68Ga-labeled Prostate-specific Membrane Research Articles

A comparison between 68Ga-labeled prostate-specific membrane antigen-PET/CT and multiparametric MRI for excluding regional metastases prior to radical prostatectomy.

To compare the ability of 68Ga -PSMA PET/CT (PSMA PET/CT) and multiparametric MRI (mpMRI) to exclude lymph node invasion (LNI) in patients who undergo radical prostatectomy (RP). A multicenter cohort of patients who underwent PSMA PET/CT and pelvic mpMRI prior to RP with pelvic lymph node dissection (PLND) was analyzed. Increased Ga68-PSMA uptake on PET/CT and enlarged (> 10mm) or abnormal lymph nodes on mpMRI were considered positive findings. The final surgical pathology served as the standard of reference. The negative predictive value (NPV) was calculated for each modality separately, as well as the combined value. Included were 89 patients with D'Amico intermediate (45%) or high-risk (55%) prostate cancer. The median number of extracted LN was 9 (IQR 6-14). LNI was found in 12 (13.5%) patients. The NPV of mpMRI, PSMA PET/CT, and the two tests combined were 87%, 89%, and 90%, in the entire cohort, 95%, 97%, and 97% in patients with intermediate-risk disease, and 80%, 82%, and 83% in patients with high-risk disease, respectively. The median diameter of LN missed by both imaging and the median intranodal tumor diameter was 5.5 (IQR 3-10) mm and 1 (IQR 1-3) mm, respectively. PSMA PET/CT and mpMRI demonstrated similar performance in excluding pelvic LNI with NPV of approximately 90%. The combination of both tests does not improve NPV significantly. Therefore, even in the era of advanced imaging, PLND is still recommended for accurate staging, especially in the high-risk population.

68Ga-PSMA PET/MRI for the diagnosis of primary and biochemically recurrent prostate cancer: A meta-analysis

PurposeOur meta-analysis aimed to evaluate the diagnostic performance of 68Ga-labelled prostate-specific membrane antigen ligand positron emission tomography/magnetic resonance imaging (68Ga-PSMA PET/MRI) in patients with primary and biochemically recurrent prostate cancer (PCa). MethodsWe searched for relevant articles in PubMed, EMBASE, the Cochrane Library and Web of Science until September 12, 2019. Studies regarding the diagnostic performance of68Ga-PSMA PET/MRI in detecting primary PCa and biochemical recurrence (BCR) after definitive treatment were included. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The pooled sensitivity and specificity of PET/MRI in identifying primary PCa and the pooled detection rate of PET/MRI for BCR were calculated using a random-effects model. ResultsA total of 13 studies with 707 patients were included in the analysis, and the pooled sensitivity and specificity of PET/MRI in detecting primary PCa were 0.83 (95 % CI, 0.73–0.90) and 0.81 (95 % CI, 0.61–0.93), respectively. In the pooled analysis of BCR, the pooled detection rate was 76 % (95 % CI, 72 %–79 %). For four levels of PSA (0−0.2 ng/mL, 0.2−1 ng/mL, 1−2 ng/mL and more than 2 ng/mL), the pooled detection rates were 38 %, 67 %, 74 %, and 95 %, respectively. There was no distinct publication bias, but there was significant study heterogeneity. Conclusions68Ga-PSMA PET/MRI is likely an effective imaging method in the diagnosis of primary PCa. In addition, the diagnostic accuracy of 68Ga-PSMA PET/MRI in patients with BCR was also high, positively correlating with PSA levels.

Impact of the 68Ga Prostate-Specific Membrane Antigen (68Ga-PSMA) PET/CT on the Management of Prostate Cancer

This review discusses the efficiency and sensitivity of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) imaging in comparison to other radiotracers and imaging techniques. It also conveys its impact on the treatment or management of prostate cancer patients. PSMA, observed in almost all prostate cancer cells, is used for staging and treatment, due to its high multiplication in this cancer when compared to normal tissues. PSMA PET/magnetic resonance imaging (MRI) has applications in the management of prostate cancer. Though PSMA PET/MRI has yielded preliminary results, it is still studied as an imaging biomarker for tumor responses. PSMA-PET/CT is known for its highly sensitive resolution, as it lights up only the parts harboring prostate cancer or tumor cells and not any other kind of lesion. Therefore, 68Ga-PSMA-PET imaging is chosen over other variants of 68Ga-PSMA-11, such as 177Lu-PSMA or 225Ac-PSMA, and it is used for its greater ability to detect metastatic sites in patients with biochemical recurrence and low serum prostate-specific antigens values. The efficacy of 68Ga-PSMA PET/CT also allows for estimation of oligometastases, as it supports the design of therapeutic trials in measuring long-term effects in patients. Finally, 68Ga-PSMA PET/CT is effective in identifying recurrence localization and, hence, permits the ability to choose the best therapeutic strategy as early as possible.

Prospective Evaluation of 68Ga-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography in Primary Prostate Cancer Diagnosis

BackgroundPositron emission tomography (PET)/computed tomography (CT) with 68Ga-labeled prostate-specific membrane antigen ligand (68Ga-PSMA) may represent the most promising alternative to multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis. ObjectiveTo test the diagnostic performance of 68Ga-PSMA PET/CT in this clinical context. Design, setting, and participantsFrom January 2017 to December 2018 we prospectively enrolled 97 patients with persistently elevated prostate-specific antigen and/or Prostate Health Index score, negative digital rectal examination, and previous negative biopsy. We also included patients with either negative mpMRI or contraindications to or positive mpMRI but previous negative biopsy. InterventionPatients underwent 68Ga-PSMA PET/CT with additional pelvic reconstruction. Outcome measurements and statistical analysisThe primary endpoint of the study was the diagnostic performance of 68Ga-PSMA PET/CT in detecting malignant lesions and clinically significant PCa (Gleason score [GS] ≥7). Results and limitations68Ga-PSMA PET/transrectal ultrasound fusion biopsy was performed in 64 of 97 patients (66%) for 114 regions of interest (ROIs). Forty patients (41%) had already undergone mpMRI with either a negative result for PCa (n = 15; 22 ROIs) or a positive mpMRI result but a previous negative biopsy. According to pathology, 23 patients (36%) had evidence of PCa: eight (16 ROIs) with GS 6, 13 (21 ROIs) with GS 7 (3 + 4 or 4 + 3), one (2 ROIs) with GS 8, and one (2 ROIs) with GS 10. Clinically significant PCa was identified in four patients with previous negative mpMRI (25%). PET/CT demonstrated PCa in seven patients (14 ROIs) with previous positive mpMRI and negative biopsy. The median maximum standardized uptake value (SUVmax) and median SUV ratio were significantly higher for PCa lesions than for benign lesions (p < 0.001). Optimal cutoff points obtained for SUVmax (>5.4) and SUV ratio (>2.2) could identify clinically significant PCa with accuracy of 81% and 90%, respectively. ConclusionsIn our cohort of patients with high suspicion of cancer,68Ga-PSMA PET/CT was capable of detecting malignancy and accurately identifying clinically relevant PCa. Patient summaryPositron emission tomography/computed tomography with a 68Ga-labeled ligand for prostate-specific membrane antigen is capable of detecting prostate cancer in patients with a high suspicion of cancer and a previous negative biopsy.

3-Year Freedom from Progression After 68Ga-PSMA PET/CT-Triaged Management in Men with Biochemical Recurrence After Radical Prostatectomy: Results of a Prospective Multicenter Trial.

68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in men with biochemical recurrence (BCR) after radical prostatectomy (RP), but its longer-term prognostic or predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for a 3-y freedom from progression (FFP) in men with BCR after RP undergoing salvage radiotherapy (sRT). Methods: This prospective multicenter study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA PET with a rising level of prostate-specific antigen (PSA) after RP. Management after PSMA PET was recorded but not mandated. PSMA PET protocols were standardized across sites and reported prospectively. Clinical, pathologic, and surgical information; sRT; timing and duration of androgen deprivation; 3-y PSA results; and clinical events were documented. FFP was defined as a PSA rise of no more than 0.2 ng/mL above nadir after sRT, with no additional treatment. Results: The median PSA was 0.26 ng/mL (interquartile range, 0.15-0.59 ng/mL), and follow-up was 38 mo (interquartile range, 31-43 mo). PSMA PET had negative results in 34.6% (90/260), showed disease confined to the prostatic fossa in 21.5% (56/260), showed disease in the pelvic nodes in 26.2% (68/260), and showed distant disease in 17.7% (46/260). Of the patients, 71.5% (186/260) received sRT: 38.2% (71/186) to the fossa only, 49.4% (92/186) to the fossa plus the pelvic nodes, and 12.4% (23/186) to the nodes alone or stereotactic body radiation therapy. PSMA PET was highly predictive of FFP at 3 y after sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative results or fossa-confined findings versus 45% (39/86) with extrafossa disease (P < 0.0001). On logistic regression, PSMA PET was more independently predictive of FFP than established clinical predictors, including PSA, T stage, surgical margin status, or Gleason score (P < 0.002). Thirty-two percent of men with a negative PSMA PET result did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59 ng/mL over the 3 y. Conclusion: PSMA PET results are highly predictive of FFP at 3 y in men undergoing sRT for BCR after RP. In particular, men with negative PSMA PET results or disease identified as still confined to the prostatic fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional androgen deprivation therapy than those with extrafossa disease.

Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed to predict 68Ga-labeled Prostate-Specific Membrane Antigen-Ligand Positron-Emission Tomography/Computer Tomography positivity in patients with biochemical recurrent prostate

Evaluating the predictive accuracy and the clinical benefit of a nomogram aimed to predict 68Ga-labeled Prostate-Specific Membrane Antigen-Ligand Positron-Emission Tomography/Computer Tomography positivity in patients with biochemical recurrent prostate

Gallium-68-Labeled Prostate-Specific Membrane Antigen-11 PET/CT of Prostate and Nonprostate Cancers.

OBJECTIVE. The purpose of this study is to provide a concise summary of the current experience with 68Ga-labeled prostate-specific membrane antigen (PSMA)-11 imaging of prostate and nonprostate malignancies and benign conditions. CONCLUSION. PSMA is overexpressed in prostate cancer and in the neovasculature of many other malignancies. The relevance of PSMA as a biologic target, coupled with advances in the design, synthesis, and evaluation of PSMA-based radionuclides for imaging and therapy, is anticipated to play a major role in patient care.

Meningioma: A false positive finding of metastasis from prostate adenocarcinoma using 68Ga-PSMA PET/CT scan

A 73-year-old man with history of prostatic adenocarcinoma radical prostatectomy underwent 99mTc-MDP whole-body bone scan and subsequent 68Ga-labeled prostate-specific membrane antigen (PSMA) ligand PET/CT for restaging due to a gradual rise of prostate-specific antigen levels. Whole-body bone scan showed two focal zones of slightly increased uptake in the right fronto-parietal and temporal bones. 68Ga-PSMA PET/CT scan showed local recurrence in the prostatic bed and two foci of slightly increased uptake in the right temporal and fronto-parietal lobes. A brain CT scan, with IV contrast confirmed that foci of increased uptake in the temporal and parietal lobes were consistent with typical meningioma.

(68Ga)-PSMA-PET/CT for the detection of postoperative prostate cancer recurrence: Possible implications on treatment volumes for radiation therapy

PurposeThe aim of this study was to define the pattern of relapse of postoperative prostate cancer in patients by using 68Ga-labeled prostate-specific membrane antigen positron-emission tomography/computed tomography ([68Ga]-PSMA PET/CT). Material and methodsForty patients received a (68Ga)-PSMA PET/CT for biochemical failure. Following the Radiation Therapy Oncology Group (RTOG) guidelines, the pelvic clinical target volume has been contoured. Bone metastases were considered as outside the clinical target volume. Two subgroups of patients were defined, patients having relapse: (1) inside, or (2) outside the clinical target volume. ResultsGlobally, eight patients out of 32 presented with a positive lymph node failure inside the clinical target volume according to RTOG guidelines (25%), 22 patients had nodal relapses outside this clinical target volume (68.75%) and in two patients nodal relapses occurred both inside and outside of the clinical target volume (6.25%). Overall, 36 positive lymph node lesions were identified: of these, 23 nodal relapses were identified within the clinical target volume contoured according to RTOG and/or at the lomboaortic level (63%). To cover 95% of these 23 relapses, a hypothetical clinical target volume should encompass the nodal regions of the RTOG-defined clinical target volume as well as the paraaortic lymph node level up to T12-L1. ConclusionMost of the patients in the present study, presented with distant lymph node and/or bone metastases. Therefore, larger target volumes should be adopted to treat at least 95% of lymph node regions at risk for an occult relapse.

Single-Center Prospective Evaluation of 68Ga-PSMA-11 PET in Biochemical Recurrence of Prostate Cancer.

OBJECTIVE. The purpose of this study was to determine the diagnostic accuracy of 68Ga-labeled prostate-specific membrane antigen 11 (PSMA-11) PET for disease detection in patients with prostate cancer who have biochemically recurrent disease after radiation therapy or prostatectomy. SUBJECTS AND METHODS. One hundred fifty patients underwent 68Ga-PSMA-11 PET/CT or PET/MRI, and the images were interpreted by two blinded board-certified radiologists. Each reader evaluated for the presence or absence of PSMA-positive disease within the prostate bed, pelvic lymph nodes, bones, and soft tissues (extrapelvic lymph nodes and visceral structures). The presence or absence of disease was confirmed by histopathologic analysis if available. For patients who did not have pathologic analysis, a composite of imaging and clinical follow-up was used as the reference standard. RESULTS. The median prostate-specific antigen level was 2.1 ng/mL. Forty-three patients had pathologic correlation, and for 29 patients a composite of imaging and follow-up was used to determine the presence or absence of disease. With substantial to almost perfect interreader reliability by region (κ = 0.78-0.87), 68Ga-PSMA-11 PET had high sensitivity per region (up to 100%) and per patient (up to 89.8%). It also had high positive predictive value per region (up to 100%) and per patient (up to 91.5%). Sensitivity was highest for bone metastases and lowest for soft-tissue metastases. Positive predictive value was highest for bone metastases and lowest for prostate bed recurrence. CONCLUSION. Gallium-68-labeled PSMA-11 PET is sensitive for prostate cancer metastases in patients with biochemically recurrent prostate cancer. It has high positive predictive value and substantial to almost perfect interrater reliability.

Clinical Impact of Lower-Limb Imaging in 68Ga-PSMA PET/CT for Patients with Prostate Cancer.

Our purpose was to determine whether there is a clinical benefit to add lower-limb imaging in 68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT scans for patients with prostate cancer. Methods: In total, 701 patients with prostate cancer who underwent 68Ga-PSMA PET/CT were evaluated retrospectively. All patients underwent additional lower-limb imaging. Images were reanalyzed by experienced nuclear medicine physicians, and metastatic sites were documented. The prostate-specific antigen (PSA) level and Gleason score were also compared with 68Ga-PSMA PET/CT findings. Results: In 601 patients (85.7%), at least 1 tumoral lesion was observed on 68Ga-PSMA PET/CT. The number of patients with bone metastasis in 2 forms was 278 patients (39.6%); 108 (15.4%) were oligometastatic (<4 metastases) and 170 (24.2%) were multimetastatic (≥4 metastases). In lower-limb imaging, bone metastasis was detected in 61 patients (8.7%), the specific locations of which were as follows: middle-distal femur (n = 54), tibia (n = 19), fibula (n = 24), and calcaneus (n = 1). Lower-limb metastasis was detected mostly in symptom-positive patients (70.1%) but in only 4% of the symptom-negative group. All patients with lower-extremity metastasis also had multiple bone metastases shown on limited whole-body 68Ga-PSMA PET/CT. The median PSA level was significantly higher in multimetastatic patients with lower-limb metastasis than in those without lower-limb metastasis (P < 0.001, Mann-Whitney U test), but no statistical differences was found in terms of Gleason score (χ2 = 0.042, P = 0.837). According to receiver-operating-characteristic analysis, PSA has a good predictive value for detecting lower-limb metastasis, with 76.6% sensitivity and 72% specificity (using a reference cutoff PSA level of 24 ng/mL [area under the curve, 0.81; 95% confidence interval, 0.74-0.87]). Conclusion: Lower-limb imaging did not change the metastatic status of disease or significantly affect the therapeutic approach. However, if multimetastatic patients present relevant symptoms for lower-limb metastasis, it could be beneficial to consider including lower-limb imaging for possible palliative therapies.

Improving 68Ga-PSMA PET/MRI of the Prostate with Unrenormalized Absolute Scatter Correction.

A limitation of using 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) for detection and staging of prostate cancer is a frequently observed halo artifact around the urinary bladder caused by inaccurate scatter correction (SC) of PET data. The aim of this study was to investigate the impact of unrenormalized absolute SC on 68Ga-PSMA PET quantification in PET/MRI of the prostate in 100 patients. Methods: The PET data of 100 patients were reconstructed twice using standard SC and improved unrenormalized SC. The visual presence of the halo artifact was rated in each PET data reconstruction using 5 grades (0, no halo artifact; 4, severe halo artifact). The number of visible lesions in the pelvis was recorded. SUVmean and SUVmax were measured in the lesions, in the bladder, in the gluteus maximus, and within the halo margin. Furthermore, the signal-to-noise-ratio and image noise were measured in all PET data. Relative differences between standard and unrenormalized SC were calculated. Results: With standard SC, the average grade in the presence of the halo artifact was 2 (moderate halo artifact), whereas for unrenormalized SC, the average grade was 0.9 (slight halo artifact). The same number of congruent lesions (n = 74) was detected for both PET data reconstructions. Relative changes in PET signal-to-noise-ratio and image noise were not statistically significant (P > 0.05). The mean (±SD) increase in SUVmean using unrenormalized SC was 23.0% ± 9.2% in the gluteus maximus, 7.1% ± 4.5% in the bladder, 325.4% ± 748.5% in the halo margin, and 12.4% ± 16.8% in all 74 detected lesions. The mean increase using unrenormalized SC in SUVmean was 17.5% for lesions inside the halo margin (38 lesions) and 6.9% for lesions outside the halo margin (36 lesions). Conclusion: For PET/MRI of prostate cancer using 68Ga-PSMA, a proper SC is important to ensure the best possible diagnostic quality and PET quantification. Unrenormalized absolute SC significantly reduces the halo artifact around the bladder and improves PET/MRI of the prostate.

Identifying the Optimal Candidate for Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer: Results from a Large, Multi-institutional Analysis

BackgroundSalvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients. ObjectiveTo identify the optimal candidates for SLND based on preoperative characteristics. Design, setting, and participantsThe study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga-labeled prostate-specific membrane antigen ligand. InterventionSLND. Outcome measurements and statistical analysisThe study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model. Results and limitationsMedian follow-up was 30 (interquartile range, 16–50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p<0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]: 2.04; p<0.0001), time from RP to PSA rising (HR: 0.99; p=0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p=0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p=0.038), three or more positive spots at PET/CT scan (HR: 1.26; p=0.019), and PSA level at SLND (HR: 1.05; p<0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel'sC index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the “treat-all” option at all the threshold probabilities. ConclusionsWe reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach. Patient summaryThe risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery.

68Ga-Labeled PSMA Uptake in Nonprostatic Malignancies

PET/CT with Ga-labeled prostate-specific membrane antigen (PSMA) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in a number of nonprostatic benign and malignant pathologies. Apparently, angioneogenesis is the mechanism attributed to increased Ga-PSMA uptake at these sites. Here we illustrate the utility of Ga-PSMA in 5 nonprostatic malignancies that could open up new possibilities for diagnostics and theranostic concepts with PSMA labeled radioligands in nonprostate tumor entities.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study

68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging. In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater). A total of 45 patients with a median age of 64 years were referred for 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68Galabeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively. Our findings support the use of 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men.

Efficacy, Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen–ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy

Recently, 68Ga-labeled prostate-specific membrane antigen (PSMA)–ligand positron-emission tomography (PET) imaging has been shown to improve detection rates in recurrent prostate cancer (PC). However, published studies include only small patient numbers at low prostate-specific antigen (PSA) values. For this study, 272 consecutive patients with biochemical recurrence after radical prostatectomy and PSA value between 0.2 and 1ng/ml were included. The 68Ga-PSMA-ligand PET/computed tomography (CT) was evaluated, and detection rates were determined and correlated to various clinical variables using univariate and multivariable analyses. Subgroups of patients with very low (0.2–0.5ng/ml) and low (>0.5–1.0ng/ml) PSA values were analyzed. In total, lesions indicative of PC recurrence were detected in 55% (74/134) and 74% (102/138) with very low and low PSA values, respectively. Main sites of recurrence were pelvic or retroperitoneal lymph nodes metastases, followed by local recurrence and bone metastases with higher probability in the low versus very low PSA subgroup. Detection rates significantly increased with higher PSA values, primary pT≥3a, primary pN+ disease, grade group ≥4, previous radiation therapy, and concurrent androgen deprivation therapy (ADT) in univariate analysis. In a multivariable logistic regression model, concurrent ADT and PSA values were identified as most relevant predictors of positive 68Ga-PSMA-ligand PET/CT. Further, prediction nomograms were established, which may help in estimating pretest PSMA-ligand PET positivity in clinical practice. Patient summaryIn our study, 68Ga-labeled prostate-specific membrane antigen (PSMA)–ligand positron-emission tomography (PET)/computed tomography (CT) detected recurrent disease after radical prostatectomy in 55% (74/134) and 74% (102/138) of patients with very low (0.2–0.5ng/ml) and low (>0.5–1.0ng/ml) prostate-specific antigen values, respectively. On the basis of these data, it seems reasonable to perform 68Ga-PSMA-ligand PET/CT also in patients with early biochemical recurrence, as it can tailor further therapy decisions (eg, local vs systemic treatment). The established prediction nomograms can further assist urologists in discussions on the use of 68Ga-PSMA-ligand PET/CT with their patients in specific clinical settings.

Nonspecific Uptake of 68Ga-Prostate-Specific Membrane Antigen in Diseases other than Prostate Malignancy on Positron Emission Tomography/Computed Tomography Imaging: A Pictorial Assay and Review of Literature.

68Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography imaging (PET/CT) is a rapidly evolving imaging modality for prostate cancer. Many studies have proved its superiority in staging, restaging, and detecting the recurrent prostate cancer. However, case reports describing the incidental tracer uptake in benign and nonprostatic malignancies are also reported in the literature, thus questioning the specificity of the tracer. This pictorial assay illustrates the nonspecific tracer uptake encountered during PSMA PET/CT imaging, knowledge of which can increase the confidence of interpreting physicians and may also open a new path for peptide receptor radionuclide therapy in nonprostatic malignancies.

Impact of 68Ga-PSMA-11 PET/CT on the Management of Prostate Cancer Patients with Biochemical Recurrence.

In this prospective survey of referring physicians, we investigated whether and how 68Ga-labeled prostate-specific membrane antigen 11 (68Ga-PSMA-11) PET/CT affects the implemented management of prostate cancer patients with biochemical recurrence (BCR). Methods: We conducted a prospective survey of physicians (NCT02940262) who referred 161 patients with prostate cancer BCR (median prostate-specific antigen value, 1.7 ng/mL; range, 0.05-202 ng/mL). Referring physicians completed one questionnaire before the scan to indicate the treatment plan without 68Ga-PSMA-11 PET/CT information (Q1; n = 101), one immediately after the scan to denote intended management changes (Q2; n = 101), and one 3-6 mo later to document the final implemented management (Q3; n = 56). The implemented management was also obtained via electronic chart review or patient contact (n = 45). Results: A complete documented management strategy (Q1 + Q2 + implemented management) was available for 101 of 161 patients (63%). Seventy-six of these (75%) had a positive 68Ga-PSMA-11 PET/CT result. The implemented management differed from the prescan intended management (Q1) in 54 of 101 patients (53%). The postscan intended management (Q2) differed from the prescan intended management (Q1) in 62 of 101 patients (61%); however, these intended changes were not implemented in 29 of 62 patients (47%). Pelvic nodal and extrapelvic metastatic disease on 68Ga-PSMA-11 PET/CT (PSMA T0N1M0 and PSMA T0N1M1 patterns) was significantly associated with implemented management changes (P = 0.001 and 0.05). Conclusion: Information from 68Ga-PSMA-11 PET/CT brings about management changes in more than 50% of prostate cancer patients with BCR (54/101; 53%). However, intended management changes early after 68Ga-PSMA-11 PET/CT frequently differ from implemented management changes.

68Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning.

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.

Immunohistochemical Validation of PSMA Expression Measured by 68Ga-PSMA PET/CT in Primary Prostate Cancer

68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) PET/CT has a proven role in staging and restaging of prostate cancer (PCA). The aims of this study were to evaluate the association of intraprostatic 68Ga-PSMA PET/CT findings and PSMA expression in immunohistochemical staining and generate a cutoff value for differentiation between normal prostate (PN) and PCA. Methods: The data of 31 patients (mean age, 67.2 y) who underwent prostatectomy and preoperative PET were retrospectively analyzed. On PET, focally increased uptake in the prostate was suggestive of tumor. A region of interest was placed on the suggestive area to generate an SUVmax; a similar region of interest was placed on adjacent visually PN. Both PCA and PN were stained with monoclonal anti-PSMA antibody (clone 3E6, 1:100, M3620). Results: All intraprostatic PCA lesions on PET could be confirmed histopathologically. In PN sections (n = 31), median staining intensity was mild, median percentage of stained cells was 20% ± 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections (n = 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% ± 16.46%. The mean SUVmax (±SD) of PCA (14.06 ± 15.56) was significantly higher than that of PN (2.43 ± 0.63; P < 0.001). Receiver-operating-characteristic curve analyses of the SUVmax of PCA, validated by immunohistochemical staining in 62 tissue samples, showed the best cutoff to be 3.15 (sensitivity, 97%; specificity, 90%; area under curve, 0.987). Applied to multifocal PCA, it resulted in sensitivity and specificity of 87% and 97% respectively. The mean SUVmax of PCA and PN for an IRS of less than 2 (n = 26; 2.52 ± 0.64) was significantly lower than the mean SUVmax for an IRS of 2 or more (n = 36; 12.38 ± 15.02; P < 0.001). The mean SUVmax was significantly lower in PCA samples with fewer than 50% stained cells (n = 30; 2.81 ± 2.35) than in samples with 50% or more (n = 32; 13.34 ± 15.55; P < 0.001). There was no correlation between the SUVmax of PCA and Gleason score (P = 0.54). Conclusion: This study showed that SUVmax on 68Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.