Prostate-specific Membrane Antigen Positron Emission Research Articles

Prostate-Specific Membrane Antigen PET Response Associates with Metastasis-Free Survival Following Stereotactic Ablative Radiation Therapy in Oligometastatic Castration-Sensitive Prostate Cancer

<h3>Purpose/Objective(s)</h3> Emerging data suggest metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET/CT) can detect occult metastatic disease and has been proposed as a biomarker for treatment response. Herein we identify and validate a PSMA-PET biomarker for clinical outcomes following MDT in omCSPC. <h3>Materials/Methods</h3> This was an international multi-institutional retrospective study of two independent cohorts of omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation therapy (SABR). Patients underwent PSMA-PET/CT prior to and 3-6 months after treatment. Pre- and post-SABR PSMA-PET/CT standardized uptake value (SUV) was measured for all lesions and PSMA response defined discretely using a cutpoint of ≥ 30% decrease in SUV_max. PSMA-PET response was correlated with lesion local control (LLC), and metastasis-free survival (MFS), defined per ICECaP working group by a new metastasis on conventional imaging alone (not including pelvic lymph node metastases) or death. <h3>Results</h3> A total of 131 patients (discovery n=35, validation n=96) with 261 treated metastases were included in the analysis, with median follow-up of 29 months (IQR 18.5-41.3). Following SABR, 78.4% of lesions experienced a partial or complete PSMA response. Multivariable analysis demonstrated SUV response significantly associated with improved LLC (HR=0.10, 95%CI 0.04-0.26; p<0.01). Patients with PSMA response in all lesions experienced significantly better MFS (HR=0.37, 95%CI 0.21-0.65; p<0.01) compared to their counterparts, and this maintained significance within both the discovery (p=0.02) and validation (p<0.01) cohorts. <h3>Conclusion</h3> Following SABR, PSMA-PET response is a robust and externally validated radiographic biomarker for MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated as an early response indicator biomarker in localized and other advanced states of prostate cancer.

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography–based Lymph Node Atlas for Salvage Radiotherapy in Patients with Recurrent Prostate Cancer: A Validation of the New NRG Oncology 2020 guideline

BackgroundApproximately 20–40% of patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience relapse, with the majority of these cases developing pelvic lymph node (LN) metastases. Taking new data from the prostate-specific membrane antigen (PSMA) positron emission tomography (PET) era into account, the Radiation Therapy Oncology Group (RTOG) 2009 contouring guideline for the pelvic LNs from 2009 was updated by the NRG Oncology group in 2020 (NRG 2020). ObjectiveTo evaluate and validate the updated NRG 2020 guideline with our established LN atlas. Design, setting, and participantsWe screened 1653 PSMA PET/computed tomography (CT) data sets for patients with biochemical relapse who underwent a PET scan between November 2012 and November 2017. After screening, we developed an LN atlas using data from 233 patients. Outcome measurements and statistical analysisWe evaluated LN overlap (OL) with the RTOG 2009 and NRG 2020 contouring guidelines. OL was defined as within (>90%), partly within (10–90%), or outside (<10%). Results and limitationsIn comparison to the RTOG 2009 guideline, 403 (52%), 134 (17%), and 241 (31%) of the LNs were not, were partly, or were fully covered within the overall group, respectively. By contrast, using the NRG 2020 guideline, 302 (39%), 190 (24%), and 286 (37%) of the LNs were not, were partly, or were fully covered, respectively (p < 0.001). Limitations include the retrospective design with missing data and no histopathological confirmation of the PET results. ConclusionsThe updated NRG 2020 contouring guideline improves coverage of the pelvic LNs in patients undergoing salvage radiation therapy. However, PET/CT should be considered whenever possible to ensure coverage of untypical LN spread. Patient summaryWe compared the 2009 and 2020 guidelines on the radiation area for the pelvis for patients with recurrent prostate cancer that has spread to lymph nodes. The newer guideline provides better coverage of pelvic lymph nodes than the older one and is useful in planning radiation therapy. However, a scan of the pelvis using the newest technique should be considered for individual patients to ensure coverage of untypical lymph nodes.

Unexpected Metastatic Localizations of Prostate Cancer Determined by 68Ga PSMA PET/CT: Series of Four Cases.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein with overexpression in most prostate cancer cells. Gallium-68-(68Ga) PSMA positron emission tomography/computed tomography (PET/CT) imaging is a game-changer in the management of prostate cancer. 68Ga PSMA PET/CT scan is advanced and a promising radioligand has high sensitivity in determining lesions of prostate cancer with a high tumor to background ratio. The most common areas of metastasis are the bone and pelvic lymph nodes. The prognosis of prostate cancer is mainly determined by the status of metastases. The presence and the localization of metastases affects treatment planning. In our cases, we presented some examples of uncommon sites of metastases such as the brain, adrenal glands, penis and orbit. Improvements in imaging techniques, such as 68Ga PSMA PET/CT have led to the possibility to make more determi nation of rare metastase sites in prostate cancer patients.

Mild 68Ga PSMA-11 Uptake in Incidental Pituitary Adenoma.

A 76-year-old man with metastatic prostate cancer was referred to 68Ga prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) for restaging. A consecutive 18F-fluorodeoxyglucose (FDG) PET/CT was performed due to the history of lung cancer in the left lung treated with stereotactic radiotherapy. Intense 18F-FDG uptake was detected in the pituitary gland despite the mild uptake of 68Ga PSMA. Contrast-enhanced magnetic resonance imaging confirmed pituitary adenoma.

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.

A Preclinical Study of an 125I-Labeled PSMA Ligand for Prostate-Cancer Puncture

Purpose: Prostate cancer (PCa) is characterized by high expression of prostate-specific 1membrane antigen (PSMA), a type II transmembrane protein. Prostate-specific membrane antigen positron emission tomography (PSMA PET) has high sensitivity and specificity and can therefore be potentially used to detect PCa. Exploiting the advantages of PSMA PET imaging, in this study, we aim to develop a novel radiopharmaceutical to facilitate biopsy punching of PCa. Methods: We synthesized a high-affinity radiopharmaceutical of PSMA (125I-PSMA-7). We evaluated the properties of 125I-PSMA-7, including the purity, stability, affinity, partition coefficient, and toxicity. (PSMA+) 22Rv1 and (PSMA−) PC3 cell lines were used to evaluate 125I-PSMA-7 in vitro. BALB/c nude mice bearing 22Rv1 and PC3 xenografts were used for biodistribution and imaging. The uptake of the main organs was evaluated in vivo using single photon emission computed tomography (SPECT). Results: 125I-PSMA-7 had a purity of 99.6% and remained stable for seven days and was therefore always safe to use. 125I-PSMA-7 had a Ki of 4.037 × 10−11 and a partition coefficient of −1.80. The results of in vitro cellular experiments showed a high uptake by 22Rv1 cells (ranging from 2.88 ± 0.14 IA%/106 at 5 min to 61.98 ± 3.43 IA%/106 at 24 h, where the internalization was 46.1% at 1 h and 88.06% at 24 h). However, the uptake of PC3 cells was very low (ranging from 0.34 ± 0.08 IA%/106 at 5 min to 1.60 ± 0.15 IA%/106 at 24 h). The tumors’ uptake of 125I-PSMA-7 ranged from 9.02 ± 0.30 ID%/g at 1 h to 4.11 ± 1.04 ID%/g at 7 d and the tumor/muscle ratios and tumor/blood ratios increased over time. In addition, we used γ-counter to measure cpm per milligram of tumor and muscle on days 4 and 7. The background on day 4 is 42 cpm and the tumor is 1739 cpm/mg and the muscle is 45 cpm/mg, and the background on day 7 is 74 cpm and the tumor is 1404cpm/mg and the muscle is 32 cpm/mg. At 1 h post-injection, the high uptake of 125I-PSMA-7 resulted in clear delineation of 22Rv1-derived tumors upon imaging. By comparison, 22Rv1-blocking mice took up less 125I-PSMA-7. Conclusions: These results show that 125I-PSMA-7 is a promising radiotracer that could be used to puncture the prostate. 125I-PSMA-7 could be applied to targeted biopsy, reducing the need for saturated biopsy.

Dose-Escalated Salvage Radiotherapy for Macroscopic Local Recurrence of Prostate Cancer in the Prostate-Specific Membrane Antigen Positron Emission Tomography Era.

The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Between February 2010 and June 2021, 367 patients received SRT after radical prostatectomy. Out of the 367 screened patients, 111 patients were staged by PSMA PET/CT before SRT. A total of 59 out of these 111 (53.2%) patients were treated for PSMA PET-positive macroscopic prostatic fossa recurrence. Dose-escalated SRT was applied with a simultaneous integrated boost at a median prescribed dose of 69.3 Gy (IQR 69.3-72.6 Gy). The oncological outcome was investigated using Kaplan-Meier and Cox regression analyses. The genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (version 5.0). The median follow-up was 38.2 months. The three-year biochemical progression-free survival rate was 89.1% (95% CI: 81.1-97.8%) and the three-year metastasis-free survival rate reached 96.2% (95% CI: 91.2-100.0%). The cumulative three-year late grade 3 GU toxicity rate was 3.4%. No late grade 3 GI toxicity occurred. Dose-escalated PSMA PET/CT-guided salvage radiotherapy for macroscopic prostatic fossa recurrence resulted in favorable survival and toxicity rates.

Recommendations for radiation therapy in oligometastatic prostate cancer: An ESTRO-ACROP Delphi consensus

Background and purposeOligometastatic prostate cancer is a new and emerging treatment field with only few prospective randomized studies published so far. Despite the lack of strong level I evidence, metastasis-directed therapies (MDT) are widely used in clinical practice, mainly based on retrospective and small phase 2 studies and with a large difference across centers. Pending results of ongoing prospective randomized trials, there is a clear need for more consistent treatment indications and radiotherapy practices. Material and methodsA European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee consisting of radiation oncologists’ experts in prostate cancer was asked to answer a dedicated questionnaire, including 41 questions on the main controversial issues with regard to oligometastatic prostate cancer. ResultsThe panel achieved consensus on patient selection and routine use of prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging as preferred staging and restaging imaging. MDT strategies are recommended in the de novo oligometastatic, oligorecurrent and oligoprogressive disease setting for nodal, bone and visceral metastases. Radiation therapy doses, volumes and techniques were discussed and commented. ConclusionThese recommendations have the purpose of providing standardization and consensus to optimize the radiotherapy treatment of oligometastatic prostate cancer until mature results of randomized trials are available.

Single-fraction prostate-specific membrane antigen positron emission tomography- and multiparametric magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer local recurrences.

To analyse the efficacy and safety of focal prostate-specific membrane antigen positron emission tomography (PSMA-PET)- and multiparametric magnetic resonance imaging (mpMRI)-guided single-fraction stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer (PCa) local recurrences. Patients with PSMA-PET-positive PCa local recurrences treated with single-fraction SBRT between 2016 and 2020 were included. Identification for subsequent recurrences or metastatic spread based on increasing prostate-specific antigen (PSA) levels were evaluated using PSMA-PET imaging. A total of 64 patients were identified. Patients received various treatments before SBRT (31 patients with radical prostatectomy [RP], 18 external beam radiotherapy [EBRT] with RP, five EBRT, and the remaining 10 other combinations). The median follow-up was 21.6 months. The median PSA level before SBRT was 1.47 ng/mL. All patients received a single-fraction treatment with a median prescription dose and isodose line of 21 Gy and 65%, respectively. At the time of SBRT, six patients (9%) received an androgen deprivation therapy (ADT). PSA levels decreased after SBRT (P = 0.03) and three local recurrences were detected during the follow-up. The progression-free survival after 1-, 2-, and 3-years was 85.3%, 65.9%, and 51.2%, respectively. Six patients (9%) started ADT after SBRT due to disease progression. The rates of newly started ADT after 1-, 2-, and 3-years were 1.8%, 7.3%, and 22.7%, respectively. Grade 1 or 2 toxicities occurred in six patients (9%); no high-grade toxicity was observed. While the available data for SBRT in the PCa local recurrence setting describe outcomes for fractionated irradiations, the findings of this first analysis of single-fraction, PSMA-PET- and mpMRI-guided focal SBRT are encouraging. Such treatment appears to be a safe, efficient, and time-saving therapy even in intensively pretreated patients. Recurrence-directed treatments can delay the use of ADT and could avoid prostate bed irradiation in selected patients.

Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters

BackroundAccurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas.MethodsTwenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied.ResultsIn total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson’s test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein.ConclusionIn this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.

The Role of PSMA PET Imaging in Prostate Cancer Theranostics: A Nationwide Survey

Introduction: Prostate-specific membrane antigen (PSMA)-based imaging and theranostics have played an important role in the diagnosis, staging, and treatment of prostate cancer (PCa). We aimed to evaluate the acceptance and use of PSMA theranostics among German urologists. Methods: An anonymous online questionnaire was sent via survio.com to the members of the German Society of Urology (DGU). Results: Seventy-two percent of participants performed PSMA positron emission tomography (PET) imaging regularly in biochemically recurrent PCa. Overall, 61% of participants considered PSMA-radioligand therapy to be very useful or extremely useful. PSMA PET imaging in high-risk PCa is more often considered by urologists working in a university setting than in nonuniversity settings or medical practices (51% vs. 25%, p < 0.001). Most perform PSMA-radioligand therapy as an option after all approved systemic treatments for metastatic castration-resistant PCa (56%) or after cabazitaxel (14%). A total of 93.9% and 70.3% of respondents consider the lack of reimbursement by health insurance to be the main obstacle to using PSMA PET imaging or radioligand therapy, respectively. Discussion/Conclusion: PSMA-based imaging/theranostics are already widely applied but would find even more widespread use if reimbursement is clearly regulated by health insurance in Germany.

Prognostic impact of coronary artery calcifications in patients with newly diagnosed prostate cancer

Abstract Background Patients diagnosed with prostate cancer (PCa) are known to be at increased risk of cardiovascular events. Because of the ageing population and better cancer treatment, the number of these patients is increasing. A prostate-specific membrane antigen positron emission tomography (PSMA-PET) is guideline recommended as part of the diagnostic workup. This scan includes a non-ECG-gated computed tomography (CT) of the thorax, allowing assessment of coronary artery calcifications (CAC). It is not well-established, whether estimation of CAC based on this CT scan can identify patients with increased risk of major adverse cardiac events (MACE) and thus possibly improve therapy and prognosis. Purpose This study aims to assess CAC and evaluate whether high calcium scores predict the risk of MACE in patients newly diagnosed with PCa. Methods We identified 634 consecutive patients diagnosed with PCa and undergoing PSMA-PET from 2016 to 2019 in an area of 300.000 residents. In total, 63 patients were excluded due to prior revascularization. The remaining 571 patients (mean age 69.9±6.7 years) were included. Patients were followed until June 2021 or until an event occurred (mean follow-up 962±372 days). We used a standard cardiac CT software to assess CAC. Information on MACE defined as all-cause mortality, stroke and myocardial infarction were obtained from electronic patient files. We divided patients into five groups based on their coronary artery calcium score (CACS): 0–10, 11–99, 100–399, 400–999, and + 1000. Cox regression analysis was used to compute the hazard ratios (HR) for MACE with CACS 0–10 as reference while adjusting for age, hypertension diabetes, and treatment with aspirin and statins. Results We found a significantly increasing risk of MACE with increasing CACS after adjustment for risk factors. For CACS 100–399 (n=136): HR 2.10 (95% CI: 0.98–4.51, p=0.056), for CACS 400–999 (n=79): HR of 2.99 (95% CI: 1.35–6.59, p=0.007) and for CACS +1000 (n=150): HR 3.06 (95% CI: 1.37–6.85, p=0.006) (Figure 1). Cardiovascular disease prevention treatment with statins and aspirin was 53% and 16% in patients with CACS 400–999 and 52% and 19% in patients with CACS + 1000. Conclusion In patients with PCa, estimating coronary calcium score based on non-ECG-gated CT scans, which are performed as part of the diagnostic workup, predicts the occurrence of MACE. In the patient group with the highest CAC, a four-year event rate of 24% was found. In combination with the finding of infrequent use of statin and aspirin, this emphasizes the possibility of early detection of high CAC in patients with PCa and illustrates the potential for more extensive use of preventive treatment. Future studies should investigate the effect of preventive treatment being initiated in patients with PCa and high CAC. Funding Acknowledgement Type of funding sources: None.

Modern paradigms for prostate cancer detection and management.

Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials. Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans. Biopsies are now performed transperineally, substantially reducing the risk of post-procedure sepsis. Australian-led research has shown that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole-body bone scan). Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3=6; and ISUP grade group 2, Gleason score 3 + 4=7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment. Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients. The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone-sensitive and castration-resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended. PSMA-based radioligand therapy has emerged as a treatment option for metastatic castration-resistant prostate cancer and is currently being evaluated in earlier disease states.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

Is there any additional benefit of 68Ga-PSMA PET on radiotherapy target volume definition in patients with glioblastoma?

To investigate the contribution of 68Gallium (68Ga)-PSMA (prostate-specific membrane antigen) positron emission tomography (PET) in defining radiotherapy (RT) target volume for glioblastoma and to compare the target volumes defined by Magnetic Resonance Imaging (MRI). RT planning Computed Tomography (CT) images were fused separately with pre-operative MRI and PET/MRI images of 10 glioblastoma patients, retrospectively. The contrast-enhanced area in T1 weighted MRI was contoured as gross tumor volume (GTV) and clinical target volume (CTV1) was obtained by including the cavity and T2/FLAIR hyperintense areas after giving a margin of 2 cm to the GTV. 68Ga-PSMA uptake area was contoured as biological tumor volume (BTV) and CTV2 was obtained with a margin of 2 cm to BTV. Planning target volumes (PTVs) were created with the 3 mm added to the CTVs. Conformity index (CI), dice similarity coefficient (DSC) and overlap volume (OV) were calculated by obtaining the intersection and union volumes. Volumetric comparison, similarity and overlap analyzes were performed statistically by Wilcoxon signed rank and One sample t-test. The median GTV was 21,96 cc (1,04 - 82,04) and BTV was 25,58 cc (2,43 - 99,47). BTV was on average 47% larger than GTV which was statistically significant (p = 0.03). For GTV-BTV, CTV1-CTV2 and PTV1-PTV2; mean values of CI were 0,56, 0,76 and 0,76; DSC were 0,70, 0,86 and 0,86; OV were 0,88, 0,94 and 0,94, respectively. There was no significant difference on size and spatial similarity between CTV1 and CTV2, PTV1 and PTV2. Altough BTV was larger than GTV, this significance was lost while we gave the same CTV margin including the peripheral edema. It seems that it may help to improve defining non-enhancing tumor part and also recurrent tumor volume. Recent studies have focused on the role of 68Ga-PSMA PET in imaging of glial tumors. It has been observed that 68Ga-PSMA PET can clearly define the tumor borders and it can be beneficial in target volume delineation, especially in reirradiation of recurrent tumors.

The prognostic value of lymph node staging with prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and extended pelvic lymph node dissection in node-positive patients with prostate cancer.

To investigate whether patients with suspected pelvic lymph node metastases (molecular imaging [mi] N1) on staging prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) had a different oncological outcome compared to those in whom the PSMA PET/CT did not reveal any pelvic lymph node metastases (miN0). All patients with pelvic lymph node metastatic (pN1) disease after robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) between January 2017 and December 2020 were included. To assess predictors of biochemical progression of disease after RARP, a multivariable Cox regression analysis was performed, including number of tumour-positive lymph nodes, diameter of the largest nodal metastasis, and extranodal extension. In total, 145 patients were diagnosed with pN1 disease after ePLND. The median biochemical progression-free survival in patients with miN0 on PSMA PET/CT was 13.7 months, compared to 7.9 months in patients with miN1 disease (P = 0.006). On multivariable Cox regression analysis, both number of tumour-positive lymph nodes (>2 vs 1-2: hazard ratio [HR] 1.97; P = 0.005) and diameter of the largest nodal metastasis (HR 1.12; P < 0.001) were significant independent predictors of biochemical progression of disease. Patients in whom pelvic lymph node metastases were suspected on preoperative PSMA imaging (miN1), patients diagnosed with >2 tumour-positive lymph nodes, and patients with a larger diameter of the largest nodal metastasis had a significantly increased risk of biochemical disease progression after surgery.

Failure Patterns by PSMA PET for Recurrent Prostate Cancer after Prostatectomy and Salvage Radiation

ObjectiveTo characterize patterns of failure using prostate-specific membrane antigen positron emission tomography (PSMA PET) after radical prostatectomy (RP) and salvage radiotherapy (SRT). MethodsPatients with rising PSA post-RP+SRT underwent 68Ga‐HBED‐iPSMA PET/CT on a single-arm, prospective imaging trial (NCT03204123). Scans were centrally reviewed with pattern-of-failure analysis by involved site. Positive scans were classified using 3 failure categories: pelvic nodal, extra-pelvic nodal or distant non-nodal. Associations with failure categories were analyzed using cumulative incidence and generalized logits regression. ResultsWe included 133 men who received SRT a median of 20 months post-RP; 56% received SRT to the prostatic fossa alone, while 44% received pelvic SRT. PSMA PET/CT was performed a median of 48 months post-SRT. Overall, 31% of PSMA PET/CT scans were negative, 2% equivocal and 67% had at least 1 positive site. Scan detection was significantly associated with PSA level prior to PSMA PET/CT. Analysis of 89 positive scans demonstrated pelvic nodal (53%) was the most common relapse and fossa relapse was low (9%). Overall, positive scans were pelvic (n = 35, 26%), extra-pelvic nodal (n = 26, 20%) or distant non-nodal failure (n = 28, 21%), and 70% of positive scans were oligorecurrent. We observed similar cumulative incidence for all failure categories and relatively few clinicodemographic associations. Men treated with pelvic SRT had reduced odds of pelvic failure versus exclusive fossa treatment. ConclusionPelvic, extra-pelvic nodal, and distant non-nodal failures occur with similar incidence post-SRT. Regional nodal relapse is relatively common, especially with fossa-only SRT. A high oligorecurrence rate suggests a potentially important role for PSMA-guided focal therapies.

Risk of Tumor Upstaging With Prostate-Specific Membrane Antigen Positron Emission Tomography in Patients With High-Risk Prostate Cancer

This cross-sectional study of data from the National Comprehensive Cancer Network assesses the association of prostate-specific membrane antigen positron emission tomography with tumor upstaging risk in patients with high-risk prostate cancer.

Role of PSMA PET-guided metastases-directed therapy in oligometastatic recurrent prostate cancer.

Oligometastatic prostate cancer (OMPC) has been proposed as an intermediary state between localised disease and widespread metastases, with varying definitions including 1, 3, or ≤5 visceral or bone metastasis. Traditional definitions of OMPC are based on staging with conventional imaging, such as computerised tomography (CT) and whole-body bone scan (WBBS). Novel imaging modalities such as prostate-specific membrane antigen positron emission tomography (PSMA PET) have improved diagnostic utility in detecting early metastatic prostate cancer (PC) metastases compared with conventional imaging. Specifically, meta-analytical data suggest that PSMA PET is sensitive in detecting oligometastatic disease in patients with biochemical recurrence (BCR) post-radical treatment of PC. Recent trials have evaluated PSMA PET-guided metastases-directed therapy (MDT) in oligometastatic recurrent disease, typically with salvage surgery or radiotherapy (RT). To date, these preliminary studies demonstrate promising results, potentially delaying the need for systemic therapy. We aim to report a comprehensive, multidisciplinary review of PSMA-guided MDT in OMPC. In this review, we highlight the utility of PMSA PET in biochemically recurrent disease and impact of PSMA PET on the definition of oligometastatic disease and outline data pertaining to PSMA-guided MDT.

64Cu-DOTHA2-PSMA, a Novel PSMA PET Radiotracer for Prostate Cancer with a Long Imaging Time Window.

Prostate cancer imaging and late-stage management can be improved with prostate-specific membrane antigen (PSMA)-targeting radiotracers. We developed a PSMA positron emission tomography (PET) radiotracer, DOTHA2-PSMA radiolabeled with 64Cu (T1/2: 12.7 h), to leverage its large imaging time window. This preclinical study aimed to evaluate the biological and imaging properties of 64Cu-DOTHA2-PSMA. Its stability was assessed in plasma ex vivo and in mice. Cellular behavior was studied for up to 48 h in LNCaP cells. Biodistribution studies were performed in balb/c mice for up to 48 h. Dynamic (1 h) and static (4 h and 24 h) PET imaging was completed in LNCaP tumor-bearing mice. 64Cu-DOTHA2-PSMA was stable ex vivo in plasma and reached cellular internalization up to 34.1 ± 4.9% injected activity (IA)/106 cells at 48 h post-injection (p.i.). Biodistribution results showed significantly lower uptake in kidneys than 68Ga-PSMA-617, our reference PET tracer (p < 0.001), but higher liver uptake at 2 h p.i. (p < 0.001). PET images showed 64Cu-DOTHA2-PSMA’s highest tumoral uptake at 4 h p.i., with a significant difference between blocked and non-blocked groups from the time of injection to 24 h p.i. The high stability and tumor uptake with a long tumor imaging time window of 64Cu-DOTHA2-PSMA potentially contribute to the prostate cancer theranostic approach and its local recurrence detection.