/yr (P = .03) were significantly associated with a postoperative PSA DT of at least 12 months or no PSA failure. Most men with these preoperative characteristics and a postoperative PSA DT of 12 months or more had a persistent postoperative PSA level of at least 0.2 ng/mL that did not exceed 0.25 ng/mL after a median follow-up of 3.6 years. CONCLUSION: A postoperative PSA DT less than 3 months is associated with a preoperative PSA velocity more than 2.0 ng/mL/yr and high-grade disease. Select men with a postoperative PSA DT more than 12 months may not require salvage radiation therapy.

Aged↗

PubMed2005

High-grade prostatic intraepithelial neoplasia in needle biopsy as risk factor for detection of adenocarcinoma: current level of risk in screening population.

OBJECTIVES: To assess the current incidence of prostate carcinoma detection in serial biopsies in a prostate-specific antigen-based screening population after a diagnosis of isolated high-grade prostatic intraepithelial neoplasia (HG-PIN) in needle biopsy tissue. METHODS: We retrospectively identified 190 men with a diagnosis of isolated HG-PIN in needle biopsy tissue. Most men (86%) were diagnosed from 1996 to 2000. Logistic regression analysis was used to predict the presence of carcinoma in these 190 men and in a control group of 1677 men with only benign prostatic tissue in needle biopsy tissue. RESULTS: The cumulative risk of detection of carcinoma on serial sextant follow-up biopsies was 30.5% for those with isolated HG-PIN compared with 26.2% for the control group (P = 0.2). Patient age (P = 0.03) and serum prostate-specific antigen level (P = 0.02) were significantly linked to the risk of cancer detection, but suspicious digital rectal examination findings (P = 0.1), the presence of HG-PIN (P = 0.2), and the histologic attributes of PIN were not (all with nonsignificant P values). HG-PIN found on the first repeat biopsy was associated with a 41% risk of subsequent detection of carcinoma compared with an 18% risk if benign prostatic tissue was found on the first repeat biopsy (P = 0.01). CONCLUSIONS: The results of our study have shown that the current level of risk for the detection of prostate carcinoma in a screened population is 30.5% after a diagnosis of isolated HG-PIN in a needle biopsy. This risk level is lower than the previously reported risk of 33% to 50%. HG-PIN is a risk factor for carcinoma detection only when found on consecutive sextant biopsies. The data presented here should prompt reconsideration of repeat biopsy strategies for HG-PIN, and re-evaluation of the absolute necessity of repeat biopsy for all patients with HG-PIN.

Adenocarcinoma↗