Prostate-specific Membrane Antigen Positron Emission Tomography Research Articles

The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography

BackgroundMultiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.MethodsWe analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsWe find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.ConclusionsBy co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.

Prostate-specific membrane antigen positron emission tomography in addition to multiparametric magnetic resonance imaging and biopsies to select prostate cancer patients for focal therapy.

To evaluate the additional value of prostate-specific membrane antigen positron emission tomography (PSMA-PET) to conventional diagnostic tools to select patients for hemi-ablative focal therapy (FT). We performed a retrospective analysis on a multicentre cohort (private and institutional) of 138 patients who underwent multiparametric magnetic resonance imaging (mpMRI), PSMA-PET, and systematic biopsies prior to radical prostatectomy between January 2011 and July 2021. Patients were eligible when they met the consensus criteria for FT: PSA <15 ng/mL, clinical/radiological T stage ≤T2b, and International Society of Urological Pathology (ISUP) grade 2-3. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥2, extracapsular extension >0.5 mm or seminal vesicle involvement at final histopathology. The diagnostic accuracy of mpMRI, systematic biopsies and PSMA-PET for csPCa (separate and combined) was calculated within a four-quadrant prostate model by receiver-operating characteristic and 2 × 2 contingency analysis. Additionally, we assessed whether the diagnostic tools correctly identified patients suitable for hemi-ablative FT. In total 552 prostate quadrants were analysed and 272 (49%) contained csPCa on final histopathology. The area under the curve, sensitivity, specificity, positive predictive value and negative predictive value for csPCa were 0.79, 75%, 83%, 81% and 77%, respectively, for combined mpMRI and systematic biopsies, and improved after addition of PSMA-PET to 0.84, 87%, 80%, 81% and 86%, respectively (P < 0.001). On final histopathology 46/138 patients (33%) were not suitable for hemi-ablative FT. Addition of PSMA-PET correctly identified 26/46 (57%) non-suitable patients and resulted in 4/138 (3%) false-positive exclusions. Addition of PSMA-PET to the conventional work-upby mpMRI and systematic biopsies could improve selection for hemi-ablative FT and guide exclusion of patients for whom whole-gland treatments might be a more suitable treatment option.

PSMA PET Guided Salvage Radiotherapy Among Prostate Cancer Patients in the Post-Prostatectomy Setting: A Single Center Post-Hoc Analysis.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) shows improved sensitivity and specificity for detection of locoregional and distant metastatic prostate cancer (PCa) compared to conventional imaging, especially at lower PSA levels as is often the case in the biochemically recurrent (BCR), post radical prostatectomy (RP) setting. Providers are now utilizing PSMA PET findings to guide their salvage radiotherapy (sRT) treatment fields and doses, although it is not well understood how PSMA PET guided sRT impacts patient outcomes. This was a post-hoc analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP. Patients were included in this retrospective study if they initiated sRT within 3 months of PSMA PET, had at least 12 months of follow up after sRT completion, had available sRT treatment details, and did not have distant metastases (DM) by conventional imaging on upfront staging. Patients treated with palliative RT were excluded. BCR following sRT was defined as an increase in PSA of 0.2 ng/ml above the post sRT nadir. Metastasis directed therapy (MDT) was defined as sRT to all PSMA+ N1 and M1 lesions. Baseline patient demographics, PSMA PET findings, sRT & ADT treatment details, and patient outcome data were collected. A total of 176 patients were included in this study. Median time between RP and PSMA PET was 38 months (range 1-329). Median PSA at the time of the PSMA PET was 0.625 ng/mL (range 0.063-35). PSMA PET was positive in 128 patients (73%): 21 (12%) miT+N0M0, 55 (31%) miTxN1M0 and 52 (30%) miTxNxM1 with 19 (11%) miTxNxM1a, 31 (18%) miTxNxM1b, and 2 (1%) miTxNxM1c. Median number of lesions seen on positive PSMA scans was 1 (range 1-8). 39 (22%) patients were subsequently treated with sRT to the prostate bed (PB) only, 59 (34%) to PB + pelvic lymph nodes (PLNs), 33 (19%) to PLNs only, 7 (4%) to PB + PLNs + DM, 7 (4%) to PLNs + DM, and 31 (18%) to DM only. 59 (34%) patients were treated with concurrent ADT at a median duration of 6 months (range 1-39). At a median follow-up of 32 months (range 12-70) after sRT, 80 patients (45%) did not develop BCR or imaging relapse (IR) following sRT, 24 patients (14%) developed BCR but not IR, 1 patient (<1%) developed IR only, and 70 patients (40%) developed both BCR and IR. The median time to BCR and IR following sRT was 15 months (range 1-48) and 19 months (range 6-61), respectively. 1 year post sRT biochemical recurrence free survival was 77%. Of the 83 patients treated with MDT, 32 (39%) did not develop subsequent disease relapse. This post hoc analysis assessed the outcomes of 176 patients treated with PSMA PET guided salvage RT, proving it to be an effective method for treating both pelvic and extrapelvic recurrent PCa. Further investigation is needed to assess the full extent of patient outcomes in this population.

Predictive Value of Genomic Classifier Scores and Transcriptomic Data for Prostate Cancer Distant Metastasis Risk: A Multicenter Retrospective Study.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has a greater specificity and sensitivity for detection of extraprostatic prostate cancer than conventional imaging. The Decipher genomic classifier is an established prognostic biomarker being evaluated for its ability to predict systemic treatment intensification. The relationship between Decipher scores and PSMA-based spread remains unknown, as do differences in transcriptomic patterns of PSMA PET-based spread in the de novo vs. recurrent setting. We retrospectively identified patients who (a) had undergone staging with a PSMA PET prior to treatment or for evaluation of recurrence post-radical prostatectomy (RP) at two institutions and (b) had transcriptomic data available from the Genomics Resource for Intelligent Discovery (GRID) database from either biopsy or RP specimens. We classified the PSMA PET pattern of spread using molecular imaging (mi) staging as localized (miT+N0M0), node-positive (miN1M0), distant metastasis (miM1a-c), or negative/non-diagnostic. We used logistic regression to calculate the odds ratios (OR) with 95% confidence intervals (CI) for distant metastasis risk based on Decipher score both pre-treatment and post-RP. As an exploratory analysis, we compared each of the staging groups for differences in important transcriptomic signatures. Kruskal-Wallis and Pearson chi-squared tests were used for continuous and categorical variables, respectively. A total of 315 patients were included in this analysis (n = 164 pre-treatment, n = 151 post-RP). Eighty PSMA PET scans were negative, while 147 were miT+N0M0, 45 were miN1M0, and 43 were miM1a-c. A higher Decipher score was associated with distant metastasis (miM1a-c) on PSMA PET both pre-treatment (OR 1.3 [95% CI: 1.0-1.7] per 0.1 increase in Decipher score, P = 0.05) and post-RP (OR 1.2 [1.0-1.4] per 0.1 increase in Decipher score, P = 0.04). There were higher TP53 mutation (P = 0.01) and cell cycle progression (P = 0.04) signature scores in miM1a-c patients compared to miN1M0 or miT+N0M0 patients. Basal subtype was more prevalent per PAM50 in miM1a-c or miN1M0 patients (36%) than miT+N0M0 patients (19%, P=0.01). Patients with de novo miN1M0 or miM1a disease (n = 19) had higher Decipher scores (0.85 vs 0.57, P = 0.10) and IFNa response (P = 0.08) than patients with recurrent miN1M0 or miM1a disease (n = 35). Higher Decipher scores were associated with distant metastasis on PSMA PET in both the de novo and recurrent setting. Transcriptomic differences in pathways related to proliferation, p53 status, and PAM50 classification were seen when comparing localized, node-positive, and distant metastatic disease. Patients with de novo miN1M0 or miM1a disease may harbor more aggressive disease than those with miN1M0 or miM1a disease at recurrence.

Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy

Rationale177Lu-PSMA ([177Lu]Lutetium-PSMA-617) therapy is an effective treatment option for patients with prostate specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, but still shows a non-responder rate of approximately 30%. Combination...

Dosimetric Plan Evaluation of Biology Guided Radiotherapy Using [18F]-DCFPyL PSMA Radiotracer in Patients with Prostate Cancer

The X1 system represents a cutting-edge solution in radiotherapy delivery, with its capability to perform Biology Guided Radiotherapy (BgRT). The system utilizes real-time positron emission tomography (PET) signal as biological fiducials to provide tracked dose delivery and is initially available for use with [18F]-Fluorodeoxyglucose (FDG). The aim of this research study is to assess the quality of BgRT treatment plans for prostate cancer using patients' PSMA PET images obtained on the X1 system. Sixteen patients with at least one PET-avid tumor identified on their whole-body diagnostic PSMA PET scan were selected. These patients were scanned on X1 following their diagnostic scan without additional radiotracer administration. Based on the X1 PET images, a BgRT plan was created for each patient, with the prescription dose determined by the location of treatment sites. The planning objectives of organs-at-risk (OARs) were established in accordance with the 2018 Timmerman guidelines. Target coverage objective was the dose covering 95% (D95%) of the planning target volume (PTV) to be higher than 100%. The following parameters were analyzed: PTV D95%, the minimal dose (Dmin) of gross tumor volume (GTV), plan maximum dose (Dmax), conformity index (CI), gradient index (GI), and maximum point dose (D0.03cc) to the nearest OARs. The X1 BgRT planning system also generated dose volume histogram (DVH) bounds, which model variations in BgRT delivery. The low boundary of GTV Dmin, representing the minimum GTV dose in the worst-case scenario, was recorded. BgRT plans were created for all patients, except for one where the target signal was indistinguishable from the bladder. The prescription dose was 2700 cGy or 3000 cGy in 3 fractions for lymph node lesions, 2400 cGy to 3000 cGy in 3 fractions for bone metastasis, and 4500 cGy in 5 fractions for lesions in prostate. All plans met the dose constraints for OARs as per the Timmerman guidelines. The Dmax of all plans was 129.9% ± 6.9% (mean ± standard deviation). The PTV D95% and GTV Dmin were 101.7% ± 1.0% and 111.0% ± 7.6%, respectively. The low boundary of GTV Dmin was 95.9% ± 5.8%. The CI and GI were 1.22 ± 0.11 and 9.40 ± 2.12, respectively. The D0.03cc to nearest OARs was 84.6% ± 25.4%. The estimated treatment time was 699 ± 228 seconds. This study is a pioneering effort to evaluate the quality of BgRT plans for prostate cancer patients using the [18F]-DCFPyL PSMA radiotracer. Our results showed that all BgRT plans met the planning objectives defined in the Timmerman protocol. BgRT with [18F]-DCFPyL represents a promising treatment modality for patients with prostate cancer. Further research is needed to validate this approach, including a comprehensive assessment of the dosimetric and tracking accuracy through physical measurements.

Viability of focal dose escalation to prostate cancer intraprostatic lesions using HDR prostate brachytherapy

This study aimed to determine the viability of focal dose escalation to prostate cancer intraprostatic lesions (IPLs) from multiparametric magnetic resonance (mpMRI) and prostate-specific membrane antigen positron emission tomography (PSMA-PET) images using high-dose-rate (HDR) prostate brachytherapy (pBT). Retrospective data from 20 patients treated with HDR pBT was utilized. The interobserver contouring variability of 5 observers was quantified using the dice similarity coefficient (DSC) and mean distance to agreement (MDA). Uncertainty in propagating IPL contours to trans-rectal ultrasound (TRUS) was quantified using a tissue equivalent prostate phantom. Feasibility of incorporating IPLs into HDR pBT planning was tested on retrospective patient data. The average observer DSC was 0.65 (PSMA-PET) and 0.52 (mpMRI). The uncertainty in propagating IPL contours was 0.6 mm (PSMA-PET), and 0.4 mm (mpMRI). Uncertainties could be accounted for by expanding IPL contours by 2 mm to create IPL PTVs. The mean D98% achieved using HDR pBT was 166% and 135% for the IPL and IPL PTV contours, respectively. Focal dose escalation to IPLs identified on either PSMA-PET or mpMRI is viable using TRUS-based HDR pBT. Utilizing HDR pBT allows dose escalation of up to 166% of the prescribed dose to the prostate.

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy

AimThe optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding.MethodsThis retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes.ResultsThree hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS.ConclusionFavorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

European Association of Nuclear Medicine Focus 5: Consensus on Molecular Imaging and Theranostics in Prostate Cancer

BackgroundIn prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications. ObjectiveWe aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa. Design, setting, and participantsThe results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting. Outcome measurements and statistical analysisForty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores. Results and limitationsAfter two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy. ConclusionsThere was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community. Patient summaryThere are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.

Oligometastatic Prostate Cancer Treated with Stereotactic Body Radiation Therapy: The Role of Three-Dimensional Tumour Volume in Patient Survival

AimsThe definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy. Materials and methodsThis monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan–Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes. ResultsBetween 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm3, with a range from 0.01 to 233.4 cm3. In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4–93.4), 74.9% (95% confidence interval 66.1–81.7) and 57.2% (95% confidence interval 45.8–67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06–3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01–3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm3 (hazard ratio 2.37, 95% confidence interval 1.34–4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4–70.9), 31.5% (95% confidence interval 22.8–40.6) and 24.7% (95% confidence interval 16.0–34.3). ConclusionsThis study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome.

Using prostate-specific membrane antigen positron-emission tomography to guide prostate biopsies and stage men at high-risk of prostate cancer.

To assess whether a diagnostic pathway in which prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is used as a single imaging modality is feasible to guide targeted biopsy and to detect clinically significant prostate cancer (csPCa) in biopsy-naïve men at high-risk of disease. A total of 60 men with a prostate-specific antigen (PSA) level of 20-50 ng/mL underwent 18 F-PSMA(DCFPyL)-PET/CT prior to prostate biopsies in this prospective, non-randomised cohort study. Magnetic resonance imaging (MRI) was not performed. Using a 12-segment mapping model of the prostate, PSMA-guided targeted biopsy was performed along with systematic biopsies. The detection rate of PCa and csPCa was assessed for combined systematic and targeted biopsy, and for targeted biopsy only. csPCa was defined as a prostate biopsy with an International Society of Uropathology (ISUP) Grade Group ≥2. Lesions suspicious for PCa in the prostate gland were observed on all PSMA-PET/CTs. A total of 27/60 men (45%) already had metastatic disease on staging 18 F-PSMA(DCFPyL)-PET/CT. Combined PSMA-guided targeted and systematic biopsies detected PCa in 56/60 (93.3%) patients, with 52 of them (92.9%) having csPCa. PSMA-guided targeted biopsy, if performed as a single biopsy modality, identified PCa in 52/60 men (86.7%) and in 27/27 men (100%) men with metastases. Using the PSMA-driven single imaging modality pathway in biopsy-naïve men at high-risk of PCa, a substantial number of diagnostic MRI scans could be avoided while at the same time obtaining adequate targeting, staging, and detection of csPCa.

Application of next-generation imaging in biochemically recurrent prostate cancer.

Biochemical recurrence (BCR) following primary interventional treatment occurs in approximately one-third of patients with prostate cancer (PCa). Next-generation imaging (NGI) can identify local and metastatic recurrence with greater sensitivity than conventional imaging, potentially allowing for more effective interventions. This narrative review examines the current clinical evidence on the utility of NGI for patients with BCR. A search of PubMed was conducted to identify relevant publications on NGI applied to BCR. Given other relevant recent reviews on the topic, this review focused on papers published between January 2018 to May 2023. NGI technologies, including positron emission tomography (PET) radiotracers and multiparametric magnetic resonance imaging, have demonstrated increased sensitivity and selectivity for diagnosing BCR at prostate-specific antigen (PSA) concentrations <2.0 ng/ml. Detection rates range between 46% and 50%, with decreasing PSA levels for choline (1-3 ng/ml), fluciclovine (0.5-1 ng/ml), and prostate-specific membrane antigen (0.2-0.49 ng/ml) PET radiotracers. Expert working groups and European and US medical societies recommend NGI for patients with BCR. Available data support the improved detection performance and selectivity of NGI modalities versus conventional imaging techniques; however, limited clinical evidence exists demonstrating the application of NGI to treatment decision-making and its impact on patient outcomes. The emergence of NGI and displacement of conventional imaging may require a reexamination of the current definitions of BCR, altering our understanding of early recurrence. Redefining the BCR disease state by formalizing the role of NGI in patient management decisions will facilitate greater alignment across research efforts and better reflect the published literature.

Clinical impact of Prostate-Specific Membrane Antigen Positron Emission Tomography (PET) on intensification or deintensification of advanced renal cell carcinoma management

PurposeThere is an emerging role of the use of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in renal cell carcinoma. Herein, we report our experience in use of PSMA PET in recurrent or metastatic renal cell carcinoma (RCC).MethodsA retrospective analysis of all patients who underwent PSMA PET for suspected recurrent or de-novo metastatic RCC between 2015 and 2020 at three institutions was performed. The primary outcome was change in management (intensification or de-intensification) following PSMA PET scan. Secondary outcomes included histopathological correlation of PSMA avid sites, comparison of sites of disease on PSMA PET to diagnostic CT and time to systemic treatment.Results

Presurgical 68Ga-PSMA-11 Positron Emission Tomography for Biochemical Recurrence Risk Assessment: A Follow-up Analysis of a Multicenter Prospective Phase 3 Imaging Trial

BackgroundIn the initial staging of patients with high-risk prostate cancer (PCa), prostate-specific membrane antigen positron emission tomography (PSMA-PET) has been established as a front-line imaging modality. The increasing number of PSMA-PET scans performed in the primary staging setting might be associated with decreases in biochemical recurrence (BCR)-free survival (BCR-FS). ObjectiveTo assess the added prognostic value of presurgical PSMA-PET for BCR-FS compared with the presurgical Cancer of the Prostate Risk Assessment (CAPRA) and postsurgical CAPRA-Surgery (CAPRA-S) scores in patients with intermediate- to high-risk PCa treated with radical prostatectomy (RP) and pelvic lymph node dissection. Design, setting, and participantsThis is a follow-up study of the surgical cohort evaluated in the multicenter prospective phase 3 imaging trial (n = 277; NCT03368547, NCT02611882, and NCT02919111). Outcome measurements and statistical analysisEach 68Ga-PSMA-11-PET scan was read by three blinded independent readers. PSMA-PET prostate uptake (low vs high), PSMA-PET extraprostatic disease (N1/M1), and CAPRA and CAPRA-S scores were used to assess the risk of BCR. Patients were followed after RP by local investigators using electronic medical records. BCR was defined by a prostate-specific antigen (PSA) level increasing to ≥0.2 ng/ml after RP or initiation of PCa-specific secondary treatment (>6 mo after surgery). Univariate and multivariable Cox models, and c-statistic index were performed to assess the prognostic value of PSMA-PET and for a comparison with the CAPRA and CAPRA-S scores. Results and limitationsFrom December 2015 to December 2019, 277 patients underwent surgery after PSMA-PET. Clinical follow-up was obtained in 240/277 (87%) patients. The median follow-up after surgery was 32.4 (interquartile range 23.3–42.9) mo. Of 240 BCR events, 91 (38%) were observed. PSMA-PET N1/M1 was found in 41/240 (17%) patients. PSMA-PET prostate uptake, PSMA-PET N1/M1, and CAPRA and CAPRA-S scores were significant univariate predictors of BCR. The addition of PSMA-PET N1/M1 status to the presurgical CAPRA score improved the risk assessment for BCR significantly in comparison with the presurgical CAPRA score alone (c-statistic 0.70 [0.64–0.75] vs 0.63 [0.57–0.69]; p < 0.001). The C-index of the postsurgical model utilizing the postsurgical CAPRA-S score alone was not significantly different from the presurgical model combining the presurgical CAPRA score and PSMA-PET N1/M1 status (p = 0.19). ConclusionsPresurgical PSMA-PET was a strong prognostic biomarker improving BCR-FS risk assessment. Its implementation in the presurgical risk assessment with the CAPRA score improved the performance and reduced the difference with the reference standard (postsurgical CAPRA-S score). Patient summaryThe use prostate-specific membrane antigen positron emission tomography improved the assessment of biochemical recurrence risk in patients with intermediate- and high-risk prostate cancer who were treated with radical prostatectomy and pelvic lymph node dissection.

Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

Stereotactic Body Radiation Therapy Salvage for Lymph Node Recurrent Prostate Cancer in the Era of PSMA PET Imaging.

Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.

PSMA PET guided salvage radiotherapy among patients with prostate cancer in the post-prostatectomy setting: A single center post-hoc analysis.

5009 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) shows improved sensitivity and specificity for detection of locoregional and distant metastatic prostate cancer (PCa) compared to conventional imaging, especially at lower PSA levels as is often the case in the biochemically recurrent (BCR), post radical prostatectomy (RP) setting. Providers are now utilizing PSMA PET findings to guide their salvage radiotherapy (sRT) treatment fields and doses, although it is not well understood how PSMA PET guided sRT impacts patient outcomes. Methods: This was a post-hoc analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP. Patients were included in this retrospective study if they initiated sRT within 3 months of PSMA PET, had at least 12 months of follow up after sRT completion, had available sRT treatment details, and did not have distant metastases (DM) by conventional imaging on upfront staging. Patients treated with palliative RT were excluded. BCR following sRT was defined as an increase in PSA of 0.2 ng/ml above the post sRT nadir. Metastasis directed therapy (MDT) was defined as sRT to all PSMA+ N1 and M1 lesions. Baseline patient demographics, PSMA PET findings, sRT &amp; ADT treatment details, and patient outcome data were collected. Results: 176 patients were included in this study. Median time between RP and PSMA PET was 38 months (range 1-329). Median PSA at the time of the PSMA PET was 0.625 ng/mL (range 0.063-35). PSMA PET was positive in 128 patients (73%): 21 (12%) miT+N0M0, 55 (31%) miTxN1M0 and 52 (30%) miTxNxM1 with 19 (11%) miTxNxM1a, 31 (18%) miTxNxM1b, and 2 (1%) miTxNxM1c. Median number of lesions seen on positive PSMA scans was 1 (range 1-8). 39 (22%) patients were subsequently treated with sRT to the prostate bed (PB) only, 59 (34%) to PB + pelvic lymph nodes (PLNs), 33 (19%) to PLNs only, 7 (4%) to PB + PLNs + DM, 7 (4%) to PLNs + DM, and 31 (18%) to DM only. 59 (34%) patients were treated with concurrent ADT at a median duration of 6 months (range 1-39). At a median follow-up of 32 months (range 12-70) after sRT, 80 patients (45%) did not develop BCR or imaging relapse (IR) following sRT, 24 patients (14%) developed BCR but not IR, 1 patient (&lt;1%) developed IR only, and 70 patients (40%) developed both BCR and IR. The median time to BCR and IR following sRT was 15 months (range 1-48) and 19 months (range 6-61), respectively. 1 year post sRT biochemical recurrence free survival was 77%. Of the 83 patients treated with MDT, 32 (39%) did not develop subsequent disease relapse. Conclusions: This post-hoc analysis assessed the outcomes of 176 patients treated with PSMA PET guided salvage RT, proving it to be an effective method for treating both pelvic and extrapelvic recurrent PCa. Further investigation is needed to assess the full extent of patient outcomes in this population.

Identification of the Optimal Candidates for Nodal Staging with Extended Pelvic Lymph Node Dissection Among Prostate Cancer Patients Who Underwent Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography. External Validation of the Memorial Sloan Kettering Cancer Center and Briganti Nomograms and Development of a Novel Tool

BackgroundAlthough the therapeutic role of extended pelvic lymph node dissection (ePLND) in patients with prostate cancer (PCa) is still under debate, this procedure is recommended for staging purposes in selected cases. Nomograms for predicting lymph node invasion (LNI) do not account for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, which is characterized by a high negative predictive value for nodal metastases. ObjectiveTo externally validate models predicting LNI in patients with miN0M0 PCa at PSMA PET and to develop a novel tool in this setting. Design, setting, and participantsOverall, 458 patients with miN0M0 disease undergoing radical prostatectomy (RP) and ePLND at 12 centers between 2017 and 2022 were identified. Outcome measurements and statistical analysesAvailable tools were externally validated using calibration plots, the area under the receiver operating characteristic curve (AUC), and decision curve analyses to assess calibration, discrimination, and the net benefit. A novel coefficient-based model was developed, internally validated, and compared with available tools. Results and limitationsOverall, 53 patients (12%) had LNI. The AUC was 69% for the Briganti 2012, 64% for the Briganti 2017, 73% for the Briganti 2019, and 66% for the Memorial Sloan Kettering Cancer Center nomogram. Multiparametric magnetic resonance imaging stage, biopsy grade group 5, the diameter of the index lesion, and the percentage of positive cores at systematic biopsy were independent predictors of LNI (all p ≤ 0.04). Internal cross-validation confirmed a coefficient-based model with AUC of 78%, better calibration, and a higher net benefit in comparison to the other nomograms assessed. Use of a 5% cutoff would have spared 47% ePLND procedures (vs 13% for the Briganti 2019 nomogram) at the cost of missing only 2.1% LNI cases . The lack of central review of imaging and pathology represents the main limitation. ConclusionsTools for predicting LNI are associated with suboptimal performance for men with miN0M0 PCa. We propose a novel model for predicting LNI that outperforms available tools in this population. Patient summaryTools currently used to predict lymph node invasion (LNI) in prostate cancer are not optimal for men with negative node findings on PET (positron emission tomography) scans, leading to a high number of unnecessary extended pelvic lymph node dissection (ePLND) procedures. A novel tool should be used in clinical practice to identify candidates for ePLND to reduce the risk of unnecessary procedures without missing LNI cases.

Do bone scans over-stage disease compared to PSMA PET? An international multicenter retrospective study with blinded independent readers.

5011 Background: PSMA positron emission tomography (PET) has a higher accuracy than computed tomography (CT) and bone scans to stage patients with prostate cancer. However, we do not understand how to apply clinical trial data based on conventional imaging to patients staged using PSMA PET. Therefore, we aim to evaluate the ability of bone scans to detect osseous metastases using PSMA PET as a reference standard. Methods: In this multicenter retrospective diagnostic study, 167 patients with prostate cancer, who were imaged with bone scan and PSMA PET performed within 100 days were included for analysis. Each study was interpreted by three blinded readers, and the results of the PSMA PET were used as the reference standard. Endpoints were positive predictive value (PPV), negative predictive value (NPV) and specificity for bone scans. Additionally, inter-reader reproducibility, positivity rate, uptake on PSMA PET, and number of lesions were evaluated. Results: 167 patients were included in the study, with 77 at initial staging, 60 in the BCR/CSPC setting and 30 in the CRPC setting. BS findings for metastatic disease validated by PSMA PET were tabulated. In all patients, the PPV, NPV and specificity for bone scans were 0.73 [0.61,0.82], 0.82 [0.74,0.88] and 0.82 [0.74,0.88]. In patients at initial staging, the PPV, NPV and specificity for bone scans were 0.43 [0.26,0.63], 0.94 [0.85,0.98], and 0.80 [0.68,0.88]. At initial staging 13/23 (57%) of positive bone scans were false positive. Inter-reader agreement for bone disease was moderate for bone scans (Fleiss k, 0.51) and substantial for the PSMA PET reference standard (Fleiss k, 0.80). Conclusions: In this multicenter retrospective study, the PPV of bone scans was low in patients at initial staging with majority of positive bone scans being false positives. This suggests that a large proportion of patients considered low volume metastatic by bone scan actually have localized disease. [Table: see text]

Salvage radiotherapy is effective in patients with PSMA-PET-negative biochemical recurrence- results of a retrospective study

Background/PurposeThe present study aimed to assess whether SRT to the prostatic fossa should be initiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and MethodsThis retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradiation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint. ResultsThe median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not multivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64–3.32). The 3-year BPFS in PET-negative cases was significantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) ≥ 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023–1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139–0.826, p = 0.017) remained significant. ConclusionTo our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU recommendation to initiate SRT in a timely manner after detecting BR in PET negative patients.