Gallium-68 Prostate-specific Membrane Antigen Positron Research Articles

Lutetium-177 Prostate-Specific Membrane Antigen-617 Treatment in Metastatic Castration-Resistant Prostate Adenocarcinoma: Results of Single-Center Experience.

Lutetium-177 prostate-specific membrane antigen-617 is a novel alternative therapeutic option in metastatic castration-resistant prostate cancer, especially useful for patients who do not respond to standard therapy methods. The aim of this study was to define the efficacy and safety profile of lutetium-177 prostate- specific membrane antigen-617 treatment in a group of patients with metastatic castration-resistant prostate cancer. Study group included 34 men with metastatic castration-resistant prostate cancer (median, 69.6 ± 7.7 years) who were treated with lutetium-177 prostate-specific membrane antigen-617 therapy (22/34; 4 courses, 12/34; 2 courses). Patients were evaluated by physical examination, Eastern coop- erative oncology group performance status, gallium-68 prostate-specific membrane antigen positron emis- sion tomography/computed tomography, brief pain inventory-short form questionnaire, biochemical tests, and complete blood counts. Treatment response and adverse effects were examined by brief pain inventory scores, SUVmax values, biochemical tests, and complete blood counts. Independent variables were analyzed statistically (significance; P < .05). The Eastern cooperative oncology group performance was grade 0 in 5/34 (14.7%), grade 1 in 25/34 (73.5%), and grade 2 in 4/34 (11.8%) patients. Distribution of patient numbers according to brief pain inven- tory scores (score: <1, scores: 1-4, and scores: 5-10) was 2, 10 and 22 at the beginning, 6, 16 and 12 after the second course, and 10, 10 and 2 after the fourth course of treatment, respectively. Serum prostate-specific antigen decreased in 15 of 22 patients (68%) (P < .05). Before and after the treatment, we found a substan- tial decrease in SUVmax values (22.3 vs. 11.8, P < .001) and brief pain inventory scores (score ≥ 5; 22/34 pts vs. 0/22 pts). The counts of white blood cells (P < .05), hemoglobin (P < .05), and thrombocytes (P = .001) were all significantly lower at the conclusion of the therapy. The most important adverse events were severe leukopenia (1/34 pts; 2.29 × 103/μL) and thrombocytopenia (3/34 pts; 32 000, 36 000, 32 000 106/L). Q1 Conclusion: We found that lutetium-177 prostate-specific membrane antigen-617 therapy is a promising treatment method for metastatic castration-resistant prostate cancer patients who are unresponsive to conventional therapy, according to our biochemical, positron emission tomography/computed tomography, and pain score outcomes.

DEPROMP Trial: the additive value of PSMA-PET/CT-guided biopsy for prostate cancer management in biopsy naïve men—study protocol for a randomized trial

BackgroundThe primary objective is to determine the proportion of men with suspected prostate cancer (PCA) in whom the management plans are changed by additive gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) guided prostate biopsy (PET-TB) in combination with standard of care (SOC) using systematic (SB) and multiparametric magnetic resonance imaging-guided biopsy (MR-TB) compared with SOC alone. The major secondary objectives are to determine the additive value of the combined approach of SB + MR-TB + PET-TB (PET/MR-TB) for detecting clinically significant PCA (csPCA) compared to SOC; to determine sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of imaging techniques, respective imaging classification systems, and each biopsy method; and to compare preoperatively defined tumor burden and biomarker expression and pathological tumor extent in prostate specimens.MethodsThe DEPROMP study is a prospective, open-label, interventional investigator-initiated trial. Risk stratification and management plans after PET/MR-TB are conducted randomized and blinded by different evaluation teams of experienced urologists based on histopathological analysis and imaging information: one including all results of the PET/MR-TB and one excluding the additional information gained by PSMA-PET/CT guided biopsy. The power calculation was centered on pilot data, and we will recruit up to 230 biopsy-naïve men who will undergo PET/MR-TB for suspected PCA. Conduct and reporting of MRI and PSMA-PET/CT will be performed in a blinded fashion.DiscussionThe DEPROMP Trial will be the first to evaluate the clinically relevant effects of the use of PSMA-PET/CT in patients with suspected PCA compared to current SOC. The study will provide prospective data to determine the diagnostic yields of additional PET-TB in men with suspected PCA and the impact on treatment plans in terms of intra- and intermodal changes. The results will allow a comparative analysis of risk stratification by each biopsy method, including a performance analysis of the corresponding rating systems. This will reveal potential intermethod and pre- and postoperative discordances of tumor stage and grading, providing the opportunity to critically assess the need for multiple biopsies.Trial registrationGerman Clinical Study Register DRKS 00024134. Registered on 26 January 2021.

Incidental Tc-99m MDP Uptake in Cortical-subcortical Parietotemporal Cerebral Area in a Patient with a History of Recent Ischemic Cerebrovascular Event who Underwent Whole-body Bone Scan.

The authors present Tc-99m methylene diphosphonate (MDP) uptake in the right parietotemporal area at whole-body bone scan (WBBS) in 75 years male patient with prostate adenocarcinoma Gleason score 3+4 (pT2N0Mx). No residual or metastatic disease was detected in the patient's Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography four months before WBBS. The patient had undetectable prostate-specific antigen levels and underwent WBBS to restage prostate cancer due to equivocal findings in previous WBBS. Current WBBS planar views revealed heterogeneous Tc-99m MDP uptake in the right parietotemporal area and the sphenoid bone in addition to equivocal uptake on the lower lumbar vertebrae. Single-photon emission computed tomography study to identify the MDP-avid lesion on the right cranial area revealed heterogeneous Tc-99m MDP uptake in the right parietotemporal area and sphenoid bone. The patient had a history of transsphenoidal surgery for a hypophyseal tumor two years ago and a recent cerebrovascular event (CVE). Diffusion-weighted magnetic resonance imaging revealed a cortical-subcortical patchy area of restricted diffusion in the parietotemporal region compatible with acute ischemia. Heterogeneous Tc-99m MDP uptake in the right parietotemporal area was attributed to recent CVE and secondary vascular-tissue change-related dystrophic calcification.

Effects of Androgen Deprivation Therapy on Extraocular Muscles, Retrobulbar Orbital Fat, and the Optic Nerve in Patients with Prostate Cancer

Introduction: The aim of this study was to evaluate radiologically the effects of long-term luteinizing hormone-releasing hormone (LHRH) agonist therapy on extraocular muscle thickness, retrobulbar orbital fat (ROF), and the optic nerve (ON) in prostate cancer (PCa) patients. Methods: The retrospective study included patients with primary or recurrent PCa who received androgen deprivation therapy (ADT) for at least 12 months. Each patient underwent gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography both before and at the end of the 12-month treatment. Thickness of the ON, lateral rectus muscle, medial rectus muscle, superior rectus muscle, and inferior rectus muscle were measured by using the coronal CT sections in soft tissue window. ROF, ocular protrusion, and ON length were measured in sagittal and coronal planes. Changes in these anatomical structures induced by LHRH analogs were investigated by comparing pre- and post-treatment measurements. Results: A total of 57 patients were included in the study. Median PSA and TT values ​​of the patients before treatment were 36.5 (range, 19.6–51.2) ng/mL and 614.0 (range, 472.0–743.0) ng/dL, respectively, and these values ​​decreased significantly after the treatment (10.6 [range, 5.2–14.2] ng/mL and 36.5 [range, 19.6–51.2] ng/dL, respectively, p < 0.001 for both). After the treatment, there was a statistically significant decrease in the areas of inferior rectus muscle, superior rectus muscle, lateral rectus muscle, and medial rectus muscle (p < 0.001 for all), while significant increases were observed in ROF (11.9%, p < 0.001) and ON thickness (14.3%, p = 0.004). The amount of ocular protrusion also showed a significant increase of approximately 14% after the treatment (14.0 [range, 12.0–16.0] mm vs. 16.0 [range, 14.0–17.2] mm, p < 0.001). Discussion/Conclusion: Our findings, for the first time in the literature, indicated that ADT causes a decrease in extraocular muscle mass and an increase in ROF with ocular protrusion. It can be asserted that these changes are similar to the changes in skeletal muscle and fat mass in other body parts. Further studies with a higher level of evidence are needed to clinically evaluate the increase in ocular protrusion and ON enlargement, which are likely to be caused by the increase in ROF.

Gallium-68 Prostate-Specific Membrane Antigen Positron Emission Tomography: A Practical Guide for Radiologists and Clinicians.

Prostate cancer (PCa) is the third most common form of cancer and the most common cancer diagnosis in men in the United States. It is known that prostate-specific membrane antigen (PSMA) is overexpressed in PCa. PSMA is a type II transmembrane glycoprotein expressed in several benign and malignant tissues. In December 2020, FDA approved Gallium-68 (68Ga) PSMA, which is a PSMA-targeted positron emission tomography (PET) imaging agent. Molecular imaging targeting PSMA has shown substantial advancement in PCa imaging. In this article, we discuss the radiopharmaceutical, indications to do PSMA PET, technical aspects of PSMA PET imaging, normal biodistribution of PSMA, other benign and malignant conditions that can take up PSMA, staging of prostate cancer, and how to report PSMA PET.

Incremental Impact of [68\xa0Ga]Ga-PSMA-11 PET/CT in Primary N and M Staging of Prostate Cancer Prior to Curative-Intent Surgery: a Prospective Clinical Trial in Comparison with mpMRI

PurposeThe main objective of this prospective study was to assess the value of gallium-68 prostate-specific membrane antigen ([68 Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in primary N and M staging of intermediate- and high-risk prostate cancer (PCa) patients before planned curative-intent radical prostatectomy (RPE) and extended pelvic lymph node dissection (ePLND). The second objective was to compare the [68 Ga]Ga-PSMA-11 PET/CT findings with standard of care pelvic multi-parametric magnetic resonance imaging (mpMRI) in the detection of locoregional lymph node metastases and intraprostatic prostate cancer.ProceduresA total of 81 patients (mean age: 64.5 years, baseline mean trigger PSA (tPSA) 15.4 ng/ml, ± 15.9) with biopsy proven PCa (24 intermediate- and 57 high risk) scheduled for RPE and ePLND were enrolled in this prospective study. In 52 patients [68 Ga]Ga-PSMA-11 PET/CT, pelvic mpMRI, and RPE with ePLND have been performed. Clinical risk stratification and related biomarkers as well as Gleason score (GS) were recorded. The location of the index lesion (IL) was documented systematically for each modality using a standardized segmentation of the prostate in six segments. Distant bone and lymph node metastasis detected by [68 Ga]Ga-PSMA-11 PET/CT were documented. [68 Ga]Ga-PSMA-11 PET/CT findings were correlated with results of mpMRI and histopathology. A consensus of imaging, clinical and/or follow-up findings were used for determining the distant metastases, which were not verified by histopathology.ResultsIn the patient cohort who underwent RPE, [68 Ga]Ga-PSMA-11 PET/CT and mpMRI detected the IL in 86.5% and 98.1% of the patients, respectively. The median of the maximum standardized uptake value (SUVmax) in the intraprostatic IL was 12 (range, 4.7–67.8). Intraprostatic IL of the high-risk patients showed significantly higher SUVmax than those in patients with intermediate risk for distant metastases (n = 48; median: 17.84 vs. 8.77; p = 0.02).In total 729 LN were removed by ePLND in 48 patients. The histopathology verified 26 pelvic lymph node metastases (pLNM) in 20.8% (10/48) of the patients, which have been correctly identified in 60% of the patients on [68 Ga]Ga-PSMA-11 PET/CT, and in 50% on mpMRI. All but one pLNM had a maximum diameter below 10 mm.Bone metastases (BM) and distant LNM (dLNM) were found in 17.3% of the patients on [68 Ga]Ga-PSMA-11 PET/CT imaging. 39.0% of the [68 Ga]Ga-PSMA-11 PET-positive BM showed no suspicious morphological correlation on CT.Conclusion[68 Ga]Ga-PSMA-11 PET/CT shows high diagnostic performance for N and M staging of patients with intermediate- and high-risk prostate cancer and seems to be superior to pelvic mpMRI in the detection of locoregional lymph node metastases. A significant correlation was found between SUVmax of the intraprostatic index lesion and risk stratification based on tPSA level and GS. The results of this study emphasize again on the role of metabolic molecular imaging using specific tracers in selected patients, leading to tailored therapy approach.

Vesico‐urethral anastomosis sampling: a forgotten tool for guiding salvage radiation after radical prostatectomy

To review the utility of vesicourethral anastomosis (VUA)-directed biopsy in the setting of biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (PCa) in patients who have undergone evaluation by gallium-68 prostate-specific membrane antigen positron emission tomography with computed tomography (68 Ga-PSMA PET/CT). We completed a retrospective review of a prospectively maintained dataset from January 2015 to August 2020. Patient demographics were recorded for those who experienced BCR, as defined by a rise in prostate-specific antigen (PSA) level to above 0.2 ng/mL, who had a 68 Ga-PSMA PET/CT that did not demonstrate recurrence within the prostate bed, and who subsequently underwent a transperineal ultrasonography (TPUS)-guided biopsy directed at the VUA. Histological reporting of the biopsies was undertaken in order to determine whether the benefits of salvage radiation therapy (SRT) could be justified by the presence of cancer cells. Eighteen patients who had a 68 Ga-PSMA PET/CT and underwent VUA-directed biopsy were identified as having BCR. 68 Ga-PSMA PET/CT scans demonstrated avidity at the VUA in none of the patients, although two out of 18 patients showed avidity in the seminal vesicles and two out of 18 patients showed avidity within regional lymph nodes. Histology from the TPUS-guided, VUA-directed biopsies demonstrated no prostatic tissue in six out of 18 and presence of prostatic tissue in 12 out of 18 of patients, respectively. In 7 out of 18 cases, there was histological evidence of recurrent PCa at the VUA in the absence of a positive 68 Ga-PSMA PET/CT scan. This study highlights the potential value of VUA-directed biopsy. We are reminded that a negative 68 Ga-PSMA PET/CT does not exclude local recurrence and that the addition of a VUA-directed biopsy may aid in the decision-making process for patients with BCR following RP, especially when 68 Ga-PSMA PET/CT is locally negative. When the result of both 68 Ga-PSMA PET/CT and VUA-directed biopsy are negative, it should encourage clinicians to share decision-making in regard to undertaking SRT vs continuing BCR surveillance. This may delay the possible side effects associated with SRT, despite its excellent PSA failure-free survival rate.

Comparison of Multiparametric Magnetic Resonance Imaging and Gallium-68 Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Detecting Carcinoma Prostate in Patients with Serum Prostate-Specific Antigen between 4 and 20 ng/ml.

Introduction:We carried out this study to compare the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) and gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-68 PSMA PET/CT) to detect prostatic carcinoma in patients with serum prostate-specific antigen (PSA) between 4 and 20 ng/ml in prebiopsy setting.Materials and Methods:This prospective study evaluated men with serum PSA values between 4 and 20 ng/ml. All patients underwent mpMRI and Ga-68 PSMA PET/CT, followed by 12-core transrectal ultrasonography (TRUS)-guided biopsy to detect prostatic carcinoma. The diagnostic accuracy of mpMRI and PSMA PET/CT scan was compared with histopathological findings.Results:There were thirty patients included in the study with a median age of 73 years (age range: 69–79 years). The median total serum PSA was 8.0 ng/ml (5.0–19.9 ng/ml). Of these, 18 had an identifiable lesion on imaging and had histopathological findings suggestive of carcinoma prostate. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI were 100%, 92.30%, 94.73%, and 100%, respectively, and that of PSMA PET scan were 94.44%, 100%, 100%, and 92.31%, respectively. The diagnostic accuracy of both was 96.67%.Conclusion:PSMA PET scan showed higher PPV and specificity while mpMRI showed higher sensitivity and NPV. The accuracy in predicting presence of carcinoma was the same for both. PSMA PET showed higher specificity and PPV and predicted the subsequent need of biopsy. In our study, the NPV of PET, though good, was lower than mpMRI. Prospective trials with larger sample size are needed. In combination, PET/MRI may achieve greater accuracy and may serve as investigation of choice.

Combined Intravenous Urogram and 68Ga-PSMA PET/ CT for Improved Staging and Restaging of Prostate Cancer.

Staging/restaging of prostate cancer utilizing Gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in combination with an intravenous urogram allows improved discrimination between radiotracer activity in the renal tract and small pelvic nodes or local recurrences. Within this pictorial essay, we describe the imaging protocol utilized at our institution and present cases which demonstrate the utility of this combined imaging approach.

Machine Learning Facilitates Hotspot Classification in PSMA-PET/CT with Nuclear Medicine Specialist Accuracy.

Gallium-68 prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET) is a highly sensitive method to detect prostate cancer (PC) metastases. Visual discrimination between malignant and physiologic/unspecific tracer accumulation by a nuclear medicine (NM) specialist is essential for image interpretation. In the future, automated machine learning (ML)-based tools will assist physicians in image analysis. The aim of this work was to develop a tool for analysis of 68Ga-PSMA-PET images and to compare its efficacy to that of human readers. Five different ML methods were compared and tested on multiple positron emission tomography/computed tomography (PET/CT) data-sets. Forty textural features extracted from both PET- and low-dose CT data were analyzed. In total, 2419 hotspots from 72 patients were included. Comparing results from human readers to those of ML-based analyses, up to 98% area under the curve (AUC), 94% sensitivity (SE), and 89% specificity (SP) were achieved. Interestingly, textural features assessed in native low-dose CT increased the accuracy significantly. Thus, ML based on 68Ga-PSMA-PET/CT radiomics features can classify hotspots with high precision, comparable to that of experienced NM physicians. Additionally, the superiority of multimodal ML-based analysis considering all PET and low-dose CT features was shown. Morphological features seemed to be of special additional importance even though they were extracted from native low-dose CTs.

Metastasis-directed Therapy (SBRT) Guided by PET-CT 18F-CHOLINE Versus PET-CT 68Ga-PSMA in Castration-sensitive Oligorecurrent Prostate Cancer: A Comparative Analysis of Effectiveness.

The present analysis aims to compare the impact of 18F-fluorocholine (18F-choline) and gallium-68 prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)-guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC). Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3)≤ 3 hypermetabolic oligorecurrent lesions detected by 18F-choline or 68Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered. A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68Ga-PSMA and choline PET group (P= .06). The ADT administration rate was higher after choline-PET-guided SBRT (P= .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68Ga-PSMA-based SBRT. In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18F-choline-PET cohort. Randomized trials are advocated.

68 Ga-PSMA-PET/CT helps to select patients for salvage radical prostatectomy with local recurrence after primary radiotherapy for prostate cancer.

To investigate the diagnostic performance of gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) in patients with recurrent prostate cancer with regard to the presence of lymph node metastases (LNM) and local recurrences after primary radiotherapy. We retrospectively reviewed 142 patients following salvage radical prostatectomy (sRP), 50 of which had a 68 Ga-PSMA PET/CT performed as a preoperative staging module. Predictive clinical parameters were analysed in a multivariate Cox regression analysis. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and the accuracy of 68 Ga-PSMA PET/CT were analysed with regard to LNM and local recurrence. In all, 613 lymph nodes were resected in 40 patients and 23 lymph nodes had metastatic deposits in 14 patients. In all patients local recurrence could have been found with 68 Ga-PSMA PET/CT. Sensitivity, specificity, PPV and NPV and accuracy on a per lymph node basis were 34.78% (16.38-57.2%), 100% (99.38-100%), 100%, 97.52% (96.69-98.15%) and 97.55% (96.00-98.62%). For detecting local recurrence, the sensitivity and PPV were both 100% with an accuracy of 100% (92.89-100%). 68 Ga-PSMA PET/CT should be the standard imaging in biochemical recurrent prostate cancer. With this imaging module one detects first local recurrence and can detect locoregional and distant metastases more precisely than standard CT and bone scan.

Prostate penile metastasis: Incidence and imaging pattern on 68 Ga-PSMA PET/CT.

Prostate cancer commonly metastasises to bone and regional lymphatics and more rarely to locations such as the brain, skin and penis. Gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has widely become the routine imaging modality for prostate cancer staging and re-staging in Australia. The aim of this study was to retrospectively review all 68 Ga-PSMA PET/CT examinations performed to date at our institution to determine the frequency of penile metastases. A total of 4860 68 Ga-PSMA PET/CT examinations were performed between 16/07/2014 and 31/10/2019. Radiology reports for each examination were filtered to identify those with the words 'penis' or 'penile'. Once identified, relevant reports and images were individually reviewed to confirm the presence of a PSMA-avid penile lesion. The incidence of penile metastasis of prostate cancer observed in this study was 0.1% with six examinations identified as having PSMA-avid penile lesions in five prostate cancer patients (age range: 71-88years). The patients had a 1-8year history of prostate cancer with varying severity of disease. Appearance of PSMA-avidity varied between single focal lesion, multiple focal lesions and diffuselesion. An incidence of 0.1% in our study confirms the rarity of penile metastases of prostate cancer. Although rare, identification of prostate cancer penile metastases is important for appropriate treatment management and symptom-relief.

PSMA-PET/CT–based Lymph Node Atlas for Prostate Cancer Patients Recurring After Primary Treatment: Clinical Implications for Salvage Radiation Therapy

BackgroundMany patients experience recurrence of prostate cancer after radical prostatectomy. ObjectiveThe aim of this study was to visually analyze typical patterns of lymph node (LN) involvement for prostate cancer (PC) patients with biochemical recurrence after radical prostatectomy and lymphadenectomy by creating a color-coded heat map using gallium-68 prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET) imaging. Further, we evaluated which LNs were covered by the Radiation Therapy Oncology Group (RTOG) clinical target volume (CTV) contouring guidelines. Design, setting, and participantsA total of 1653 68Ga-PSMA-PET/computed tomography (CT) datasets were screened retrospectively. After meeting the eligibility criteria, 233 patients with 799 LN metastases were included in our study. Outcome measurements and statistical analysisWe created a comprehensive three-dimensional color-coded LN atlas. Further, the coverage of LN metastases by RTOG CTV was assessed and stratification for risk factors was performed. Results and limitationsIn the overall, mainly high risk, collective, complete coverage by the standard RTOG CTV was accomplished in 31.0% of all LN metastases. The vast majority of uncovered LNs are situated in the para-aortal, pararectal, paravesical, preacetabular, presacral, and inguinal regions. Concerning examined stratification factors, prostate-specific antigen (PSA) levels at the time of PET/CT imaging had the highest predictive value for extrapelvic metastatic LN spread. Every increase of 1 ng/mL in PSA raises the risk of metastases outside the CTV by a factor of 1.43. ConclusionsWe developed the first LN atlas for patients with recurrent PC using a heat map technique, in order to illustrate hot spots of LN recurrence. The vast majority of detected LNs are not covered by a standard CTV as recommended by the RTOG. Application of the standard RTOG CTV for pelvic irradiation in the salvage setting for high-risk PC patients seems to be inappropriate. Patient summaryWe visualized typical lymph node recurrence sites for patients after prostate cancer surgery.

68Ga-PSMA PET/CT versus CT and bone scan for investigation of PSA failure post radical prostatectomy

ObjectiveTo evaluate the use of Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT), compared with conventional CT abdomen/pelvis (CTAP) and whole body single photon emission CT bone scan (BS), for detection of local or distant metastasis following biochemical failure/recurrence in post-prostatectomy patients. MethodsWe conducted a review of our prospectively maintained, institutional database to identify 384 patients with post-prostatectomy biochemical failure/recurrence who underwent PSMA PET/CT, CTAP and BS from February 2015 to August 2017 in Nepean Hospital, tertiary referral centre. The results of the three imaging modalities were analysed for their ability to detect local recurrence and distant metastases. PSMA PET/CT and CTAP imaging were separately performed on the same day and the BS was performed within several days (mostly in 24 h). Difference in detection rates was determined between the modalities and the Chi square test was used to determine significance. ResultsA total of 384 patients were identified with a median prostate-specific antigen (PSA) of 0.465 ng/mL (interquartile range =0.19–2.00 ng/mL). Overall, PSMA PET/CT was positive for 245 (63.8%) patients whereas CTAP and BS were positive in 174 patients (45.3%). A total of 98 patients (25.5%) had local or distant metastasis detected on PSMA only, while 20 patients (5.2%) had recurrences detected on CTAP but not on PSMA PET/CT. ConclusionThe use of PSMA PET/CT has a higher detection rate of predicted local or distant metastasis compared to CTAP and BS in the staging of patients with biochemical recurrences after radical prostatectomy.

In primary lymph nodal staging of patients with high-risk and intermediate-risk prostate cancer, how critical is the role of Gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography?

To assess the diagnostic performance of Gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography (Ga-PSMA PET-CT) in primary lymphnodal staging of patients with intermediate-risk and high-risk prostate cancer and to compare it with multiparametric MRI (mp-MRI) whenever available. Ga-PSMA PET-CT scans of 51 patients (average age 66.0 ± 7.0 years) with biopsy-proven intermediate-risk and high-risk prostatic cancer who were managed by radical prostatectomy and extended pelvic lymph nodal dissection were retrospectively analyzed. Diagnostic performance of Ga-PSMA PET-CT in primary lymph nodal staging was analyzed using histopathology as reference. Diagnostic performance of mp-MRI, which was available in 35/51 patients was compared with that of Ga-PSMA PET-CT. Univariate analysis of patient characteristics showed significant influence of the pathological T-stage and maximum standard uptake value (SUV)max of the primary lesion on presence of nodal metastasis. In 51 patients, for patient-based analysis, the sensitivity, specificity and accuracy of Ga-PSMA PET-CT in detecting lymphnodal metastases were 80, 90.3 and 86.3%, respectively, and for lesion-based analysis 69.2, 99.6 and 98.4%, respectively. In 35/51 patients (who also had undergone mp-MRI), the patient-based and lesion-based sensitivity, specificity, and accuracy of Ga-PSMA PET-CT were 81.3, 84.2, 82.8% and 70.9, 99.5, 98.2%, respectively, and that of mp-MRI were 43.7, 78.9, 62.8% and 32.2, 98.5, 95.5%, respectively. For lesion-based analysis, Ga-PSMA PET-CT performed better than mp-MRI (P value = 0.04). Ga-PSMA PET-CT allows accurate detection of lymphnodal metastases in patients with intermediate-risk and high-risk prostate cancer prior to definitive surgical treatment. It performed better than mp-MRI in a subset of patients.

Diagnostic Accuracy of Prebiopsy Ga-68 PSMA PET/CT in Detecting Primary Prostate Carcinomas with Prostate-Specific Antigen

Background and Aim:Serum prostate-specific-antigen (PSA) guided systematic transrectal ultrasound (TRUS)-guided biopsies are known to have a low predictive value in detection of primary prostate carcinomas (PCa). Our aim was to evaluate the accuracy of gallium-68 (Ga-68) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) for the detection of PCa with serum PSA <50 ng/ml.Patients and Methods:We retrospective analyzed prebiopsy Ga-68 PSMA PET/CT's of all patients with suspected PCa from October 2019 to March 2020. Several quantitative clinical and PET/CT variables were compared in benign and malignant groups and assessed for significance using an independent t-test. Diagnostic performance of PSMA PET/CT for detection of cancer was evaluated and compared with the diagnostic performance of cancer risk predicting calculator (European Randomized Study for Screening of Prostate Cancer [ERSPC3]). The standard of reference was 12-core TRUS-guided biopsies.Results:Sixty-four patients were included with mean age 70 years (range 48–94 years); mean PSA 15.67 ng/ml (range 1.74–44), mean PSA density 0.32 ng/ml2 (range 0.01–0.99) and mean prostate volume 54.55 cc (range 16.5–182). 64% (n = 41/64) patients had benign histology and 36% (n = 23/64) had carcinoma. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PSMA PET/CT for detecting PCa reported using the prostate cancer molecular imaging standardized evaluation (PROMISE) was 74%, 92%, 85%, 86%, and 86%, respectively. Mean prostate maximum standardized uptake value (SUVmax) was significantly higher in PCa versus Benign lesions (19.56 ± 18.11 vs. 4.21 ± 1.5, P = 0.00001), in patients with PSA >20 ng/ml versus PSA <20 ng/ml (19.1 ± 20.6 vs. 6.01 ± 5.4, P-0.0052), and in patients with Gleason's score (GS) score >7 versus GS ≤7 (28.1 ± 20.3 vs. 10.2 ± 8.9, P-0.010). SUVmax cutoff value of 5.6 on PSMA PET/CT showed a sensitivity of 95% and specificity of 90.9% (area under the curve 0.990, P < 0.0001).Conclusion:Ga-68 PSMA PET/CT can differentiate benign and malignant lesions of the prostate with very high accuracy and when used alongside with ERSPC3 calculator and magnetic resonance imaging, could potentially reduce painful and often unnecessary prostate biopsies.

Diagnostic performance of Gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography in intermediate and high risk prostate cancer.

Gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography (Ga-68 PSMA PET/CT) is an imaging modality that promises improved sensitivity and specificity of detection of prostate cancer lesions based on their increased uptake of PSMA-based radiotracers. It remains an emerging modality that has not yet been endorsed in the guidelines for the management of prostate cancer pending more established evidence to prove its efficacy. The objective of the study is to assess the value of Ga-68 PSMA PET/CT in the detection and localization of patients diagnosed with intermediate or high risk prostate cancer.Twenty three patients with intermediate or high risk prostate cancer had undergone Ga-68 PSMA PET/CT imaging prior to robotic assisted radical prostatectomy. Surgical specimens were then submitted for histological examinations. Lesions visualized on PET/CT and histology were independently mapped unto a 36-segment (Prostate Imaging Reporting and Data System version 2 [PI-RADS v.2]) map of the prostate. Concordance of visualization on PET/CT as compared to the histology as gold standard reference was then assessed. Lesions visualized on PET/CT and histology were independently mapped unto a 36-segment (PI-RADS v.2) map of the prostate. Concordance of visualization on PET/CT as compared to the histology as gold standard reference was then assessed.Sensitivity for all lesions identified on Ga-68 PSMA PET/CT was 42.37%; specificity was 88.61%. Both parameters were higher when considering only index lesions for which sensitivity was 68.42% and specificity was 98.23%. Sensitivity for the index lesions in intermediate risk group was 53.2% and was higher in the high risk group reaching 83.33%.Ga-68 PSMA PET/CT provides accurate localization of tumor lesions in patients with intermediate and high risk prostate cancer.

Prediction nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for prostate cancer.

The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure. Seven hundred three (n= 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced-stage PCa before second-line systemic therapies: group 4). First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram's derived cutoff. Decision curve analysis (DCA) was implemented to quantify nomogram's clinical benefit. 68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p< 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cutoff value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%. This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cutoff in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging.

Prospective Validation of Gallium-68 Prostate Specific Membrane Antigen-Positron Emission Tomography/Computerized Tomography for Primary Staging of Prostate Cancer.

Prospective validation of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the diagnostic accuracy of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer. Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported. A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%). In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.