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Practical Radiation Oncology 2022This study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after...
PURPOSE
This study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after definitive radiation treatment with conventionally fractionated, hypofractionated, stereotactic body radiation therapy, or brachytherapy, both high-dose and low-dose rate.
METHODS AND MATERIALS
This retrospective analysis includes low- and intermediate-risk patients with prostate cancer treated between 1998 and 2018 at an National Cancer Institute-designated comprehensive cancer center. Demographics and treatment characteristics were prospectively collected. Patients had at least 2 PSA measurements within 24 months of treatment and were free from biochemical recurrence. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed at 24 months after radiation therapy. Ideal PSA kinetics were characterized for each modality and compared.
RESULTS
Of 1042 patients, 45% had low-risk cancer, 37% favorable intermediate risk, and 19% unfavorable intermediate risk. nPSAs were higher for ablative modalities, both as absolute nPSA and relative to initial PSA. Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% treated with nonablative therapy (conventionally fractionated, hypofractionated, and low-dose rate) reached an nPSA threshold of ≤0.5 ng/mL compared with 23% of stereotactic body radiation therapy and 33% of high-dose rate cohorts. The incidence of bPSA was 13.3% and not affected by treatment modality, Gleason score, or prostate volume. PSA decay rate was faster for ablative therapies in the 6- to 24-month period.
CONCLUSIONS
Analysis of PSA within 24 months after radiation therapy revealed ablative therapies are associated with a latent PSA response and higher nPSA. Multivariable logistics modeling revealed younger age, initial PSA above the median, presence of bPSA, and ablative therapy as predictors for not achieving nPSA ≤0.5 ng/mL. PSA decay rate appears to be faster in ablative therapies after a latent period. Understanding the different PSA kinetic profiles is necessary to assess treatment response and survey for disease recurrence.
Topics: Brachytherapy; Follow-Up Studies; Humans; Kinetics; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies
PubMed: 34303033
DOI: 10.1016/j.prro.2021.07.003 -
Journal of Proteomics Apr 2021Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach...
Early detection of prostate cancer may lead to the overdiagnosis and overtreatment of patients as well as missing significant cancers. The current diagnostic approach uses elevated serum concentrations of prostate-specific antigen (PSA) as an indicator of risk. However, this test has been widely criticized as it shows poor specificity and sensitivity. In order to improve early detection and diagnosis, several studies have investigated whether different PSA proteoforms are correlated to prostate cancer. Until now, studies and methodologies for the comprehensive characterization of PSA proteoforms from biofluids are scarce. For this purpose, we developed an intact protein assay to analyze PSA by capillary electrophoresis-electrospray ionization-mass spectrometry after affinity purification from patients' urine. Here, we determined six proteolytic cleavage variants. In regard to glycosylation, tri-, di-, mono- and non-sialylated complex-type N-glycans were found on non-cleaved PSA, as well as the non-glycosylated variant. The performance of the intact protein assay was assessed using a pooled sample, obtaining an inter-day variability of 15%. Furthermore, urinary patient samples were analyzed by intact protein analysis and a bottom-up approach (glycopeptide analysis). This combined approach revealed complimentary information on both levels, demonstrating the benefit of using two orthogonal techniques to provide a thorough profile of urinary PSA. SIGNIFICANCE: The detection of clinically relevant prostate cancer requires a more specific and sensitive biomarker and, in this case, several PSA proteoforms may be able to aid or improve the current PSA test. However, a comprehensive analysis of the intact PSA proteoform profile is still lacking. This study investigated the PSA proteoforms present in urine and, in particular, determined the relative contribution of cleaved PSA and non-cleaved PSA forms to the total glycosylation profile. Importantly, intact protein analysis did not require further sample treatment before being measured by CE-ESI-MS. Furthermore, its glycosylation was also assessed in a bottom-up approach to provide complementary information. Overall, these results represent an important basis for future characterization and biomarker studies.
Topics: Electrophoresis, Capillary; Glycopeptides; Glycosylation; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 33618028
DOI: 10.1016/j.jprot.2021.104148 -
In Vivo (Athens, Greece) 2023This study aimed to compare the prostate volume (PV) and prostate-specific antigen density (PSAD) obtained using the ellipsoid volume formula or segmentation methods on...
BACKGROUND/AIM
This study aimed to compare the prostate volume (PV) and prostate-specific antigen density (PSAD) obtained using the ellipsoid volume formula or segmentation methods on magnetic resonance imaging (MRI) and further predict prostate cancer (PCa).
PATIENTS AND METHODS
Retrospectively, the enrolled patients underwent prostate MRI and had PSA levels between 4 and 10 ng/ml. The PV was measured with both the ellipsoid volume formula (PVe) and the segmentation method (PVs). The transitional zone volume (TZV) was measured with the segmentation method. The PSADe, PSADs, and PSAD_TZV were calculated. Bland-Altman plots were used to compare the agreements. ROC curve analysis was used to compare the diagnostic accuracies to predict PCa. The results were also compared between the PCa and the no-PCa groups, and among tumors with different locations and different Gleason scores (GS).
RESULTS
Seventy-six of the 117 enrolled patients were classified into the PCa group. There were high agreements between PVs and PVe as well as between PSADs and PSADe, while several outliers were mainly due to post-transurethral resection of the prostate changes and irregular hyperplastic nodules. The diagnostic accuracy of PSADe (AUC: 0.732) was slightly higher than that of PSADs (AUC: 0.729) and PSAD_TZV (AUC: 0.715). The PSADe and PSADs were not different among different tumor locations but were higher in GS ≥7 lesions (both p=0.006).
CONCLUSION
The segmentation method can be an alternative method to measure PV and calculate PSAD before prostate biopsy, particularly in post-transurethral resection of the prostate patients or those with irregular hyperplastic nodules.
Topics: Male; Humans; Prostate-Specific Antigen; Prostate; Retrospective Studies; Transurethral Resection of Prostate; Hyperplasia; Magnetic Resonance Imaging
PubMed: 36881046
DOI: 10.21873/invivo.13142 -
Investigative and Clinical Urology May 2023
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Prostate-Specific Antigen
PubMed: 37340999
DOI: 10.4111/icu.20230106 -
The Prostate Sep 2022Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate...
BACKGROUND
Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate volume ≥30 cc and total prostate specific antigen (PSA) ≥1.5 ng/ml. However, BPH is highly pleomorphic and response to 5ARIs is highly variable. An understanding of cellular composition based on a noninvasive PSA density test could lead to improved clinical decision making.
METHODS
The histological composition of 307 BPH specimens was scored by a pathologist for stromo-glandular content and associated with total PSA, prostate volume, PSA density and other clinical variables using univariate and multivariate linear regression.
RESULTS
The percentage of glandular composition in prostates of 5ARI-naïve men was positively and independently associated with PSA and PSA density. It was determined through statistical modeling that a PSA density ≤0.05 ng/ml associated with a glandular composition of ≤30% with 76% sensitivity.
CONCLUSIONS
PSA density could provide a decisive variable for estimating BPH cellular content and may eventually improve selection of patients for 5ARI treatment. Further work is needed to demonstrate that patients with higher glandular content are more responsive to 5ARI treatment.
Topics: 5-alpha Reductase Inhibitors; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia
PubMed: 35652548
DOI: 10.1002/pros.24367 -
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 -
Systematic Reviews Dec 2020This study aimed to review studies on willingness to pay (WTP) for prostate cancer screening. (Review)
Review
BACKGROUND
This study aimed to review studies on willingness to pay (WTP) for prostate cancer screening.
METHODS
This systematic-review was conducted based on the Preferred Reporting Items for Systematic Reviews guidelines. By searching six-health-database, WTP studies on prostate cancer screening using contingent valuation method published in English until March 2020 were included and those with unavailable full-text and inadequate quality-assessment scores were excluded. Smith checklist was used for the quality assessment. Extracted WTPs were converted to US dollar in 2018 using exchange rate parity and net present value formula to make comparison. Factors' effect was assessed by vote counting.
RESULTS
Six final studies published after 2006 reported above 70% Smith checklist items needed to be considered in contingent valuation study reports. Seven factors have positive effects on WTP. The reported WTP value varied from 11$ to 588$ in Japan and Germany, respectively.
CONCLUSION
WTP for prostate cancer screening was positive among all studied men. The results of factors' effect assessment showed that better understanding prostate cancer risks or screening tests and factors such as age, income, family history of cancer, hospitalization history, and educational level have positive effects. Moreover, prostate-specific antigen history, health insurance, employment, and subject's health assessment received less attention. The results' generalization to all countries is not applicable because there are no studies for low- and middle-income countries.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO 2020 CRD42020172789.
Topics: Humans; Male; Early Detection of Cancer; Germany; Insurance, Health; Prostate-Specific Antigen; Prostatic Neoplasms; Surveys and Questionnaires
PubMed: 33298175
DOI: 10.1186/s13643-020-01522-3 -
Investigative and Clinical Urology Mar 2022To document nationwide serum prostate-specific antigen (PSA) testing trends over the past decade and to investigate the impact of testing on prostate cancer (PCa)...
PURPOSE
To document nationwide serum prostate-specific antigen (PSA) testing trends over the past decade and to investigate the impact of testing on prostate cancer (PCa) detection.
MATERIALS AND METHODS
Using annual National Health Insurance Service of Korea data for the period 2006 to 2016, PSA testing rates were investigated for men aged ≥40 years by decade, and associations between test rates and registered PCa cases were analyzed.
RESULTS
During the study period, the incidence of PCa increased about threefold (4,415 in 2006 to 15,046 in 2016). PCa incidences increased with age (p<0.001) and about 60% of cases were over 70 years old. Despite a fourfold increase in PSA testing (246,911 in 2006 to 937,548 in 2016), the average exposure rate among all men was only 7.27% in 2016, and the mean number of repeat tests for those that did not develop PCa during the study period was 2.9. PSA test rates increased with age and in 2016 were 1.65% for those in their 40s, 4.90% for those in their 50s, 12.0% for those in their 60s, 19.2% for those in their 70s, and 21.6% for those aged ≥80. Regardless of the age groups, a significant association was found between PSA test numbers and the detection of PCas.
CONCLUSIONS
In contrast to the soaring incidence of PCa especially in those aged over 70 years who have a more frequent chance for PSA testing triggered by concomitant voiding symptoms, low exposure in general and among relatively younger men favors a countrywide screening policy.
Topics: Aged; Humans; Incidence; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Republic of Korea
PubMed: 35244992
DOI: 10.4111/icu.20210463 -
Asian Journal of Surgery Jun 2023
Topics: Humans; Male; Neoplasm Grading; Overdiagnosis; Prostate-Specific Antigen; Overtreatment
PubMed: 36624005
DOI: 10.1016/j.asjsur.2022.12.147 -
NEJM Evidence Aug 2023BACKGROUND: Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life,...
BACKGROUND: Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life, and there remain no validated predictive models to guide its use. METHODS: We used digital pathology images from pretreatment prostate tissue and clinical data from 5727 patients enrolled in five phase 3 randomized trials, in which treatment was radiotherapy with or without ADT, as our data source to develop and validate an artificial intelligence (AI)–derived predictive patient-specific model that would determine which patients would develop the primary end point of distant metastasis. The model used baseline data to provide a binary output that a given patient will likely benefit from ADT or not. After the model was locked, validation was performed using data from NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 (n=1594), a trial that randomly assigned men to radiotherapy plus or minus 4 months of ADT. Fine–Gray regression and restricted mean survival times were used to assess the interaction between treatment and the predictive model and within predictive model–positive, i.e., benefited from ADT, and –negative subgroup treatment effects. RESULTS: Overall, in the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis. Of these enrolled patients, 543 (34%) were model positive, and ADT significantly reduced the risk of distant metastasis compared with radiotherapy alone. Of 1051 patients who were model negative, ADT did not provide benefit. CONCLUSIONS: Our AI-based predictive model was able to identify patients with a predominantly intermediate risk for prostate cancer likely to benefit from short-term ADT. (Supported by a grant [U10CA180822] from NRG Oncology Statistical and Data Management Center, a grant [UG1CA189867] from NCI Community Oncology Research Program, a grant [U10CA180868] from NRG Oncology Operations, and a grant [U24CA196067] from NRG Specimen Bank from the National Cancer Institute and by Artera, Inc. ClinicalTrials.gov numbers NCT00767286, NCT00002597, NCT00769548, NCT00005044, and NCT00033631.)
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Prostate-Specific Antigen; Artificial Intelligence; Hormones
PubMed: 38320143
DOI: 10.1056/EVIDoa2300023