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JAMA Oncology Oct 2021Men with prostate cancer who are undergoing active surveillance are at an increased risk of cardiovascular death and disease progression. Exercise has been shown to... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Exercise on Cardiorespiratory Fitness and Biochemical Progression in Men With Localized Prostate Cancer Under Active Surveillance: The ERASE Randomized Clinical Trial.
IMPORTANCE
Men with prostate cancer who are undergoing active surveillance are at an increased risk of cardiovascular death and disease progression. Exercise has been shown to improve cardiorespiratory fitness, physical functioning, body composition, fatigue, and quality of life during and after treatment; however, to date only 1 exercise study has been conducted in this clinical setting.
OBJECTIVE
To examine the effects of exercise on cardiorespiratory fitness and biochemical progression in men with prostate cancer who were undergoing active surveillance.
DESIGN, SETTING, AND PARTICIPANTS
The Exercise During Active Surveillance for Prostate Cancer (ERASE) trial was a single-center, 2-group, phase 2 randomized clinical trial conducted at the University of Alberta, Edmonton, Canada. Eligible patients were recruited from July 24, 2018, to February 5, 2020. Participants were adult men who were diagnosed with localized very low risk to favorable intermediate risk prostate cancer and undergoing active surveillance. They were randomized to either the high-intensity interval training (HIIT) group or usual care group. All statistical analyses were based on the intention-to-treat principle.
INTERVENTIONS
The HIIT group was asked to complete 12 weeks of thrice-weekly, supervised aerobic sessions on a treadmill at 85% to 95% of peak oxygen consumption (V̇o2). The usual care group maintained their normal exercise levels.
MAIN OUTCOMES AND MEASURES
The primary outcome was peak V̇o2, which was assessed as the highest value of oxygen uptake during a graded exercise test using a modified Bruce protocol. Secondary and exploratory outcomes were indicators of biochemical progression of prostate cancer, including prostate-specific antigen (PSA) level and PSA kinetics, and growth of prostate cancer cell line LNCaP.
RESULTS
A total of 52 male patients, with a mean (SD) age of 63.4 (7.1) years, were randomized to either the HIIT (n = 26) or usual care (n = 26) groups. Overall, 46 of 52 participants (88%) completed the postintervention peak V̇o2 assessment, and 49 of 52 participants (94%) provided blood samples. Adherence to HIIT was 96%. The primary outcome of peak V̇o2 increased by 0.9 mL/kg/min in the HIIT group and decreased by 0.5 mL/kg/min in the usual care group (adjusted between-group mean difference (1.6 mL/kg/min; 95% CI, 0.3-2.9; P = .01). Compared with the usual care group, the HIIT group experienced decreased PSA level (-1.1 μg/L; 95% CI, -2.1 to 0.0; P = .04), PSA velocity (-1.3 μg /L/y; 95% CI, -2.5 to -0.1; P = .04), and LNCaP cell growth (-0.13 optical density unit; 95% CI, -0.25 to -0.02; P = .02). No statistically significant differences were found in PSA doubling time or testosterone.
CONCLUSIONS AND RELEVANCE
The ERASE trial demonstrated that HIIT increased cardiorespiratory fitness levels and decreased PSA levels, PSA velocity, and prostate cancer cell growth in men with localized prostate cancer who were under active surveillance. Larger trials are warranted to determine whether such improvement translates to better longer-term clinical outcomes in this setting.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03203460.
Topics: Cardiorespiratory Fitness; Exercise Therapy; High-Intensity Interval Training; Humans; Male; Prostatic Neoplasms; Quality of Life; Watchful Waiting
PubMed: 34410322
DOI: 10.1001/jamaoncol.2021.3067 -
Physiological Reports Nov 2021Postural control is often quantified by recording the trajectory of the center of pressure (COP)-also called stabilogram-during human quiet standing. This quantification... (Review)
Review
Postural control is often quantified by recording the trajectory of the center of pressure (COP)-also called stabilogram-during human quiet standing. This quantification has many important applications, such as the early detection of balance degradation to prevent falls, a crucial task whose relevance increases with the aging of the population. Due to the complexity of the quantification process, the analyses of sway patterns have been performed empirically using a number of variables, such as ellipse confidence area or mean velocity. This study reviews and compares a wide range of state-of-the-art variables that are used to assess the risk of fall in elderly from a stabilogram. When appropriate, we discuss the hypothesis and mathematical assumptions that underlie these variables, and we propose a reproducible method to compute each of them. Additionally, we provide a statistical description of their behavior on two datasets recorded in two elderly populations and with different protocols, to hint at typical values of these variables. First, the balance of 133 elderly individuals, including 32 fallers, was measured on a relatively inexpensive, portable force platform (Wii Balance Board, Nintendo) with a 25-s open-eyes protocol. Second, the recordings of 76 elderly individuals, from an open access database commonly used to test static balance analyses, were used to compute the values of the variables on 60-s eyes-open recordings with a research laboratory standard force platform.
Topics: Accidental Falls; Aged; Algorithms; Biomechanical Phenomena; Databases, Factual; Humans; Postural Balance; Risk Assessment
PubMed: 34826208
DOI: 10.14814/phy2.15067 -
BJU International Jun 2022To assess the correlation of pathological radical prostatectomy (RP) specimen features and prostate-specific antigen (PSA) characteristics to imaging findings on...
OBJECTIVES
To assess the correlation of pathological radical prostatectomy (RP) specimen features and prostate-specific antigen (PSA) characteristics to imaging findings on subsequent F-DCFPyL positron emission tomography/computed tomography (PET/CT) in patients with biochemical failure (BF).
PATIENTS AND METHODS
Retrospective analysis of combined F-DCFPyL PET/CT database of patients from centres in Australia and New Zealand was performed. A total of 205 patients presenting with BF after RP were included in this study. Imaging findings on F-DCFPyL PET/CT were recorded and correlated with the PSA characteristics at BF and pathological features of the original tumour.
RESULTS
Of the 205 patients, 120 (58.5%) had evidence of abnormal prostate-specific membrane antigen (PSMA) expression compatible with recurrent prostate cancer. Increasing PSA velocity (P = 0.01), International Society of Urological Pathology (ISUP) Grade Group (P = 0.02), lymphovascular invasion (P = 0.05) and nodal positivity (P = 0.02) at the time of RP were more likely to demonstrate PSMA positivity. Multivariable logistic regression revealed a higher PSA level prior to PSMA PET/CT (P < 0.01), adjuvant radiotherapy (P = 0.09), Gleason score ≥8 (P < 0.01) and nodal positivity (P = 0.05) were all predictive of PSMA positivity.
CONCLUSION
F-DCFPyL PET/CT positivity, both generally and site specific, correlates with PSA and RP pathological factors. Our results echo cohorts focussing on post-RP patients, those imaged with Ga-PSMA and those concerning biochemical persistence. Nomograms that include risk factors for 'PSMA-positive recurrence' in the BF population may increase the catchment of patients with disease confined to the prostate bed or pelvis who have a greater probability of prolonged disease-free survival.
Topics: Gallium Radioisotopes; Humans; Male; Neoplasm Recurrence, Local; Positron Emission Tomography Computed Tomography; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Retrospective Studies
PubMed: 35768883
DOI: 10.1111/bju.15724 -
The Science of the Total Environment Mar 2022Marine phages have been applied to trace ground- and surface water flows. Yet, information on their transport in soil and related particle intactness is limited. Here we...
Marine phages have been applied to trace ground- and surface water flows. Yet, information on their transport in soil and related particle intactness is limited. Here we compared the breakthrough of two lytic marine tracer phages (Pseudoalteromonas phages PSA-HM1 and PSA-HS2) with the commonly used Escherichia virus T4 in soil- and sand-filled laboratory percolation columns. All three phages showed high mass recoveries in the effluents and a higher transport velocity than non-reactive tracer Br. Comparison of effluent gene copy numbers (CN) to physically-determined phage particle counts or infectious phage counts showed that PSA-HM1 and PSA-HS2 retained high phage particle intactness (I > 81%), in contrast to T4 (I < 36%). Our data suggest that marine phages may be applied in soil to mimic the transport of (bio-) colloids or anthropogenic nanoparticles of similar traits. Quantitative PCR (qPCR) thereby allows for highly sensitive quantification and thus for the detection of even highly diluted marine tracer phages in environmental samples.
Topics: Bacteriophages; Colloids; Soil; Viruses
PubMed: 34973315
DOI: 10.1016/j.scitotenv.2021.152704 -
European Urology Focus Sep 2022Prostate-specific antigen (PSA) kinetics, defined as the change in PSA over time, may be of use as a predictor of prostate cancer. PSA kinetics can be assessed as the...
BACKGROUND
Prostate-specific antigen (PSA) kinetics, defined as the change in PSA over time, may be of use as a predictor of prostate cancer. PSA kinetics can be assessed as the PSA velocity, which is traditionally evaluated dichotomously and classified as abnormal if greater than either 0.35 or 0.75 ng/ml/yr. Machine learning models may provide additional benefit in assessing risk using PSA kinetics instead of PSA velocity.
OBJECTIVE
To improve the utility of PSA kinetics by constructing a generalizable, universal machine learning model.
DESIGN, SETTING, AND PARTICIPANTS
Data were obtained from the PLCO and PCPT trials and from a contemporary Australian cohort. PSA data were interpolated using a modified Gaussian process. A machine learning model based on a two-headed approach was designed, in which the multivariable input was fed into a one-dimensional ResNet18 model.
OUTCOME MEASURES AND STATISTICAL ANALYSIS
The model performance was assessed compared to PSA levels and PSA velocity in terms of area under the receiver operator characteristic curve (AUC).
RESULTS AND LIMITATIONS
A total of 10719 patients were included in the analysis. In tests on a validation set of the complete database to diagnose grade group ≥2, the AUC was 0.886 (95% confidence interval [CI] 0.870-0.902) for the machine learning model, compared to 0.807 (95% CI 0.796-0.819) for PSA and 0.627 (95% CI 0.607-0.648) for PSA velocity.
CONCLUSIONS
Machine learning models can be used to augment the diagnostic utility of PSA kinetics in the diagnosis of prostate cancer. We demonstrated significant improvements in accuracy compared to the traditional approaches of PSA velocity and PSA thresholds.
PATIENT SUMMARY
Prostate cancer diagnosis is limited by the diagnostic accuracy of the prostate-specific antigen (PSA) blood test. Advances in techniques such as machine learning algorithms can greatly improve the diagnostic accuracy of prostate cancer screening without additional costs or tests.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms; Early Detection of Cancer; Kinetics; Risk Factors; Risk Assessment; Australia; Machine Learning
PubMed: 34920976
DOI: 10.1016/j.euf.2021.11.009 -
Cancers Apr 2022Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes....
Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes. This study aimed to assess if ctDNA associates with PSA kinetics. Methods: In this prospective biomarker study, we evaluate ctDNA fraction and AR CN from plasma samples. We divided patients into high and low ctDNA level and in AR gain and AR normal. Results: 220 baseline samples were collected from mCRPC treated with abiraterone (n = 140) or enzalutamide (n = 80). A lower rate of PSA decline ≥ 50% was observed in patients with high ctDNA (p = 0.017) and AR gain (p = 0.0003). Combining ctDNA fraction and AR CN, we found a different median PSA progression-free survival (PFS) among four groups: (1) low ctDNA/AR normal, (2) high ctDNA/AR normal, (3) low ctDNA/AR gain, and (4) high ctDNA/AR gain (11.4 vs. 5.0 vs. 4.8 vs. 3.7 months, p < 0.0001). In a multivariable analysis, high ctDNA, AR gain, PSA DT, PSA DT velocity remained independent predictors of PSA PFS. Conclusions: Elevated ctDNA levels and AR gain are negatively and independently correlated with PSA kinetics in mCRPC men treated with abiraterone or enzalutamide.
PubMed: 35565349
DOI: 10.3390/cancers14092219 -
Journal of Clinical Medicine Oct 2020Prostate-specific antigen velocity (PSAV) is used to monitor men with clinical suspicion of prostate cancer (PCa), with a normal cut-off point of 0.3-0.5 ng/mL/year. The...
INTRODUCTION
Prostate-specific antigen velocity (PSAV) is used to monitor men with clinical suspicion of prostate cancer (PCa), with a normal cut-off point of 0.3-0.5 ng/mL/year. The aim of the study is to establish the predictive capacity of PSAV (value and acceleration) and of the free PSA/total PSA index or ratio.
METHOD
Prospective multicentre observational study in 2035 men of over 47 years of age.
INCLUSION CRITERIA
men who wished to be informed on the health of their prostate.
EXCLUSION CRITERIA
men with a previously diagnosed prostate condition. Groups: GA: ( = 518): men with serum PSA equal to or greater than 2.01 ng/mL. GB: ( = 775): men with serum PSA greater than or equal to 0.78 ng/mL and less than 2.01 ng/mL. GC: ( = 742): men with serum PSA less than 0.78 ng/mL.
VARIABLES
prostate-specific antigen (PSA); age; body mass index (BMI); PSA velocity (PSAV) (ng/mL per year); free PSA/total PSA index (iPSA); PSAV acceleration (increasing: positive, or decreasing: negative); prostate diagnosis (benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), or infectious and non-infectious prostatitis and prostatic adenocarcinoma (PCa)); de novo diagnoses of urinary tract diseases or conditions; concomitant treatments, diseases and conditions; final diagnosis of prostate health.
RESULTS
Mean age 62.35 years (SD 8.12), median 61 (47-94); age was lowest in GC. Mean BMI was 27.89 kg/m (SD 3.96), median 27.58 (18.56-57.13); no differences between groups. Mean PSAV was 0.69, SD 2.16, median 0.13 (0.001-34.46); PSAV was lowest in GC. Mean iPSA was 27.39 u/L (SD 14.25), median 24.29 (3.7-115); iPSA was lowest in GA. PSAV had more positive acceleration in GA and more negative acceleration in GC. There were 1600 (78.62%) cases of normal prostate or BPH, 322 (15.82%) cases of PIN or non-infectious prostatitis, and 113 (5.55%) cases of PCa. There were more cases of BPH in GC and more cases of PIN or prostatitis and cancer in GA ( = 0.00001). De novo diagnoses: 15 cases of urinary incontinence (UI), 16 discomfort/pain in LUT, 112 cases of voiding disorders, 12 urethral strictures, 19 hematuria, 51 cystitis, 3 pyelonephritis, 4 pelvic inflammatory disease; no differences were found between groups. In the multivariate analysis, PSAV and the direction of PSAV acceleration (positive or negative) were the variables which were correlated most strongly with prostate health. iPSA was associated with the presence of prostatitis, PCa, and BPH. Men in GA had more prostatitis, PCa, treatment with alpha blockers, and history of previous smoking. GB had more cases of BPH and more positive acceleration of PSAV. GC had more normal prostates, more BPH, more use of ranitidine, and more PSAV with negative acceleration.
CONCLUSIONS
PSAV, direction of PSAV acceleration, and iPSA in PSA cut-off points of 0.78 ng/mL and 2.01 ng/mL in a priori healthy men over 47 predict the probability of benign or malignant pathology of the prostate.
PubMed: 33114134
DOI: 10.3390/jcm9113400 -
Scientific Reports Apr 2023To define a normal range for PSA values (ng/mL) by age and create a prediction model for prostate cancer incidence. We conducted a retrospective analysis using 263,073...
To define a normal range for PSA values (ng/mL) by age and create a prediction model for prostate cancer incidence. We conducted a retrospective analysis using 263,073 observations of PSA values in Japanese men aged 18-98 years (2007-2017), including healthy men and those diagnosed with prostate cancer. Percentiles for 262,639 PSA observations in healthy men aged 18-70 years were calculated and plotted to elucidate the normal fluctuation range for PSA values by age. Univariable and multivariable logistic regression analyses were performed to develop a predictive model for prostate cancer incidence. PSA levels and PSA velocity increased with age in healthy men. However, there was no difference in PSA velocity with age in men diagnosed with prostate cancer. Logistic regression analysis showed an increased risk of prostate cancer for PSA slopes ranging from 0.5 to 3.5 ng/mL/year. This study provides age-specific normal fluctuation ranges for PSA levels in men aged 18-75 years and presents a novel and personalized prediction model for prostate cancer incidence. We found that PSA slope values of > 3.5 ng/mL/year may indicate a rapid increase in PSA levels caused by pathological condition such as inflammation but are unlikely to indicate cancer risk.
Topics: Humans; Male; Big Data; East Asian People; Incidence; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Japan; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Reference Values; Risk Assessment; Risk Factors; Biomarkers, Tumor; Predictive Value of Tests
PubMed: 37085532
DOI: 10.1038/s41598-023-33725-8 -
European Journal of Medical Research Jul 2023Although prostate-specific antigen (PSA) is widely used in prostate cancer (PCa) screening, nearly half of PCa cases are missed and less than one-third of cases are...
BACKGROUND
Although prostate-specific antigen (PSA) is widely used in prostate cancer (PCa) screening, nearly half of PCa cases are missed and less than one-third of cases are non-lethal. Adopting diagnostic criteria in population-based screening and ignoring PSA progression are presumed leading causes.
METHODS
A total of 31,942 participants with multi-round PSA tests from the PLCO trial were included. Time-dependent receiver-operating-characteristic curves and area under curves (tdAUCs) were performed to determine the screening reference level and the optimal subgroup-specific progression indicator. Effects of risk-stratified multi-round PSA screening were evaluated with multivariable Cox regression and measured with hazard ratio [HR (95%CIs)].
RESULTS
After a median follow-up of 11.6 years, a total of 3484 PCa cases and 216 PCa deaths were documented. The tdAUC of 10-year incidence PCa with PSA was 0.816, and the cut-off value was 1.61 ng/ml. Compared to subgroup with stable negative PSA in both first-round (FR) and last-round (LR) tests [FR(-)/LR(-)], HRs (95%CI) of PCa incidence were 1.66 (1.20-2.29), 8.29 (7.25-9.48), and 14.52 (12.95-16.28) for subgroups with loss of positive PSA[FR(+)/LR(-)], gain of positive PSA[FR(-)/LR(+)], and stable positive PSA[FR(+)/LR(+)]; while HRs(95%CI) of PCa mortality were 1.47 (0.52-4.15), 5.71 (3.68-8.86), and 5.01 (3.41-7.37). After excluding regressive PSA [(namely FR(+)/LR(-)], absolute velocity was the shared optimal progression indicator for subgroups with FR(-)/LR(-), FR(-)/LR(+), and FR(+)/LR(+), with tdAUCs of 0.665, 0.681 and 0.741, and cut-off values of 0.07, 0.21, and 0.33 ng/ml/year. After reclassifying participants into groups with positive and negative progression based on subgroup-specific progression indicators, incidence HR (95%CI) were 2.41 (1.87-3.10), 2.91 (2.43-3.48), and 3.16 (2.88-3.46) for positive progression compared to negative progression within subgroups of FR(-)/LR(-), FR(-)/LR(+), and FR(+)/LR(+), while mortality HR (95%CI) were 2.22 (0.91-5.38), 2.37 (1.28-4.38), and 2.98 (1.94-4.59). To improve screening performances by excluding regressive PSA and low-risk positive progression in FR(-)/LR(-), optimized screening strategy not only significantly reduce 32.4% of missed PCa (54.0% [1881/3484] vs. 21.6% [754/3484], P < 0.001), but also detected additional 8.0% of high-grade PCa (Gleason score 7-10: 36.0% [665/1849] vs. 28.0% [206/736], P < 0.001) than traditional screening strategy.
CONCLUSIONS
Risk-stratified multi-round PSA screening strategy integrating the screening reference level and the optimal subgroup-specific progression indicator of PSA could be recommended as a fundamental strategy to reduce missed diagnosis and improve the detection of high-grade PCa cases.
Topics: Male; Humans; Prostate-Specific Antigen; Early Detection of Cancer; Prostatic Neoplasms; ROC Curve
PubMed: 37496058
DOI: 10.1186/s40001-023-01228-x -
Frontiers in Medicine 2021We determined the effect of prostate-specific antigen velocity (PSAV) on the surgical outcome of thulium laser enucleation of the prostate (ThuLEP) in patients with...
We determined the effect of prostate-specific antigen velocity (PSAV) on the surgical outcome of thulium laser enucleation of the prostate (ThuLEP) in patients with benign prostatic hyperplasia (BPH). A retrospective review was performed of prospectively collected data of patients with BPH who underwent ThuLEP at any time from 2017 to 2019. Patients who had undergone BPH surgery or had prostate cancer previously were excluded, and patients with prostate-specific antigen (PSA) > 4 ng/ml were examined through transrectal ultrasound-guided prostate biopsy to rule out prostatic malignancy. Furthermore, patients were excluded if prostatic malignancy was diagnosed during postsurgery follow-up. The PSA level, International Prostate Symptom Score (IPSS), and quality of life (QoL) of 27 male patients at 3 and 15 months postsurgery differed significantly from those at presurgery; the maximum flow rate (Qmax) and postvoid residual (PVR) significantly differed between 3 months postsurgery and presurgery; and 22 and 5 patients had to and to outcomes, respectively, at 15 months postsurgery. Patients were divided into two groups ( and vs. and outcomes at 15 months postsurgery), which significantly differed with respect to PSAV at 3 months postsurgery ( = 0.04), IPSS presurgery ( < 0.02), surgical length ( = 0.01), and hospitalization duration ( = 0.04). In a receiver operating characteristic (ROC) analysis, the optimal cutoff value of PSAV of -0.52 ng/ml characterized effectiveness at 15 months after ThuLEP, and the area under the curve (AUC), sensitivity, and specificity were 0.82 ( < 0.02), 0.80, and 0.82, respectively. For PSAV < -0.52 and ≥-0.52 ng/ml, the percentages of reduction for IPSS, QoL, Qmax, and PVR were -78.6 and -71.4%, -33.3 and 0.0%, 94.4 and 40.0%, and -85.1 and -38.7%, respectively. Postsurgical PSAV was positively correlated with surgical success, and the PSAV cutoff was -0.52 ng/ml. PSAV can, thus, be used to guide the postsurgical follow-up treatment at 3 months after BPH surgery.
PubMed: 35047531
DOI: 10.3389/fmed.2021.783221