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JAMA Jun 2024
PubMed: 38922607
DOI: 10.1001/jama.2024.9997 -
Annals of Laboratory Medicine Jun 2024In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory...
BACKGROUND
In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests.
METHODS
We collected 2021-2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤ 1 for the three levels.
RESULTS
Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤ 1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level.
CONCLUSIONS
We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field.
PubMed: 38919008
DOI: 10.3343/alm.2024.0082 -
Asian Pacific Journal of Cancer... Jun 2024There have been several reports on rechallenge with docetaxel, cabazitaxel, abiraterone acetate, or ethinylestradiol for metastatic castration-resistant prostate cancer...
OBJECTIVE
There have been several reports on rechallenge with docetaxel, cabazitaxel, abiraterone acetate, or ethinylestradiol for metastatic castration-resistant prostate cancer (mCRPC). However, the efficacy of enzalutamide rechallenge for mCRPC has not been evaluated.
METHODS
We retrospectively reviewed 63 consecutive patients who received enzalutamide for mCRPC at our institution between 2014 and 2022. Eight of these patients underwent rechallenge with enzalutamide after disease progression on prior enzalutamide and other therapy and were the focus of this study. The prostate-specific antigen (PSA) response (PSA decrease >50%), PSA progression-free survival, treatment duration, overall survival (OS) after CRPC, and treatment-related adverse events were evaluated.
RESULTS
PSA decline to enzalutamide rechallenge was observed in 6 patients (75%), of which 2 patients had a PSA response. The median treatment duration was 4 months (range 1-12) and median PSA progression-free survival was 3 months (range 1-7). Median OS after CRPC was 41 months. OS after CRPC was not increased in patients with a PSA response. No toxicities were worse than grade ≥3.
CONCLUSION
Enzalutamide rechallenge achieved a PSA response in a quarter of our patients with mCRPC after disease progression on prior enzalutamide. However, no improvement of OS was identified in these patients.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Phenylthiohydantoin; Nitriles; Benzamides; Retrospective Studies; Aged; Middle Aged; Prostate-Specific Antigen; Follow-Up Studies; Survival Rate; Prognosis; Aged, 80 and over; Antineoplastic Agents
PubMed: 38918645
DOI: 10.31557/APJCP.2024.25.6.1863 -
JAMA Network Open Jun 2024Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including... (Observational Study)
Observational Study
IMPORTANCE
Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including race and ethnicity. Disparities in incidence, stage at diagnosis, and survival rates have been observed between Black men and those of other races and ethnicities.
OBJECTIVE
To compare prostate cancer outcomes between Black men and men with other race (Asian, Hispanic, Indigenous, Middle Eastern, White, Multiracial, and Other) in a universal health care system, with race and ethnicity self-reported.
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, observational cohort study of men diagnosed with prostate cancer between June 1, 2014, and August 28, 2023, who self-identified race and ethnicity. Participants included men who had been prospectively enrolled in the Alberta Prostate Cancer Research Initiative from the 2 major urology referral centers in Alberta (University of Alberta and University of Calgary). All men with prostate cancer enrolled in the initiative were included.
EXPOSURE
Race and ethnicity.
MAIN OUTCOMES AND MEASURES
The primary outcome was the stage and grade of prostate cancer at diagnosis. Further outcomes included age and prostate-specific antigen level at diagnosis, initial treatment modality, time from diagnosis to initial treatment, and prostate cancer-specific, metastasis-free, and overall survivals.
RESULTS
A total of 6534 men were included; 177 (2.7%) were Black, and 6357 (97.3%) had another race or ethnicity. Men who identified as Black were diagnosed with prostate cancer at an earlier age (mean [SD], 62.0 [8.2] compared with 64.6 [7.7] years; P < .001) and had a lower Charlson Comorbidity Index rating (14% compared with 7% ≤ 1; P < .001) compared with men of other races. Men who identified as Black had similar prostate-specific antigen levels at diagnosis, TNM category (74% vs 74% with T1-T2; P = .83) and Gleason Grade Group (34% compared with 35% Gleason Grade Group 1; P = .63). Black men had similar rates of prostate cancer-specific (hazard ratio [HR], 1.10; 95% CI, 0.41-2.97; P = .85), metastasis-free (HR, 0.88; 95% CI, 0.42-1.46; P = .44), and overall (HR, 0.55; 95% CI, 0.25-1.24; P = .15) survival.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that Black men, despite being diagnosed at a younger age, experience comparable prostate cancer outcomes compared with men of other races.
Topics: Male; Humans; Prostatic Neoplasms; Aged; Middle Aged; Prospective Studies; Alberta; Canada; Black or African American; Neoplasm Grading; Black People; Neoplasm Staging; Prostate-Specific Antigen
PubMed: 38916889
DOI: 10.1001/jamanetworkopen.2024.18475 -
Radiology Jun 2024
PubMed: 38916513
DOI: 10.1148/radiol.249017 -
Journal of Vascular and Interventional... Jun 2024To evaluate the safety and effectiveness of MRI-guided cryoablation of prostate cancer metastatic lymph nodes(LN).
PURPOSE
To evaluate the safety and effectiveness of MRI-guided cryoablation of prostate cancer metastatic lymph nodes(LN).
MATERIALS AND METHODS
Fifty-two patients with prostate cancer who underwent MRI guided lymph node (LN) ablation from September 2013 to June 2022 were retrospectively reviewed. Of these, 6 patients were excluded because adequate ablation margins (3-5mm) could not be achieved secondary to adjacent structures. The remaining 46 patients (mean age, 70±7 years) underwent 55 MRI-guided cryoablation procedures of metastatic LN (25 in pelvic side wall, 20 within pelvic region and 10 in the abdomen) with procedural intent of complete ablation. Locoregional tumor control (i.e. technical success in the target LN) was evaluated on initial follow-up PET scans at mean of 4±2 months. Pre- and post-ablation prostate specific antigen (PSA) levels were recorded. Imaging follow-up continued until a median of 27.5 months (3-108 months).
RESULTS
Ninety-five percent (52/55) of treated LN demonstrated no considerable activity on PET scans at initial follow-up at 4±2 months. PSA decreased to undetectable level of <0.1ng/mL after cryoablation in 14/46 patients (30.4%) with corresponding lack of activity in 13/46 (28.2%) patients on continued PET imaging follow-up. Only 6/55 (10.9%) patients had transient adverse events which all resolved with no long term sequalae.
CONCLUSIONS
MRI-guided percutaneous cryoablation of metastatic LN is a safe and technically effective technique for treating metastatic prostate cancer in LN.
PubMed: 38914160
DOI: 10.1016/j.jvir.2024.06.015 -
The Canadian Journal of Urology Jun 2024Prostate cancer is the second most common cancer in men across the world. Prior to PSA testing, men usually presented with locally advanced disease detected on digital...
Prostate cancer is the second most common cancer in men across the world. Prior to PSA testing, men usually presented with locally advanced disease detected on digital rectal exam or with metastatic disease. PSA ushered in the era of serum biomarkers for prostate cancer. It has taken over three decades to refine the role of PSA in prostate cancer detection. The lack of specificity has spurred research into finding better, readily obtainable biomarkers with high sensitivity and specificity. The trick is to find the prostate cancers that are a threat, not the ones that aren't. Over the last decade and more, many biomarkers have been proposed and tested (HK-2, Pro-PSA, PCA3, TMPRSS2:ERG fusion transcripts, miRNA, just to name a few) but we still await that magical combination of a readily available, reproducible, and hopefully inexpensive biomarker with high sensitivity and specificity. The authors describe the use of a peptide labeled fluorophore for the VPAC1 receptors that are expressed on malignant prostate cancer cells shed in the urine. After initial feasibility work, the authors collected urine from 318 men with lower urinary tract symptoms and a PSA > 4. The patients underwent prostate biopsy yielding Grade Group 2 or higher prostate cancer in 158 patients. One hundred fifty-four or those patients with cancer had a positive result for the biomarker. The sensitivity of the test was 100%, the specificity was 97.56%, positive predictive value was 97.47%, and negative predictive value was 100%.1 These are impressive numbers for a urine biomarker (or any biomarker). This work is certainly promising, BUT, we have seen promising early data on many biomarkers. In this study, the mean PSA in the cancer group was 34.53 ng/mL versus 9.41 in the control (negative) group. Since patients with infection were excluded, the significantly different PSA levels seemed to be selecting the cancers as well. Time and follow up will determine if the "negative biopsy" controls were truly negative. Can the technique and these results be reproduced? The true test will be how this biomarker consistently performs across a broader population of men with a lower, more homogenous PSA elevation. I will eagerly await results of continued study of this promising biomarker for prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms; Biomarkers, Tumor; Sensitivity and Specificity; Prostate-Specific Antigen; Aged; Middle Aged
PubMed: 38912943
DOI: No ID Found -
The Canadian Journal of Urology Jun 2024To define the smallest prostate needle biopsy (PNB) template necessary for accurate tissue diagnosis in men with markedly elevated PSA while decreasing procedural...
INTRODUCTION
To define the smallest prostate needle biopsy (PNB) template necessary for accurate tissue diagnosis in men with markedly elevated PSA while decreasing procedural morbidity.
MATERIALS AND METHODS
We performed a chart review of 80 men presenting with a newly elevated PSA > 100 ng/mL who underwent biopsy (PNB or metastatic site). For patients who underwent a full 12-core biopsy, simulated templates of 2- to 10-cores were generated by randomly drawing subsets of biopsies from their full-template findings. Templates were iterated to randomize core location and generate theoretical smaller template outcomes. Simulated biopsy results were compared to full-template findings to determine accuracy to maximal Grade Group (GG) diagnosis.
RESULTS
Amongst those that underwent PNB, 93% had GG 4 or 5 disease. Twenty-two (40%) underwent a full 12-core biopsy, 20 (37%) a 6-core biopsy, and only 8 (15%) had fewer than six biopsy cores sampled at our hospital. Simulated templates with 2-, 4-, 6-, and 8-cores correctly diagnosed prostate cancer in all patients, and accurately identified the maximal GG in 82%, 91%, 95%, and 97% of patients, respectively. The biopsy locations most likely to detect maximal GG were medial mid and base sites bilaterally. A 4-core template of these sites would have accurately detected the maximal GG in 95% of patients relative to a full 12-core template.
CONCLUSIONS
In men presenting with PSA > 100 ng/mL, decreasing from a 12-core to a 4-core prostate biopsy template results in universal cancer detection and minimal under-grading while theoretically decreasing procedural morbidity and cost.
Topics: Humans; Male; Prostatic Neoplasms; Prostate-Specific Antigen; Aged; Middle Aged; Biopsy, Large-Core Needle; Prostate; Retrospective Studies; Neoplasm Grading; Biopsy, Needle
PubMed: 38912941
DOI: No ID Found -
ACS Nano Jun 2024Targeted nanoparticles have been extensively explored for their ability to deliver their payload to a selective cell population while reducing off-target side effects....
Targeted nanoparticles have been extensively explored for their ability to deliver their payload to a selective cell population while reducing off-target side effects. The design of actively targeted nanoparticles requires the grafting of a ligand that specifically binds to a highly expressed receptor on the surface of the targeted cell population. Optimizing the interactions between the targeting ligand and the receptor can maximize the cellular uptake of the nanoparticles and subsequently improve their activity. Here, we evaluated how the density and presentation of the targeting ligands dictate the cellular uptake of nanoparticles. To do so, we used a DNA-scaffolded PLGA nanoparticle system to achieve efficient and tunable ligand conjugation. A prostate-specific membrane antigen (PSMA) expressing a prostate cancer cell line was used as a model. The density and presentation of PSMA targeting ligand ACUPA were precisely tuned on the DNA-scaffolded nanoparticle surface, and their impact on cellular uptake was evaluated. It was found that matching the ligand density with the cell receptor density achieved the maximum cellular uptake and specificity. Furthermore, DNA hybridization-mediated targeting chain rigidity of the DNA-scaffolded nanoparticle offered ∼3 times higher cellular uptake compared to the ACUPA-terminated PLGA nanoparticle. Our findings also indicated a ∼ 3.7-fold reduction in the cellular uptake for the DNA hybridization of the non-targeting chain. We showed that nanoparticle uptake is energy-dependent and follows a clathrin-mediated pathway. Finally, we validated the preferential tumor targeting of the nanoparticles in a bilateral tumor xenograft model. Our results provide a rational guideline for designing actively targeted nanoparticles and highlight the application of DNA-scaffolded nanoparticles as an efficient active targeting platform.
PubMed: 38907991
DOI: 10.1021/acsnano.4c01640 -
Seminars in Nuclear Medicine Jun 2024The aim of this overview was to consolidate existing evidence syntheses and provide a comprehensive overview of the evidence for F-prostate specific membrane antigen... (Review)
Review
Diagnostic Accuracy of F-Prostate Specific Membrane Antigen (PSMA) PET/CT Radiotracers in Staging and Restaging of Patients With High-Risk Prostate Cancer or Biochemical Recurrence: An Overview of Reviews.
The aim of this overview was to consolidate existing evidence syntheses and provide a comprehensive overview of the evidence for F-prostate specific membrane antigen (PSMA) PET/CT in the staging of high-risk prostate cancer and restaging after biochemical recurrence. An overview of reviews was performed and reported in line with the preferred reporting items for overview of reviews (PRIOR) statement and synthesis without meta-analysis (SWiM) reporting guidelines. A comprehensive database and grey literature search were conducted up to July 18, 2023. Systematic reviews were assessed using the risk of bias in systematic reviews (ROBIS) tool. The certainty of the evidence was assessed using grading of recommendations, assessment, development and evaluations (GRADE). 11 systematic reviews were identified; 10 were at high or unclear risk of bias. Evidence reported on a per-patient, per-lymph node, and per-lesion basis for sensitivity, specificity and overall accuracy was identified. There was a lack of data on dose, adverse events and evidence directly comparing F-PSMA PET/CT to other imaging modalities. Evidence with moderate to very low certainty indicated high sensitivity, specificity and accuracy of F-PSMA PET/CT in patients with high-risk prostate cancer and biochemical recurrence. There was considerably lower certainty evidence and greater variability in effect estimates for outcomes for the combined intermediate/high-risk cohort. While evidence gaps remain for some outcomes, and most systematic reviews were at high or unclear risk of bias, the current evidence base is broadly supportive of F-PSMA PET/CT imaging in the staging and restaging of patients with high-risk prostate cancer and biochemical recurrence.
PubMed: 38906759
DOI: 10.1053/j.semnuclmed.2024.05.003