Log Prostate-specific Antigen Research Articles

A risk model for detecting clinically significant prostate cancer based on bi-parametric magnetic resonance imaging in a Japanese cohort

Selective identification of men with clinically significant prostate cancer (sPC) is a pivotal issue. Development of a risk model for detecting sPC based on the prostate imaging reporting and data system (PI-RADS) for bi-parametric magnetic resonance imaging (bpMRI) and clinical parameters in a Japanese cohort is expected to prove beneficial. We retrospectively analyzed clinical parameters and bpMRI findings from 773 biopsy-naïve patients between January 2011 and December 2016. A risk model was established using multivariate logistic regression analysis and presented on a nomogram. Discrimination of the risk model was compared using the area under the receiver operating characteristic curve. Statistical differences between the predictive model and clinical parameters were analyzed using DeLong test. sPC was detected in 343 men (44.3%). Multivariate logistic regression analysis to predict sPC revealed age (P = 0.002), log prostate-specific antigen (P < 0.001), prostate volume (P < 0.001) and PI-RADS scores (P < 0.001) as significant contributors to the model. Area under the curve was higher for the risk model (0.862), than for age (0.646), log prostate-specific antigen (0.652), prostate volume (0.697) or imaging score (0.822). DeLong test results also showed that the novel risk model performed significantly better than those parameters (P < 0.05). This novel risk model performed significantly better compared with PI-RADS scores and other parameters alone, and is thus expected to prove beneficial in making decisions regarding biopsy on suspicion of sPC.

PROSPER subgroup analysis by age and region: Overall survival and safety in men with nonmetastatic castration-resistant prostate cancer receiving androgen deprivation therapy plus enzalutamide.

84 Background: Previous reports on the PROSPER trial have shown that enzalutamide (ENZA) plus androgen deprivation therapy (ADT) significantly improves metastasis-free survival and overall survival (OS) over placebo (PBO) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) and rapidly rising prostate-specific antigen (PSA) levels. (Hussain et al. N Engl J Med. 2018;378:2465-2474/Sternberg et al. N Engl J Med. 2020;382:2197-2206). To inform decision-making for specific patients, we report here a post hoc analysis of OS and safety in subgroups of PROSPER by age and region. Methods: PROSPER included men with nmCRPC and a PSA doubling time ≤ 10 months. Enrolled men continued ADT and were randomized 2:1 to ENZA 160 mg once daily vs PBO. We performed a multivariable analysis for OS, including age (≤ 70 yrs and &gt; 70 yrs), geographic region, and other variables and further examined exposure-adjusted adverse events (AEs) by age and region. Results: Based on this post hoc analysis, OS benefit with ENZA treatment was similar across geographic regions (table) and for patients aged ≥ 70 yrs (hazard ratio [HR] 0.73; 95% CI 0.58-0.9) and those aged &lt; 70 yrs (HR 0.72, 95% CI 0.5-1.04). In our multivariate analysis, 3 factors emerged as significantly impacting estimated OS: Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0; HR 1.7; 95% CI 1.4-2.1), log of PSA (HR 1.2; 95% CI 1.1-1.3), and use of subsequent therapy (yes vs no; HR 2.5; 95% CI 2.1-3.1). Overall safety was consistent between age groups and across geographic regions. The proportion of patients reporting any grade treatment-emergent AEs (TEAEs) related to ENZA use was similar between age groups but decreased with increasing age. Conclusions: In men with nmCRPC and rapidly rising PSA, ENZA plus ADT treatment reduced the risk of death, regardless of age or geographic location. Patients reported any grade TEAEs at a similar proportion in both arms. Variables impacting OS included ECOG status, log PSA, and subsequent therapy. Clinical trial information: NCT02003924. [Table: see text]

The Modulating Effects of Benign Prostate Enlargement Medications on Upgrading Predictors in Patients with Gleason 6 at Biopsy

Background: Upgrading following prostate biopsy is very common in clinical practice. This study investigated whether the use of 5-alpha reductase inhibitors (ARI) and alpha blockers affect known clinical predictors of Gleason score upgrading or not. Materials and Methods: A retrospective study on 998 patients treated with robotic assisted laparoscopic prostatectomy for clinically localized biopsy Gleason score 6 prostate cancer were studied. The logarithm of prostate specific antigen concentration, prostate size and tumor volume were compared on the basis of the medication history of 5-ARIs and alpha blockers in the cohort of biopsy Gleason 6 patients with benign prostatic hyperplasia history, and patients whose prostate sizes fall in the top quartile. We compared known clinical and pathologic characteristics associated with upgrading in regression models with and without the addition of medications. Results: Alpha blockers, but not 5-ARI were associated with a bigger prostate. Upgrading was associated with older age (OR 1.03, 95% CI 1.01-1.06), higher BMI (OR 1.00 CI 1.01-1.08), higher log prostate specific antigen (OR 7.32, CI 3.546-15.52), smaller prostate size (OR 0.97, CI 0.96-0.98), fewer biopsy cores (OR 0.96 CI 0.92-0.99), more positive cores (OR 1.20, CI 1.08-1.34), and higher percentage of tumor at biopsy (OR 1.02, CI 1.01-1.03). Neither of the two medication classes were a significant predictor of upgrading. Medications made minimal changes in the multivariate predictive models. Conclusion: Although, alpha blockers were associate with bigger prostate size, the modulating effects of alpha blockers and 5-ARIs on common predictors of Gleason score upgrading was not significant.

Prostate-specific antigen (PSA) trajectories correlate with overall survival (OS) in men treated with abiraterone acetate plus prednisone (AA+P) or placebo plus prednisone: A post-hoc analysis of COU-AA-301 trial data.

e16528 Background: Treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) have been expanding. AA+P is one therapy that prolongs OS in men with mCRPC. However, it remains challenging to predict the prognosis of men shortly after starting therapy. We identified patterns of PSA change over time (trajectories) for men in the COU-AA-301 trial and examined the association between PSA trajectory and OS. Methods: Data from both treatment arms of the COU-AA-301 trial were used, restricting to men with ≥6 months of follow-up. Log PSA at the first 2 visits post-randomization (84 and 168 days) was used in a modelling procedure to stratify men into 3 groups, each comprised of men with a differing PSA trajectory. Univariate Cox regression assessed the association between trajectory group and OS. Among AA+P patients, predictors of a better trajectory group were identified using multivariate multinomial logistic regression. Results: A total of 913 men (634 AA+P; 279 placebo) were included in the analysis. Group 1 had the lowest mean PSA at both visits post-randomization while Group 3 had the highest. The percent of men in each group and associations with OS are shown in the table. AA+P treated men were more likely to be in a favorable group. Versus Group 1, risk of death was 2.8 and 4.9 times higher in Group 2 and 3, respectively. Exploratory modelling among AA+P patients identified that older age and higher baseline log PSA were among the most important predictors of being assigned to a worse PSA trajectory group (Group 2 or 3 vs 1). Conclusions: In a post-hoc analysis of COU-AA-301 trial data, 3 PSA trajectories over the first 6-months post-randomization were identified and correlated with OS. AA+P treated men were more likely to have a favorable PSA trajectory. The findings suggest that AA+P may be associated with PSA changes post-initiation that may in turn predict survival, although further study is needed. [Table: see text]

Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.

BackgroundA possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy.MethodsThree hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values.ResultsCompared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002).ConclusionsWe found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.

Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy.

Increases in serum levels of prostate-specific antigen (PSA) occur commonly in prostate cancer after radical prostatectomy and are designated "biochemical recurrence." Because the phytochemical sulforaphane has been studied extensively as an anticancer agent, we performed a double-blinded, randomized, placebo-controlled multicenter trial with sulforaphane in 78 patients (mean age, 69 ± 6 years) with increasing PSA levels after radical prostatectomy. Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months (M0-M6) followed by 2 months without treatment (M6-M8). The study was designed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6. The primary endpoint was not reached. For secondary endpoints, median log PSA slopes were consistently lower in sulforaphane-treated men. Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group (+0.099 ± 0.341 ng/mL) than in placebo (+0.620 ± 1.417 ng/mL; P = 0.0433). PSA doubling time was 86% longer in the sulforaphane than in the placebo group (28.9 and 15.5 months, respectively). PSA increases >20% at M6 were significantly greater in the placebo group (71.8%) than in the sulforaphane group (44.4%); P = 0.0163. Compliance and tolerance were very good. Sulforaphane effects were prominent after 3 months of intervention (M3-M6). After treatment, PSA slopes from M6 to M8 remained the same in the 2 arms. Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy.

The risk of prostate cancer for men on aspirin, statin or antidiabetic medications

BackgroundA decreased risk of prostate cancer (PCa) has been suggested in men taking aspirin, statins and metformin, although the evidence has been conflicting. We estimated the association between prescribed medications, prostate specific antigen (PSA) levels and the risk of either any PCa or high-grade PCa. MethodsThis population-based cohort study included 185,667 men having a first recorded PSA test and 18,574 men having a first prostate biopsy in Stockholm County, Sweden for the period 2007–2012. Detailed clinical information including PSA levels, biopsy results, comorbidities and educational level were obtained from population-based registers. High-grade prostate cancer was defined as a Gleason score of seven or higher. Differences in PSA levels by medication status were estimated using linear regression on log PSA values. PCa risk was estimated using multivariate logistic regression. ResultsCompared with men who were not on medication, the PSA level at the first PSA test was lower among men using 75mg/dose aspirin (−3.9% change in PSA concentration; 95% confidence interval (CI): −5.8 to −2.1), statin (−4.6%; 95% CI: −6.2 to −2.9), metformin (−14%; 95% CI: −17 to −12) and insulin (−16%; 95% CI: −18 to −14). Men using any statins had an increased risk of both high-grade PCa (odds ratio (OR) 1.25; 95% CI: 1.10–1.42) and PCa of any grade (OR 1.16; 95% CI 1.04–1.29). There were no significant associations between aspirin or any antidiabetic medication and the risk of PCa. ConclusionWe found no protective effect of aspirin, statins or antidiabetics in terms of risk for any PCa or high-grade PCa. Use of any statins was associated with an elevated risk of being diagnosed with high-grade prostate cancer.

Genetic variants at 1q32.1, 10q11.2 and 19q13.41 are associated with prostate-specific antigen for prostate cancer screening in two Korean population-based cohort studies

Prostate-specific antigen (PSA) levels are affected by non-cancerous conditions such as benign prostatic hyperplasia, inflammations, and inherited factors. To search for genetic variants associated with PSA levels, we conducted a genome-wide association study (GWAS) using a two-stage design. A total of 554 men from the Korean Cancer Prevention Study-II were used as a discovery stage and 1575 men collected by the Korean Genome Epidemiology Study were used as a replication stage. Analysis by Genome-wide Human single-nucleotide polymorphism (SNP) array 5.0 was performed by using DNAs derived from venous blood. We analyzed the association between genetic variants and PSA levels using multivariate linear regression models, including age as a covariate. We detected 12 genome-wide significant signals on chromosome 1q32.1, 10q11.2, and 19q13.41 between PSA levels and SNPs. The top SNP associated with log PSA levels was rs2153904 in SLC45A3 (p values, 5.24×10−9 to 2.00×10−6). We also investigated GWAS using 754 subjects from KCPS-II cohort whether our genome-wide significant loci were associated with a risk of prostate cancer (PCa) (200 PCa cases and 554 controls). Three of the SNPs on 10q11.2, rs7077830, rs2611489, and rs4631830, were associated with a risk of PCa. However, two loci, 1q32.1 and 19q13, were not significantly associated with a PCa risk. We suggest that our results for some but not all PCa risk SNPs to be associated with PSA levels could be used as an evidence for the advance of individual PCa screening strategies, such as applying a personalized cutoff value for PSA.

Poor Glycemic Control is Associated with Reduced Prostate Specific Antigen Concentrations in Men with Type 1 Diabetes

Previous studies have revealed lower prostate specific antigen concentrations in men with type 2 diabetes, paralleling the reported lower prevalence of prostate cancer in diabetic men. Data are lacking on prostate specific antigen in men with type 1 diabetes whose insulin and obesity profiles differ from those with type 2 diabetes mellitus. In this study we examined the relationship between long-term glycemic control and prostate specific antigen in men with type 1 diabetes mellitus. Total prostate specific antigen was measured at one time in 639 men in the EDIC, the observational followup of participants in the DCCT. The relationship between DCCT/EDIC weighted mean hemoglobin A1c and log prostate specific antigen was assessed using linear regression modeling after adjusting for age, body mass index, total testosterone, statin and thiazide medication use, diabetes duration, and DCCT randomization arm and cohort. Median subject age was 52 years, body mass index was 28.4 kg/m(2) and DCCT/EDIC time-weighted hemoglobin A1c was 7.9%. Median prostate specific antigen was 0.64 ng/ml (IQR 0.43, 1.05). Prostate specific antigen increased significantly with age (p <0.0001) and with lower time-weighted hemoglobin A1c (p <0.0001). Each 10% increase in hemoglobin A1c was accompanied by an 11% reduction in prostate specific antigen (p=0.0001). Prostate specific antigen decreases as hemoglobin A1c increases in men with type 1 diabetes mellitus. This relationship is independent of age, body mass index, androgen levels, medication use and measures of diabetes severity, which suggests that factors related to glycemia may directly affect prostate specific antigen levels.

Prostate-Specific Antigen Kinetics and Outcomes in Patients with Bone Metastases from Castration-Resistant Prostate Cancer Treated with or Without Zoledronic Acid

BackgroundZoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear. ObjectiveTo evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database. Design, setting, and participantsExploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n=643) randomized to ZOL or placebo every 3 wk. Outcome measurements and statistical analysisPSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression (BDP), and death were calculated per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the study median (PSA: 77.3 ng/ml) as the high/low cut-off point. Results and limitationsA total of 202 placebo- and 434 ZOL-treated patients were assessable. In both groups, PSA increases correlated with significantly increased risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated increases in risk per 1 log (nanograms per milliliter) PSA increase were 29% (p<0.0001) and 10% (p<0.0074), respectively, for BDP, and 24% (p=0.0010) and 13% (p=0.0079), respectively, for first SRE. Limitations include the retrospective nature of these analyses and the potential confounding effects of concurrent antineoplastic therapies. ConclusionsPSA is an important prognostic tool for survival in patients with bone metastases from CRPC, and these analyses show that PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy.

Should prostate-specific antigen velocity be abandoned?

Should prostate-specific antigen velocity be abandoned?

Evaluation of Prostate Specific Antigen Acceleration for Prostate Cancer Diagnosis

Prostate specific antigen acceleration can be calculated as the slope of log prostate specific antigen vs time, where log is the natural logarithm. We determined the best interval in which prostate specific antigen acceleration can be calculated with the best result in terms of specificity and sensitivity for prostate cancer diagnosis. Entered in the study were 741 men who underwent transrectal ultrasound guided prostate biopsy with 12 or more cores and at least 3 prior consecutive prostate specific antigen measurements in at least 365 days. Prostate specific antigen acceleration was calculated as the slope of log prostate specific antigen vs time using a minimum of 3 prostate specific antigen measurements. Acceleration was evaluated at different intervals, including within 1 year (365 days), 2 years (730 days), 3 years (1,095 days), 4 years (1,460 days), 5 years (1,825 days) and 6 years (2,190 days) before the last measurement. A total of 255 cancers (34.4%) were found. On ROC analysis the AUC of prostate specific antigen acceleration (0.728, 95% CI 0.694-0.760) was better than that of prostate specific antigen, prostate specific antigen velocity and prostate specific antigen doubling time. The highest AUC of prostate specific antigen kinetics was for prostate specific antigen acceleration calculated within 3 to 4 years (731 to 1,460 days) before the last measurement. Three or more prostate specific antigen measurements within 3 to 4 years (731 to 1,460 days) before the last measurement enabled more accurate calculation of prostate specific antigen acceleration than measurement within 1 to 2 years (0 to 730 days).

Positive biopsy (bx) rates for prostate cancer (PCA) based on prostate specific antigen (PSA) grouping in a large cancer screening trial: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

4563 Background: PLCO is a large-scale, randomized study to determine whether certain screening tests reduce the number of deaths from these cancers. Methods: PLCO compared certain screening procedures to a control group to determine the sensitivity, specificity and overall mortality reduction of these screening tests. For PCA, digital rectal examination (DRE) and PSA were done at baseline and annually × 5. 38,342 men were randomized to the screening arm. 6,301 men had a PSA >4 and were analyzed for PCA by PSA groupings. Results: Four groups were analyzed. Group 1 (first positive PSA) 2,830 men; Group 2 (prior PSA, first positive PSA) 3,471 men; Group 3 (multiple positive PSA, no bx) 2,350 men; Group 4 (multiple positive PSA, prior negative bx) 1,557 men. Biopsy rates for the groups were: Group 1 1,125/2,830 (39%), Group 2 1,244/3,471 (35%), Group 3 960/2,350 (40%), Group 4 474/1,557 (30.4%). Positive biopsies for PCA were: Group 1 502/1,125 (44.6%), Group 2 472/1,244 (37.9%), Group 3 402/960 (41.8%), Group 4 177/474 (37.3%). Factors were analyzed to determine if demographic factors influenced positive bx rates for cancer. Factors analyzed included PSA, age, prior bx, prostate symptoms, education, race, hypertension, smoking, heart disease, BMI, prior STD's. Chi-squared and logistic regression analyses were used to determine factors. For all groups not controlling for PSA with prostate cancer as an outcome, race (Black) and family history of prostate cancer increased likelihood bx resulted in cancer. Prior negative PSA, prostate problems, decreased likelihood bx resulted in PCA diagnosis. When controlling for log PSA, family history of PCA and race (Black) remained significant factors for positive PCA bx. Factors demonstrating decreased risk for prostate cancer with bx were prostate problem, >1 PSA, education <12 years, race (Asian). Other medical conditions (hypertension, heart disease), BMI, STD did not affect positive bx rates. PCA did not vary significantly by stage of PCA or Gleason score for the groups. Conclusions: Factors influencing positive PCA biopsy rates include family history of PCA and log PSA and race. No significant financial relationships to disclose.

Definition of Biochemical Recurrence After Radical Prostatectomy Does Not Substantially Impact Prognostic Factor Estimates

Biochemical recurrence serves as a surrogate end point after radical prostatectomy. Many definitions of biochemical recurrence are currently used in the research literature. We examined various definitions in a large clinical cohort to explore whether estimation differs by definition. The cohort included 5,473 patients who underwent radical prostatectomy from 1985 to 2007 at our cancer center. Separate analysis was done with 12 definitions of biochemical recurrence used in published studies. Cox regression was done to estimate HRs for established predictors. Predictive accuracy was determined using the concordance index. Depending on the definition the recurrence-free probability was 86% to 91% at 3 years and 81% to 87% at 5 years. HRs tended to be smaller for the most inclusive definitions but were fairly similar across all definitions. The univariate HR was 2.1 to 2.4 for log prostate specific antigen, 2.4 to 2.6 for clinical stage T2b vs T2a or less and 9.8 to 15 for biopsy Gleason grade 8 or greater vs 6 or less. Multivariate HRs were more homogeneous across the definitions. The concordance index was 0.79 to 0.83 and 0.83 to 0.87 for the preoperative and postoperative nomograms, respectively. Estimates of risk ratios and predictive accuracy are generally robust to the biochemical recurrence definition. For clinical research, groups using different definitions will come to similar conclusions on prognostic factors. The definition should be factored into studies comparing overall recurrence probabilities.

Changes in Baseline PSA Levels in Japanese Men From 1988 to 2003

According to epidemiologic surveys, the number of deaths from prostate cancer in Japanese men increased rapidly from 1970 to 2006. However, it is difficult to know the real incidence of, and mortality due to, prostate cancer because the reliability of death certificates and the cancer registry system in Japan are poor. Recently, several studies have demonstrated that baseline prostate-specific antigen (PSA) levels could be one of the most important predictive factors for developing prostate cancer. Therefore, we hypothesized that changes in the baseline PSA distribution in the screening population could reflect trends in the true incidence rate of prostate cancer. From 1988 to 2003, 32,274 men, aged 50-79 years, participated in population-based screening for prostate cancer for the first time in Gunma Prefecture, Japan. Changes in the baseline PSA distributions, stratified by a 5-year age range and calendar year, were investigated. The relationships between age and log(10) PSA levels were also investigated and stratified by calendar year. The median baseline PSA level was 0.9-1.2 ng/mL and had not recently increased. No specific trends were found in the percentages of participants with a PSA level greater than 2.0, 4.0, or 10.0 ng/mL within the same age range during the 16-year period. The increase in the incidence of, and mortality rates for, prostate cancer demonstrated by epidemiologic research might have been misleading in Japan. Investigational changes in the baseline prostate-specific antigen (PSA) distribution of the screened populations revealed that the true incidence rate of prostate cancer in Japan might have been almost the same during the past 16 years.

A Dietary Intervention for Recurrent Prostate Cancer After Definitive Primary Treatment: Results of a Randomized Pilot Trial

Considerable evidence has shown that diet can affect both the incidence and the progression of prostate cancer. The objective of this study was to determine whether men in this situation could make a change to a diet emphasizing plant-based foods and fish and to examine the effect on quality of life (QOL) and prostate-specific antigen (PSA) velocity. A total of 36 men and their partners were randomly assigned to attend a series of 11 dietary and cooking classes that also integrated mindfulness practice as a support in making the change or a wait-list control group. Assessments were made of dietary intake, QOL, and PSA at baseline, after intervention (11 weeks), and 3 months after intervention. The intervention group showed significant reductions in the consumption of saturated fat and increased consumption of vegetable proteins with accompanying reductions in animal proteins, including dairy products. They also showed increased QOL. Although no significant change was found in the rate of PSA increase between the two groups, the mean PSA doubling time for the intervention group was substantially longer at the 3-month follow-up visit than that of the controls. Men with a increasing PSA level after primary treatment were able to make a change to a prostate-healthy diet, accompanied by increases in QOL. No significant difference was found in the log PSA slope between the two groups; however, the PSA doubling time increased substantially in the intervention group compared with that in the controls. Future trials should examine the effect of the prostate-healthy diet with a larger sample of men for a longer period.

Comparison of calcaneal bone density in operative versus non-operative army personnel

Purpose: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels.Methods and Materials: Weekly serum PSA values were determined during radiotherapy (RT)_in nine patients (“treatment group”) without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes fr the rate of change in PSA was determined using model: log PSA = β0 + β1∗week + β2∗week2 + error. These results are compared with 17 normal volunteers (“control group”) who were not exposed to ionizing irradiation. an attempt is made to compare any similarities and differences in subsets of 64 T1–T4NOMO PC patients who received pelvic RT.Results: An elevation in the serum PSA levels were noted in eight of nine patients in the “treatment group” with a median time of 4.2 weeks to reach the maximum serum PSA values. After an initial increase, PSA values declined. In some patients, manifold increase in PSA was noted, for exampel, from 1.8 to 13.5 ng/ml and 3.3 to 9.8 ng/ml in two patients. The PSA increase ranged from 50–650%. The median slope was 0.601 week−1 (range 0.192–3.045 week−1). No such increases were seen in the “control group” (median slope = 0.03 week−1; range, 0.18–0.13 week−1). When diffrences between the mean increase/decrease for each week compared to pretreatment values were analyzed, the irradiated group had statistically significant elevations in the PSA for weeks 3 (p = 0.034), 4 (p = 0.24). A similar ternd of increasing PSA levels during radiotherapy was noted in prostate cancer patients whose initial PSA values were ≤ 20 ng/ml: whereas positive slopes (i.e., increasing PSA levels during radiotherapy course) was seen in 7.1% of those with > 20 ng/ml preradiotherapy PSA values, such trends were seen in52.7% of those with ≤ 20 ng/ml preradiotherapy PSA values.Conclusion: (a) Incidental exposure of noncancerous prostate to ionizing irradiation appears to lead to an initial elevation followed by a decline in serum PSA. (b) Similar elevations in serum (PSA) levels are seen in over 50% of prostate cancer patients with ≤ 20 ng/ml pretreatment PSA. (c) Acinal cell death and sudden release of PSA into the circulation is the most likely explanation for our observations, although other mechanism cannot be excluded. (d) Our observations have to be considered in modeling PSA kinetics induced by RT and in correlating such kinetics to long-term outcomes. (e0 Our findings in the control group indicate that there appears to be no significant variation in serum PSA over many weeks under physiological conditions in normal healthy ambulatory men.

The Relationship Between Serum Prostate Specific Antigen Level and Tumor Volume Persists in the Current Era

We compared the relationships of serum prostate specific antigen to tumor volume and to noncancerous prostate tissue volume using multivariate analysis in men undergoing prostatectomy during 2 periods. From our prostatectomy database we randomly selected 200 men from 1991 to 1994 (early group) and 200 from 2000 to 2003 (recent group) who underwent radical prostatectomy without neoadjuvant therapy. The variables analyzed were patient age, log prostate specific antigen, pathological stage, Gleason score, log total tumor volume and log noncancerous prostate tissue volume. Univariate correlation and multiple regression analyses were performed to assess the linearity of the relationships among the variables. There was a significant difference between the early and recent groups in age (median 64 years, IQR 58-67 vs 59, IQR 53-65; p<0.001), prostate specific antigen (8.3 ng/ml, IQR 5.7-12.5 vs 5.8, IQR 4.4-7.8; p<0.001), total tumor volume (2.0 cc, IQR 1.0-3.6 vs 1.4, IQR 0.6-2.9; p<0.001), Gleason score (7, IQR 7-8 vs 7, IQR 7-7; p<0.001) and the incidence of extraprostatic disease (39% vs 18.5%, p<0.001) but not in noncancerous prostate tissue volume (35.7 cc, IQR 28.6-46.5 vs 37.1, IQR 28.9-50.1). There was a relationship between log prostate specific antigen and log total tumor volume (r=0.486, p<0.001 and r=0.237, p<0.01), and between log prostate specific antigen and log noncancerous prostate tissue volume (r=0.179, p<0.05 and r=0.138, p=0.051) in the early and the recent groups, respectively. Multiple regression analyses revealed that log total tumor volume, log noncancerous prostate tissue volume and Gleason score were significant independent variables for predicting log prostate specific antigen in the 2 groups. In the recent group log noncancerous prostate tissue volume had the most significant association with log prostate specific antigen (p<0.001), whereas in the early group log total tumor volume had the most significant association (p<0.001). Although the relationship between serum prostate specific antigen and tumor volume decreased from early treatment years to recent years, the association remained at a significant level. In recent years noncancerous prostate tissue volume had the most significant association with prostate specific antigen.

Prostate volume and prostate-specific antigen levels in men enrolled in a large screening trial

Objectives Prostate volume correlates both with prostate-specific antigen (PSA) values and with the presence of benign prostatic hyperplasia (BPH). Here we examine the relationship between prostate volume and PSA level in a large, geographically diverse sample of men undergoing prostate cancer screening. Methods We followed 35,323 men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Each man was screened with digital rectal examination (DRE) and PSA levels for up to 4 years. Prostate volume was estimated by DRE performed by trained examiners at the PLCO sites. Linear and logistic regression was used to assess the effect of prostate volume and age on PSA levels. Regression coefficients were adjusted for the effect of prostate volume measurement error. Results Prostate volume estimated by DRE showed considerable measurement error. Averaging volume over screening visits and accounting for examiner bias greatly reduced this error. Linear regression analysis showed a slope of 0.030/cm 3 of log PSA on prostate volume when correcting for measurement error (95% confidence interval [CI], 0.029 to 0.031). Age was independently associated with (log) PSA, with a slope of 0.022 per year. Logistic regression analysis of the risk of having an elevated PSA value (exceeding 4 ng/mL) showed an odds ratio of 1.9 (95% CI, 1.8 to 2.0) associated with a 10 cm 3 increase in prostate volume. The correlation of log PSA and prostate volume was 0.37. Prostate volume was not correlated with body mass index and showed weak correlation ( r = 0.14) with age. Conclusions Prostate volume and age are independently associated with increased PSA levels in a population of men undergoing screening.

Markers of Bone Metabolism and Survival in Men with Hormone-Refractory Metastatic Prostate Cancer

To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer. The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status. Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95% confidence interval, 0.628-0.715; P < 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAP. Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival.