The positivity rate of 68Gallium-PSMA-11 ligand PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.
ABSTRACT: Background: The aim of the present study is to analyze the efficacy of 68Gallium (Ga)-PSMA-11 PET/CT for detecting and localizing recurrent prostate carcinoma (PC) in patients with different prostate-specific antigen (PSA), PSA velocity (PSAvel) and doubling time (PSAdt). Results: The PR of 68Ga-PSMA-11 PET/CT showed a positive relationship with PSA levels. Even at restaging PSA-values (PSAV) of lower than 0.2 ng/ml, PR was 41%. For PSAV of 0.2-<0.5 ng/ml the PR was 45%, 62% for PSAV of 0.5-<1.0 and 72% for PSAV of 1.0-<2.0 ng/ml. The PR increased to 85% for PSAV of 2.0-<5.0 and reached 94% at PSAV of ?5.0 ng/ml. At PSA of <1 ng/ml/y the PR of PSAvel was 50% and increased to 98% at PSA >5 ng/ml/y. No significant association was found for PSAdt. Methods: PET/CT scans of 660 patients with biochemical recurrence (BCR) after primary therapy of PC were included in the analysis. We correlated serum PSA levels, measured at the time of imaging with PSMA PET/CT-positivity rates (PR) as well as PSAvel (in 225 patients) and PSAdt (660 patients). Additionally we compared the incidence of localized disease to metastases as related to these PSA-biomarkers. Conclusion: We have shown, in a large cohort of patients, that 68Ga-PSMA-11 PET/CT is a sensitive tool for restaging PC and has a high detection efficacy, even in patients with very low PSA levels (<0.2 ng/ml). Thus 68Ga-PSMA-11 PET/CT both identify and localize recurrent disease with implications for a more direct treatment approach (localized vs. systemic therapy).
Project description:Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome.
Project description:The study was aimed at assessing the diagnostic performance of 68Ga-PSMA-617 PET/CT in the detection of prostate cancer (PCa) in patients with a prostate-specific antigen (PSA) level of 4-20 ng/ml and to compare its efficacy with that of multiparametric MRI (mpMRI). We analyzed the data of 67 consecutive patients with PSA levels of 4-20 ng/ml who almost simultaneously underwent 68Ga-PSMA-617 PET/CT and mpMRI. 68Ga-PSMA-617 PET/CT and mpMRI diagnostic performances were compared via receiver operating characteristic (ROC) curve analysis. Of the 67 suspected PCa cases, 33 had pathologically confirmed PCa. 68Ga-PSMA-617 PET/CT showed a patient-based sensitivity, specificity, and positive and negative predictive values (PPVs and NPVs) of 87.88%, 88.24%, 87.88%, and 88.24%, respectively. The corresponding values for mpMRI were 84.85%, 52.94%, 63.64%, and 78.26%. The area under the curve values for 68Ga-PSMA-617 PET/CT and mpMRI were 0.881 and 0.689, respectively. 68Ga-PSMA-617 PET/CT showed a better diagnostic performance than mpMRI in the detection of PCa in patients with PSA levels of 4-20 ng/ml.
Project description:Since the clinical introduction of 68Ga-PSMA-11 PET/CT, this imaging method has rapidly spread and is now regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). The aim of this study was to analyse the influence of several variables with possible influence on PSMA ligand uptake in a large cohort.We performed a retrospective analysis of 1007 consecutive patients who were scanned with 68Ga-PSMA-11 PET/CT (1 h after injection) from January 2014 to January 2017 to detect recurrent disease. Patients with untreated primary PCa or patients referred for PSMA radioligand therapy were excluded. The possible effects of different variables including PSA level and PSA doubling time (PSADT), PSA velocity (PSAVel), Gleason score (GSC, including separate analysis of GSC 7a and 7b), ongoing androgen deprivation therapy (ADT), patient age and amount of injected activity were evaluated.In 79.5% of patients at least one lesion with characteristics suggestive of recurrent PCa was detected. A pathological (positive) PET/CT scan was associated with PSA level and ADT. GSC, amount of injected activity, patient age, PSADT and PSAVel were not associated with a positive PET/CT scan in multivariate analysis.68Ga-PSMA-11 PET/CT detects tumour lesions in a high percentage of patients with recurrent PCa. Tumour detection is clearly associated with PSA level and ADT. Only a tendency for an association without statistical significance was found between higher GSC and a higher probability of a pathological PET/CT scan. No associations were found between a pathological 68Ga-PSMA-11 PET/CT scan and patient age, amount of injected activity, PSADT or PSAVel.
Project description: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 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-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%; P < 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 (P = 0.22). The average number of PSMA-positive regions also increased with serum PSA level (P < 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. Conclusion: Bone metastases as assessed with 68Ga-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 68Ga-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 68Ga-PSMA-11 PET/CT imaging revealed additional bone lesions in 6% of patients, but without significantly affecting patient management.
Project description:PURPOSE:Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemically recurrent prostate cancer (BCR), mostly using gallium-68 (168Ga)-labelled radiotracers. Alternatively, fluorine-18 (18F)-labelled PSMA tracers are available, such as 18F-DCFPyL, which offer enhanced image quality and therefore potentially increased detection of small metastases. In this study we evaluate the lesion detection efficacy of 18F-DCFPyL PET/CT in patients with BCR and determine the detection efficacy as a function of their PSA value. METHODS:A total of 248 consecutive patients were evaluated and underwent scanning with 18F-DCFPyL PET/CT for BCR between November 2016 and 2018 in two hospitals in the Netherlands. Patients were examined after radical prostatectomy (52%), external-beam radiation therapy (42%) or brachytherapy (6%). Imaging was performed 120 min after injection of a median dose of 311 MBq 18F-DCFPyL. RESULTS:In 214 out of 248 PET/CT scans (86.3%), at least one lesion suggestive of cancer recurrence was detected ('positive scan'). Scan positivity increased with higher PSA values: 17/29 scans (59%) with PSA values <0.5 ng/ml; 20/29 (69%) with PSA 0.5 to <1.0 ng/ml; 35/41 (85%) with PSA 1.0 to <2.0 ng/ml; 69/73 (95%) with PSA 2.0 to <5.0 ng/ml; and 73/76 (96%) with PSA ≥5.0 ng/ml. Interestingly, suspicious lesions outside the prostatic fossa were detected in 39-50% of patients with PSA <1.0 ng/ml after radical prostatectomy (i.e. candidates for salvage radiotherapy). CONCLUSION:18F-DCFPyL PET/CT offers early detection of lesions in patients with BCR, even at PSA levels <0.5 ng/ml. These results appear to be comparable to those reported for 68Ga-PSMA and 18F-PSMA-1007, with potentially increased detection efficacy compared to 68Ga-PSMA for patients with PSA <2.0.
Project description:Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on 68Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (<2 ng/ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with 18F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, 68Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics.
Project description:OBJECTIVES:The aim of this study was the validation of a recently established comprehensive and compact prediction model for 68Ga-PSMA-11-ligand positron-emission tomography (PET) positivity with an independent subsequent patient series. METHODS:A total of 292 consecutive patients with early biochemical recurrence after radical prostatectomy and PSA values between 0.2 and 1?ng/ml who underwent 68Ga-PSMA-11-ligand PET/computed tomography (CT) between January 2016 and June 2017 were retrospectively included. The cohort was divided into a very low PSA value (0.2-0.5?ng/ml, n = 151) and a low PSA value (> 0.5-1?ng/ml, n = 141) subgroup. First, pre-test positivity probabilities for each patient were calculated according to the previously published comprehensive prediction model using all clinical variables (PSA value, ISUP grade group, T- and N-stage, patient under androgen deprivation therapy (ADT), previous radiation therapy) and the compact model using just the most predictive factors PSA value, ADT, and grade group. Then, all 68Ga-PSMA-11-ligand PET/CTs were analysed by one experienced nuclear medicine physician, and the results were correlated to the calculated pre-test probabilities. RESULTS:In the very low PSA value subgroup, mean pre-test probability for positive findings in 68Ga-PSMA-11-ligand PET/CT was 57% (95% CI 55-60%) according to the compact model and 59% (95% CI 56-61%) according to the comprehensive model. In the low PSA value subgroup, mean pre-test probability was 72% (95% CI 70-74%) in the compact model and 74% (95% CI 72-76%) in the comprehensive model. After image analysis, 59% (89/151) of the patients in the very low PSA value subgroup revealed positive imaging findings. Seventy-nine percent (112/141) of the patients in the low PSA value subgroup presented with positive findings in the 68Ga-PSMA-11-ligand PET/CT. The accuracy (AUC) of the prediction models was 0.71 (95% CI 0.65-0.78) for the compact model and 0.74 (95% CI 0.68-0.80) for the comprehensive model. CONCLUSION:External validation of the recently proposed prediction models showed a high concordance of the calculated pre-test probabilities and actual 68Ga-PSMA-11-ligand PET/CT findings in the validation cohort confirming the prediction models' ability to determine the presence of a positive lesion at 68Ga-PSMA-11-ligand PET. However, the predictive accuracy of the nomogram itself is suboptimal and should be used with caution. Furthermore, the model's generalizability may be hampered due to the study design (in-house validation). Nevertheless, given the limited health resources and the costs of hybrid imaging techniques, prediction models might be a benefit in patient selection.
Project description:OBJECTIVE:To evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions. MATERIAL AND METHODS:We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making. RESULTS:The median time from RP to BCR was 36 months (IQR 16-72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58-1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ?2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. CONCLUSIONS:We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.
Project description:18F-labeled prostate-specific membrane antigen (PSMA) PET tracers are increasingly used in preference to 68Ga-PSMA-11 for restaging biochemical recurrence (BCR) of prostate cancer. They are associated with longer half-lives, larger-scale production, and lower positron range than their 68Ga-labeled counterparts. Here, we describe the efficacy of an 18F-labeled radiohybrid PSMA, rhPSMA-7, a novel theranostic PSMA-targeting agent for imaging BCR of prostate cancer. Methods: Datasets from 261 consecutive patients with noncastrate BCR after radical prostatectomy who underwent 18F-rhPSMA-7 PET/CT at our institution between June 2017 and March 2018 were reviewed retrospectively. All lesions suspected of being recurrent prostate cancer were recorded. The detection rate for sites of presumed recurrence was correlated with patients' prostate-specific antigen (PSA) level, primary Gleason score, and prior therapy (androgen deprivation therapy and external-beam radiation therapy). Results: The 261 patients had a median PSA level of 0.96 ng/mL (range, 0.01-400 ng/mL). The median injected activity of 18F-rhPSMA-7 was 336 MBq, with a median uptake time of 76 min. In total, 211 patients (81%) showed pathologic findings on 18F-rhPSMA-7 PET/CT. The detection rates were 71% (42/59), 86% (44/51), 86% (42/49), and 95% (76/80) at PSA levels of 0.2 to <0.5 ng/mL, 0.5 to <1 ng/mL, 1 to <2 ng/mL, and ?2 ng/mL, respectively. In 32% patients (7/22) with a PSA of less than 0.2 ng/mL, suggestive lesions were present. 18F-rhPSMA-7 PET/CT revealed local recurrence in 43% of patients (113). Lymph node metastases were present in the pelvis in 42% of patients (110), in the retroperitoneum in 17% (45), and in a supradiaphragmatic location in 8.0% (21). Bone and visceral metastases were detected in 21% (54) and 3.8% (10), respectively. Detection efficacy was not influenced by prior external-beam radiation therapy (79.1% vs. 82.1%, P = 0.55), androgen deprivation therapy within the 6 mo preceding imaging (80.6% vs. 80.9%, P = 0.54), or primary Gleason score (77.9% for ?7 vs. 82.6% for ?8, P = 0.38). Conclusion: 18F-rhPSMA-7 PET/CT offers high detection rates in early BCR after radical prostatectomy, especially among patients with low PSA values.
Project description:PURPOSE:To 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 METHODS:In 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. RESULTS:The 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. CONCLUSION:PSMA-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.