Changes In Serum Prostate-specific Antigen Levels Research Articles

Prognostic Performance of RECIP 1.0 Based on [18F]PSMA-1007 PET in Prostate Cancer Patients Treated with [177Lu]Lu-PSMA I&T.

In metastatic castration-resistant prostate cancer (mCRPC) patients treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), the recently proposed criteria for evaluating response to PSMA PET (RECIP 1.0) based on 68Ga- and 18F-labeled PET agents provided prognostic information in addition to changes in prostate-specific antigen (PSA) levels. Our aim was to evaluate the prognostic performance of this framework for overall survival (OS) in patients undergoing RLT and imaged with [18F]PSMA-1007 PET/CT and compare the prognostic performance with the PSA-based response assessment. Methods: In total, 73 patients with mCRPC who were scanned with [18F]PSMA-1007 PET/CT before and after 2 cycles of RLT were retrospectively analyzed. We calculated the changes in serum PSA levels (ΔPSA) and quantitative PET parameters for the whole-body tumor burden (SUVmean, SUVmax, PSMA tumor volume, and total lesion PSMA). Men were also classified following the Prostate Cancer Working Group 3 (PCWG3) criteria for ΔPSA and RECIP 1.0 for PET imaging response. We performed univariable Cox regression analysis, followed by multivariable and Kaplan-Meier analyses. Results: Median OS was 15 mo with a median follow-up time of 14 mo. Univariable Cox regression analysis provided significant associations with OS for ΔPSA (per percentage, hazard ratio [HR], 1.004; 95% CI, 1.002-1.007; P < 0.001) and PSMA tumor volume (per unit, HR, 1.003; 95% CI, 1.000-1.005; P = 0.03). Multivariable Cox regression analysis confirmed ΔPSA (per percentage, HR, 1.004; 95% CI, 1.001-1.006; P = 0.006) as an independent prognosticator for OS. Kaplan-Meier analyses provided significant segregation between individuals with versus those without any PSA response (19 mo vs. 14 mo; HR, 2.00; 95% CI, 0.95-4.18; P = 0.04). Differentiation between patients with or without progressive disease (PD) was also feasible when applying PSA-based PCWG3 (19 mo vs. 9 mo for non-PD and PD, respectively; HR, 2.29; 95% CI, 1.03-5.09; P = 0.01) but slightly failed when applying RECIP 1.0 (P = 0.08). A combination of both response systems (PCWG3 and RECIP 1.0), however, yielded the best discrimination between individuals without versus those with PD (19 mo vs. 8 mo; HR, 2.78; 95% CI, 1.32-5.86; P = 0.002). Conclusion: In patients with mCRPC treated with RLT and imaged with [18F]PSMA-1007, frameworks integrating both the biochemical (PCWG3) and PET-based response (RECIP 1.0) may best assist in identifying subjects prone to disease progression.

99mTc-MIP-1404 SPECT/CT for Assessment of Whole-Body Tumor Burden and Treatment Response in Patients With Biochemical Recurrence of Prostate Cancer.

This study aims to investigate the value of Tc-MIP-1404 SPECT/CT for assessment of whole-body tumor burden and treatment response in patients with biochemical recurrence of prostate cancer who undergo androgen deprivation therapy (ADT) or external beam radiation therapy (EBRT). A total of 125 patients with biochemical recurrence of prostate cancer underwent Tc-MIP-1404 SPECT/CT. All 364 prostate-specific membrane antigen (PSMA)-positive lesions in the field of view were assessed quantitatively to calculate PSMA-derived metabolic tumor parameters, including whole-body PSMA tumor volume and whole-body total lesion PSMA. These metrics were correlated with serum prostate-specific antigen (PSA) levels and Gleason scores. In a subset of 50 patients who underwent Tc-MIP-1404 SPECT/CT before the initiation of ADT or EBRT, TL-PSMA and SUVmax were compared with radiographic response assessment by CT based on RECIST 1.1 and to biochemical response (BR) determined by changes in serum PSA levels. Serum PSA levels correlated with SUVmax, whole-body PSMA tumor volume, and whole-body total lesion PSMA in patients with 1 and in those with more than 1 PSMA-positive lesion (P < 0.05). The correlations were significant for both well-differentiated (Gleason score ≤7) and poorly differentiated tumors (Gleason score ≥8) (P < 0.05). The agreement between TL-PSMA derived from SPECT and BR in patients who underwent Tc-MIP-1404 SPECT/CT before and after initiation of ADT was 80% (95% confidence interval [CI], 0.43-0.91; Cohen κ = 0.68; P < 0.05); in these patients, the agreement between TL-PSMA and CT was 60% (95% CI, 0.20-0.72; Cohen κ = 0.46; P < 0.05) and the agreement between BR and CT was 52% (0.07-0.61; Cohen κ = 0.34; P < 0.05). Comparable results were found for patients who underwent SPECT/CT before and after initiation of EBRT, with the strongest agreement between TL-PSMA and BR (80%; 95% CI, 0.38-0.93; Cohen κ = 0.66; P < 0.05) compared with the agreement between TL-PSMA and CT (60%; 95% CI, 0.13-0.69; Cohen κ = 0.69; P < 0.05) and between BR and CT (48%; 95% CI, 0-0.54; Cohen κ = 0.26; P = 0.11). Discordant findings between SPECT and CT were most likely due to limitations in the assessment of small lymph node metastases and bone involvement, which were detectable on SPECT but not on CT. The results of our study show that Tc-MIP-1404 SPECT/CT is a promising method for the evaluation of treatment response in patients with biochemical recurrence of prostate cancer who undergo either ADT or EBRT. TL-PSMA for assessment of treatment response has the strongest correlation with serum PSA levels, superior to SUVmax-based evaluation and response assessment based on CT data and RECIST 1.1.

Flutamide as an Alternative Anti-androgen Agent and Predictor of the Efficacy of Novel Androgen Receptor-targeted Agents.

There are few reports that verify the relationship between the therapeutic effects of flutamide and novel androgen receptor-targeted agents. We aimed to evaluate the benefits of flutamide as an alternative anti-androgen agent and its effects on the efficacy of novel androgen receptor-targeted agents. Patients with castration-resistant prostate cancer on novel androgen receptor-targeted agents without prior docetaxel therapy were included. Changes in prostate-specific antigen (PSA) level were recorded. Patients who responded well to flutamide (Flutamide effective) following initial maximum androgen blockade (MAB) showed significantly higher changes in serum PSA levels (p=0.039) and PSA-progression-free survival (PFS) rate (p=0.016) following enzalutamide therapy compared to those who did not respond well to flutamide. Multivariate analysis showed that the factor of Flutamide effective was significantly associated with a good PSA-PFS rate following enzalutamide therapy (HR=7.36, 95%CI=1.4-38.71, p=0.018). Patients showing good response to flutamide following initial MAB may achieve a satisfactory PSA-PFS rate with subsequent enzalutamide therapy.

Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan.

To clarify the recent trends in prostate-specific antigen (PSA) distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54–69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng ml−1 in 2000, and gradually decreased to approximately 1.30 ng ml−1 in 2006. That of participants excluding prostate cancer patients was 1.46 ng ml−1 in 2000, and there was no remarkable change during the study period. The 95th percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54–59, 60–64, and 65–69 years old were 2.90, 3.60, and 4.50 ng ml−1, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

Changes in S-PSA after transurethral resection of prostate and its correlation to postoperative outcome

Although different factors may affect prostate-specific antigen (PSA) reduction after transurethral resection of prostate, an approximate 70 % decrease from baseline is expected. We hereby undertook a prospective study to analyze changes in serum PSA (S-PSA) after transurethral resection of the prostate (TURP) and its correlation with the residual prostatic weight and clinical symptom score improvement. Seventy patients who underwent TURP for bladder outlet obstruction were included in the study. Patient's evaluation included history, International Prostate Symptom Score (IPSS), S-PSA, Qmax, post-void residual urine and prostate size. On follow-up, trans-rectal ultrasonography, S-PSA and IPSS score were calculated. Patients were analyzed in three groups based on the amount of tissue resected: less than 40, 40-60 and more than 60 % tissue resected. Preoperative prostate size, IPSS, Qmax and S-PSA were 62.56 ml, 23.84, 11.68 ml/sec and 3.3 ng/ml. There was a significant decrease in the IPSS score, prostate size and S-PSA levels after TURP in all the three groups. There was a significant positive correlation of the amount of tissue resected with change in S-PSA levels, change in IPSS score and postoperative IPSS score. Reduction in IPSS score significantly correlated with patient's satisfaction. The amount of tissue resected in TURP has a direct bearing on the S-PSA levels, change in symptom score and residual prostate volume. It is the percentage change in IPSS score and not the absolute value of IPSS, which has a direct bearing with the patient satisfaction and with the amount of tissue resected. Percentage fall in S-PSA by 70 % was found to be predictor of more than 60 % resection.

Sixteen-Year Longitudinal Changes in Serum Prostate-Specific Antigen Levels: The Olmsted County Study

Objective To determine the distribution of longitudinal changes in serum prostate-specific antigen (PSA) levels from a population-based sample of men. Patients and Methods In this prospective cohort study, a random sample of Olmsted County, Minnesota, men aged 40 to 79 years in 1990 were followed up biennially from January 1, 1990, through August 29, 2007. Serum PSA levels were determined at each examination, and men were censored for follow-up with a diagnosis of prostate cancer or treatment for benign prostatic hyperplasia. The empirical distributions of annual percent change and annual absolute change in serum PSA level were calculated and tabulated, including the median and 75th and 95th percentiles. Results For men with PSA measurements 2 years apart, the median annual percent change in serum PSA level was 4.83% and the 95th percentile was about 49.76%. The variability in estimated annual change decreased with increasing time between assessments, with a 95th percentile of 21.82% after 8 or more years between assessments. Although the median absolute change per year increased with increasing age, the median percent change per year was fairly consistent across age groups. Conclusion These data demonstrate that, with shorter intervals between assessments, greater variability should be expected. These distributions should prove helpful to patients and clinicians in interpreting changes in serum PSA levels observed in typical clinical practices.

The Effects of Type 2 Diabetes and Hypertension on Changes in Serum Prostate Specific Antigen Levels: Results From the Olmsted County Study

Men with type 2 diabetes have lower concomitant prostate-specific antigen (PSA) levels; however, the influence of metabolic conditions on PSA changes over time remains unknown. Therefore, the goal of this study was to assess associations between type 2 diabetes and hypertension and changes in serum PSA levels. In 1990, a randomly selected cohort of Caucasian men, ages 40-79, from Olmsted County, MN completed questionnaires ascertaining demographic characteristics, current medical conditions and medications biennially, with 633 men undergoing blood draws. Men with a physician diagnosis of diabetes or hypertension at baseline, or who reported using medications to treat these conditions prior to baseline were considered exposed. Men with at least two serum PSA measurements (n = 569) were included in this analysis. Linear mixed models were used to estimate the annual percent change in serum PSA levels associated with diabetes and hypertension, adjusting for baseline age. The overall mean change in serum PSA levels was 3.6% per year and increased with age (P = .009). Men with diabetes experienced less annual change in serum PSA levels (1.1%) than did non-diabetic men (3.7%), adjusting for age (P = .02). Age-adjusted change in serum PSA levels differed little by hypertension status (3.7% vs. 3.6%; P = .49). Our results suggest that Caucasian men with type 2 diabetes experience smaller increases in serum PSA levels as they age compared to men without diabetes. Additional research is needed to elucidate whether this difference results in a relatively lower incidence of prostate cancer or less cancer detection among diabetic men.

Zoledronate Stimulates γδ T Cells in Prostate Cancer Patients

Androgen deprivation therapy is the mainstay of treatment for prostate cancer. Given its frequent failure, new therapy that reduces prostate cancer progression would be a breakthrough in treating this disease. Bisphosphonates are well-established agents for treating skeletal-related events (SREs) in prostate cancer patients with bone metastases. Exposure to bisphosphonates may not only reduce the incidence of SREs, but also have anticancer effects by modulating a patient's immunity. The purpose of this study was to examine the effect of zoledronate (ZOL) on gamma delta T cells, serum prostate-specific antigen (PSA) levels, and velocities. The effect of ZOL, with and without IL-2, on gamma delta T cell activation was examined in vitro. Furthermore, the activated state and the number of gamma delta T cells and changes in serum PSA levels were examined for patients who received ZOL infusion for the prevention of SREs. We found that ZOL activated gamma delta T cells, and the number of gamma delta T cell was increased when IL-2 was administered with ZOL in vitro. Comparisons before and after the first ZOL infusion revealed that gamma delta T cells in peripheral blood were activated by ZOL. Moreover, after the first ZOL treatment, reduction in serum PSA was observed in 3 of 11 patients, and reduction in PSA velocity was observed in 5 of 10 patients. Our findings indicate that ZOL stimulates gamma delta T cells in vivo and in vitro. This study provides further insight into the ability of gamma delta T cells to induce an antitumor immune response.

The Magnitude of Early Castration-Induced Primary Tumour Regression in Prostate Cancer Does Not Predict Clinical Outcome

IntroductionThis study was designed to test whether early castration-induced short-term cellular changes in primary prostate tumours could predict clinical outcome in advanced disease. Patients and methodsBiopsies from 83 patients obtained before and within two weeks after surgical castration were investigated. Tumour epithelial cell apoptosis, proliferation, and prostate specific antigen (PSA) levels were quantified using immunohistochemistry, laser capture micro-dissection, and real time RT-PCR. Cellular effects were related to changes in serum PSA levels and clinical outcome. ResultsDecreased proliferation and PSA mRNA levels, and increased apoptosis were observed in most tumours. These early cellular responses were not correlated to each other and did not predict serum PSA response or cancer-specific survival. A nadir PSA level below 1ng/ml predicted a longer cancer-specific survival after castration therapy. ConclusionCastration therapy causes primary tumour regression in most patients with advanced prostate cancer, but these primary tumour effects are not predictive for systemic disease control. Studies of early changes in metastases during hormonal therapy will probably give more predictive information for clinical outcome than further studies in primary tumours.

Selenomethionine does not affect PSA secretion independent of its effect on LNCaP cell growth.

Individuals supplemented with selenium have reduced incidence of prostate cancer. This study determines whether selenomethionine specifically affects the secretion of prostate specific antigen (PSA) in vitro. LNCaP cells were supplemented with selenomethionine for 7 days. PSA secretion was determined by ELISA. Cell proliferation was assessed by enumeration of trypan blue excluding cells. Colony formation was determined in soft agar. Cell cycle distribution was determined by FACS analysis of propidium iodide stained cells. Selenomethionine at > or = 70 microM inhibited LNCaP cell growth and colony formation. 0-100 microM selenomethionine did not affect the secretion of PSA by LNCaP cells in cell culture supernatants when normalized to the number of cells in culture. At supra-nutritional concentrations of selenomethionine, LNCaP cells had longer G(0)/G(1) phase in agreement with the inhibitory effects on cell growth. PSA secretion is not specifically inhibited by concentrations of selenomethionine corresponding to plasma selenium concentrations found in individuals supplemented with chemopreventive concentrations of selenized yeast. These data suggest that changes in serum PSA levels in individual patients during selenium supplementation is not an effect specific for PSA secretion, but rather may be a useful indicator for changes in disease progression in individual patients.

Daily variability of serum prostate-specific antigen in men over 50 years of age.

In order to investigate the variability of serum prostate-specific antigen (PSA) levels a total of 44 men 50 years or older with normal digital rectal examination were enrolled. Blood samples were obtained three times within a day, and, immediately before and 72 hours after hospitalisation. Alterations in serum PSA value during the day and after hospitalisation, which might affect clinical decision, occurred in 15% of the cases with borderline PSA values. The results indicate that there may be significant changes in serum PSA levels within a day and after hospitalisation.

Changes in serum prostate-specific antigen following prostatectomy in patients with benign prostate hyperplasia.

To investigate how prostatectomy for patients with benign prostate hyperplasia (BPH) affected the serum prostate-specific antigen (PSA) levels. In 193 patients who underwent prostatectomy for BPH, serum PSA levels were measured before and three months after the operation. The total prostate weight measured by transrectal ultrasonography (TRUS) and the weight of the surgical specimen were examined in relation to the pretreatment PSA value and the changes in PSA levels after the operation. The transition zone volume measured by TRUS could well estimate the weight of the surgical specimen in patients who underwent subcapsular prostatectomy and transurethral resection of the prostate. The concentration of preoperative serum PSA showed a significant correlation with the prostatic volume and with the transition zone volume. Removal of 1 g of BPH tissue reduced serum PSA levels by an average of 0.18 ng/mL. The change in serum PSA levels after the prostatectomy correlated with the total prostatic gland volume and with the transition zone volume. The elevated PSA levels in patients with BPH were caused by the enlargement of the transition zone. After the resection of the adenoma, PSA levels should be expected to decrease to the normal range.

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.

The Effect of Digital Rectal Examination on Prostate-Specific Antigen Levels

OBJECTIVE--To identify the effect of digital rectal examination (DRE) on serum prostate-specific antigen (PSA) levels. DESIGN--A prospective trial before and after DRE. SETTING--Multicenter outpatient screening program. PATIENTS--A total of 2754 healthy men aged 40 years and older who presented to a prostate cancer screening program and consented to two phlebotomies. MAIN OUTCOME MEASURE--Changes in serum PSA levels after DRE. RESULTS--Patients were divided into four groups based on their initial serum PSA levels. The levels were chosen based on previous studies that showed different incidences of prostate cancer within these groups. The two groups with the lowest initial PSA values (0.1 through 4 micrograms/L and 4.1 through 10 micrograms/L) were found to have statistically insignificant changes in the serum PSA levels after DRE. The group with initial PSA levels of 10.1 through 20 micrograms/L had increases in serum PSA values that showed a trend toward statistical significance. The group with initial PSA levels of greater than 20 micrograms/L had statistically significant increases in serum PSA values after DRE. The alterations in serum PSA levels in the two groups with the highest PSA values were not clinically important as the patients' clinical treatment was not altered. CONCLUSIONS--No clinically important effects on serum PSA levels were noted after DRE.