Rate Of Prostate-specific Antigen Change Research Articles

Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost and whole pelvic radiotherapy for intermediate- and high-risk prostate cancer.

Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate specific antigen (PSA) kinetics after SBRT has not been well characterized. The objective of the current study is to analyze the rate of PSA decline and PSA nadir following SBRT boost after whole pelvis radiotherapy (WPRT) in intermediate- and high-risk prostate cancer. From March 2008 to July 2014, 42 patients newly diagnosed, intermediate- and high-risk (NCCN definition) localized prostate cancer were treated with SBRT boost using Cyberknife after WPRT. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy) and the SBRT boost dose was 21 Gy (3 fractions of 7 Gy). No one received androgen deprivation therapy (ADT) before biochemical relapse. PSA nadir and rate of change in PSA (slope) were calculated and compared. With a median follow-up of 53.6 months (range, 14-74), the median rates of decline of PSA were -0.605, -0.229 and -0.166 ng/mL/month, respectively, for durations of 1, 2 and 3 years postradiotherapy, respectively. The median PSA nadir was 0.32 ng/mL after a median 36 months. 4-year biochemical failure (BCF) free survival was 100 percent for intermediate-risk and 71.4 percent for high-risk patients (P = 0.002). In this report of intermediate- and high-risk prostate cancer, continuously greater rates of decline PSA for duration 1, 2 and 3 year following SBRT boost after WPRT resulted in lower PSA nadir. Also, SBRT boost after WBPT leads to favorable BCF-free survival.

Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy for low- and intermediate-risk prostate cancer

Abstract Background Stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate-specific antigen (PSA) kinetics after SBRT has not been well characterized. The objective of the current study is to analyze the rate of PSA decline and PSA nadir following hypofractonated SBRT in low- and intermediate-risk prostate cancer. Methods From 2008 to 2014, 36 patients newly diagnosed, low- and intermediate-risk (NCCN definition) prostate cancer were treated with SBRT using Cyberknife. Total dose of 36.25 Gy in 5 fractions of 7.25 Gy were administered. No one received androgen deprivation therapy (ADT). PSA nadir and rate of change in PSA (slope) were calculated and compared. Results With a median follow-up of 52 months (range, 13–71), the median rates of decline of PSA were −0.359, −0.199 and −0.127 ng/mL/month, respectively, for durations of 1, 2 and 3 years after radiotherapy, respectively. The decline of PSA was maximal in the first year and continuously decreased for durations of 2 and 3 year. The median PSA nadir was 0.27 ng/mL after a median 33 months. 5-year biochemical failure (BCF)-free survival was 100% for low- and intermediate-risk patients. Conclusions In this report of low- and intermediate-risk prostate cancer, continuous decrease of PSA level for duration 1, 2 and 3 year following SBRT using Cyberknife resulted in lower PSA nadir. Also, SBRT leaded to long-term favorable BCF-free survival in low- and intermediate-risk prostate cancer.

Prostate-specific antigen kinetics following hypofractionated stereotactic body radiotherapy boost as post-external beam radiotherapy versus conventionally fractionated external beam radiotherapy for localized prostate cancer.

BackgroundStereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. The purpose of this study was to compare the prostate-specific antigen (PSA) kinetics between conventionally fractionated external beam radiotherapy (CF-EBRT) and SBRT boost after whole pelvis EBRT (WP-EBRT) in localized prostate cancer.MethodsA total of 77 patients with localized prostate cancer [T-stage, T1–T3; Gleason score (GS) 5–9; PSA < 20 ng/mL] were enrolled. A total of 35 patients were treated with SBRT boost (21 Gy in 3 fractions) after WP-EBRT and 42 patients were treated with CF-EBRT (45 Gy WP-EBRT and boost of 25.2–30.6 Gy in 1.8-Gy fractions). PSA nadir and rate of change in PSA (slope) were calculated and compared.ResultsWith a median follow-up of 52.4 months (range, 14–74 months), the median PSA nadir and slope for SBRT boost were 0.29 ng/mL and −0.506, −0.235, −0.129, and −0.092 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for CF-EBRT, the median PSA nadir and slopes were 0.39 ng/mL and −0.720 ng/mL/mo, −0.204 ng/mL/mo, −0.121 ng/mL/mo, and −0.067 ng/mL/mo, respectively. The slope of CF-EBRT was significantly different with a greater median rate of change for 1 year postradiotherapy than that of SBRT boost (P = 0.018). Contrastively, the slopes of SBRT boost for durations of 2 years, 3 years, and 4 years tended to be continuously greater than that of CF-EBRT. The significantly lower PSA nadir was observed in SBRT boost (median nadir 0.29 ng/mL) compared with CF-EBRT (median nadir 0.35 ng/mL, P = 0.025). Five-year biochemical failure (BCF) free survival was 94.3% for SBRT boost and 78.6% for CF-EBRT (P = 0.012).ConclusionPatients treated with SBRT boost after WP-EBRT experienced a lower PSA nadir and there tended to be a continuously greater rate of decline of PSA for durations of 2 years, 3 years, and 4 years than with CF-EBRT. The improved PSA kinetics of SBRT boost over CF-EBRT led to favorable BCF free survival.

Prostate-specific antigen kinetics after stereotactic body radiotherapy as monotherapy or boost after whole pelvic radiotherapy for localized prostate cancer.

PurposeStereotactic body radiotherapy (SBRT) has emerged as an effective treatment for localized prostate cancer. However, prostate-specific antigen (PSA) kinetics after SBRT has not been well characterized. The purpose of the current study is to assess the kinetics of PSA for low- and intermediate-risk prostate cancer patients treated with SBRT using Cyberknife as both monotherapy and boost after whole pelvic radiotherapy (WPRT) in the absence of androgen deprivation therapy.MethodsA total of 61 patients with low- and intermediated-risk prostate cancer treated with SBRT as monotherapy (36.25 Gy in 5 fractions in 32 patients) and SBRT (21 Gy in 3 fractions in 29 patients) boost combined with WPRT (45 Gy in 25 fractions). Patients were excluded if they failed therapy by the Phoenix definition or had androgen deprivation therapy. PSA nadir and rate of change in PSA over time (slope) were calculated and compared.ResultsWith a median follow-up of 52.4 months (range, 14–74 months), for SBRT monotherapy, the median PSA nadir was 0.31 ng/mL (range, 0.04–1.15 ng/mL) and slopes were –0.41 ng/mL/mo, –0.17 ng/mL/mo, –0.12 ng/mL/mo, and –0.09 ng/mL/mo, respectively, for durations of 1 year, 2 years, 3 years, and 4 years postradiotherapy. Similarly, for SBRT boost after WPRT, the median PSA nadir was 0.34 ng/mL (range, 0.04–1.44 ng/mL) and slopes were –0.53 ng/mL/mo, –0.25 ng/mL/mo, –0.14 ng/mL/mo, and –0.09 ng/mL/mo, respectively. The median nadir and slopes of SBRT monotherapy did not differ significantly from those of SBRT boost after WPRT. Benign PSA bounces were common in 30.4% of all cohorts, and the median time to PSA bounce was 12 months (range, 6–25 months).ConclusionsIn this report of low- and intermediate-risk prostate cancer patients, an initial period of rapid PSA decline was followed by a slow decline, which resulted in a lower PSA nadir. The PSA kinetics of SBRT monotherapy appears to be comparable to those achieved with SBRT boost with WPRT.

Abstract 1856: DNA damage and repair markers (H2AX and RAD51) improve accuracy of prostate cancer diagnosis and improve identification of aggressive disease

Abstract Background: Prostate biopsy is the gold standard test for diagnosing prostate cancer. However, due to the sampling error involved, it has low accuracy. Using markers associated with DNA damage and the concept of field effect, this study attempts to improve the diagnostic accuracy of prostate biopsies in men at high risk for this disease. Methods: Data were obtained from men participating in the Negative Biopsy Trial, a randomized multicenter phase 3 chemoprevention trial designed to investigate the effects of selenium supplementation on prostate cancer incidence in men who were at high risk for prostate cancer (PSA (prostate specific antigen) &amp;gt; 4ng/ml &amp;/or PSA velocity (rate of PSA change over time) &amp;gt; 0.75ng/ml/yr &amp;/or positive digital rectal examination) and had a negative prostate biopsy. 699 men were randomized to three treatment arms (placebo, 200ug Se/d, 400ug Se/d) and were followed every 6 months for up to five years. During the course of the study, 73 subjects were diagnosed with prostate cancer on repeat biopsy. For the current study, prostate biopsy samples from 73 subjects and 144 matched controls were stained for RAD51 and H2AX, markers of DNA repair, using immunohistochemistry techniques. Image analysis was conducted using ScanScope and Spectrum software from Aperio Technologies (Vista, California), which provided percentage of positive nuclei. Statistical analysis was conducted using Stata12 statistical software (Statacorp, College station, Texas). Results: Subjects diagnosed with prostate cancer, as compared to controls, demonstrated higher expression levels of both H2AX (mean(SD), 33.8(17.7) and 19.4(14.5)) as well as RAD51 (55.8(24.1) and (44.7(26.5)). As compared to the model containing baseline PSA, age and race (k1), the model containing RAD51 and H2AX data in addition to the data included in k1 showed improved positive predictive value, negative predictive value and area under the curve (70%, 78.9%, 0.77 and 80%, 87.06%, 0.90 respectively, p= 0.025). The above also holds true when data from subjects diagnosed with low grade disease are compared with those having high grade disease (100%, 80%, 0.72 and 100%, 85%, 0.82, p=0.07). Conclusions: Results of this study indicate that DNA damage markers may improve diagnostic accuracy for prostate cancer and also for aggressive disease in both men at high risk, and men diagnosed with prostate cancer. Citation Format: Amit M. Algotar, Anne E. Cress, Raymond B. Nagle, Dan Drinkwitz, Naran S. Lodhia, Patricia A. Thompson, Steven P. Stratton. DNA damage and repair markers (H2AX and RAD51) improve accuracy of prostate cancer diagnosis and improve identification of aggressive disease. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1856. doi:10.1158/1538-7445.AM2014-1856

Change in PSA levels over time can predict aggressive prostate cancer

Measurements of prostate-specific antigen (PSA) taken over time versus only 1 measurement appear to improve the accuracy of detecting aggressive prostate cancer, according to a Kaiser Permanente study published in the British Journal of Urology International.1 Researchers examined the electronic health records of nearly 220,000 men aged 45 years and older over a 10-year period who had at least 1 PSA measurement and no previous diagnosis of prostate cancer. They learned that annual percentage changes in PSA more accurately predicted the presence of aggressive prostate cancer but only marginally improved the prediction of the disease overall. The use of a single PSA screening, which is considered controversial, may lead to unnecessary prostate biopsies and treatments because it does not distinguish that well between slow-growing and aggressive disease, according to Lauren Wallner, PhD, the study's lead author and a research fellow at Kaiser Permanente Southern California's department of research and evaluation. Study participants experienced on average a 2.9% change in PSA levels per year, and the rate of change in PSA increased modestly with age. Dr. Wallner notes that the study results could provide clinicians with a better way to differentiate between men with aggressive cancer and those with a slow-growing cancer who may not need treatment. Although she does not suggest that patients seek out additional PSA measurements, she says those who have had multiple PSAs should consider discussing the change in their levels with their physician when deciding on future treatments.

Negative association of smoking with PSA and PSA velocity.

e16060 Background: Smoking and obesity have been implicated in the pathogenesis of various chronic diseases and carcinogenic processes. However, their role in prostate cancer (PCa) &amp; their association with important biomarkers such as prostate specific antigen (PSA) &amp; PSA velocity (rate of PSA change over time) remains unresolved. This study investigates the association of these risk factors with PSA &amp; PSA velocity (PSAV) in men at high risk for PCa. Methods: Data were obtained from 699 men participating in a Phase 3 clinical trial aimed at investigating the effect of selenium supplementation on incidence of PCa. During the course of this trial 73 men were diagnosed with PCa. Multiple linear regressions were used to investigate the association with PSA and mixed effects models were used to investigate the association with PSAV. Results: As compared to non-smokers, smokers demonstrated statistically significant negative association with PSA (8.0 &amp; 6.7ng/ml, p=0.02). This association was more pronounced in men diagnosed with PCa (14.7 &amp; 9.9ng/ml) as compared to those not diagnosed with PCa (4.5 &amp; 3.6ng/ml). As compared to non-obese subjects, obese subjects did not demonstrate a statistically significant association with PSA (6.8 &amp; 7.1ng/ml, p= 0.64) nor do these results change after stratifying the analysis by PCa status. Smoking was associated with statistically significant lower PSAV (p=0.008) whereas obesity was not (p=0.42). Using the standard PSA level of 4ng/ml as a cut off for conducting prostate biopsy, 14.6% of smokers in this study would not have been prescribed a prostate biopsy and thus misclassified as being negative for PCa. Conclusions: The negative association of smoking with PSA and PSA velocity could potentially be due to its negative effect on testosterone. Hence, increased vigilance may be warranted among smokers with borderline PSA to prevent the risk of delayed diagnosis and metastasis thus reducing morbidity and mortality associated with PCa.

Changes in serum prostate‐specific antigen levels and the identification of prostate cancer in a large managed care population

To determine whether the rate of change in total serum prostate-specific antigen (PSA) levels accurately detects prostate cancer and to evaluate whether it adds any predictive value to a single measurement of serum PSA alone, in general practice settings. A retrospective cohort of 219,388 community-dwelling men, aged ≥45 years, enrolled in the Kaiser Permanente Southern California health plan, with no history of prostate cancer and at least three PSA measurements, were followed from 1 January 1998 to 31 December 2007, for the development of biopsy-confirmed prostate cancer. Annual percent changes in total serum PSA levels were estimated using linear mixed models. The accuracy of prostate cancer prediction was assessed for prostate cancer overall and for aggressive disease (Gleason score ≥7) and compared with that of a single measure of PSA level using area under the receiver-operating characteristic curves (AUCs). The men in this cohort experienced a mean change of 2.9% in PSA levels per year and the rate of change in PSA increased modestly with age (P ≤ 0.001). Annual percent changes in PSA accurately predicted the presence of prostate cancer (AUC = 0.963) and aggressive disease (AUC = 0.955) and had more predictive accuracy for aggressive disease than did a single measurement of PSA alone (AUC = 0.727). Longitudinal measures of PSA improve the accuracy of aggressive prostate cancer detection when compared with a single measurement of PSA alone. Findings from this study provide insight into the usefulness of PSA velocity as a detection marker for aggressive prostate cancer.

The Effects of Body Mass Index on Changes in Prostate-Specific Antigen Levels and Prostate Volume Over 15 Years of Follow-up: Implications for Prostate Cancer Detection

To investigate the association of body mass index (BMI) and BMI change with change in prostate-specific antigen (PSA) level and to assess the possible roles of PSA hemodilution and prostate volume in explaining the obesity and PSA association. In 1990, a randomly selected cohort of Caucasian men, aged 40 to 79 years, from Olmsted County, Minnesota, completed questionnaires ascertaining demographic characteristics, current medical conditions, and medications biennially, with a subset undergoing blood draws and clinical examinations. Linear mixed models were used to predict annual changes and intercepts of individual changes in BMI, PSA, prostate volume, plasma volume, and PSA mass, adjusting for age in 545 men with at least 2 serial PSA, BMI, and prostate volume measurements. Baseline BMI was inversely associated with the annual percent change in PSA, adjusting for age, baseline PSA, and prostate volume and for the rates of change in BMI and prostate volume (β=-0.003, 95% CI: -0.006 to -0.0003). Baseline obesity was positively associated with mean baseline levels and the rate of change in prostate volume (P=0.002) and plasma volume (both P<0.001) but was not associated with either the mean baseline values or the rate of change in PSA mass. Baseline obesity was associated with baseline PSA and prostate volume and with the rate of change in PSA over 15 years of follow-up. The inverse association of obesity with prostate cancer diagnosis may be at least partly due to detection bias, which is due to larger prostate volumes and PSA hemodilution in obese men.

Prostate-Specific Antigen Velocity in Healthy Korean Men with Initial PSA Levels of 4.0 ng/mL or Less

To assess the longitudinal changes in serial prostate-specific antigen (PSA) levels in healthy Korean men with initial PSA levels of 4.0 ng/mL. The rate of PSA change or PSA velocity (PSAV) in 24 869 healthy men with an initial PSA level of 4.0 ng/mL or less who were clinically free of genitourinary disease was analyzed at intervals of at least 12 months. The influence of age, initial PSA level, and the interval between measurements was assessed. The mean age, initial PSA level, interval between measurements, and change in PSA and PSAV was 46.2 years, 0.86 ng/mL, 21.9 months, and 0.03 ng/mL and 0.02 ng/mL/y, respectively. A cumulative frequency plot of PSAV demonstrated that 50%, 95%, and 97% of subjects had a PSAV of 0.01, 0.40, and 0.52 ng/mL/y or less, respectively. The PSAV correlated with age, initial PSA level, and interval between measurements. The percentage of men with a PSAV greater than 0.75 ng/mL/y was 0.61% (151 of 24 869) and was 0.51% (92 of 17 985) for those with an initial PSA level of less than 1.0 ng/mL, 0.86% (50 of 5807) for those with a PSA level of 1.1-2.0 ng/mL, and 0.84% (9 of 1077) for those with an initial PSA level of 2.1-4.0 ng/mL. In healthy Korean men with an initial PSA level of 4.0 ng/mL or less, most will have a PSAV of less than 0.75 ng/mL/y. Thus, traditional PSAV cutoff values are not applicable in this population. We propose that a lower PSAV cutoff value should be used to indicate biopsy. Additional large-scale prospective studies, including biopsy data, are required to assess the cutoff value of PSAV for healthy Korean men with a PSA level of 4.0 ng/mL or less.

Prostate-Specific Antigen Levels as a Predictor of Lethal Prostate Cancer

Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided. During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline (P = .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level. Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.

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.

Interval from prostate biopsy to radical prostatectomy: Effect on PSA, Gleason sum, and risk of recurrence

Objectives To determine whether the change in prostate-specific antigen (PSA), change in Gleason sum, and/or interval between prostate biopsy and radical prostatectomy have an association with biochemical recurrence. Methods The relationship between biochemical recurrence and the interval between biopsy and surgery, as well as the rate and amount of change in PSA and Gleason sum from biopsy to surgery, was evaluated in 151 patients with prostate cancer treated with radical prostatectomy. Results A statistically significant increase was found in PSA level and Gleason sum between biopsy and surgery ( P = 0.01 and P <0.0001, respectively). No significant association was found between prebiopsy PSA level ( P = 0.27) or biopsy Gleason sum ( P = 0.07) with biochemical recurrence as independent variables or in a combined model ( P = 0.12). An association was also not found between recurrence and preprostatectomy PSA level ( P = 0.15) or the rate of PSA change ( P = 0.28) as independent variables. However, a significant association was found with the prostatectomy Gleason sum ( P = 0.001). In a combined model, a significant association was noted between the preprostatectomy PSA level and prostatectomy specimen Gleason sum and biochemical recurrence ( P = 0.003). No increased risk of biochemical recurrence was noted with increasing time from biopsy to prostatectomy (odds ratio 1.00) or the rate (odds ratio 1.03) and degree (odds ratio 1.30) of serum PSA or Gleason sum (odds ratio 1.07). Conclusions The interval between biopsy and radical prostatectomy is not a predictor of biochemical failure. An association was noted between an increased risk of biochemical failure and the amount of serum PSA and Gleason sum increase between biopsy and surgery.

EVALUATION OF CHANGES IN PROSTATE SPECIFIC ANTIGEN IN CLINICALLY LOCALIZED PROSTATE CANCER MANAGED WITHOUT INITIAL THERAPY

Purpose We define changes in prostate specific antigen (PSA) measurements with time in 49 men 71.9 +/− 7.0 years old (mean plus or minus standard deviation) with clinically localized prostate cancer who remain untreated. Materials and Methods We retrospectively analyzed PSA changes in prostate cancer patients managed by watchful waiting. In all patients a minimum of 3 PSA levels were measured at intervals of at least 6 months after malignancy was diagnosed. The rate of change in serum PSA level with time (PSA velocity) was determined using an exponential, log linear model. Results In 49 patients treated conservatively mean initial PSA level plus or minus standard deviation was 12.3 +/− 11.1 ng./ml. and mean PSA followup during which no therapy for prostate cancer was introduced was 32.1 +/− 13.2 months. PSA levels decreased during the observation period in 11 of the 49 patients (22%) and median PSA doubling time in the remaining 38 was 55.7 months (range 15.1 to 994.5). There was no significant correlation between age at diagnosis, Gleason sum, initial PSA level or clinical stage and PSA velocity. The short-term rate of change in PSA during the first 9 months after prostate cancer was diagnosed correlated poorly with overall PSA velocity. The short-term rate of PSA change was greater than the overall rate of change in 14 of 37 patients (38%). Conclusions There is significant variability in the rate of change of PSA with time in men with clinically localized prostate cancer who remain untreated. The usefulness of serial PSA measurements in the management of watchful waiting is unclear. Changes in PSA may not be helpful or appropriate in determining the need for therapy after a period of observation.

Constitutive expression of high levels of prostate-specific antigen in the absence of prostate carcinoma

To identify distinguishing serologic features in patients with stable marked elevation in prostate-specific antigen (PSA) and multiple negative biopsies. The study population consisted of 7 patients with a stable PSA level of greater than 20 ng/mL (average 27.0), followed for at least 34 months (average 56), and with two or more negative prostatic biopsies including transition zone biopsies. The PSA density (PSAD), rate of change in PSA, reverse transcriptase/polymerase chain reaction (RT/PCR), and free/total PSA were obtained. Rate of change in PSA level was stable (0.18 +/- 1.2 ng/mL/yr), suggesting that there was no occult cancer; PSAD was high (0.34 +/- 0.5 ng/mL/cc), indicating that prostate size was not the sole cause of the elevation. The RT/PCR was negative in 6 of 7 patients, further decreasing the likelihood of an occult malignancy. Free versus total PSA was not consistent, averaging 16.8%, but with a range of 6% to 34%. Novel PSA tests were not found to be useful in this cohort of patients with multiple negative biopsies and PSA elevations greater than 20 ng/mL. Additional studies with larger sample size are required to confirm this finding.

Measurement of weekly prostate specific antigen levels in patients receiving pelvic radiotherapy for nonprostatic malignancies

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 ∗week 2 + 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.

Prostate-specific antigen variability in men without prostate cancer: effect of sampling interval on prostate-specific antigen velocity

Objectives To evaluate short-term and long-term variability between prostate-specific antigen (PSA) measurements to determine the most appropriate PSA sampling interval and rate of PSA change (PSA velocity) to distinguish between men with and without prostate cancer. Methods Retrospective study of PSA variability and PSA velocity in three groups of men without a diagnosis of prostate cancer and PSA levels less than 10 ng/mL: 56 men with a histologic diagnosis of benign prostatic hyperplasia (BPH; histologic BPH group) and 527 men with no history of cancer (noncancer group) who were part of the Baltimore Longitudinal Study of Aging and had PSA sampled at 2-year intervals (long-term), and 223 men with a clinical diagnosis of BPH (clinical BPH group) who had PSA sampled at 3-month intervals (short-term). PSA variability (deviation between consecutive measurements) and PSA velocity based on both two consecutive measurements and three consecutive measurements (average velocity) were calculated for each study group. Results PSA velocity is the deviation in PSA measurements relative to the elapsed time between the measurements. Because the variability in PSA between measurements was similar for the groups, the major factors that influenced PSA velocity were the sampling interval between PSA measurements, and to a lesser extent, the number of repeat PSA measurements. The 99th percentile for PSA velocity was 0.7 (histologic BPH group) and 0.75 ng/mL per year for the noncancer group when three measurements with a 24-month PSA sampling interval were used. However, the 99th percentile for PSA velocity was 5.8 and 2.4 ng/mL per year when three measurements with 3-month and 6-month PSA sampling intervals were used. Using three measurements, the percentage of subjects with a PSA velocity more than 0.75 ng/mL per year was 1 % for the groups with a 24-month PSA sampling interval and 28% and 17% for 3-month and 6-month PSA sampling intervals, respectively. The 99th percentile for PSA velocity and the percentage of subjects with a PSA velocity more than 0.75 ng/mL per year was higher using two measurements compared to three measurements regardless of PSA sampling interval. Conclusions PSA velocity is inversely related to the interval between PSA measurements. A PSA velocity more than 0.75 ng/mL per year is useful in distinguishing between men with and without prostate cancer when: (1) velocity is based on three consecutive measurements; and (2) PSA is sampled long-term (2 years) but not short-term (3 to 6 months).

Natural History of Changes in Prostate Specific Antigen in Early Stage Prostate Cancer

Until recently, the only information on the growth rate of prostate tumors has been derived from cross-sectional histological labeling studies, autopsy data and clinical studies of patients managed expectantly. However, serial measurements of prostate specific antigen (PSA) may now allow studies of the natural history of the earliest stages of prostate cancer. Frozen sera samples from the Baltimore Longitudinal Study of Aging have been used to compare the patterns of change in PSA levels in men with and without prostate cancer up to 25 years before the diagnosis of cancer. Men with no prostatic disease exhibited a slow linear increase in PSA levels, whereas benign prostatic hyperplasia cases showed a gradual acceleration in the rate of change in PSA. In contrast, cancer cases exhibited an early linear phase followed by an exponential phase of increase in PSA levels before diagnosis. On average, the exponential phase of PSA increases began 7 to 9 years before the tumors were detected clinically. Thus, there is a significant window of opportunity for early detection of prostate cancer. The changes in PSA observed in men with and without prostate cancer are consistent with available information on prostatic growth and the long natural history of prostate cancer. A better understanding of the various factors that affect serum PSA levels may allow more effective use of PSA measurements to detect early stage tumors and predict the biological potential of a tumor.

Serial Prostatic Biopsies in Men with Persistently Elevated Serum Prostate Specific Antigen Values

The objective of this study was to determine the need for repeat prostatic biopsies in men whose initial biopsy results revealed no evidence of cancer or atypia. We evaluated 1,136 men who underwent 1 or more prostatic biopsies in a longitudinal prostate specific antigen (PSA) based prostate cancer screening study that called for biopsy if the serum PSA level was greater than 4.0ng./ml. (Hybritech assay) and findings on rectal examination or ultrasonography were abnormal or suspicious for cancer. Of the 1,136 men who underwent prostatic biopsy 391 (34%) had prostate cancer on the initial biopsy. Of 427 men who had negative initial biopsy results, a persistent serum PSA level of greater than 4.0ng./ml. and abnormal rectal or ultrasound examination findings 82 (19%) had cancer on biopsy 2. Of 203 men with persistent abnormalities 16 (8%) had cancer on biopsy 3 and 6 of 91 (7%) had cancer on biopsy 4 or later. Thus, 96% of the cancers were detected through either biopsy 1 or 2. The median initial PSA level, followup PSA levels and the yearly rate of change in PSA were significantly greater in men whose cancer was detected compared with those of men whose cancer was not detected (6.4 versus 5.4ng./ml., 7.4 versus 6.6ng./ml. and 1.1 versus 0.7ng./ml. per year, respectively). There was a trend for a higher percentage of tumors detected through serial screening to be pathologically organ confined compared with those detected through initial screening (73% versus 62%, p = 0.07). We conclude that men with a persistently elevated serum PSA value after an initial negative prostatic biopsy should routinely undergo at least 1 repeat biopsy to exclude adequately the presence of detectable prostate cancer.