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Prostate Cancer and Prostatic Diseases Dec 2015To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal...
BACKGROUND
To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.
METHODS
Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations.
RESULTS
A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8-10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5-14.9, 15-49.9 and ⩾ 50 ng ml(-1), respectively (P-trend <0.001). Men with PSADT ⩾ 15, 9-14.9, 3-8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan.
CONCLUSIONS
PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans.
Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Bone and Bones; Humans; Male; Neoplasm Grading; Odds Ratio; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Sensitivity and Specificity
PubMed: 26171882
DOI: 10.1038/pcan.2015.25 -
BJU International Jan 2021To develop a model and methodology for predicting the risk of Gleason upgrading in patients with prostate cancer on active surveillance (AS) and using the predicted...
OBJECTIVE
To develop a model and methodology for predicting the risk of Gleason upgrading in patients with prostate cancer on active surveillance (AS) and using the predicted risks to create risk-based personalised biopsy schedules as an alternative to one-size-fits-all schedules (e.g. annually). Furthermore, to assist patients and doctors in making shared decisions on biopsy schedules, by providing them quantitative estimates of the burden and benefit of opting for personalised vs any other schedule in AS. Lastly, to externally validate our model and implement it along with personalised schedules in a ready to use web-application.
PATIENTS AND METHODS
Repeat prostate-specific antigen (PSA) measurements, timing and results of previous biopsies, and age at baseline from the world's largest AS study, Prostate Cancer Research International Active Surveillance (PRIAS; 7813 patients, 1134 experienced upgrading). We fitted a Bayesian joint model for time-to-event and longitudinal data to this dataset. We then validated our model externally in the largest six AS cohorts of the Movember Foundation's third Global Action Plan (GAP3) database (>20 000 patients, 27 centres worldwide). Using the model predicted upgrading risks; we scheduled biopsies whenever a patient's upgrading risk was above a certain threshold. To assist patients/doctors in the choice of this threshold, and to compare the resulting personalised schedule with currently practiced schedules, along with the timing and the total number of biopsies (burden) planned, for each schedule we provided them with the time delay expected in detecting upgrading (shorter is better).
RESULTS
The cause-specific cumulative upgrading risk at the 5-year follow-up was 35% in PRIAS, and at most 50% in the GAP3 cohorts. In the PRIAS-based model, PSA velocity was a stronger predictor of upgrading (hazard ratio [HR] 2.47, 95% confidence interval [CI] 1.93-2.99) than the PSA level (HR 0.99, 95% CI 0.89-1.11). Our model had a moderate area under the receiver operating characteristic curve (0.6-0.7) in the validation cohorts. The prediction error was moderate (0.1-0.2) in theGAP3 cohorts where the impact of the PSA level and velocity on upgrading risk was similar to PRIAS, but large (0.2-0.3) otherwise. Our model required re-calibration of baseline upgrading risk in the validation cohorts. We implemented the validated models and the methodology for personalised schedules in a web-application (http://tiny.cc/biopsy).
CONCLUSIONS
We successfully developed and validated a model for predicting upgrading risk, and providing risk-based personalised biopsy decisions in AS of prostate cancer. Personalised prostate biopsies are a novel alternative to fixed one-size-fits-all schedules, which may help to reduce unnecessary prostate biopsies, while maintaining cancer control. The model and schedules made available via a web-application enable shared decision-making on biopsy schedules by comparing fixed and personalised schedules on total biopsies and expected time delay in detecting upgrading.
Topics: Aged; Appointments and Schedules; Area Under Curve; Biopsy; Clinical Decision-Making; Decision Making, Shared; Humans; Internet; Male; Middle Aged; Models, Statistical; Neoplasm Grading; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Risk Assessment; Risk Factors; Software; Watchful Waiting
PubMed: 32531869
DOI: 10.1111/bju.15136 -
European Urology Nov 2008Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known... (Comparative Study)
Comparative Study
BACKGROUND
Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known about the relative utility of pretreatment PSA doubling time (PSA DT) to predict tumor aggressiveness.
OBJECTIVE
To compare the utility of PSAV and PSA DT for the prediction of life-threatening prostate cancer.
DESIGN, SETTING, AND PARTICIPANTS
From the Baltimore Longitudinal Study of Aging, we identified 681 men with serial PSA measurements.
MEASUREMENTS
Receiver operating characteristic analysis was used to evaluate the relationship between PSAV, PSA DT, and the presence of high-risk disease.
RESULTS AND LIMITATIONS
Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among men with high-risk or fatal prostate cancer than men without it. By contrast, PSA DT was not significantly associated with high-risk or fatal disease. On multivariate analysis, including age, date of diagnosis, and PSA, the addition of PSAV significantly improved the concordance index from 0.85 to 0.88 (p<0.001), whereas PSA DT did not.
CONCLUSIONS
These data suggest that PSAV is more useful than PSA DT in the pretreatment setting to help identify those men with life-threatening disease.
Topics: Adult; Aged; Aged, 80 and over; Baltimore; Biomarkers, Tumor; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; ROC Curve; Risk Assessment; Risk Factors; Time Factors
PubMed: 18614274
DOI: 10.1016/j.eururo.2008.06.076 -
European Journal of Medical Research Nov 2018Both psoriasis (Ps) and psoriasis arthritis (PsA) have been associated with increased cardiovascular risk. Also, both are characterized by increased neovascularization....
BACKGROUND
Both psoriasis (Ps) and psoriasis arthritis (PsA) have been associated with increased cardiovascular risk. Also, both are characterized by increased neovascularization. Endothelial progenitor cells (EPCs) have been implicated in promoting vascular repair in ischemic diseases. The aim of the study was to correlate the EPC system with CV risk factors and with parameters of vascular stiffness in Ps and PsA.
METHODS
Twenty-six healthy subjects, 30 patients with Ps, and 31 patients PsA were included in the study. eEPC regeneration was evaluated by a colony-forming assay, circulating eEPCs were measured by cytometric analysis. For vascular analysis, all subjects underwent quantification of pulse wave velocity (PWV) and augmentation index (AIX).
RESULTS
Patients were categorized upon the duration of disease, severity of skin involvement (PASI-Ps), individual pain as reflected by the VAS (PsA), CRP values, and history of treatment with one or more biologicals. Regarding the eEPC system, no significant differences were observed between the respective categories. Correlation analyses between parameters of vascular stiffness (PWV and AIX) and patterns of colony formation/circulating eEPCs did not show any correlation at all.
CONCLUSION
Parameters of vascular stiffness are not significantly deteriorated in Ps/PsA. Thus, pulse wave analysis may not be suitable for CVR assessment in certain autoimmune-mediated diseases. Regenerative activity of the eEPC system/circulating eEPC numbers are not altered in Ps/PsA. One may conclude that malfunctions of the eEPC are not substantially involved in perpetuating the micro-/macrovascular alterations in Ps/PsA.
Topics: Arthritis, Psoriatic; Cardiovascular Diseases; Endothelial Progenitor Cells; Female; Humans; Male; Middle Aged; Psoriasis; Pulse Wave Analysis; Risk Assessment; Risk Factors; Vascular Stiffness
PubMed: 30413175
DOI: 10.1186/s40001-018-0352-7 -
Cancers Oct 2023To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen...
EAU Biochemical Recurrence Risk Classification and PSA Kinetics Have No Value for Patient Selection in PSMA-Radioguided Surgery (PSMA-RGS) for Oligorecurrent Prostate Cancer.
OBJECTIVE
To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS.
METHODS
We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS).
RESULTS
Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR ( = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR ( = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, = 0.2). Consistent negative findings were recorded for PSA-V.
CONCLUSIONS
The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.
PubMed: 37894375
DOI: 10.3390/cancers15205008 -
Cancer Mar 2012Several phase II trials in men with noncastrate PSA-recurrent prostate cancer have assessed the impact of novel nonhormonal agents on PSA kinetics. However, it is...
Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials.
BACKGROUND
Several phase II trials in men with noncastrate PSA-recurrent prostate cancer have assessed the impact of novel nonhormonal agents on PSA kinetics. However, it is unknown whether changes in PSA kinetics influence metastasis-free survival (MFS).
METHODS
We performed a retrospective post hoc analysis of 146 men treated in 4 phase II trials examining the investigational agents marimastat (a matrix metalloproteinase inhibitor; n = 39), imatinib (a tyrosine kinase inhibitor; n = 25), ATN-224 (a copper/zinc-superoxide dismutase inhibitor; n = 22), and lenalidomide (an antiangiogenic/immunomodulatory drug; n = 60). We investigated factors influencing MFS, including within-subject changes in PSA kinetics (PSA slope, doubling time, and velocity) before and after treatment initiation.
RESULTS
After a median follow-up of 16.8 months, 70 patients (47.9%) developed metastases. In multivariable Cox regression models, factors that were independently predictive of MFS after adjusting for age and other clinical prognostic variables were baseline PSA doubling time (PSADT) (P = .05), baseline PSA slope (P = .01), on-study change in PSADT (P = .02), and on-study change in PSA slope (P = .03). In a landmark Kaplan-Meier analysis, median MFS was 63.5 months (95% confidence interval [CI], 34.6-not reached) and 28.9 months (95% CI, 13.5-68.0) for men with or without any decrease in PSA slope by 6 months after treatment, respectively.
CONCLUSIONS
This hypothesis generating analysis suggests that within-subject changes in PSADT and PSA slope after initiation of experimental therapy may correlate with MFS in men with biochemically recurrent prostate cancer. If validated in prospective trials, changes in PSA kinetics may represent a reasonable intermediate end point for screening new agents in these patients.
Topics: Aged; Aged, 80 and over; Clinical Trials, Phase II as Topic; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies
PubMed: 21960118
DOI: 10.1002/cncr.26437 -
British Journal of Cancer Jan 2018Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in...
BACKGROUND
Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.
METHODS
PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.
RESULTS
1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.
CONCLUSIONS
PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.
Topics: Adult; Aged; BRCA1 Protein; BRCA2 Protein; Early Detection of Cancer; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Kallikreins; Logistic Models; Male; Middle Aged; Neoplasm Grading; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 29301143
DOI: 10.1038/bjc.2017.429 -
Journal of Nuclear Medicine : Official... Jan 2018The objective of this study was to assess the impact of Ga-prostate-specific membrane antigen (Ga-PSMA) PET/CT on the management of prostate cancer in patients with...
The objective of this study was to assess the impact of Ga-prostate-specific membrane antigen (Ga-PSMA) PET/CT on the management of prostate cancer in patients with biochemical recurrence (BCR). Documented management plans before and after Ga-PSMA PET/CT in 100 patients with BCR were retrospectively reviewed, and changes in plans were recorded. Management changed after Ga-PSMA PET/CT in 39 patients (39%). The management changes occurred in 23 (33.8%) of 68 patients with radical prostatectomy and 16 (50%) of 32 patients previously treated with radical radiotherapy. Positive scan results ( < 0.001) and higher prostate-specific antigen (PSA) levels ( = 0.024) were associated with management changes. No significant association with management change was found for Gleason grade, stage, presence of metastatic disease, PSA velocity, or PSA doubling time. Ga-PSMA PET/CT altered management in 39% of patients with BCR, and changes occurred more often in patients with radical radiotherapy treatment, positive Ga-PSMA scan results, and higher PSA levels.
Topics: Aged; Aged, 80 and over; Edetic Acid; Gallium Isotopes; Gallium Radioisotopes; Humans; Male; Middle Aged; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Recurrence; Retrospective Studies
PubMed: 28747520
DOI: 10.2967/jnumed.117.192625 -
Journal of Nuclear Medicine : Official... Jun 2023Monitoring therapy response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with novel hormonal therapies, taxanes, and newly approved... (Observational Study)
Observational Study
Monitoring therapy response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with novel hormonal therapies, taxanes, and newly approved therapies is crucial for optimizing treatment. [Ga]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PSMA PET/CT) is a promising target for managing treatment in patients with prostate cancer. PSMA is overexpressed in patients with mCRPC; understanding how expression might change in patients undergoing treatment could determine its potential for guiding clinical decisions. We examined PSMA expression in patients with CRPC and compared PET/CT response with prostate-specific antigen (PSA) variation as a prognostic factor for progression-free survival and overall survival (PFS and OS, respectively). This was a single-center, retrospective observational cohort study in patients with CRPC enrolled in the PSMA-PROSTATA registry study (EudraCT: 2015-004589-27). A first and second (if applicable) PSMA PET/CT were performed to determine PSMA expression (absence or presence). PET/CT response was assessed as responders (patients with stable disease, partial or complete response) versus nonresponders (patients with progressive disease) by comparing the first with the second PET/CT. PSA variation (increase or decrease from baseline) was assessed across the same time period. PFS was defined as the time between second PET/CT and PSA recurrence or evidence of radiologic progression. Overall, 160 patients with CRPC were included in the analysis. At first PET/CT, nearly all ( = 152; 95.0%) patients had PSMA expression (classified as mCRPC), irrespective of prior systemic therapy. SUV was positively associated with baseline PSA levels and velocity (both < 0.001). According to PET/CT response, median SUV on first PET/CT was numerically lower in nonresponders than in responders (17.5 vs. 20.4; = 0.127). Similarly, patients with a PSA increase had significantly lower median SUV on first PET/CT (15.8) than did those with a PSA decrease (30.4; = 0.018). PSA change was, on average, 146% in nonresponders and -57% in responders between first and second PET/CT ( < 0.001). Agreement between PET/CT and PSA response was 79% (k = 0.553, < 0.001). Among the 63 patients included in PFS/OS analyses, 76.2% had a relapse and 36.5% died before 24-mo follow-up; median PFS and OS were 6.1 and 24 mo, respectively. PET/CT response, independent of PSA variation, was a significant prognostic factor for PFS. OS was not significantly different between PET/CT responders and nonresponders. PSMA PET/CT may be a useful imaging method predictive of treatment response in patients with mCRPC, regardless of ongoing systemic therapy. Data also suggest that response assessed by PET/CT is a potentially more significant prognostic factor than PSA for PFS. Further studies are needed to understand the potential involvement of PSMA expression on survival.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Retrospective Studies; Prostate; Neoplasm Recurrence, Local; Treatment Outcome; Gallium Radioisotopes
PubMed: 36635087
DOI: 10.2967/jnumed.122.264964 -
Nanomaterials (Basel, Switzerland) Aug 2023In the present work, a new kind of nanocomposite (NC)-based solid component was prepared for formulating nanofluids (NFs). The NC comprised metal oxide (titanium...
In the present work, a new kind of nanocomposite (NC)-based solid component was prepared for formulating nanofluids (NFs). The NC comprised metal oxide (titanium dioxide, TiO) dispersed in a conducting polymer with polyaniline (PANI) and chemically linked silyl-alkyl units in it (PSA) that were designated as T-PSA NC. The NFs with ethylene glycol (EG) as a base fluid were prepared with T-PSA NCs with various compositions of TiO and PSA as well for various concentrations of T-PSA NCs. The scanning electron microscopic evaluation of the NC revealed that PSA deposition on TiO nanoparticles (NPs) decreased particle agglomeration. The PSA coating on the TiO NPs did not influence the crystalline structure of the TiO NPs, according to the X-ray diffraction patterns. The thermophysical characterization and molecular interaction features of the NFs at 303 K including a novel inorganic-organic T-PSA NC, were detailed. Furthermore, the stability of the T-PSA NC-based NFs was investigated experimentally using the zeta potential, and the particle size distribution change was analyzed using the dynamic light scattering (DLS) method. The T-PSA NCs had particle sizes that were significantly bigger than pristine PSA and pure TiO. Most of the preparation conditions used to produce the T-PSA NCs resulted in moderately stable suspensions in EG. The results revealed that the ultrasonic velocity increased with the increase in the concentration of T-PSA NC mass % in the NFs, the refractive index and thermal conductivity increased with the increase in the concentration, and the surface tension exhibited a linear change when the ratio of mass % concentration of the T-PSA NCs increased. The combined presence of components that synergistically contribute to the electro, thermal, optical, and rheological properties is expected to attract advanced applications for NFs.
PubMed: 37630918
DOI: 10.3390/nano13162332