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PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: an expedited systematic review.

ABSTRACT: BACKGROUND:PSMA PET is a promising method for primary lymph node staging in prostate cancer. However, recent systematic reviews have identified only a limited number of studies with histopathology as a reference test. METHODS:A systematic search was performed in PubMed and the Cochrane Library. An expedited systematic review was performed where we identified diagnostic studies in prostate cancer where a preoperative PSMA PET for primary lymph node staging was compared to histopathology. The trials must have diagnostic data on a patient level. RESULTS:Eighteen eligible clinical trials included 969 patients. The median patient number per study was 32 (range 10 to 208). Five trials were prospective, and nine trials had a consecutive enrolment of patients. Sixteen studies used Ga-68-PSMA-11; there was one study with Cu-64-PSMA and one study with F-18-DCDFPyL. Twelve studies used PET/CT, four trials used PET/MR. Most trials included patients with intermediate and high-risk. Diagnostic accuracy varied notably among the studies; sensitivity ranged from 23 to 100%, specificity 67-100%, positive predictive value 20-100%, and negative predictive value 41-100%. Weighted sensitivity was 59%, weighted specificity was 93%. Four studies compared PSMA PET with anatomical imaging (CT or MRI); in all cases, sensitivity and specificity were superior with PSMA PET. Three studies compared PSMA PET with multi-parametric or diffusion-weighted MRI with mixed results. CONCLUSIONS:PSMA PET showed promising diagnostic accuracy for primary lymph node staging with pathology as reference. Recommendation for PSMA PET for high-risk patients in clinical guidelines should be supported by confirmatory, prospective trials with patient-relevant outcomes.

SUBMITTER: Petersen LJ

PROVIDER: S-EPMC6979382 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: an expedited systematic review.

Petersen Lars J LJ Zacho Helle D HD

Cancer imaging : the official publication of the International Cancer Imaging Society 20200123 1

<h4>Background</h4>PSMA PET is a promising method for primary lymph node staging in prostate cancer. However, recent systematic reviews have identified only a limited number of studies with histopathology as a reference test.<h4>Methods</h4>A systematic search was performed in PubMed and the Cochrane Library. An expedited systematic review was performed where we identified diagnostic studies in prostate cancer where a preoperative PSMA PET for primary lymph node staging was compared to histopath ...[more]

PMID: 31973751

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Project description:PurposeTo evaluate the performance of combined PET and multiparametric MRI (mpMRI) radiomics for the group-wise prediction of postsurgical Gleason scores (psGSs) in primary prostate cancer (PCa) patients.MethodsPatients with PCa, who underwent [68 Ga]Ga-PSMA-11 PET/MRI followed by radical prostatectomy, were included in this retrospective analysis (n = 101). Patients were grouped by psGS in three categories: ISUP grades 1-3, ISUP grade 4, and ISUP grade 5. mpMRI images included T1-weighted, T2-weighted, and apparent diffusion coefficient (ADC) map. Whole-prostate segmentations were performed on each modality, and image biomarker standardization initiative (IBSI)-compliant radiomic features were extracted. Nine support vector machine (SVM) models were trained: four single-modality radiomic models (PET, T1w, T2w, ADC); three PET + MRI double-modality models (PET + T1w, PET + T2w, PET + ADC), and two baseline models (one with patient data, one image-based) for comparison. A sixfold stratified cross-validation was performed, and balanced accuracies (bAcc) of the predictions of the best-performing models were reported and compared through Student's t-tests. The predictions of the best-performing model were compared against biopsy GS (bGS).ResultsAll radiomic models outperformed the baseline models. The best-performing (mean ± stdv [%]) single-modality model was the ADC model (76 ± 6%), although not significantly better (p > 0.05) than other single-modality models (T1w: 72 ± 3%, T2w: 73 ± 2%; PET: 75 ± 5%). The overall best-performing model combined PET + ADC radiomics (82 ± 5%). It significantly outperformed most other double-modality (PET + T1w: 74 ± 5%, p = 0.026; PET + T2w: 71 ± 4%, p = 0.003) and single-modality models (PET: p = 0.042; T1w: p = 0.002; T2w: p = 0.003), except the ADC-only model (p = 0.138). In this initial cohort, the PET + ADC model outperformed bGS overall (82.5% vs 72.4%) in the prediction of psGS.ConclusionAll single- and double-modality models outperformed the baseline models, showing their potential in the prediction of GS, even with an unbalanced cohort. The best-performing model included PET + ADC radiomics, suggesting a complementary value of PSMA-PET and ADC radiomics.

Project description:PurposeTo assess the accuracy of [68Ga]-PSMA-11 PET/CT or [68Ga]-PSMA-11 PET/MRI (PSMA-11 PET/CT(MRI)) for lymph node (LN) staging using salvage LN dissection (SLND) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP).Patients and methodsIn a prospective study, 65 consecutive patients who developed BCR after RP underwent SLND after PSMA-11 PET/CT(MRI) between 2014 and 2018. Extended SLND up to the inferior mesenteric artery was performed in all patients. Regional and template-based correlations between the presence of LN metastases on histopathology and whole-body PSMA-11 PET/CT(MRI) results were evaluated. The diagnostic accuracy of PSMA-11 PET/CT(MRI) was also evaluated in relation to PSA level at the time of SLND.ResultsThe median age of the patients at the time of SLND was 65 years (IQR 63-69 years) and the median PSA level was 1.4 ng/ml (IQR 0.8-2.9 ng/ml). Before SLND, 50 patients (77%) had additional therapy after RP (26.2% androgen-deprivation therapy and 50.8% radiotherapy). The median number of LNs removed on SLND was 40 (IQR 33-48) and the median number of positive nodes was 4 (IQR 2-6). LN metastases were seen in 13.8% of resected LNs (317 of 2,292). LNs positive on PSMA-11 PET/CT(MRI) had a median diameter of 7.2 mm (IQR 5.3-9 mm). Metastatic LNs in regions negative on PSMA-11 PET had a median diameter of 3.4 mm (IQR 2.1-5.4 mm). In a regional analysis, the sensitivity of PSMA-11 PET/CT(MRI) ranged from 72% to 100%, and the specificity from 96% to 100%. Region-specific positive and negative predictive values ranged from 95% to 100% and 93% to 100%, respectively.ConclusionPSMA-11 PET/CT(MRI) has a very good performance for the identification of LN metastases in patients with BCR after RP. The high diagnostic accuracy in the regional and subregional analyses demonstrates the potential of this approach to enable a region-directed instead of a complete bilateral therapeutic intervention. The performance of PSMA-11 PET/CT(MRI) is dependent on the PSA level and the size of the metastatic deposit.

Project description:BackgroundAccurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [68Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [18F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [18F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis.ResultsThe median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease.ConclusionMetastatic disease according to [18F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [18F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax.

Project description:Background: By targeting the prostate-specific membrane antigen (PSMA) on prostate cancer (PCa) cells PSMA-PET/CT shows great potential in locating the site of biochemical recurrence even at low PSA (Prostate-specific antigen)-levels. Accurate imaging of PCa recurrent lymph node metastases (LNM) is crucial for metastases directed therapies such as salvage-lymph node dissection (salvage-LND). Objective: To evaluate the diagnostic accuracy of PSMA-PET/CT for detection of affected lymph-node regions at salvage-LND for nodal recurrence of PCa. Design, setting and participants: 30 patients with the suspicion of exclusively nodal PCa-relapse after primary therapy underwent a template pelvic and/or retroperitoneal salvage-LND after whole body 68-Ga-PSMA-PET/CT. The diagnostic accuracy of PET/CT was evaluated in comparison to the histopathology of 965 resected lymph nodes (LN) dissected from 68 main regions (pelvic left/right, retroperitoneal) and 289 subregions (common iliac, external iliac, obturator, internal iliac, presacral, aortic-bifurcation, aortal, caval). LNM and tumor deposits in LNM were measured bidimensionally in the histopathology. PSMA-expression was analyzed by immunohistochemistry in LNM. Results: LNM were present in 11.4% of the resected LN (110/965) resulting in 45 positive main regions and 85 positive subregions. PET/CT was true positive in 41 main regions and 69 subregions. Three PET-negative main regions and 16 PET-negative subregions finally contained LNM, the majority of these false negative subregions (13/16) were in neighboring regions of true-positive subregions. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were: main region-based 93.2%, 100%, 100%, 88.9% and 95.6%, subregion-based 81.2%, 99.5%, 98.6%, 92.7 and 94.1%. Median short diameters of tumor deposits in LNM resected from false-negative subregions (1.3 mm) were significantly smaller than in LNM removed from true-positive subregions (5.5 mm, p<0.0001). Based on anatomical subregions containing just one LNM, the necessary short diameter of tumor deposits in LNM required to reach a detection rate of 50% and 90% was estimated to be ? 2.3 mm and ? 4.5 mm, respectively. Conclusion: In men with biochemical PCa-relapse and positive PSMA-PET/CT, PET/CT detects metastatic affected anatomical regions with high accuracy at a main region and at a subregion-level. If the decision for salvage-LND is prompted by a positive PSMA-PET/CT, the size of metastases is crucial for accurate detection of affected regions. All LNM showed a clear PSMA-expression in the immunohistochemistry. Further studies need to investigate how to translate the high anatomical correlation observed between PET/CT and surgical findings into optimal approaches for target salvage-LND.

Project description:PurposeTo prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa).MethodsMen with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used.ResultsSeventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively.Conclusion18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.Clinical trial registrationClinicaltrials.gov ID: NCT03537391.

Dataset Information

PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: an expedited systematic review.

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PSMA PET for primary lymph node staging of intermediate and high-risk prostate cancer: an expedited systematic review.

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