Ga-PSMA PET/CT for Primary Lymph Node and Distant Metastasis NM Staging of High-Risk Prostate Cancer.
Klingenberg Søren,Jochumsen Mads R,Ulhøi Benedicte P,Fredsøe Jacob,Sørensen Karina D,Borre Michael,Bouchelouche Kirsten
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
With the largest high-risk prostate cancer (PCa) cohort to date undergoing Ga-prostate-specific membrane antigen (PSMA) PET/CT primary staging, we aimed to, first, characterize the metastatic spread of PCa in relation to tumor Ga-PSMA uptake and the D'Amico classification and, second, compare Ga-PSMA PET/CT findings with radical prostatectomy and pelvic lymph node dissection (PLND) histopathology findings. The study included 691 consecutive newly diagnosed, biopsy-proven, treatment-naïve, D'Amico high-risk PCa patients primary-staged by Ga-PSMA PET/CT. PSMA SUV and metastatic findings were compared with prostate-specific antigen level, International Society of Urological Pathology (ISUP) grade, and clinical stage as traditional risk stratification parameters. Moreover, Ga-PSMA PET/CT findings were compared with histology findings in radical prostatectomy patients undergoing PLND. Undetected lymph node metastases (LNMs) underwent immunohistochemical PSMA staining. Advanced disease (N1/M1) was observed in 35.3% of patients (244/691) and was associated with increasing prostate-specific antigen level, ISUP grade, and clinical stage. LNMs (N1/M1a) were detected in 31.4% (217/691) and bone metastases (M1b) in 16.8% (116/691). Advanced disease frequencies in patients with ISUP grades 2 and 3 were 10.8% (11/102) and 37.1% (33/89), respectively. Risk of advanced disease for cT2a, cT2b, and cT2c tumors was almost equal (24.2%, 27.9%, and 22.4%, respectively). We observed a weak correlation between SUV and biopsy ISUP grade (ρ = 0.21; < 0.001) and a modest correlation between SUV and postprostatectomy ISUP grade (ρ = 0.38; < 0.001). Sensitivity, specificity, positive and negative predictive value, and accuracy for LNM detection on Ga-PSMA PET/CT in the PLND cohort were 30.6%, 96.5%, 68.8%, 84.5%, and 83.1%, respectively. Undetected LNMs either were micrometastases located in the lymph node border or were without PSMA expression. In this high-risk PCa cohort, we identified advanced disease in about one third at diagnosis. ISUP grade was the superior predictor for advanced disease at diagnosis. We found a significant difference in frequency of advanced disease between ISUP grades 2 and 3, as supports the Gleason score 7 subdivision. Interestingly, we observed no significant differences in risk of advanced disease when comparing the different cT2 stages. The undetected LNMs were either PSMA-negative or micrometastases.
Ga-PSMA-PET/CT in comparison with F-fluoride-PET/CT and whole-body MRI for the detection of bone metastases in patients with prostate cancer: a prospective diagnostic accuracy study.
Dyrberg Eva,Hendel Helle W,Huynh Tri Hien Viet,Klausen Tobias Wirenfeldt,Løgager Vibeke B,Madsen Claus,Pedersen Erik M,Pedersen Maria,Thomsen Henrik S
OBJECTIVES:To determine the diagnostic accuracy of gallium prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in comparison with F-fluoride-based PET/CT (NaF-PET/CT) and whole-body magnetic resonance imaging (WB-MRI) for the detection of bone metastases in patients with prostate cancer. METHODS:Sixty patients with prostate cancer were included in the period May 2016 to June 2017. The participants underwent three scans (index tests) within 30 days: a NaF-PET/CT, a WB-MRI and a PSMA-PET/CT. Experienced specialists assessed the scans. In the absence of a histological reference standard, the final diagnosis was determined as a panel diagnosis. Measures of the diagnostic performances of the index tests were calculated from patient-based dichotomous outcomes (0 or ≥ 1 bone metastasis) and pairwise compared (McNemar test). For each index test, the agreement with the final diagnosis with regard to the number of bone metastases detected (0, 1-5, > 5) and the inter-reader agreement was calculated (kappa coefficients). RESULTS:Fifty-five patients constituted the final study population; 20 patients (36%) were classified as having bone metastatic disease as their final diagnosis. The patient-based diagnostic performances were (sensitivity, specificity, overall accuracy) PSMA-PET/CT (100%, 100%, 100%), NaF-PET/CT (95%, 97%, 96%) and WB-MRI (80%, 83%, 82%). The overall accuracy of PSMA-PET/CT was significantly more favourable compared to WB-MRI (p = 0.004), but not to NaF-PET/CT (p = 0.48). PSMA-PET/CT classified the number of bone metastases reliably compared to the final diagnosis (kappa coefficient 0.97) and with an "almost perfect" inter-reader agreement (kappa coefficient 0.93). CONCLUSIONS:The overall accuracy of PSMA-PET/CT was significantly more advantageous compared to WB-MRI, but not to NaF-PET/CT. KEY POINTS:• PSMA-PET/CT assessed the presence of bone metastases correctly in all 55 patients • PSMA-PET/CT was more advantageous compared to WB-MRI • No difference was found between PSMA-PET/CT and NaF-PET/CT.
A prospective intra-individual comparison of [Ga]Ga-PSMA-11 PET/CT, [Ga]Ga-NODAGA PET/CT, and [Tc]Tc-MDP bone scintigraphy for radionuclide imaging of prostate cancer skeletal metastases.
Lawal Ismaheel O,Mokoala Kgomotso M G,Mahapane Johncy,Kleyhans Janke,Meckel Marian,Vorster Mariza,Ebenhan Thomas,Rösch Frank,Sathekge Mike M
European journal of nuclear medicine and molecular imaging
PURPOSE:Prostate cancer (PCa) commonly metastasizes to the bones. There are several radionuclide techniques for imaging PCa skeletal metastases. We aimed to compare the lesion detection rate of [Ga]Ga-PSMA-11 PET/CT, [Ga]Ga-NODAGA-zoledronate ([Ga]Ga-NODAGA) PET/CT, and [Tc]Tc-MDP bone scan in the assessment of bone metastases in patients with advanced PCa. METHODS:We prospectively recruited two cohorts of patients (staging and re-staging cohorts) with advanced prostate cancer. The staging cohort was treatment-naïve PCa patients who showed skeletal metastases on bone scan. These patients were subsequently imaged with [Ga]Ga-PSMA-11 PET/CT and [Ga]Ga-NODAGA PET/CT. Re-staging cohort was patients who were previously treated with PSMA-based radioligand therapy and were experiencing PSA progression. The re-staging cohort was imaged with [Ga]Ga-PSMA-11 PET/CT and [Ga]Ga-NODAGA PET/CT. We performed a per-patient and per-lesion analysis of skeletal metastases in both cohorts and made a comparison between scan findings. RESULTS:Eighteen patients were included with a median age of 68 years (range = 48-80) and a median Gleason score of 8. There were ten patients in the staging cohort with a median PSA of 119.26 ng/mL (range = 4.63-18,948.00) and eight patients in the re-staging cohort with a median PSA of 48.56 ng/mL (range = 6.51-3175.00). In the staging cohort, skeletal metastases detected by [Ga]Ga-PSMA-11 PET/CT, [Ga]Ga-NODAGA PET/CT, and bone scan were 322, 288, and 261, respectively, p = 0.578. In the re-staging cohort, [Ga]Ga-PSMA-11 PET/CT and [Ga]Ga-NODAGA PET/CT detected 152 and 191 skeletal metastases, respectively, p = 0.529. In two patients with negative [Ga]Ga-PSMA-11 PET/CT findings, [Ga]Ga-NODAGA detected one skeletal metastasis in one patient and 12 skeletal metastases in the other. CONCLUSION:In patients with advanced prostate cancer, [Ga]Ga-PSMA-11 PET/CT may detect more lesions than [Ga]Ga-NODAGA PET/CT and [Tc]Tc-MDP bone scan for the staging of skeletal metastases. In patients who experience PSA progression on PSMA-based radioligand therapy, [Ga]Ga-NODAGA PET/CT is a more suitable imaging modality for the detection of skeletal lesions not expressing PSMA. In the setting of re-staging, [Ga]Ga-NODAGA PET/CT may detect more lesions than [Ga]Ga-PSMA-11 PET/CT.
Bone Uptake in Prostate Cancer Patients: Diagnostic Performances of PSMA-RADS v1.0, Clinical, Biological, and 68 Ga-PSMA-11 PET Features to Predict Metastasis After Biochemical Recurrence.
Clinical nuclear medicine
PURPOSE:68 Gallium-labeled prostate-specific membrane antigen-11 (PSMA) PET/CT is the new reference to identify relapse during biochemical recurrence of prostate cancer (PCa). However, this method lacks specificity for bone foci. This study aimed to report the prevalence of PCa bone metastases and to assess the diagnostic performances of PSMA reporting and data systems (RADS), clinical, biological, and imaging features for identification. PATIENTS AND METHODS:A multicentric retrospective cohort of consecutive patients with biochemical recurrence after local treatment was analyzed. Clinical and biological features at initial staging and during recurrence were retrieved from medical reports. The metastatic status of each bone uptake on PSMA PET/CT was determined according to histopathology, comparisons with concomitant and previous conventional imaging, prostate-specific antigen kinetic, and follow-up. Two nuclear medicine physicians assessed PSMA-RADS, anatomic location, radiological patterns, SUV max , and the presence of other molecular lesions. Univariate and multivariate analyses were conducted to identify independent predictors of PCa metastases. RESULTS:In the eligible population, 98/298 patients (32.9%) showed bone uptake on PSMA PET/CT. In patients with a final diagnosis, 28/81 lesions (34.6%) were metastases. PSMA-RADS-4 or 5 showed sensitivity of 79%, specificity of 94%, and accuracy of 89%. PSMA-RADS had a significantly higher area under the receiver operating characteristic curve than the initial reading in clinical practice (0.91 vs 0.83, P = 0.0074). Initial Gleason score ≥8, age ≤71 years at recurrence, and SUV max >6.21 were independent predictors of PCa metastases in multivariate logistic regression ( P = 0.0314, 0.0179, and 0.0003, respectively). CONCLUSIONS:Most bone uptakes at PSMA PET/CT were benign lesions. PSMA-RADS, patients and tumor characteristics, and SUV max could help identify PCa bone metastases.
Total-Body Ga-PSMA-11 PET/CT for Bone Metastasis Detection in Prostate Cancer Patients: Potential Impact on Bone Scan Guidelines.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (<5, 5-10, 10-20, and >20 ng/mL) and the incidence of bone metastases detected by total-body Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging ( = 93/388, 24%), biochemical recurrence (BCR) localization ( = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy ( = 70/388, 18%) between September 2017 and May 2018. In total, 321 of 388 patients (83%) had a positive Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (<10 ng/mL, 21%; 10-20 ng/mL, 41%; ≥20 ng/mL, 41%; < 0.001). This association was maintained for all 3 indications: initial staging, BCR, and restaging M1. Bone metastases occurred most frequently in restaging M1, followed by BCR and initial staging. Bone metastasis incidence was not significantly associated with National Comprehensive Cancer Network risk score ( = 0.22). The average number of PSMA-positive regions also increased with serum PSA level ( < 0.001). Eighteen of 388 (5%) and 18 of 388 (5%) had lesions above the superior orbital ridge and below the proximal third of the femur, respectively. There was only 1 of 388 patients (0.26%) in whom the total-body PET acquisition had an impact on management. Bone metastases as assessed with Ga-PSMA-11 PET/CT are prevalent even in patients with low serum PSA levels. Therefore, current guidelines for bone assessments in prostate cancer patients should be revisited because Ga-PSMA-11 PET/CT may provide additional information for accurate bone staging at low serum PSA levels. Including the total body (from vertex to toes) in Ga-PSMA-11 PET/CT imaging revealed additional bone lesions in 6% of patients, but without significantly affecting patient management.
Comparison of hybrid Ga-PSMA-PET/CT and Tc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: Additional value of morphologic information from low dose CT.
Janssen Jan-Carlo,Meißner Sebastian,Woythal Nadine,Prasad Vikas,Brenner Winfried,Diederichs Gerd,Hamm Bernd,Makowski Marcus R
PURPOSE:This study compared Gallium-prostate-specific-membrane-antigen based Positron-emission-tomography (Ga-PSMA-PET) and technetium-3,3-diphospho-1,2-propanedicarbonacid (Tc-DPD-SPECT) in performing skeletal staging in prostate cancer (PC) patients and evaluated the additional value of the information from low-dose-computed tomography (CT). MATERIALS AND METHODS:In this retrospective study, 54 patients who received Ga-PSMA-PET/CT and Tc-DPD-SPECT/CT within 80 days were extracted from our database. Osseous lesions were classified as benign, malignant or equivocal. Lesion, region and patient based analysis was performed with and without CT fusion. The reference standard was generated by defining a best valuable comparator (BVC) containing information from all available data. RESULTS:In the patient based analysis, accuracies measured as "area-under-the-curve" (AUC) for Ga-PSMA-PET, Tc-SPECT, Ga-PSMA-PET/CT and Tc-SPECT/CT were 0.97-0.96, 0.86-0.83, 1.00 and 0.83, respectively (p<0.05) (ranges = optimistic vs. pessimistic view). Region based analysis resulted in the following sensitivities and specificities: 91.8-97.7%, 100-99.5% (PET); 61.2-70.6%, 99.8-98.3% (SPECT); 97.7%, 100% (PET/CT), 69.4% and 98.3% (SPECT/CT) (p<0.05). The amount of correct classifications of equivocal lesions by CT was significantly higher in PET (100%) compared to SPECT (52.4%) (p<0.05). CONCLUSION:Ga-PSMA-PET outperforms Tc-DPD-SPECT in detecting bone metastases in PC patients. Additional information from low-dose-CT resulted in a significant reduction in equivocal lesions in both modalities, however Ga-PSMA-PET benefited most. KEY POINTS:• Ga-PSMA-PET outperforms Tc-DPD-SPECT in skeletal staging in prostate cancer patients • Proportion of equivocal decisions was significantly reduced by CT-fusion in both modalities • Ga-PSMA-PET benefits more from CT information, compared to Tc-DPD-SPECT.
Assessment of malignancy and PSMA expression of uncertain bone foci in [F]PSMA-1007 PET/CT for prostate cancer-a single-centre experience of PET-guided biopsies.
European journal of nuclear medicine and molecular imaging
PURPOSE:Uncertain focal bone uptake (UBU) with intensive radiopharmaceutical avidity are frequently observed in patients undergoing [F]PSMA-1007 PET/CT for the detection of prostate cancer (PC). Such foci can pose diagnostic conundrums and risk incorrect staging. The aim of this short communication is to share the results of PET-guided biopsies of such foci. METHODS:A retrospective analysis revealed 10 patients who were referred to our department for PET-guided biopsy of UBU visible in a previous [F]PSMA-1007 PET/CT. [F]-PSMA-1007 PET-guided biopsy was conducted for 11 PSMA-avid bone foci in these 10 patients. The biopsy materials were analysed for tissue typing, and immunohistochemistry (IHC) was performed for prostate-specific-membrane-antigen (PSMA) expression. The scans were analysed by two experienced physicians in a consensus read for clinical characteristics and radiopharmaceutical uptake of foci. RESULTS:One out of 11 (9.1%) of the foci biopsied was confirmed as bone metastasis of PC with intense PSMA-expression, while 10/11 (90.9%) foci were revealed to be unremarkable bone tissue without evidence of PSMA expression at IHC. Amongst all bone foci assessed by biopsy, eight were visually classified as being at high risk of malignancy in the PET/CT (SUVmean 12.0 ± 8.1; SUVmax 18.8 ± 13.1), three as equivocal (SUVmean 4.6 ± 2.1; SUVmax 7.2 ± 3.0) and zero as low risk. No UBU had any CT correlate. CONCLUSIONS:This cohort biopsy revealed that a small but relevant number of UBU are true metastases. For those confirmed as benign, no PSMA expression at IHC was observed, suggesting a non-PSMA mediated cause for intensive [F]PSMA-1007 uptake of which the reason remains unclear. Readers must interpret such foci with caution in order to reduce the risk of erroneous staging and subsequent treatment. PET-guided biopsy, particularly in the absence of morphological changes in the CT, can be a useful method to clarify such foci.