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Archives of Pathology & Laboratory... Jun 2024Laboratory testing, beyond what is essential for managing health, is considered low-value care, posing patient risks and wasting resources. Measuring excess testing on a...
CONTEXT.—
Laboratory testing, beyond what is essential for managing health, is considered low-value care, posing patient risks and wasting resources. Measuring excess testing on a national level is crucial to identify waste and optimize healthcare resource allocation for maximum impact.
OBJECTIVE.—
To measure inappropriate laboratory testing and its cost across Medicare and many US commercial payers.
DESIGN.—
A retrospective analysis on 2019 claims data measured the frequency of 4 commonly used laboratory tests among 64 million individuals with Medicare and 168 million with commercial insurance. Tests included 25-hydroxy vitamin D, prostate-specific antigen, lipid panel, and hemoglobin A1c. Clinical guidelines, medical literature, and payer recommendations were used to determine appropriate testing frequencies. Costs of excessive testing were calculated using the 2019 clinical lab fee schedule. A targeted analysis of 2022 data confirmed 2019 trends.
RESULTS.—
Analysis of ∼84 million tests from ∼1 billion outpatient test claim records revealed that 7% to 51% of tests exceeded recommended frequencies, with some egregious overuse: for example hemoglobin-A1c or prostate-specific antigen every week. The conservative cost estimate for 4 excess tests surpassed $350 million.
CONCLUSIONS.—
This extensive study, involving 232 million people, found that 14.4 million of 60.5 million individuals (23.8%) tested had undergone excessive laboratory testing, with likely little benefit and possible harm. Extrapolating findings to all laboratory testing suggests that Medicare alone may have incurred direct excess expenses from $1.95 to $3.28 billion in 2019, without factoring the hidden costs of excessive testing (eg, downstream care). Addressing unnecessary testing is crucial to lowering costs and redirecting resources for greater patient benefit.
PubMed: 38839058
DOI: 10.5858/arpa.2023-0486-OA -
ESMO Open Jun 2024This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients...
BACKGROUND
This phase II nonrandomized study evaluated the efficacy and safety of AZD4635 in combination with durvalumab (Arm A) or durvalumab plus cabazitaxel (Arm B) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and ≥1 novel hormonal agent.
PATIENTS AND METHODS
The primary endpoint was radiographic progression-free survival (rPFS) per RECIST v1.1 (soft tissue) or the Prostate Cancer Clinical Trials Working Group 3 (bone). Secondary endpoints included safety, tolerability, overall survival, confirmed prostate-specific antigen (PSA) response, pharmacokinetics, and objective response rate. Enrollment in Arm A was stopped following a sponsor decision unrelated to safety. The study was stopped based on the planned futility analysis due to low PSA response in Arm B.
RESULTS
In the final analysis (1 November 2021), 30 patients were treated (Arm A, n = 2; Arm B, n = 28). The median rPFS in Arm B was 5.8 months (95% confidence interval 4.2-not calculable). Median rPFS was 5.8 months versus 4.2 months for patients with high versus low blood-based adenosine signature. The most common treatment-related adverse events in Arm B were nausea (50.0%), diarrhea (46.4%), anemia and neutropenia (both 35.7%), asthenia (32.1%), and vomiting (28.6%). Overall, AZD4635 in combination with durvalumab or AZD4635 in combination with cabazitaxel and durvalumab showed limited efficacy in patients with mCRPC.
CONCLUSIONS
Although the safety profile of both combinations was consistent with known safety data of the individual agents, the results of this trial do not support further development of the combinations.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Aged; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal; Taxoids; Aged, 80 and over; Progression-Free Survival; Neoplasm Metastasis
PubMed: 38838502
DOI: 10.1016/j.esmoop.2024.103446 -
JAMA Network Open Jun 2024Prostate-specific antigen (PSA) screening for prostate cancer is controversial but may be associated with benefit for certain high-risk groups.
IMPORTANCE
Prostate-specific antigen (PSA) screening for prostate cancer is controversial but may be associated with benefit for certain high-risk groups.
OBJECTIVES
To evaluate associations of county-level PSA screening prevalence with prostate cancer outcomes, as well as variation by sociodemographic and clinical factors.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from cancer registries based in 8 US states on Hispanic, non-Hispanic Black, and non-Hispanic White men aged 40 to 99 years who received a diagnosis of prostate cancer between January 1, 2000, and December 31, 2015. Participants were followed up until death or censored after 10 years or December 31, 2018, whichever end point came first. Data were analyzed between September 2023 and January 2024.
EXPOSURE
County-level PSA screening prevalence was estimated using the Behavior Risk Factor Surveillance System survey data from 2004, 2006, 2008, 2010, and 2012 and weighted by population characteristics.
MAIN OUTCOMES AND MEASURES
Multivariable logistic, Cox proportional hazards regression, and competing risks models were fit to estimate adjusted odds ratios (AOR) and adjusted hazard ratios (AHR) for associations of county-level PSA screening prevalence at diagnosis with advanced stage (regional or distant), as well as all-cause and prostate cancer-specific survival.
RESULTS
Of 814 987 men with prostate cancer, the mean (SD) age was 67.3 (9.8) years, 7.8% were Hispanic, 12.2% were non-Hispanic Black, and 80.0% were non-Hispanic White; 17.0% had advanced disease. There were 247 570 deaths over 5 716 703 person-years of follow-up. Men in the highest compared with lowest quintile of county-level PSA screening prevalence at diagnosis had lower odds of advanced vs localized stage (AOR, 0.86; 95% CI, 0.85-0.88), lower all-cause mortality (AHR, 0.86; 95% CI, 0.85-0.87), and lower prostate cancer-specific mortality (AHR, 0.83; 95% CI, 0.81-0.85). Inverse associations between PSA screening prevalence and advanced cancer were strongest among men of Hispanic ethnicity vs other ethnicities (AOR, 0.82; 95% CI, 0.78-0.87), older vs younger men (aged ≥70 years: AOR, 0.77; 95% CI, 0.75-0.79), and those in the Northeast vs other US Census regions (AOR, 0.81; 95% CI, 0.79-0.84). Inverse associations with all-cause mortality were strongest among men of Hispanic ethnicity vs other ethnicities (AHR, 0.82; 95% CI, 0.78-0.85), younger vs older men (AHR, 0.81; 95% CI, 0.77-0.85), those with advanced vs localized disease (AHR, 0.80; 95% CI, 0.78-0.82), and those in the West vs other US Census regions (AHR, 0.89; 95% CI, 0.87-0.90).
CONCLUSIONS AND RELEVANCE
This population-based cohort study of men with prostate cancer suggests that higher county-level prevalence of PSA screening was associated with lower odds of advanced disease, all-cause mortality, and prostate cancer-specific mortality. Associations varied by age, race and ethnicity, and US Census region.
Topics: Humans; Male; Prostatic Neoplasms; Prostate-Specific Antigen; Aged; Middle Aged; Early Detection of Cancer; United States; Aged, 80 and over; Adult; Cohort Studies; Health Services Accessibility; Hispanic or Latino
PubMed: 38833252
DOI: 10.1001/jamanetworkopen.2024.14582 -
Cancer Immunology, Immunotherapy : CII Jun 2024The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory...
BACKGROUND
The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous.
OBJECTIVES
To gain deeper insights into the inflammatory response in the process of PCa.
METHODS
A total of 233 cases were collected, including 80 cases of prostate hyperplasia as disease control, 65 cases of postoperative prostate cancer and 36 cases of prostate cancer as PCa group. Additionally, 52 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology.
RESULTS
Our findings revealed significant increases in serum IL-8 levels in PCa group compared to the healthy control group. Additionally, IL-6, IL-10, IFN-γ and IL-12p70 levels were markedly elevated in the PCa group compared to the disease control group (all p < 0.05). Conversely, the level of IL-4, TNF-α, IL-1β, IL-17A and IFN-α were lower in the PCa group compared to those in control group. Following surgery, the concentration of IL-6 decreased; whereas, the concentrations of IL-4, TNF-α, IL-17A, IL-1β, IL-12p70, and IFN-α increased, demonstrating significant differences (p < 0.05). The differential upregulation of IL-6 or downregulation of IL-17A in peripheral blood exhibited diagnostic efficacy in PCa patients. Moreover, we observed a significant increase in IL-17A levels, accompanied by decreased of IL-2, IL-4, IL-10, TNF-a, IFN-γ, IL-1β, and IL-12P70 in patients with distant metastasis.
CONCLUSION
The peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-17A may be useful as potential predictors of PCa diagnosis.
Topics: Humans; Male; Prostatic Neoplasms; Cytokines; Middle Aged; Aged; Diagnosis, Differential; Biomarkers, Tumor; Prostate-Specific Antigen; Prostatic Hyperplasia
PubMed: 38833027
DOI: 10.1007/s00262-024-03723-4 -
International Journal of Nanomedicine 2024Prostate cancer (PC) is the second most common cancer and the fifth most frequent cause of cancer death among men. Prostate-specific membrane antigen (PSMA) expression...
INTRODUCTION
Prostate cancer (PC) is the second most common cancer and the fifth most frequent cause of cancer death among men. Prostate-specific membrane antigen (PSMA) expression is associated with aggressive PC, with expression in over 90% of patients with metastatic disease. Those characteristics have led to its use for PC diagnosis and therapies with radiopharmaceuticals, antibody-drug conjugates, and nanoparticles. Despite these advancements, none of the current therapeutics are curative and show some degree of toxicity. Here we present the synthesis and preclinical evaluation of a multimodal, PSMA-targeted dendrimer-drug conjugate (PT-DDC), synthesized using poly(amidoamine) (PAMAM) dendrimers. PT-DDC was designed to enable imaging of drug delivery, providing valuable insights to understand and enhance therapeutic response.
METHODS
The PT-DDC was synthesized through consecutive conjugation of generation-4 PAMAM dendrimers with maytansinoid-1 (DM1) a highly potent antimitotic agent, Cy5 infrared dye for optical imaging, 2,2',2"-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid (NOTA) chelator for radiolabeling with copper-64 and positron emission tomography tomography/computed tomography (PET/CT), lysine-urea-glutamate (KEU) PSMA-targeting moiety and the remaining terminal primary amines were capped with butane-1,2-diol. Non-targeted control dendrimer-drug conjugate (Ctrl-DDC) was formulated without conjugation of KEU. PT-DDC and Ctrl-DDC were characterized using high-performance liquid chromatography, matrix assisted laser desorption ionization mass spectrometry and dynamic light scattering. In vitro and in vivo evaluation of PT-DDC and Ctrl-DDC were carried out in isogenic human prostate cancer PSMA PC3 PIP and PSMA PC3 flu cell lines, and in mice bearing the corresponding xenografts.
RESULTS
PT-DDC was stable in 1×PBS and human blood plasma and required glutathione for DM1 release. Optical, PET/CT and biodistribution studies confirmed the in vivo PSMA-specificity of PT-DDC. PT-DDC demonstrated dose-dependent accumulation and cytotoxicity in PSMA PC3 PIP cells, and also showed growth inhibition of the corresponding tumors. PT-DDC did not accumulate in PSMA PC3 flu tumors and did not inhibit their growth. Ctrl-DDC did not show PSMA specificity.
CONCLUSION
In this study, we synthesized a multimodal theranostic agent capable of delivering DM1 and a radionuclide to PSMA tumors. This approach holds promise for enhancing image-guided treatment of aggressive, metastatic subtypes of prostate cancer.
Topics: Dendrimers; Male; Humans; Glutamate Carboxypeptidase II; Prostatic Neoplasms; Antigens, Surface; Cell Line, Tumor; Animals; Mice; Positron Emission Tomography Computed Tomography; Drug Delivery Systems
PubMed: 38832336
DOI: 10.2147/IJN.S454128 -
World Journal of Urology Jun 2024This study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH)...
AIM
This study aims to evaluate the effectiveness and safety of administering double-dose tamsulosin (0.8 mg) for treating patients with benign prostatic hyperplasia (BPH) who have not responded to the standard single dose of tamsulosin (0.4 mg) and are deemed unsuitable for transurethral resection (TUR) intervention.
MATERIALS AND METHODS
Between November 2022 and July 2023, we prospectively analyzed 111 patients who were experiencing severe BPH symptoms. These patients received a double dose of tamsulosin for one month. We collected baseline characteristics such as age, body mass index, and underlying medical conditions. Various parameters including the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, prostate volume, peak urinary flow rate (Qmax), voided volume, and post-void residual volume were evaluated before and after treatment.
RESULTS
All 111 patients completed the study. The mean age, PSA level, and prostate volume were 63.12 ± 4.83 years, 3.42 ± 0.93 ng/ml, and 50.37 ± 19.23 ml, respectively. Of these patients, 93 showed improvement in Qmax, post-void residual volume, and IPSS score (p-value = 0.001). The total IPSS score and total Qmax improved from 24.03 ± 2.49 and 7.72 ± 1.64 ml/sec to 16.41 ± 3.84 and 12.08 ± 2.37 ml/sec, respectively.
CONCLUSION
Double-dose 0.8mg tamsulosin as an alpha-blocker therapy appears to be a viable temporary management option for BPH patients who have not responded to the standard single dose 0.4mg tamsulosin and are not suitable candidates for TUR intervention.
Topics: Humans; Tamsulosin; Male; Prostatic Hyperplasia; Middle Aged; Aged; Prospective Studies; Adrenergic alpha-1 Receptor Antagonists; Treatment Failure; Treatment Outcome; Drug Administration Schedule
PubMed: 38822877
DOI: 10.1007/s00345-024-05050-w -
BMC Cancer May 2024To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer.
PURPOSE
To explore the clinical value of tumor abnormal protein (TAP) in the diagnosis and prognosis evaluation of prostate cancer.
METHODS
This study enrolled a total of 265 patients who underwent prostate biopsy procedures from December 2017. TAP levels were assayed in their blood samples using a validated TAP testing kit. Comprehensive pathological assessments, including Gleason scores, TNM staging, and AJCC prognosis stages, were conducted on prostate cancer patients. Further analysis was carried out to examine the correlation between TAP expression levels and various clinical characteristics.
RESULTS
A significantly elevated TAP concentration was discerned in prostate cancer patients relative to those with benign prostate hyperplasia. Moreover, a significantly elevated TAP expression was detected in prostate cancer patients with high Gleason score (≥ 8) and advanced stages (III and IV), as compared to those with Gleason scores of 6 and 7 and lower stages (I and II). When diagnosing prostate cancer in gray area of PSA, TAP demonstrated superior diagnostic capabilities over PSA alone, with higher diagnostic sensitivity, specificity and accuracy than fPSA/tPSA ratio. Additionally, post-surgical or hormonal treatment, there was a marked reduction in TAP expression level among prostate cancer patients.
CONCLUSION
The assessment of TAP presents itself as a promising tool for early diagnosis and holds potential for sensitivity in monitoring treatment reponse in prostate cancer patients.
Topics: Humans; Male; Prostatic Neoplasms; Aged; Middle Aged; Neoplasm Grading; Biomarkers, Tumor; Prognosis; Neoplasm Staging; Prostate-Specific Antigen; Neoplasm Proteins; Sensitivity and Specificity
PubMed: 38822321
DOI: 10.1186/s12885-024-12418-z -
Swiss Medical Weekly May 2024Over a decade ago, the United States Preventive Services Taskforce (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer in... (Review)
Review
Over a decade ago, the United States Preventive Services Taskforce (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer in all men, which considerably influenced prostate cancer screening policies worldwide after that. Consequently, the world has seen increasing numbers of advanced stages and prostate cancer deaths, which later led the USPSTF to withdraw its initial statement. Meanwhile, the European Union has elaborated a directive to address the problem of implementing prostate cancer screening in "Europe's Beating Cancer Plan". In Switzerland, concerned urologists formed an open Swiss Prostate Cancer Screening Group to improve the early detection of prostate cancer. On the 20th of September 2023, during the annual general assembly of the Swiss Society of Urology (SGU/SSU) in Lausanne, members positively voted for a stepwise approach to evaluate the feasibility of implementing organised prostate cancer screening programs in Switzerland. The following article will summarise the events and scientific advances in the last decade during which evidence and promising additional modalities to complement PSA-based prostate cancer screening have emerged. It also aims to provide an overview of contemporary strategies and their potential harms and benefits.
Topics: Humans; Prostatic Neoplasms; Male; Switzerland; Early Detection of Cancer; Prostate-Specific Antigen; Mass Screening; Consensus; Urology; Societies, Medical
PubMed: 38820236
DOI: 10.57187/s.3626 -
Urology Annals 2024Holmium laser enucleation of the prostate (HoLEP) showed higher efficacy than transurethral resection for treating benign prostatic hyperplasia (BPH). The present study...
PURPOSE
Holmium laser enucleation of the prostate (HoLEP) showed higher efficacy than transurethral resection for treating benign prostatic hyperplasia (BPH). The present study aims to report the outcome of BPH treatment by HoLEP in a tertiary center.
PATIENTS AND METHODS
An observational prospectively collected data for consecutive symptomatic BPH patients undergoing HoLEP between January 2020 and December 2021. Demographic and perioperative data were collected with the International Prostate Symptom Score (IPSS), quality of life, peak flow rate (Q), residual urine postvoid residual (PVR), and prostate-specific antigen (PSA) changes, in addition to perioperative and late adverse events.
RESULTS
One hundred patients were included with a median age of 73 years (range 65-80). The IPSS improved by 80% postoperatively (25 vs. 5, < 0.001). Similarly, Q significantly improved. Seven patients were found to have incidental prostate cancer. No patient needed a perioperative blood transfusion. Compared to its preoperative values, follow-up PSA has been reduced by 75% ( < 0.001). Urethral stricture and bladder neck contracture were noted in < 2% of the patients.
CONCLUSIONS
HoLEP is feasible for all prostate sizes and a safe and effective treatment for BPH patients; our results are consistent with the reported data in the literature regarding functional outcomes, complication rates, and urinary incontinence rates.
PubMed: 38818436
DOI: 10.4103/ua.ua_74_23 -
Journal of Cancer 2024Due to inconsistent results in earlier investigations regarding the relationship between vitamin D and prostate-specific antigen (PSA), this study was conducted to gain...
Due to inconsistent results in earlier investigations regarding the relationship between vitamin D and prostate-specific antigen (PSA), this study was conducted to gain a deeper understanding of the association between vitamin D and PSA. A total of 7174 male samples with 25(OH)D, PSA, and other variables were obtained from the National Health and Nutrition Examination Survey (NHANES) database. Three models, created through stepwise logistic regression, were employed to examine the dose-response association between PSA and 25(OH)D. Subsequently, restricted cubic spline analysis (RCS) was used to explore the nonlinear association between 25(OH)D and PSA. The study also compared the performance of four machine learning models in predicting PSA levels. The dose-response relationship indicated a negative impact of high 25(OH)D levels on PSA (p for trend 0.05). The odds ratio (OR) of Q4 (7.73 with 95% CI (0.26, 15.76)) was significantly higher than Q1 (6.23 with 95% CI (0.24, 12.57)). OR values in Q2 and Q3 were less than 1 (Q2= 0.57 with 95% CI (-6.37, 8.04) and Q3= 0.26 with 95% CI (-5.94, 6.86)), suggesting a potential protective effect of 25(OH)D on PSA. RCS analysis revealed a U-shaped relationship between blood 25(OH)D levels and PSA, with serum 25(OH)D in the range of 20-134 ng/ml showing a potential decrease in PSA levels. Above this range, an increase in 25(OH)D might elevate PSA levels. Age (2.67 with 95% CI 2.24 to 3.1) and BMI (17.52 with 95% CI 7.65 to 26.32), along with the OR of obesity (10.36 with 95% CI 0.68 to 20.18), were identified as potential PSA risk factors. Among the machine learning models, the random forest algorithm performed the best in predicting PSA levels. This study revealed a U-shaped relationship between 25(OH)D and PSA, with PSA potentially declining when 25(OH)D is between 20 and 134 ng/mL and possibly rising above this range. The random forest method proved effective in both predicting PSA levels and guiding vitamin D dosage.
PubMed: 38817878
DOI: 10.7150/jca.96052