68Ga-PSMA PET Research Articles

Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with 68Ga-PSMA-11 PET/MRI in men with treatment-na\xefve prostate cancer

PurposeBased on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression. Therefore, we hypothesised that ADT improves the performance of PSMA-PET imaging in primary staging of prostate cancer. The purpose of the study was to demonstrate the time course effect of ADT on PSMA uptake in different types of metastatic lesions evaluated with 68Ga-PSMA-11 PET/MRI.MethodsNine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A 68Ga-PSMA-11 PET/MRI was performed once before and 3 times post-ADT (degarelix, Firmagon). Change of maximum standardised uptake values (SUVmax) in prostate, lymph nodes, bone metastases, and physiologically PSMA-avid organs were evaluated in a time frame of 1–8 weeks.ResultsAll patients reached castration levels within 10 days, and 50% decrease in prostate-specific antigen (PSA) concentration was observed 14 days post-ADT. A heterogeneous increase in PSMA uptake was observed 3 to 4 weeks post-ADT. This phenomenon was definitively more evident in bone metastases: 13 (57%) of the metastasis, with a mean (range) SUVmax increase of 77% (8–238%). In one patient, already having bone metastases at baseline, three new bone metastases were observed post-ADT. Of lesions with reduced SUVmax, none disappeared.ConclusionsBoth in patient and region level, increase in PSMA uptake post-ADT is heterogenous and is seen most evidently in bone metastases. Preliminary results on a small cohort of patients suggest the clinical impact of ADT on improving the performance of 68Ga-PSMA PET in staging seems to be minor. However, the optimal imaging time point might be 3 to 4 weeks post-ADT. Since none of the metastases with decreasing SUVmax disappeared, it seems that short-term usage of ADT does not interfere with the interpretation of 68Ga-PSMA PET.Trial registrationNCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.

203P - Long term outcomes of 2-weekly docetaxel in metastatic high-volume hormone sensitive prostate cancer

Background3-weekly Docetaxel along with androgen deprivation therapy (ADT) improves overall survival in high volume metastatic hormone sensitive prostate cancer (mHSPC). However, this regimen is associated with 30% incidence of grade 3-5 adverse events. 2-weekly Docetaxel is better tolerated than 3-weekly docetaxel in Castration Resistant Prostate Cancer (CRPC). We sought to determine toxicity and efficacy of 2-weekly docetaxel in high volume mHSPC. We also compared these outcomes to those achieved with 3-weekly docetaxel in CHAARTED Trial. Methods29 patients with high volume mHSPC (as per CHAARTED criteria) received ADT + 2-weekly docetaxel between April 2016 & December 2017. Diagnosis was established by TRUS guided prostate biopsy and staging was done by Ga68 PSMA PET CT scan in all patients. Docetaxel was administered at 50 mg/m2 every 2 weekly for total 10 doses. 23 patients received medical ADT and 6 patients underwent surgical castration. Patients were monitored every 2-weekly during treatment & 3-monthly thereafter. Adverse events were recorded as per CTCAE 4.0. Data was analyzed to determine serological complete response rate (sCR - PSA<0.2ng/ml), time to CRPC and overall survival. ResultsMedian age was 64 years & median PSA was 98 ng/ml (range 11 – 4000). Gleason score was <7 in 1 patient, 7 in 7 patients & 8-10 in 21patients, respectively. Bone, lymph node and visceral metastasis were present in 23, 8 & 8 patients, respectively. 27 patients completed the planned chemotherapy and treatment was well tolerated in most patients. 2 patients developed grade 3 paronychia, 1 patient developed pulmonary tuberculosis and 1 patient died of pneumonia. sCR (PSA<0.2ng/ml) was achieved in 12(41.4%) patients, which compares well with 32% reported in CHAARTED trial. After a median follow up of 24 months, 5 patients have died, 1 lost to follow-up while 23 are alive. 14(48.3%) patients have progressed to CRPC. Median time to CRPC was 17 months, which compares well with 20 months reported in CHAARTED trial. ConclusionsWe conclude that 2-weekly docetaxel is better tolerated and results in acceptable long term outcomes compared to 3-weekly docetaxel in mHSPC. This regimen is currently being explored in a large phase 3 randomized trial. Legal entity responsible for the studyMax Healthcare. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

68Ga-PSMA-11 PET-Based Prostate Cancer Lymph Node Atlas Reveals Patterns of Potential Geographic Miss in Consensus Pelvic Nodal Contours

Gallium-68 prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) enables highly sensitive and specific detection of metastatic prostate cancer. We aimed to characterize patterns of prostate cancer lymph node metastasis through development of a PSMA PET-based lymph node atlas. We then compared our results to the RTOG consensus prostate cancer pelvic nodal atlas to reveal areas of potential geographic miss during radiation therapy. From December 2015 to October 2018, 378 patients were enrolled in a prospective study evaluating the use of 68Ga-PSMA-11 PET in the staging of prostate cancer. We identified 84 previously untreated prostate cancer patients in the study cohort who underwent staging 68Ga-PSMA PET demonstrating pelvic lymph node metastasis. DICOM images were exported to the commercially available deformable registration algorithm, and PET avid lymph nodes were manually contoured. Each node was categorized by laterality, location and volume. Finally, rigid and deformable image fusion was performed, and the location of involved pelvic lymph nodes was compared to the RTOG consensus prostate cancer pelvic nodal contours. We identified 242 68Ga-PSMA-11 PET avid lymph nodes with an average volume of 2.3mL (range 0.9-55.96mL). Among all patients, external iliac and internal iliac nodal basins were most often involved with avid nodes found in 60.7% and 34.5% of patients respectively. Pelvic (32.1%), common iliac (25.0%), perirectal (13.1%), and presacral (10.7%) nodal basins were also commonly involved followed by low frequency involvement of obturator, inguinal, anterior bladder, and retropubic regions (1.2% each). In total, 57 of 242 (24%) PSMA PET avid lymph nodes were located outside of RTOG consensus prostate cancer pelvic nodal contours; missed nodes were found in 37 of the 84 (44%) patients. The most common sites of geographic miss were in the proximal common iliac, distal anterior external iliac, low presacral and perirectal regions. We used 68Ga-PSMA-11 PET imaging to generate a prostate cancer lymph node atlas in previously untreated prostate cancer patients, revealing that more than 1 in 5 involved lymph nodes may be prone to geographic miss by current consensus pelvic nodal contours. These findings suggest that 68Ga-PSMA-11 PET may be used to supplement conventional target delineation. Further research may refine clinical scenarios in which extended lymph node delineation is warranted.

Reply to: Improved Scatter Correction to Eliminate Halo Artifacts for 68Ga-Labeled Radiopharmaceuticals in PET Imaging.

REPLY: After reading our ahead-of-print article ([1][1]), Wangerin et al. pointed out that their paper ([2][2]) might be interesting for The Journal of Nuclear Medicine readership with regard to the subject matter of un-renormalized absolute scatter correction on 68Ga-PSMA PET quantification in PET/

Current Status of Radionuclide Renal Cortical Imaging in Pyelonephritis.

Pyelonephritis is an infection of the kidneys that is seen more commonly in children than the adults. 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scanning is a radionuclide imaging study to detect renal scarring after acute pyelonephritis (a late 99mTc-DMSA scan) and also helps to diagnose acute pyelonephritis in febrile urinary tract infections (an acute 99mTc-DMSA scan). Planar imaging in multiple views (posterior and bilateral posterior oblique) is generally used. Pinhole imaging with a high-resolution-collimator magnification of each kidney allows detection of smaller cortical defects. SPECT is optional. SPECT/CT is not recommended in children because it has a higher radiation exposure than routine 99mTc-DMSA scans. The main limitations of 99mTc-DMSA scanning include a relatively long waiting time after radiotracer injection, a long acquisition time, and a high radiation dose, which is particularly important in repeated studies on children and with the limited spatial resolution of γ-cameras. 99mTc-glucoheptonate is an alternative radiotracer when 99mTc-DMSA is not available. Radiotracers for dynamic renal functional imaging can grossly assess the renal cortex in the first few minutes of imaging. 68Ga-prostate-specific membrane antigen ligand (68Ga-PSMA ligand) PET has the ability to provide images of normal renal cortex and demonstrate renal cortical defects from cysts. In this article, we assess the current status of renal cortical imaging and present 68Ga-PSMA ligand PET images. 68Ga-PSMA ligand provides excellent renal cortical images, and studies should be done to compare 68Ga-PSMA ligand PET with 99mTc-DMSA scanning in renal diseases, particularly in pyelonephritis.

Addition of docetaxel or abiraterone to androgen deprivation therapy in metastatic castration-naive prostate cancer in South Asian population.

e16514 Background: Clinical trials have shown that addition of Docetaxel or Abiraterone to androgen deprivation therapy (ADT) achieves superior survival outcome in metastatic castration naive prostate cancer (mCNPC) in predominantly western population. We sought to evaluate treatment outcomes of adding Docetaxel or Abiraterone to ADT in South Asian population. Methods: 90 mCNPC patients who received treatment between January 2015 and June 2018 were prospectively followed. Diagnosis was established by TRUS guided prostate biopsy and staging was done by Ga68 PSMA PET CT scan in all patients. Patients who were unfit for combination therapy received ADT alone. Patients diagnosed before June 2017 &amp; fit to receive chemo-hormonal therapy, received ADT+Docetaxel. Patients diagnosed after June 2017 and fit to receive combination were offered ADT+Docetaxel or ADT+Abiraterone and therapy selected based on patient’s choice. Monthly clinical evaluation and PSA measurement was done. Outcome measures analyzed included PSA decline &gt; 90%, serological complete response (PSA &lt; 0.2 ng/ml) and progression to CRPC. 76 patients with atleast 6 months follow-up were included in outcome analysis. Results: Patients received ADT alone (N = 37) or ADT+Docetaxel (N = 31) or ADT+Abiraterone (N = 22). Median age was 72, 64 &amp; 70 years, median PSA was 88, 95 &amp; 38 ng/ml, Gleason score was ≥8 in 57%, 71% &amp; 77% patients in ADT alone, ADT+Docetaxel &amp; ADT+Abiraterone group, respectively. Bone &amp; visceral metastasis were present in 62% &amp; 24%, 74% &amp; 26%, 68% &amp; 23% patients in ADT alone, ADT+Docetaxel &amp; ADT+Abiraterone group, respectively. Outcome analysis in 76 evaluable patients is shown in Table. Conclusions: ADT+Docetaxel &amp; ADT+Abiraterone achieve deeper serological response and reduced progression to CRPC compared to ADT alone in metastatic castration naive prostate cancer patients with South Asian ethnicity. Longer follow up is required to comment on overall survival and also to determine which combination (ADT+Docetaxel or ADT+Abiraterone) is superior to other, if at all.[Table: see text]

Prostate cancer with oligometastatic relapse: Combining stereotactic ablative radiotherapy and durvalumab, a randomized phase II trial (POSTCARD - GETUG-P13).

TPS5088 Background: Following Stereotactic Body RadioTherapy (SBRT) targeting prostate cancer (PCa) oligometastasis, a tumor response assessed by PSA decrease is observed in a majority of case. To increase this tumor response, immune targeting agents can be combined with SBRT. We hypothesize that the anti-PDL1 agent Durvalumab will enhance immune response following SBRT targeting oligometastatic lesions. In this multicenter randomized phase II trial, we therefore propose to assess the comparative efficacy of SBRT with or without Durvalumab (MEDI4736) in oligometastatic recurrent hormone sensitive prostate cancer patients. Methods: Patients with PCa were eligible if they had a biochemical recurrence following treatment with curative intent, with a maximum of 5 bone or lymph node metastases, seen only on FCH-PET CT or Ga-PSMA PET CT, not seen on conventional imaging assessments (bone scan or thorax, abdomen and pelvis CT scan). Main exclusion criteria are serum testosterone level &lt; 8.5 nmol/ml, PSA doubling time less than 6 months, lung, brain, liver or other visceral metastases, any prior immune therapy. Patients were randomly assigned (2:1) to either SBRT + Durvalumab, or SBRT alone, with a stratification by investigation center, and number of metastases (1 vs 2-5). Durvalumab (1500 mg/cycle) will be started one month prior to SBRT to be able to evaluate PSA and immune response to the drug. It will be combined with SBRT (3x 9 or 3 x 11 Gy) and then given adjuvantly until progression with a maximum of 12 months. Ninety-six patients will be recruited in 15 centers over a recruitment period of 2.5 years. The primary endpoint is two-year Progression-free survival. Secondary objectives include quality of life, androgen deprivation therapy free survival, prostate cancer specific survival, overall survival, time to first symptomatic event, acute and late toxicity. Patients in both groups will be observed for PSA progression every 3 months after random assignment, with confirming imaging at PSA progression. Clinical trial information: NCT03795207.

Predictors of Overall and Disease-Free Survival in Metastatic Castration-Resistant Prostate Cancer Patients Receiving 225Ac-PSMA-617 Radioligand Therapy.

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment. Methods:225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45-85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1-17.4) and 18 mo (95% CI, 16.2-19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps < 0.05). In multivariate analyses, there was a negative association between prior 177Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.

Apport du 68Ga-PSMA-TEP dans la prise en charge initiale par radiothérapie des cancers de la prostate

Radiotherapy is one of major modality for prostate cancer treatment. Technical improvements allow to deliver higher doses to the tumor, and improve protection of healthy tissues. Those improvements are enlarging indications and change treatment modalities for prostate cancer patients, on primary staging or at time of relapse (local or metastatic). Accounting to recent publications, 68Ga-PSMA PET should have an impact on radiotherapy treatment planning for those patients, especially in case of intermediate to high risk tumor. In case of metastatic disease, early detection of metastasis allows selection of patients with oligo-metastatic cancer for whom local treatments are in development. For localized prostate cancer, diagnosis of nodal extension permit volumes and doses modifications for radiotherapy. An accurate detection of the dominant intra-prostatic lesion gives the possibility of a focalized dose escalation to this significant cancer (“index lesions”). This new treatment strategies coming from technical progress are currently evaluated to assess their clinical benefit.

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.

Diagnostic Performance of 68Gallium Labelled Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging for Staging the Prostate Cancer with Intermediate or High Risk Prior to Radical Prostatectomy: A Systematic Review and Meta-analysis.

PurposeTo compare the diagnostic efficiency of 68Gallium labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET) and magnetic resonance imaging (MRI) for staging the lymph node metastases (LNMs) in the prostate cancer.Materials and MethodsA broad search of scientific databases including PubMed, EMBASE, Web of Science, Cochrane Database, and Chinese Biomedicine Literature Database (updated prior to November 1st, 2018) was conducted systematically by two reviewers. In this paper, we evaluated the methodological quality of each included article independently and performed a systematic review and meta-analysis to reveal the summary of the diagnostic performance of 68Ga-PSMA PET and MRI in properly identifying LNMs of intermediate- and/or high-risk prostate cancer.ResultsThirteen eligible articles comprising 1,597 patients were included. For LNMs detection, the pooled sensitivity and specificity of 68Ga-PSMA PET were 0.65 (95% confidence interval [CI]: 0.49–0.79) and 0.94 (95% CI: 0.88–0.97), respectively, while the corresponding values of MRI were 0.41 (95% CI: 0.26–0.57) and 0.92 (95% CI: 0.86–0.95). The area under the symmetric receiver-operating characteristic (SROC) curve for 68Ga-PSMA PET and MRI were 0.92 and 0.83, respectively.ConclusionsIn intermediate- or high-risk pre-treatment prostate cancer, 68Ga-PSMA PET had a higher sensitivity and a slightly different specificity in probing the LNMs when comparing with MRI. Moreover, the area under the SROC curve indicated that 68Ga-PSMA PET was a more effective weapon for predicting the LNMs prior to radical surgery.

The Contribution of Multiparametric Pelvic and Whole-Body MRI to Interpretation of 18F-Fluoromethylcholine or 68Ga-HBED-CC PSMA-11 PET/CT in Patients with Biochemical Failure After Radical Prostatectomy.

Our purpose was to assess whether the addition of data from multiparametric pelvic MRI (mpMR) and whole-body MRI (wbMR) to the interpretation of 18F-fluoromethylcholine (18F-FCH) or 68Ga-HBED-CC PSMA-11 (68Ga-PSMA) PET/CT (=PET) improves the detection of local tumor recurrence or of nodal and distant metastases in patients after radical prostatectomy with biochemical failure. Methods: The current analysis was performed as part of a prospective, multicenter trial on 18F-FCH or 68Ga-PSMA PET, mpMR, and wbMR. Eligible men had an elevated level of prostate-specific antigen (PSA) (>0.2 ng/mL) and high-risk features (Gleason score > 7, PSA doubling time < 10 mo, or PSA > 1.0 ng/mL) with negative or equivocal conventional imaging results. PET was interpreted with mpMR and wbMR in consensus by 2 radiologists and compared with prospective interpretation of PET or MRI alone. Performance measures of each modality (PET, MRI, and PET/mpMR-wbMR) were compared for each radiotracer and each individual patient (for 18F-FCH, or 68Ga-PSMA for patients who had 68Ga-PSMA PET) and to a composite reference standard. Results: There were 86 patients with PET (18F-FCH [n = 76] and/or 68Ga-PSMA [n = 26]) who had mpMR and wbMR. Local tumor recurrence was detected in 20 of 76 (26.3%) on 18F-FCH PET/mpMR, versus 11 of 76 (14.5%) on 18F-FCH PET (P = 0.039), and in 11 of 26 (42.3%) on 68Ga-PSMA PET/mpMR, versus 6 of 26 (23.1%) on 68Ga-PSMA PET (P = 0.074). Per patient, PET/mpMR was more often positive for local tumor recurrence than PET (P = 0.039) or mpMR (P = 0.019). There were 20 of 86 patients (23.3%) with regional nodal metastases on both PET/wbMR and PET (P = 1.0) but only 12 of 86 (14%) on wbMR (P = 0.061). Similarly, there were more nonregional metastases detected on PET/wbMR than on PET (P = 0.683) or wbMR (P = 0.074), but these differences did not reach significance. Compared with the composite reference standard for the detection of disease beyond the prostatic fossa, PET/wbMR, PET, and wbMR had sensitivity of 50%, 50%, and 8.3%, respectively, and specificity of 97.1%, 97.1%, and 94.1%, respectively. Conclusion: Interpretation of PET/mpMR resulted in a higher detection rate for local tumor recurrence in the prostatic bed in men with biochemical failure after radical prostatectomy. However, the addition of wbMR to 18F-FCH or 68Ga-PSMA PET did not improve detection of regional or distant metastases.

Intention-to-Treat Analysis of 68Ga-PSMA and 11C-Choline PET/CT Versus CT for Prostate Cancer Recurrence After Surgery.

Biochemical recurrence (BCR) after prostate cancer surgery is common, even after additional salvage radiotherapy. BCR might be explained by target miss. Improved diagnostic accuracy provided by PET could potentially circumvent this therapeutic gap. Therefore, we evaluated consecutive 68Ga-prostate-specific membrane antigen (PSMA) PET/CT, 11C-choline PET/CT, and standard CT imaging in the same patient with regard to TNM-stage migration and accordingly adapted curative radiotherapy options including ablative treatment of oligometastases (n ≤ 5). The cost efficacy of PET- versus CT-based treatment was also calculated. Methods: The prospective register database (064/2013BO1) was retrospectively searched for patients fulfilling the following 3 inclusion criteria: BCR after radical prostatectomy (pT2-pT4 pN0-pN1 cM0, postoperative radiotherapy allowed); 11C-choline PET/CT, 68Ga-PSMA PET/CT, and diagnostic CT performed within 24 h; and available clinical data. Ten treatment routines were defined according to current practice. Furthermore, intention-to-treat and treatment-related costs depending on the shift of TNM stage after imaging were analyzed. Eighty-three patients were eligible (median prostate-specific antigen level, 1.9 ng/mL). Results: Both PET examinations led to concordant results in 72% of patients, whereas the concordance of TNM staging between 68Ga-PSMA PET and diagnostic CT was only 36%. Incorrect staging would lead to "wrong" treatment and therefore to additional costs. A 68Ga-PSMA PET study would be cost-effective if additional costs do not exceed €3,844 ($4,312) (vs. CT). The number needed to image was 2 (for CT) and 4 (for 11C-choline PET) to avoid 1 incorrect treatment. In addition, 68Ga-PSMA PET staging enabled new curative options in half the patients with previous radiotherapy who otherwise receive palliative androgen deprivation therapy. Conclusion:68Ga-PSMA PET/CT is cost-effective in all patients with regard to avoidance of incorrect treatment. It enabled new curative options for patients with previous radiotherapy who are usually treated palliatively. Therefore, 68Ga-PSMA PET/CT staging should become standard for BCR after surgery with or without radiotherapy.

HIGH-DOSE-RATE AND LOW-DOSE-RATE BRACHYTHERAPY AS MONOTHERAPY FOR CLINICALLY LOCALIZED PROSTATE CANCER

PURPOSE:To compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) and low-dose-ratebrachytherapy (LDR-BT) as monotherapy for localized prostate cancer of low and intermediate risks progression. METHODS AND MATERIALS: The study included 165 patients with localized prostate cancer in low and intermediate progression risk groups. We compared 65 patients treated with HDR-BT and 100 patients with LDR-BT as monotherapy. LDR-BT treated advanced disease with more hormonal therapy than HDR-BT. All patients were in low and intermediate risk groups for prostate cancer progression. HDR-BT as monotherapy was delivered in 2 fractions of 15 Gy, two weeks apart. LDR-BT was performed in a standard mode of 145 Gy. The median observation was 32 months. All patients gave written informed consent. RESULTS: Overall biochemical free survival rate (BFSR) is 95,8%. There are 7 people having a growing prostatic specific antigen (PSA) while the case follow-up (in the group HDR-BT - 2 patients, LDR - 5 patients). Two recurrence cases with metastases in lymph nodes and bones were brought out as a result of 68Ga-PSMA PET examination in the group of HDR-BT. In 4 cases out of 5 LDR-BT, a local recurrence was detected (p=0,085). All cases of relapse were found in patients at intermediate risk (p = 0,041). LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade &gt;2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Accumulated incidence of late grade &gt;2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. CONCLUSION: HDR-BT monotherapy showed an equivalent outcome to that of LDR-BT for low and intermediate risk patients. LDR-BT showed equivalent incidence of grade &gt;2 late GU toxicities and higher grade &gt;2 acute GU toxicity as that of HDR-BT as a monotherapy.

158 - Comparison of 68Ga-PSMA PET CT and multi-parametric MRI in the evaluation of tumor extension of primary prostate cancer

158 - Comparison of 68Ga-PSMA PET CT and multi-parametric MRI in the evaluation of tumor extension of primary prostate cancer

Comparison of percentage free PSA, MRI and GaPSMA PET scan for diagnosing cancer prostate in men with PSA between 4 and 20 ng/ml.

Introduction:We compared the diagnostic accuracy of percentage free prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and gallium-68 prostate-specific membrane antigen positron emission tomography (Ga-PSMA PET) to detect cancer prostate in men with PSA between 4 and 20 ng/ml in prebiopsy settings.Materials and Methods:This prospective study evaluated men with PSA values between 4 and 20 ng/ml, and all patients underwent percentage free PSA estimation, mpMRI, and Ga-PSMA PET scan, followed by cognitive fusion/registration biopsy along with systematic 12-core biopsy to detect cancer prostate. The diagnostic accuracy of percentage free PSA, mpMRI, and Ga-PSMA PET scan was compared with results of cognitive fusion/registration biopsy.Results:A total of 15 patients were included, of which 11 had an identifiable lesion on imaging and 9 had malignancy on the final histopathology report. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and diagnostic accuracy of mpMRI were 62.5%, 71.4%, 71.4%, 62.5%, and 66.6%, respectively, and that of Ga-PSMA PET scan were 88.8%, 66.6%, 80%, 80%, and 80%, respectively. The sensitivity of detection of clinically significant cancers for Ga-PSMA was higher (100%) compared to MRI (33.3%). However, Ga-PSMA also detected a greater number of insignificant lesions as compared to MRI.Conclusion:Ga-PSMA PET scan has high NPV and accuracy in predicting presence of cancer and can also be used to direct specific biopsy cores during systematic biopsy.

68Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy.

ObjectiveProstate cancers (PCa) in Asian individuals are molecularly distinct from those found in their Caucasian counterparts. There is no risk stratification tool for Asian men with rapid biochemical recurrence (BCR) following radical prostatectomy (RadP). This study aims to assess the detection rate of 68Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-RadP. Methods68Ga PSMA-PET and CT body with/without bone scan [conventional workup (CWU)] were performed in 55 Asian patients with BCR within 36 months post-RadP. Two blinded reviewers assessed the images. Detection rates of 68Ga PSMA-PET/CT were evaluated, and impact on management was reviewed by comparison with CWU. ResultsMedian time to BCR post-RadP was 8.1 months. Detection rate for 68Ga PSMA-PET/CT was 80% (44/55). A positive scan was significantly associated with increasing prostate-specific antigen (PSA) level [odds ratio (OR) = 1.13 (95% CI 1.05–1.30), P = 0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, 68Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44 (56.8%) patients: 10 to hormonal therapy (HT) and whole pelvis radiotherapy (RT) in addition to bed RT, and 15 to palliative HT alone. ConclusionsIn the present report, we demonstrated the diagnostic and treatment decision utility of 68Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels (< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

Radioguided surgery with \u03b2 radiation: a novel application with Ga68

Radio Guided Surgery is a technique helping the surgeon in the resection of tumors: a radiolabeled tracer is administered to the patient before surgery and then the surgeon evaluates the completeness of the resection with a handheld detector sensitive to emitted radiation. Established methods rely on γ emitting tracers coupled with γ detecting probes. The efficacy of this technique is however hindered by the high penetration of γ radiation, limiting its applicability to low background conditions. To overtake such limitations, a novel approach to RGS has been proposed, relying on β− emitting isotopes together with a dedicated β probe. This technique has been proved to be effective in first ex-vivo trials. We discuss in this paper the possibility to extend its application cases to 68Ga, a β+ emitting isotope widely used today in nuclear medicine. To this aim, a retrospective study on 45 prostatic cancer patients was performed, analysing their 68Ga-PSMA PET images to asses if the molecule uptake is enough to apply this technique. Despite the expected variability both in terms of SUV (median 4.1, IQR 3.0–6.1) and TNR (median 9.4, IQR 5.2–14.6), the majority of cases have been found to be compatible with β-RGS with reasonable injected activity and probing time (5 s).

Prostate-specific membrane antigen positron emission tomography in the management of recurrent prostate cancer.

There is an unmet clinical need for early, accurate imaging of recurrent prostate cancer to improve patient outcomes. Staging, by conventional bone scintigraphy and CT have become outdated. 68Ga-PSMA PET/CT imaging in this setting has developed rapidly, with widespread International adoption in line with evidence-based guidelines in this group of patients. A PubMed search of English language articles was performed using following keywords: PSMA, PET/CT, biochemical recurrence, prostate cancer. The search revealed 85 articles, of which 75 were original; 70 of these involved use of the most widely available type of PSMA tracer (HBED). The review also relied on the clinical experience of reporting over 1000 PSMA PET/CT studies at a major tertiary referral centre for uro-oncology, with the majority of cases having been performed in the biochemical recurrence setting from 2015 to 2018. 68Ga-PSMA PET is a game changer and superior to choline PET and other established tracers which have been used in prostate cancer evaluation. Detection of recurrence at the prostate bed remains challenging due to bladder and urethral tracer accumulation. The main strength of PSMA PET/CT is its ability to identify small (<8 mm) pathological lymph nodes, upstaging nodal status in up to two-thirds of cases. Additionally, PSMA PET/CT, detects bone and bone marrow metastases missed by conventional bone and CT imaging. Thus, PSMA PET/CT has major impact on patient management, with studies reporting overall changes in 39-76% of cases. Controversy exists regarding patient access and NHS affordability of PSMA PET/CT imaging. Currently, no reimbursement is available under the NHS tariff system. The cost outlay for tertiary hospital linked PET centres ranges from £150-170 K. Large referral volumes, and technical advances in manufacturing process will make this tracer cost neutral and similar to the current funded, but less sensitive, choline PET. Current NICE guidelines for prostate cancer management do not include a recommendation on when PSMA PET/CT should be used and this is likely to remain the case in the next revision, due in 2019. Although PSMA PET/CT imaging results in significant management change, there is a need for high quality economic evaluation and cost analysis for this modality. Lack of this data will result in poor adoption of this technique and thus limit patient access. Furthermore, it is hoped that future tracers will become even more sensitive and identify disease at earlier thresholds. Well-designed clinical trials with consideration of the health economic benefit of using PSMA PET/CT will be essential to provide a basis for entry into guidelines such as NICE and to provide a rationale for reimbursement.

Role of textural heterogeneity parameters in patient selection for 177Lu-PSMA therapy via response prediction.

PurposeProstate cancer is most common tumor in men causing significant patient mortality and morbidity. In newer diagnostic/therapeutic agents PSMA linked ones are specifically important. Analysis of textural heterogeneity parameters is associated with determination of innately aggressive and therapy resistant cell lines thus emphasizing their importance in therapy planning. The objective of current study was to assess predictive ability of tumor textural heterogeneity parameters from baseline 68Ga-PSMA PET prior to 177Lu-PSMA therapy.ResultsEntropy showed a negative correlation (rs = −0.327, p = 0.006, AUC = 0.695) and homogeneity showed a positive correlation (rs = 0.315, p = 0.008, AUC = 0.683) with change in pre and post therapy PSA levels.ConclusionsStudy showed potential for response prediction through baseline PET scan using textural features. It suggested that increase in heterogeneity of PSMA expression seems to be associated with an increased response to PSMA radionuclide therapy.Materials and MethodsRetrospective analysis of 70 patients was performed. All patients had metastatic prostate cancer and were planned to undergo 177Lu-PSMA therapy. Pre-therapeutic 68Ga- PSMA PET scans were used for analysis. 3D volumes (VOIs) of 3 lesions each in bones and lymph nodes were manually delineated in static PET images. Five PET based textural heterogeneity parameters (COV, entropy, homogeneity, contrast, size variation) were determined. Results obtained were then compared with clinical parameters including pre and post therapy PSA, alkaline phosphate, bone specific alkaline phosphate levels and ECOG criteria. Spearman correlation was used to determine statistical dependence among variables. ROC analysis was performed to estimate the optimal cutoff value and AUC.