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Diagnostics (Basel, Switzerland) Feb 2023Recently, several studies introduced the potential use of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen... (Review)
Review
BACKGROUND
Recently, several studies introduced the potential use of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in radioiodine-refractory thyroid cancer (TC).
METHODS
The authors accomplished a comprehensive literature search of original articles concerning the performance of PSMA-targeted PET/CT in TC patients. Original papers exploring this molecular imaging examination in radioiodine-refractory TC patients undergoing restaging of their disease were included.
RESULTS
A total of 6 documents concerning the diagnostic performance of PSMA-targeted PET/CT in TC (49 patients) were included in this systematic review. The included articles reported heterogeneous values of PSMA-targeted PET/CT detection rates in TC, ranging from 25% to 100% and overall inferior to [F]-fluorodeoxyglucose PET/CT when the two molecular imaging examinations were compared. Two studies reported the administration of [Lu]PSMA-radioligands with theragnostic purpose in three patients.
CONCLUSIONS
The available literature data in this setting are limited and heterogeneous. The employment of PET with PSMA-targeting radiopharmaceuticals in this setting did not affect patient management. Nevertheless, prospective multicentric studies are needed to properly assess its potential role in TC patients.
PubMed: 36766670
DOI: 10.3390/diagnostics13030564 -
International Journal of Endocrinology 2023Promoter methylation of glutathione-S-transferase 1 (GSTP1) is related to the occurrence of prostate cancer (PCa), but reports are inconsistent about the accuracy of... (Review)
Review
BACKGROUND
Promoter methylation of glutathione-S-transferase 1 (GSTP1) is related to the occurrence of prostate cancer (PCa), but reports are inconsistent about the accuracy of GSTP1 promoter methylation in PCa diagnosis and prognosis. Therefore, we systematically evaluated the diagnostic and prognostic value of GSTP1 promoter methylation in PCa.
METHODS
The PubMed, EMBASE, Web of Science, and PMC databases were searched for all relevant studies from the date of inception to November 31, 2021. We compared differences in the incidence of GSTP1 promoter methylation in cfDNA between prostate cancer patients and controls. The odds ratio (OR) and hazard ratio (HR) were used as effect sizes, and the result of each effect size is expressed as a 95% confidence interval (95% CI).
RESULTS
Our meta-analysis showed that the combined sensitivity and specificity of GSTP1 promoter methylation in cfDNA for the diagnosis of prostate cancer were 0.37 (95% CI = 0.23, 0.53) and 0.97 (95% CI = 0.88, 0.99), respectively. The area under the curve (AUC) with 95% CI was 0.78 (95% CI = 0.75, 0.82). For prognostic variables, hypermethylation of GSTP1 was associated with shorter survival in PCa (HR = 2.57, 95% CI = 1.30, 5.10), with statistical significance in between-study heterogeneity ( = 72%, =0.006). The results of the subgroup analysis indicated that the heterogeneity of studies may be due to differences in the observed indicators.
CONCLUSIONS
The results of the meta-analysis substantiate the high specificity of promoter methylation of GSTP1 in cfDNA for the diagnosis of prostate cancer, and it may be used to more precisely evaluate the prognosis of patients with prostate cancer. It may be helpful for the early detection of prostate cancer, but it still must be combined with traditional prostate-specific antigen (PSA) or other methylated genes to accomplish this goal.
PubMed: 36747996
DOI: 10.1155/2023/7279243 -
Life (Basel, Switzerland) Dec 2022The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate... (Review)
Review
The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or prostate specific membrane antigen (PSMA) ligands. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published up until to October 2022 in the English language with ≥10 enrolled patients were selected. Seven studies including 326 pts, of whom 201 (61.6%) harboring DDR defects, were selected. The majority of selected papers were retrospective and four out of seven (57.1%) had small sample size (<50 pts). Three out of seven (42.8%) studies reported a more favorable outcome (overall or progression free survival) after therapy with alpha emitters (223Ra-therapy or [225Ac]Ac-PSMA-617) in subjects with DDR defects with respect to those without mutations. In two studies employing alpha or beta emitters ([177Lu]/[225Ac]-PMSA), no significant benefit was registered in pts harboring DDR defects. In all but one paper, no significant difference in response rate was reported among pts with or without DDR mutations. Although preliminary and biased by the retrospective design, preliminary data suggest a trend towards a longer survival in PCa pts harboring DDR defects submitted to radionuclide targeted therapy with alpha emitters.
PubMed: 36676004
DOI: 10.3390/life13010055 -
Cancers Jan 2023Recent articles proposed the employment of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting... (Review)
Review
BACKGROUND
Recent articles proposed the employment of positron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals in clear cell renal cell carcinoma (ccRCC).
METHODS
The authors performed a comprehensive literature search of studies on the performance of PET/CT with PSMA-targeting radiopharmaceuticals in ccRCC. Original articles concerning this imaging examination were included in newly diagnosed ccRCC patients and ccRCC patients with disease recurrence.
RESULTS
A total of sixteen papers concerning the diagnostic performance of PSMA-targeted PET/CT in ccRCC (331 patients) were included in this systematic review. The included articles demonstrated an excellent detection rate of PSMA-targeting PET/CT in ccRCC.
CONCLUSIONS
PSMA-targeted PET/CT seems promising in detecting ccRCC lesions as well as in discriminating the presence of aggressive phenotypes. Prospective multicentric studies are warranted to strengthen the role of PSMA-targeting PET/CT in ccRCC.
PubMed: 36672305
DOI: 10.3390/cancers15020355 -
Medicine Dec 2022Conventional transrectal ultrasonography (TRUS) guided prostate biopsy is the standard method for accurate diagnosis of prostate cancer (PCa). However, the limitations... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conventional transrectal ultrasonography (TRUS) guided prostate biopsy is the standard method for accurate diagnosis of prostate cancer (PCa). However, the limitations of this technique in terms of missed diagnosis cannot be ignored. Based on previous studies, contrast-enhanced ultrasound (CEUS) may be able to more distinctly detect malignant lesions with increased microvessels. Therefore, to evaluate the diagnostic efficiency and clinical application prospects of CEUS-guided prostate biopsy for patients with suspected PCa, we performed a meta-analysis comparing CEUS-targeted with TRUS-guided systematic biopsy.
METHODS
A systematic search of PubMed, Web of Science, Embase and CNKI was performed up to March, 2022 for the relevant published studies. After data extraction and quality assessment, meta-analysis was performed using the RevMan 5.3 software.
RESULTS
The results showed that the overall sensitivity was higher for CEUS targeted biopsy than systematic biopsy (P = .03), so was the accuracy (P = .03). However, significant heterogeneity and inconsistent results from certain subgroup analyses challenged the validity of the results. Meanwhile, CEUS yielded a much higher sensitivity in patients with prostate specific antigen (PSA) level of 4 to 10 ng/mL (P = .007). On the other hand, the positive rate of each core (P < .001) and the detection rate of clinically significant PCa (P = .006) were significantly improved using CEUS.
CONCLUSION
CEUS showed the advantage of a higher detection rate of clinically significant PCa, which might provide more specific indications for subsequent treatment. More feasible, real-time data are required to confirm our findings.
Topics: Humans; Male; Image-Guided Biopsy; Magnetic Resonance Imaging; Prostate; Prostatic Neoplasms; Ultrasonography; Ultrasonography, Interventional
PubMed: 36595877
DOI: 10.1097/MD.0000000000032404 -
Hellenic Journal of Nuclear Medicine 2022The aim of this study was to assess the diagnostic value of gallium-68-prostate specific membrane antigen (Ga-PSMA) positron emission tomography/computed tomography... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to assess the diagnostic value of gallium-68-prostate specific membrane antigen (Ga-PSMA) positron emission tomography/computed tomography (PET/CT) in detecting metastases in prostate cancer (PCa) patients.
MATERIALS AND METHODS
A comprehensive literature search of studies published before August 2021 in PubMed, Embase and Cochrane Library databases was conducted.The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Studies investigating the diagnostic value of Ga-PSMA PET/CT were selected for qualitative and quantitative analysis.
RESULTS
Twenty-five articles using Ga-PSMA PET/CT for detecting metastases in PCa patients were selected for qualitative analysis, 16 of which were selected for meta-analysis. The sensitivities of Ga-PSMA PET/CT in detecting lymph node metastases ranged from 33.3% to 96.08%, with high specificities ranged from 82% to 100%. Gallium-68-PSMA PET/CT demonstrated outstanding diagnostic performance in PCa patients with bone metastases. Only two articles about Ga-PSMA PET/CT for lung metastases showed that the detection value was limited. It was difficult to distinguish lung metastases in PCa patients from benign lesions or primary lung cancer. There was only one article about Ga-PSMA PET/CT for liver metastases, which showed that about 77.7% of metastatic lesions will be Ga-PSMA-positive and 22.3% will be false negatives. Due to the lack of articles on PCa visceral metastases, we only conducted a meta-analysis on lymph node metastases and bone metastases. In our meta-analysis, the per-patient pooled sensitivity, specificity, positive likelihood ratio (LR), negative likelihood ratio (LR), diagnostic odds ratio (DOR), and the area under the ROC curve (AUC) of lymph node metastases were 0.61, 0.96, 14.4, 0.41, 35, and 0.95, respectively. The per-lesion pooled sensitivity, specificity, LR, LR, DOR, and AUC of V were 0.74, 0.99, 76.0, 0.26, 289 and 0.99, respectively. The per-patient pooled sensitivity, specificity, LR, LR, DOR, and AUC of bone metastases were 0.97, 1.00, 1100.1, 0.03, 37490 and 0.98, respectively.
CONCLUSION
Gallium-68-PSMA PET/CT demonstrated outstanding diagnostic performance for bone metastases in PCa patients. The majority of lymph node metastases, lung metastases, and liver metastases overexpressed PSMA, which could be directly detected. However, a considerable number of lesions were false negatives.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Lymphatic Metastasis; Gallium Radioisotopes; Prostatic Neoplasms
PubMed: 36576728
DOI: 10.1967/s002449912525 -
Prostate Cancer and Prostatic Diseases Jun 2023Black men are twice as likely to be diagnosed with prostate cancer than White men. Raised prostate-specific antigen (PSA) levels can indicate an increased risk of... (Review)
Review
INTRODUCTION
Black men are twice as likely to be diagnosed with prostate cancer than White men. Raised prostate-specific antigen (PSA) levels can indicate an increased risk of prostate cancer, however it is not known whether PSA levels differ for men of different ethnic groups.
METHODS
PubMed and Embase were searched to identify studies that reported levels of PSA for men of at least two ethnic groups without a prostate cancer diagnosis or symptoms suggestive of prostate cancer. An adaptation of the Newcastle-Ottawa scale was used to assess risk of bias and study quality. Findings were stratified into the following broad ethnic groups: White, Black, Asian, Hispanic, and Other. Data were analysed in a narrative synthesis due to the heterogeneity of reported PSA measures and methods in the included studies.
RESULTS
A total of 654 197 males from 13 studies were included. By ethnicity, this included 536 201 White (82%), 38 287 Black (6%), 38 232 Asian (6%), 18 029 Pacific Island (3%), 13 614 Maori (2%), 8 885 Hispanic (1%), and 949 Other (<1%) men aged ≥40 years old. Black men had higher PSA levels than White men, and Hispanic men had similar levels to White men and lower levels than Black men.
CONCLUSIONS
Black men without prostate cancer have higher PSA levels than White or Hispanic men, which reflects the higher rates of prostate cancer diagnosis in Black men. Despite that, the diagnostic accuracy of PSA for prostate cancer for men of different ethnic groups is unknown, and current guidance for PSA test interpretation does not account for ethnicity. Future research needs to determine whether Black men are diagnosed with similar rates of clinically significant prostate cancer to White men, or whether raised PSA levels are contributing to overdiagnosis of prostate cancer in Black men.
Topics: Adult; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Racial Groups; Ethnicity
PubMed: 36456698
DOI: 10.1038/s41391-022-00613-7 -
Cancers Nov 2022Recently, the development of immunotherapies such as cellular therapy, monoclonal antibodies, vaccines and immunomodulators has revolutionized the treatment of various... (Review)
Review
Recently, the development of immunotherapies such as cellular therapy, monoclonal antibodies, vaccines and immunomodulators has revolutionized the treatment of various cancer entities. In order to close the existing gaps in knowledge about cellular immunotherapy, specifically focusing on the chimeric antigen receptors (CAR) T-cells, their benefits and application in clinical settings, we conducted a comprehensive systematic review. Two co-authors independently searched the literature and characterized the results. Out of 183 records, 26 were considered eligible. This review provides an overview of the cellular immunotherapy landscape in treating prostate cancer, honing in on the challenges of employing CAR T-cell therapy. CAR T-cell therapy is a promising avenue for research due to the presence of an array of different tumor specific antigens. In prostate cancer, the complex microenvironment of the tumor vastly contributes to the success or failure of immunotherapies.
PubMed: 36428811
DOI: 10.3390/cancers14225719 -
Frontiers in Endocrinology 2022Hypogonadism has become a major cause endangering men's health and quality of life all over the world. Testosterone Therapy (TT) is a widely accepted treatment for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypogonadism has become a major cause endangering men's health and quality of life all over the world. Testosterone Therapy (TT) is a widely accepted treatment for relieving hypogonadal symptoms. However, the effect of different administrations of TT on prostate safety is still unclear.
METHODS
We did a thorough search of PubMed, Embase and Cochrane Library to identify eligible studies up to January 2022. Randomized controlled trials (RCTs) and Cohort studies evaluating the impacts of using different formulations of TT on prostate parameters were included. Changes of prostate-specific antigen (PSA) level and prostate cancer (Pca) cases were used as the primary outcomes. Quality of individual studies was estimated by RoB (Cochrane tool for assessing the risk of bias in randomized trials) and the Newcastle-Ottawa scale (Tool for assessing non-RCTs). Certainty of evidence for each study was evaluated according to the evidence assessment criteria of the Oxford Evidence-based Medicine Center. Random-effect network meta-analysis(NMA)was performed based on the Bayesian model.
RESULTS
Thirty-five studies (30 RCTs and 5 Cohort studies) with 7,740 participants were included. TT administration led to fewer Pca patients (RR=0.62, 95%CI [0.39,0.99], I=0%), while little decreasing in PSA level (MD=-0.05, 95%CI [-0.08, -0.02], I=0%). The NMA revealed that compared with other formulations, the intramuscular injection was the most likely to rank first in decreasing Pca cases. The TT also resulted in more biopsy cases (RR=2.38, 95%CI [1.01,5.60], I=0%). As for NMA, intramuscular injection also performed relatively better in fewer prostate biopsy cases compared with transdermal group.
CONCLUSION
TT does not lead to abnormal PSA changes and increased risk of Pca in patients with hypogonadism or low testosterone level. Compared with other preparations of TT, intramuscular injection proved better in minimizing Pca cases and was more likely to result in fewer prostate biopsy cases.
Topics: Male; Humans; Prostate; Testosterone; Prostate-Specific Antigen; Network Meta-Analysis; Hypogonadism
PubMed: 36419763
DOI: 10.3389/fendo.2022.1009900 -
Therapeutic Advances in Medical Oncology 2022Several therapies are available for the treatment of advanced/metastatic prostate cancer (PC). However, the systematic assessment of evidence pertaining to the use of... (Review)
Review
OBJECTIVES
Several therapies are available for the treatment of advanced/metastatic prostate cancer (PC). However, the systematic assessment of evidence pertaining to the use of these therapies in Asian patients is lacking.
METHODS
A systematic literature review (SLR) was conducted using PubMed/Medline search in May 2021 to identify the randomized/nonrandomized controlled trials (RCTs/non-RCTs) and real-world observational studies (prospective/retrospective). Only studies published as full manuscripts in English were included if reporting the efficacy, effectiveness, and/or safety of treatments in Asian patients with advanced/metastatic PC.
RESULTS
Of the 1,898 retrieved publications, 24 studies were included. These studies had patients with nonmetastatic castration-resistant PC (n = 2), metastatic castration-sensitive PC ( = 4), and metastatic castration-resistant PC ( = 18). Study designs included RCTs ( = 7), non-RCTs ( = 2), and real-world studies ( = 15). Treatments used in included studies were abiraterone acetate plus prednisone (AAP; = 6), enzalutamide, lutetium-177 prostate-specific membrane antigen (Lu-PSMA; = 4 each), docetaxel ( = 3), apalutamide, radium-223 ( = 2 each), darolutamide, cabazitaxel, and pembrolizumab ( = 1 each). The evidence from RCTs (i.e., ARAMIS, SPARTAN, ARCHES, TITAN, LATITUDE, PREVAIL) demonstrated the clinical benefits of apalutamide, darolutamide, enzalutamide, and AAP in terms of overall, disease-free, and metastasis-free survival in Asian patients. These treatments were reported to be well tolerated, with no new safety signals identified in Asian population. The efficacy and safety profiles in Asian patients were consistent with the overall trial population. Data from real-world studies supported the effectiveness and tolerability of AAP, enzalutamide, radium-223, docetaxel, cabazitaxel, Lu-PSMA, and pembrolizumab in patients with advanced/metastatic PC.
CONCLUSIONS
This SLR of the Asian data on therapies for advanced PC from the pivotal and real-world studies confirms similar efficacy and safety outcomes, consistent with the results from the pivotal clinical trials. These findings will help clinicians make better treatment decisions in clinical practice for patients with advanced/metastatic PC.
PubMed: 36407784
DOI: 10.1177/17588359221131525