-
Nuclear Medicine Communications Apr 2022177Lu-prostate-specific membrane antigen (PSMA) gained popularity as a choice of agent in the treatment of patients with advanced prostate cancer or metastatic...
BACKGROUND
177Lu-prostate-specific membrane antigen (PSMA) gained popularity as a choice of agent in the treatment of patients with advanced prostate cancer or metastatic castration-resistant stage of prostate carcinoma (mCRPC) diseases. However, this treatment may cause fatal effects, probably due to unintended irradiation of normal organs. We performed an extensive systematic review to assess the organs at risk and the absorbed dose received by tumor lesions in 177Lu-PSMA therapy.
DESIGN
In this review, published peer-reviewed articles that cover clinical dosimetry in patients following peptide radionuclide ligand therapy using 177Lu-PSMA have been included. Two senior researchers independently checked the articles for inclusion. A systematic search in the database was made using PubMed, Publons and DOAJ. All selected articles were categorized into three groups: (1) clinical studies with the technical description of dosimetry in 177Lu-PSMA therapy (2) organ dosimetry in 177Lu-PSMA therapy or (3) tumor dosimetry in 177Lu-PSMA therapy.
RESULT
In total, 182 citations were identified on PSMA therapy and 17 original articles on 177Lu-PSMA dosimetry were recognized as eligible for review. The median absorbed dose per unit of administered activity for kidneys, salivary, liver, spleen, lacrimal and bone marrow was 0.55, 0.81, 0.1, 0.1, 2.26 and 0.03 Gy/GBq, respectively. The median absorbed dose per unit of activity for tumor lesions was found in a range of 2.71-10.94 Gy/GBq.
CONCLUSION
177Lu-PSMA systemic radiation therapy (SRT) is a well-tolerated and reliable treatment option against the management of the mCRPC stage of prostate carcinoma. Lacrimal glands and salivary glands are the major critical organs in 177Lu-PSMA SRT. Besides, tumors receive 3-6 times higher absorbed doses compared to organs at risk.
Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Prostate-Specific Antigen
PubMed: 35045551
DOI: 10.1097/MNM.0000000000001535 -
Medical Principles and Practice :... 2023Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an alpha emitter, is expected to have higher efficacy and fewer side effects compared to the beta-emitters such as Lutetium-177. We have performed a meta-analysis to assess the therapeutic responses, survival effects, and significant side effects of Ac-225 PSMA RLT in patients with mCRPC.
METHODOLOGY
Systematic literature search was carried out from five electronic databases PubMed/MEDLINE, SCOPUS, EMBASE, Web of Science, and Cochrane Library until March 2021. Eight studies were found to be eligible for this metanalysis.
RESULTS
Eight studies with 226 patients were analyzed in this metanalysis. 81% (95% CI 73-89) patients had a decline in PSA levels. 60% of the patients showed more than 50% PSA decline. Two studies assessed survival effects of radioligand naïve patients compared to patients who had received Lu-PSMA therapy previously and the pooled HR for radioligand naïve patients is 0.22. The most common toxicity reported was xerostomia in 167 patients out of 226 patients (73.9%, 95% CI 67.6-79.5%); however, most of them were confined to grade I and II levels. Other reported side effects include hematologic toxicity and nephrotoxicity.
CONCLUSION
Ac-PSMA RLT is a safe and potentially effective treatment option for patients with mCRPC.
Topics: Male; Humans; Actinium; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Prostate; Dipeptides; Treatment Outcome; Retrospective Studies
PubMed: 37247612
DOI: 10.1159/000531246 -
Arab Journal of Urology 2020: To address the question of whether antibiotic therapy can obviate the need for prostate biopsy (PBx) in patients presenting with high prostate-specific antigen (PSA)... (Review)
Review
: To address the question of whether antibiotic therapy can obviate the need for prostate biopsy (PBx) in patients presenting with high prostate-specific antigen (PSA) levels. : With the increase in unnecessary PBx in men with high PSA levels, a systematic review was performed according to the Cochrane Reviews guidelines and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. : The literature search yielded 42 studies, of which 11 were excluded due to irrelevance of data. Most of the studies were retrospective, nine studies were randomised controlled trials, and there were seven prospective non-randomised trials. The age range of the patients was 51-95 years. Antibiotics, predominantly ofloxacin or ciprofloxacin, combined with a non-steroidal anti-inflammatory drug (NSAID) or not, were prescribed for 2-8 weeks. All studies focussed on PSA levels ranging from ≤ 4 to ≥ 10 ng/mL. Furthermore, antibiotic therapy normalised PSA levels by a wide variety of percentages (16-59%), and the PSA level decrease also varied widely and ranged from 17% to 80%. For patients who had unchanged or decreased PSA, carcinoma was found in 40-52% and 7.7-20.3%, respectively. No cancer was detected if the PSA level decreased to < 4 ng/mL. : Antibiotic therapy is clinically beneficial in patients with high PSA levels. PSA reduction or normalisation after medical therapy, either antibiotic and/or NSAID, for ≥ 2 weeks can avoid unnecessary PBx. Antibiotic therapy is more beneficial when the PSA level is < 20 ng/mL. : EPS: expressed prostatic secretion; PBx: prostate biopsy; (%f)(f/t)(t)PSA, (percentage free) (free/total) (total) serum PSA; PSAD: PSA density; RCT: randomised controlled trial; VB3: voided bladder urine 3.
PubMed: 32082627
DOI: 10.1080/2090598X.2019.1677296 -
The Quarterly Journal of Nuclear... Dec 2020Copper is an essential element that plays an important role in both cancer development and growth. Indeed, high levels of copper have been found in prostate cancer... (Review)
Review
Copper is an essential element that plays an important role in both cancer development and growth. Indeed, high levels of copper have been found in prostate cancer (PCa), and this finding have paved the way for the use of this element as a target for positron emission tomography (PET) imaging. Copper64 (64Cu) can be used alone, as CuCl
2 , and also as a precursor for the in-vitro radio-labelling of specific carriers for PET imaging in PCa, (e.g. associated to prostate-specific membrane antigen: PSMA). The use of Cu-PSMA can yield late acquisitions in which PET images are characterized by a higher target-to-background ratio. At the same time, the shorter positron range of Cu provides high spatial resolution, which leads to better detection of small lesions. In this context, the aim of this review was to systematically review studies evaluating the identification of PCa in humans by means of CuCl2 and other PET tracers radio-labelled with Cu.Topics: Animals; Antigens, Surface; Biomarkers, Tumor; Copper Radioisotopes; Fluorine Radioisotopes; Glutamate Carboxypeptidase II; Humans; Magnetic Resonance Imaging; Male; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Structure-Activity Relationship; Tomography, X-Ray Computed
PubMed: 32900177
DOI: 10.23736/S1824-4785.20.03277-X -
Oncology Reviews Feb 2020Prostate-specific antigen velocity (PSAV) is widely used to detect PC and predict its progression. In this study, we qualitatively synthesized the currently available...
Prostate-specific antigen velocity (PSAV) is widely used to detect PC and predict its progression. In this study, we qualitatively synthesized the currently available evidence from published studies regarding the PSAV role in PC. Electronic databases were searched to find relevant articles published until January 2019. Inclusion and exclusion criteria were applied to identify related papers. Eventually, data extraction followed by evidence synthesis was conducted. Full-text screening resulted in 42 included studies. Multiple definitions and intervals were used for PSAV calculation across studies. Results from the included studies were conflicting regarding the role of PSAV in detecting PC and predicting progression in active surveillance cases. However, there is evidence that PSAV may have a predictive role in post-treated men. There is no clear-cut evidence from the published literature to support the use of PSAV in clinical practice.
PubMed: 32399138
DOI: 10.4081/oncol.2020.449 -
International Braz J Urol : Official... 2021Prostate cancer (PC) is the second most commonly diagnosed cancer in males. 68Ga-PSMA PET/CT, a non-invasive diagnostic tool to evaluate PC with prostate-specific... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Prostate cancer (PC) is the second most commonly diagnosed cancer in males. 68Ga-PSMA PET/CT, a non-invasive diagnostic tool to evaluate PC with prostate-specific membrane antigen (PSMA) expression, has emerged as a more accurate alternative to assess disease staging. We aimed to identify predictors of positive 68Ga-PSMA PET and the accuracy of this technique.
MATERIALS AND METHODS
Diagnostic accuracy cross-sectional study with prospective and retrospective approaches. We performed a comprehensive literature search on PubMed, Cochrane Library, and Embase database in search of studies including PC patients submitted to radical prostatectomy or radiotherapy with curative intent and presented biochemical recurrence following ASTRO 1996 criteria. A total of 35 studies involving 3910 patients submitted to 68-Ga-PSMA PET were included and independently assessed by two authors: 8 studies on diagnosis, four on staging, and 23 studies on restaging purposes. The significance level was α=0.05.
RESULTS
pooled sensitivity and specificity were 0.90 (0.86-0.93) and 0.90 (0.82-0.96), respectively, for diagnostic purposes; as for staging, pooled sensitivity and specificity were 0.93 (0.86-0.98) and 0.96 (0.92-0.99), respectively. In the restaging scenario, pooled sensitivity and specificity were 0.76 (0.74-0.78) and 0.45 (0.27-0.58), respectively, considering the identification of prostate cancer in each described situation. We also obtained specificity and sensitivity results for PSA subdivisions.
CONCLUSION
68Ga-PSMA PET provides higher sensitivity and specificity than traditional imaging for prostate cancer.
Topics: Cross-Sectional Studies; Humans; Male; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prospective Studies; Prostatic Neoplasms; Radiopharmaceuticals; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 33566470
DOI: 10.1590/S1677-5538.IBJU.2019.0817 -
Prostate Cancer and Prostatic Diseases Nov 2023Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the... (Review)
Review
BACKGROUND
Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the staging of prostate cancer (PCa). Numerous PSMA-based tracers are currently available, however, there is a lack of consensus on the optimal radiotracer(s) for PSMA PET/CT. This study aims to investigate whether Fluorine-18 (F)-labelled PSMA PET/CT is significantly different from Gallium-68 (Ga) in primary diagnosis and/or secondary staging of prostate cancer following biochemical recurrence.
METHODS
A critical review of MEDLINE, EMBASE, PubMed and Web of Science databases was performed in May 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies that directly compared F-based PSMA radiotracers and [Ga]Ga-PSMA-11 in terms of the normal organ SUV or the lesion SUV or the detection rate were assessed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2).
RESULTS
Twenty-four studies were analysed. [F]DCFPyL and [F]PSMA-1007 were the two most commonly studied F based PSMA tracers. [F]JK-PSMA-7, [F]rhPSMA-7, [F]AlF-PSMA-11 were the new tracers evaluated in a limited number of studies. Overall, [F]DCFPyL was observed to have a similar lesion detection rate to [Ga]Ga-PSMA-11 with no increase in false positive rates. [F]PSMA-1007 was found to have a greater local lesion detection rate because of its predominant hepatobiliary excretory route. However, [Ga]Ga-PSMA-11 was observed to have a similar local lesion detection rate in studies that administer patients with furosemide prior to the scan. In addition, [F]PSMA-1007 was found to have a significant number of benign bone uptakes.
CONCLUSIONS
[F]DCFPyL was observed to be similar to [Ga]Ga-PSMA-11. [F]PSMA-1007 was observed to be less preferrable to [Ga]Ga-PSMA-11 due to its high benign bone uptakes. Overall, there was not enough evidence in differentiating the radiotracers based on their clinical impacts.
PubMed: 38017295
DOI: 10.1038/s41391-023-00755-2 -
Clinical Oncology (Royal College of... Dec 2023After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the... (Meta-Analysis)
Meta-Analysis
Clinical Usefulness of Prostate-specific Membrane Antigen-ligand Positron Emission Tomography/Computed Tomography for the Detection of Prostate Cancer Biochemical Recurrence after Primary Radiation Therapy in Patients with Prostate-specific Antigen Below the Phoenix Threshold: Systematic Review and...
AIMS
After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold.
MATERIALS AND METHODS
The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2).
RESULTS
In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58-0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias.
CONCLUSION
A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.
Topics: Male; Humans; Prostate-Specific Antigen; Positron Emission Tomography Computed Tomography; Prostate; Ligands; Neoplasm Recurrence, Local; Prostatic Neoplasms; Retrospective Studies
PubMed: 37802722
DOI: 10.1016/j.clon.2023.09.012 -
JMIR Cancer Sep 2021Screening for prostate cancer has long been a debated, complex topic. The use of risk calculators for prostate cancer is recommended for determining patients' individual... (Review)
Review
BACKGROUND
Screening for prostate cancer has long been a debated, complex topic. The use of risk calculators for prostate cancer is recommended for determining patients' individual risk of cancer and the subsequent need for a prostate biopsy. These tools could lead to better discrimination of patients in need of invasive diagnostic procedures and optimized allocation of health care resources.
OBJECTIVE
The goal of the research was to systematically review available literature on the performance of current prostate cancer risk calculators in healthy populations by comparing the relative impact of individual items on different cohorts and on the models' overall performance.
METHODS
We performed a systematic review of available prostate cancer risk calculators targeted at healthy populations. We included studies published from January 2000 to March 2021 in English, Spanish, French, Portuguese, or German. Two reviewers independently decided for or against inclusion based on abstracts. A third reviewer intervened in case of disagreements. From the selected titles, we extracted information regarding the purpose of the manuscript, analyzed calculators, population for which it was calibrated, included risk factors, and the model's overall accuracy.
RESULTS
We included a total of 18 calculators from 53 different manuscripts. The most commonly analyzed ones were the Prostate Cancer Prevention Trial (PCPT) and European Randomized Study on Prostate Cancer (ERSPC) risk calculators developed from North American and European cohorts, respectively. Both calculators provided high diagnostic ability of aggressive prostate cancer (AUC as high as 0.798 for PCPT and 0.91 for ERSPC). We found 9 calculators developed from scratch for specific populations that reached a diagnostic ability as high as 0.938. The most commonly included risk factors in the calculators were age, prostate specific antigen levels, and digital rectal examination findings. Additional calculators included race and detailed personal and family history.
CONCLUSIONS
Both the PCPR and ERSPC risk calculators have been successfully adapted for cohorts other than the ones they were originally created for with no loss of diagnostic ability. Furthermore, designing calculators from scratch considering each population's sociocultural differences has resulted in risk tools that can be well adapted to be valid in more patients. The best risk calculator for prostate cancer will be that which has been calibrated for its intended population and can be easily reproduced and implemented.
TRIAL REGISTRATION
PROSPERO CRD42021242110; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242110.
PubMed: 34477564
DOI: 10.2196/30430 -
European Urology Oncology Jan 2024Although digital rectal examination (DRE) is recommended in combination with prostate-specific antigen (PSA) for detection of prostate cancer (PCa), there are limited... (Review)
Review
BACKGROUND AND OBJECTIVE
Although digital rectal examination (DRE) is recommended in combination with prostate-specific antigen (PSA) for detection of prostate cancer (PCa), there are limited data to support its use as a screening/early detection test. Our objective was to assess the diagnostic value of DRE in screening for early detection of PCa.
METHODS
In August 2023, we queried the PubMed, Scopus, and Web of Science databases to identify prospective studies simultaneously investigating the diagnostic performance of DRE and PSA for PCa screening. The primary endpoints were the positive predictive value (PPV) and cancer detection rate (CDR) of DRE. Secondary endpoints included the PPV and CDR of both PSA alone and in combination with DRE. We conducted meta-regression analysis to compare the CDR and PPV of different screening strategies. This meta-analysis is registered on PROSPERO (CRD42023446940).
KEY FINDINGS AND LIMITATIONS
We identified eight studies involving 85 738 participants, of which three were randomized controlled trials and five were prospective diagnostic studies, that reported the PPV and CDR of both DRE and PSA for the same cohort. Our analysis revealed a pooled PPV of 0.21 (95% confidence interval [CI] 0.13-0.33) for DRE, which is similar to the PPV of PSA (0.22, 95% CI 0.15-0.30; p = 0.9), with no benefit from combining DRE and PSA (PPV 0.19, 95% CI 0.13-0.26; p = 0.5). However, the CDR of DRE (0.01, 95% CI: 0.01-0.02) was significantly lower than that of PSA (0.03, 95% CI 0.02-0.03; p < 0.05) and the combination of DRE and PSA (0.03, 95% CI 0.02-0.04; p < 0.05). The screening strategy combining DRE and PSA was not different to that of PSA alone in terms of CDR (p = 0.5) and PPV (p = 0.5).
CONCLUSIONS AND CLINICAL IMPLICATIONS
Our comprehensive review and meta-analysis indicates that both as an independent test and as a supplementary measure to PSA for PCa detection, DRE exhibits a notably low diagnostic value. The collective findings from the included studies suggest that, in the absence of clinical symptoms and signs, DRE could be potentially omitted from PCa screening and early detection strategies.
PATIENT SUMMARY
Our review shows that the screening performance of digital rectal examination for detection of prostate cancer is not particularly impressive, suggesting that it might not be necessary to conduct this examination routinely.
PubMed: 38182488
DOI: 10.1016/j.euo.2023.12.005