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Insights Into Imaging Jun 2024To investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific...
OBJECTIVE
To investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific antigen (PSA) levels of 4-10 ng/mL.
METHODS
A computerized search of PubMed, Embase, Cochrane Library, Medline, and Web of Science was conducted from inception until October 31, 2023. We included articles on the use of MRI to detect csPCa or PCa at 4-10 ng/mL PSA. The primary and secondary outcomes were MRI performance in csPCa and PCa detection, respectively; the estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were pooled in a bivariate random-effects model.
RESULTS
Among the 19 studies (3879 patients), there were 10 (2205 patients) and 13 studies (2965 patients) that reported MRI for detecting csPCa or PCa, respectively. The pooled sensitivity and specificity for csPCa detection were 0.84 (95% confidence interval [CI], 0.79-0.88) and 0.76 (95%CI, 0.65-0.84), respectively, for PCa detection were 0.82 (95%CI, 0.75-0.87) and 0.74 (95%CI, 0.65-0.82), respectively. The pooled NPV for csPCa detection was 0.91 (0.87-0.93). Biparametric magnetic resonance imaging also showed a significantly higher sensitivity and specificity relative to multiparametric magnetic resonance imaging (both p < 0.01).
CONCLUSION
Prostate MRI enables the detection of csPCa and PCa with satisfactory performance in the PSA gray zone. The excellent NPV for csPCa detection indicates the possibility of biopsy decision-making in patients in the PSA gray zone, but substantial heterogeneity among the included studies should be taken into account.
CLINICAL RELEVANCE STATEMENT
Prostate MRI can be considered a reliable and satisfactory tool for detecting csPCa and PCa in patients with PSA in the "gray zone", allowing for reducing unnecessary biopsy and optimizing the overall examination process.
KEY POINTS
Prostate-specific antigen (PSA) is a common screening tool for prostate cancer but risks overdiagnosis. MRI demonstrated excellent negative predictive value for prostate cancer in the PSA gray zone. MRI can influence decision-making for these patients, and biparametric MRI should be further evaluated.
PubMed: 38886256
DOI: 10.1186/s13244-024-01699-4 -
European Journal of Nuclear Medicine... Jun 2024Prostate-Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionised prostate cancer (PCa) diagnosis and treatment, offering superior... (Review)
Review
PURPOSE
Prostate-Specific Membrane Antigen (PSMA)-targeted Positron Emission Tomography (PET) has revolutionised prostate cancer (PCa) diagnosis and treatment, offering superior diagnostic accuracy over traditional methods and enabling theragnostic applications. However, a significant diagnostic challenge has emerged with identifying unspecific bone uptakes (UBUs), which could lead to over-staging and inappropriate treatment decisions if misinterpreted. This systematic review explores the phenomenon of UBUs in PCa patients undergoing PSMA-PET imaging.
METHODS
Studies assessing the prevalence, topographical distribution, and potential clinical implications of UBUs were selected according to the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) method and evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.
RESULTS
The percentage of PCa patients with UBUs on PSMA-PET scans ranged from 0 to 71.7%, depending on the radiopharmaceutical used, with [F]PSMA-1007 showing the highest incidence. The ribs are the primary site of UBUs across all PSMA-targeted radiopharmaceuticals. The spine is the second most frequent UBU site for [Ga]Ga-PSMA-11, [F]DCFPyL, [F]rhPSMA-7, while the pelvic girdle represents the second most frequent site for [F]PSMA-1007. The average maximum Standardized Uptake Value (SUV) of UBUs varied from 3.4 to 7.7 and was generally lower than that of bone metastases.
CONCLUSIONS
Our findings underscore the need for heightened awareness and precise interpretation of UBUs to avoid potential over-staging and subsequent inappropriate treatment decisions. Considering the radiopharmaceutical used, PET-derived semiquantitative parameters, the topographical distribution of UBUs, and accurately evaluating the pre-test probability based on clinical and laboratory parameters may aid nuclear medicine physicians in interpreting PSMA-PET findings.
PubMed: 38884773
DOI: 10.1007/s00259-024-06797-5 -
Supportive Care in Cancer : Official... Jun 2024The efficacy of exercise in men with prostate cancer (PCa) on active surveillance (AS) remains unclear. In this meta-analysis, we aimed to examine the effects of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The efficacy of exercise in men with prostate cancer (PCa) on active surveillance (AS) remains unclear. In this meta-analysis, we aimed to examine the effects of exercise in PCa patients on AS.
METHODS
A literature search was conducted in PubMed, EMBASE, and the Cochrane Library using search terms, including exercise, PCa, AS, and randomized controlled trials (RCTs). The means and standard deviations for peak oxygen consumption (VO), prostate-specific antigen (PSA) levels, and quality of life (QoL) were extracted for the intervention and control groups. A random-effects model was used to summarize the effects of exercise.
RESULTS
Of the 158 identified studies, six RCTs with 332 patients were included. The interventions included lifestyle modifications (aerobic exercise + diet) in three studies and different exercise modalities in three studies. The intervention duration was 2-12 months; three interventions were supervised and three were self-directed. The pooled weighted mean difference between exercise and usual care for VO was 1.42 mL/kg/min (95% confidence interval [CI]: 0.30 to 2.54, P ≤ 0.001). A non-significant effect was observed for QoL (pooled standardized mean difference [SMD]: 0.24, 95% CI: - 0.03 to 0.51, P = 0.08) which became statistically significant and stronger after excluding one outlier study (P < 0.001). Exercise also had a positive effect on PSA levels (pooled SMD: - 0.43, 95% CI: - 0.87 to 0.01, P = 0.05).
CONCLUSION
Exercise improves cardiorespiratory fitness and may improve QoL and PSA levels in men with PCa on AS. Further studies with larger sample sizes are warranted to obtain more reliable results.
Topics: Humans; Male; Prostatic Neoplasms; Quality of Life; Prostate-Specific Antigen; Randomized Controlled Trials as Topic; Oxygen Consumption; Exercise; Exercise Therapy; Watchful Waiting
PubMed: 38833183
DOI: 10.1007/s00520-024-08606-z -
European Urology Oncology May 2024Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also... (Review)
Review
BACKGROUND AND OBJECTIVE
Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.
METHODS
We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.
KEY FINDINGS AND LIMITATIONS
The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).
CONCLUSIONS AND CLINICAL IMPLICATIONS
BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.
PATIENT SUMMARY
We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.
PubMed: 38824003
DOI: 10.1016/j.euo.2024.05.003 -
Prostate Cancer and Prostatic Diseases May 2024Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in... (Review)
Review
BACKGROUND
Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in detecting recurrent PCa and is under investigation for its potential in pre-treatment staging. Despite its established efficacy in nodal and metastasis staging in trial setting, its role in primary staging awaits fuller validation due to limited evidence on oncologic outcomes. This systematic review and meta-analysis aims to appraise the diagnostic accuracy of PSMA PET/CT compared to CI for comprehensive PCa staging.
METHODS
Medline, Scopus and Web of science databases were searched till March 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Primary outcomes were specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA PET/CT for local, nodal and metastatic staging in PCa patients. Due to the unavailability of data, a meta-analysis was feasible only for detection of seminal vesicles invasion (SVI) and LNI.
RESULTS
A total of 49 studies, comprising 3876 patients, were included. Of these, 6 investigated accuracy of PSMA PET/CT in detection of SVI. Pooled sensitivity, specificity, PPV and NPV were 42.29% (95%CI: 29.85-55.78%), 87.59% (95%CI: 77.10%-93.67%), 93.39% (95%CI: 74.95%-98.52%) and 86.60% (95%CI: 58.83%-96.69%), respectively. Heterogeneity analysis revealed significant variability for PPV and NPV. 18 studies investigated PSMA PET/CT accuracy in detection of LNI. Aggregate sensitivity, specificity, PPV and NPV were 43.63% (95%CI: 34.19-53.56%), 85.55% (95%CI: 75.95%-91.74%), 67.47% (95%CI: 52.42%-79.6%) and 83.61% (95%CI: 79.19%-87.24%). No significant heterogeneity was found between studies.
CONCLUSIONS
The present systematic review and meta-analysis highlights PSMA PET-CT effectiveness in detecting SVI and its good accuracy in LNI compared to CI. Nonetheless, it also reveals a lack of high-quality research on its performance in clinical T staging, extraprostatic extension and distant metastasis evaluation, emphasizing the need for further rigorous studies.
PubMed: 38822051
DOI: 10.1038/s41391-024-00850-y -
Systematic Review of the First 40 Cases of Lu-PSMA Therapy in the Treatment of Non-prostatic Cancer.Anticancer Research Jun 2024The current systematic review aimed to collect and analyze all available published and unpublished cases in which prostate-specific membrane antigen (PSMA)-targeted...
BACKGROUND/AIM
The current systematic review aimed to collect and analyze all available published and unpublished cases in which prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (Lu-PSMA) was used to treat non-prostatic cancer.
MATERIALS AND METHODS
Literature search and evidence acquisition through contacts with organizations that use Lu-PSMA were employed. PubMed/Medline, SCOPUS, and ScienceDirect searches were performed following PRISMA recommendations. The search strategy was to screen all articles describing Lu-PSMA radioligand therapy published to date with the key word "Lu-PSMA". These articles were collected and screened for non-prostatic cancer cases. Quality assessment was performed using the GRADE criteria.
RESULTS
A total of 713 articles were screened, and the search revealed 15 eligible records. Forty patients with a mean age of 51.2±18.5 years were treated with Lu-PSMA for non-prostatic cancer. Of them, 30 cases were published, and 10 were found in medical institution records. Cancers of the salivary glands were most often targeted (13/40), followed by various brain cancer types (8/40), and osteosarcoma (6/40). The authors used previously established protocols for castration-resistant prostate cancer with the dose per cycle as 6.0-7.4 GBq and the number of cycles between one and four. Toxicity was estimated as low, and 21 out of 28 patients with reported outcomes survived to the time of the publication.
CONCLUSION
PSMA-targeted radioligand therapy was infrequently used to treat different non-prostatic cancer types in various target organs. These pioneering efforts indicate that Lu-PSMA can be used to treat non-prostatic cancer with PSMA expression. The toxicity of such treatment was low, and the outcome was relatively good.
Topics: Humans; Lutetium; Middle Aged; Radiopharmaceuticals; Male; Neoplasms; Dipeptides; Female; Glutamate Carboxypeptidase II; Aged; Radioisotopes; Antigens, Surface; Adult; Heterocyclic Compounds, 1-Ring; Prostate-Specific Antigen
PubMed: 38821587
DOI: 10.21873/anticanres.17037 -
European Urology May 2024In Europe, prostate cancer (PCa) is the most common cancer in men. Screening may therefore be crucial to lower health care costs, morbidity, and mortality. This... (Review)
Review
BACKGROUND AND OBJECTIVE
In Europe, prostate cancer (PCa) is the most common cancer in men. Screening may therefore be crucial to lower health care costs, morbidity, and mortality. This systematic review aimed to provide a contemporary overview of the costs and benefits of PCa screening programmes.
METHODS
A peer-reviewed literature search was conducted, using the PICO method. A detailed search strategy was developed in four databases based on the following key search terms: "PCa", "screening", and "cost effectiveness". Any type of economic evaluation was included. The search strategy was restricted to European countries, but no restrictions were set on the year of publication.
KEY FINDINGS AND LIMITATIONS
A total of 7484 studies were identified initially. Of these, 19 studies described the cost effectiveness of PCa screening in Europe. Among the studies using an initially healthy study population, most focussed on risk- and/or age- and/or magnetic resonance imaging (MRI)-based screening in addition to prostate-specific antigen (PSA) testing and compared this with no screening. Incremental cost ratios (ICERs) varied from €5872 per quality-adjusted life year (QALY) to €372 948/QALY, with a median of €56 487/QALY. Risk-based screening followed by MRI testing seemed to be a more cost-effective strategy than no screening.
CONCLUSIONS AND CLINICAL IMPLICATIONS
This systematic review indicates that screening programmes incorporating a risk-based approach and MRI have the potential to be cost effective.
PATIENT SUMMARY
In this review, we looked at the cost effectiveness of prostate cancer screening in Europe. We found that a risk-based approach and incorporation of magnetic resonance imaging has the potential to be cost effective. However, there remains a knowledge gap regarding cost effectiveness of prostate cancer screening. Therefore, determinants of cost effectiveness require further investigation.
PubMed: 38789306
DOI: 10.1016/j.eururo.2024.04.036 -
European Urology May 2024Biochemical recurrence (BCR) after primary definitive treatment for prostate cancer (PCa) is a heterogeneous disease state. While BCR is associated with worse oncologic... (Review)
Review
BACKGROUND AND OBJECTIVE
Biochemical recurrence (BCR) after primary definitive treatment for prostate cancer (PCa) is a heterogeneous disease state. While BCR is associated with worse oncologic outcomes, risk factors that impact outcomes can vary significantly, necessitating avenues for risk stratification. We sought to identify prognostic risk factors at the time of recurrence after primary radical prostatectomy or radiotherapy, and prior to salvage treatment(s), associated with adverse oncologic outcomes.
METHODS
We performed a systematic review of prospective studies in EMBASE, MEDLINE, and ClinicalTrials.gov (from January 1, 2000 to October 16, 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD42023466330). We reviewed the factors associated with oncologic outcomes among patients with BCR after primary definitive treatment.
KEY FINDINGS AND LIMITATIONS
A total of 37 studies were included (total n = 10 632), 25 after prostatectomy (total n = 9010) and 12 after radiotherapy (total n = 1622). Following recurrence after prostatectomy, factors associated with adverse outcomes include higher pathologic T stage and grade group, negative surgical margins, shorter prostate-specific antigen doubling time (PSADT), higher prostate-specific antigen (PSA) prior to salvage treatment, shorter time to recurrence, the 22-gene tumor RNA signature, and recurrence location on molecular imaging. After recurrence following radiotherapy, factors associated with adverse outcomes include a shorter time to recurrence, and shorter PSADT or higher PSA velocity. Grade group, T stage, and prior short-term hormone therapy (4-6 mo) were not clearly associated with adverse outcomes, although sample size and follow-up were generally limited compared with postprostatectomy data.
CONCLUSIONS AND CLINICAL IMPLICATIONS
This work highlights the recommendations and level of evidence for risk stratifying patients with PCa recurrence, and can be used as a benchmark for personalizing salvage treatment based on prognostics.
PATIENT SUMMARY
We summarize the data from previously reported clinical trials on the topic of which factors predict worse cancer outcomes for patients who recur with prostate cancer after their initial treatment.
PubMed: 38782697
DOI: 10.1016/j.eururo.2024.04.034 -
Journal of Nuclear Medicine : Official... May 2024Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated...
Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated promising results on the utility of PSMA-targeted PET/CT imaging in RCC. This report aims to provide a systematic review and metaanalysis on the utility and detection rate of PSMA PET/CT imaging in staging or evaluation of primary RCC and restaging of metastatic or recurrent RCC. Searches were performed in PubMed, Embase, and abstract proceedings (last updated, August 2023). Studies that provided a lesion-level detection rate of PSMA radiotracers in staging or restaging of RCC were included in the metaanalysis. The overall pooled detection rate with a 95% CI was estimated, and subgroup analysis was performed when feasible. Nine studies comprising 152 patients (133 clear cell RCC [ccRCC], 19 other RCC subtypes) were included in the metaanalysis. The pooled detection rate of PSMA PET/CT in evaluation of primary or metastatic RCC was estimated to be 0.83 (95% CI, 0.67-0.92). Subgroup analysis showed a pooled PSMA detection rate of 0.74 (95% CI, 0.57-0.86) in staging or evaluation of primary RCC lesions and 0.87 (95% CI, 0.73-0.95) in restaging of metastatic or recurrent RCC. Analysis based on the type of radiotracer showed a pooled detection rate of 0.85 (95% CI, 0.62-0.95) for Ga-based PSMA tracers and 0.92 (95% CI, 0.76-0.97) for F-DCFPyL PET/CT. Furthermore, in metastatic ccRCC, the available data support a significantly higher detection rate for F-DCFPyL PET/CT than for conventional imaging modalities (2 studies). Our preliminary results show that PSMA PET/CT could be a promising alternative imaging modality for evaluating RCC, particularly metastatic ccRCC. Large prospective studies are warranted to confirm clinical utility in the staging and restaging of RCC.
PubMed: 38782453
DOI: 10.2967/jnumed.124.267417 -
Clinical Nuclear Medicine May 2024The aim of this study was to perform a head-to-head comparison of multiparametric MRI (mpMRI) and the combination of prostate-specific membrane antigen (PSMA) PET plus...
PURPOSE
The aim of this study was to perform a head-to-head comparison of multiparametric MRI (mpMRI) and the combination of prostate-specific membrane antigen (PSMA) PET plus MRI (PSMA + MRI) for detecting intraprostatic clinically significant prostate cancer (csPCa).
PATIENTS AND METHODS
Relevant databases were searched through November 2023. Only studies directly comparing mpMRI and PSMA + MRI (PET/MRI or PET/CT + mpMRI) were included. A meta-analysis with a random-effects model was used to estimate pooled sensitivity, specificity, and area under the curve for each approach.
RESULTS
A total of 19 studies were included. On a patient-level analysis, PSMA + MRI had higher sensitivity (9 studies) than mpMRI for csPCa detection (96% [95% confidence interval (CI): 92%, 98%] vs 89% [95% CI: 81%, 94%]; P = 0.04). The patient-level specificity (4 studies) of PSMA + MRI was 55% (95% CI: 31%-76%) compared with 50% (95% CI: 44%-57%) of mpMRI (P = 0.67). Region-level sensitivity (10 studies) was 85% (95% CI: 74%-92%) for PSMA + MRI and 71% (95% CI: 58%-82%) for mpMRI (P = 0.09), whereas specificity (4 studies) was 87% (95% CI: 76%-94%) and 90% (95% CI: 82%-95%), respectively (P = 0.59). Lesion-level sensitivity and specificity were similar between modalities with pooled data from less than 4 studies.
CONCLUSIONS
PSMA + MRI had superior pooled sensitivity and similar specificity for the detection of csPCa compared with mpMRI in this meta-analysis of head-to-head studies.
PubMed: 38776063
DOI: 10.1097/RLU.0000000000005265