Total Lesion PSMA Research Articles

Primary tumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET/CT for the prediction of biochemical recurrence in prostate cancer

PurposeThe aim of this study is to research the value of the texture analysis of primary tumors in pre-treatment [68Ga]Ga-PSMA PET in the prediction of the development of biochemical recurrence (BCR) in prostate cancer patients who underwent definitive therapies. Methods51 patients with prostate adenocarcinoma who had a pre-treatment [68Ga]Ga-PSMA-11 PET/CT and underwent definitive radiotherapy (RT) or radical prostatectomy (RP) were included in the study. Demographics, clinicopathologic features, the presence of BCR, and the last follow-up date of patients were recorded. Textural and conventional PET parameters (maximum standardized uptake value (SUVmax), total lesion-PSMA (TL-PSMA), and PSMA-tumor volume (PSMA-TV)) were obtained from PET/CT images using LifeX program. Parameters were grouped using the Youden index in ROC analysis. Factors predicting the BCR were determined using Cox regression analyses. Results29 (56.9%) patients have received primary curative RT, while the remaining 22 (43.1%) patients have undergone RP. 5 (22.7%) patients with RP and 3 (10.3%) patients with curative RT have developed BCR during the follow-up. INTENSITY-BASED-minimum grey level (P=.050), GLCM-sum variance (P=.019), and GLCM-cluster prominence (P=.050) were associated with BCR in univariate analysis. INTENSITY-BASED-minimum grey level (P=.009) and GLCM-sum variance (P=.004) were found as independent predictors of BCR in the multivariate analysis. ConclusionTumor heterogeneity on pre-treatment [68Ga]Ga-PSMA PET is associated with a high risk of BCR in PCa patients who underwent definitive therapies.

Analysis of Molecular Imaging and Laboratory Baseline Biomarkers in PSMA-RLT: Whole-Body Total Lesion PSMA (TLP) Predicts Overall Survival.

The aim of this retrospective study was to identify pre-therapeutic predictive laboratory and molecular imaging biomarkers for response and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Pre-therapeutic laboratory and [68Ga]Ga-PSMA-11 PET/CT data of n = 102 mCRPC patients receiving [177Lu]Lu-PSMA-617 RLT within a prospective registry (REALITY Study, NCT04833517) were analyzed including laboratory parameters such as alkaline phosphatase (ALP), prostate-specific antigen (PSA), gamma glutamyl transferase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neuron specific enolase (NSE), hemoglobin (Hb), and imaging parameters such as maximum standardized uptake value of the tumor lesions (SUVmax), the mean standardized uptake value of all tumor lesions (SUVmean), the whole-body molecular tumor volume (MTV), and the whole-body total lesion PSMA (TLP). Mann-Whitney U test, univariate and multivariable Cox-regression were performed to test for association of the parameters with response and OS. The SUVmean of all lesions was significantly different between responders and non-responders (SUVmean responders 8.95 ± 2.83 vs. non-responders 7.88 ± 4.46, p = 0.003), whereas all other tested biochemical and imaging parameters did not reveal significant differences. Hb and the molecular imaging parameters MTV and TLP showed a significant association with OS (p = 0.013, p = 0.005; p = 0.009) in univariant Cox regression; however, only TLP remained significant in multivariable analysis (Hazard ratio 1.033, p = 0.009). This study demonstrates a statistically significant association between the quantitative PET/CT imaging parameter SUVmean and PSA response, as well as between the baseline TLP and OS of mCRPC patients undergoing RLT.

A Comprehensive Analysis of Volumetric 68Ga-PSMA PET/CT Parameters, Clinical and Histopathologic Features: Evaluation of the Predictive Role.

To evaluate the relationships between volumetric 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) parameters, Gleason score (GS), prostate-specific antigen (PSA) levels, histopathological data, and metastatic status in newly diagnosed prostate cancer (PCa) patients and to assess the predictive factors for progression despite treatment. A total of 78 newly diagnosed patients with PCa who had 68Ga-PSMA PET/CT scans were included. Clinical parameters, histopathological data, and metastatic status were documented, and volumetric parameters of primary prostate lesions were measured. All obtained data were compared statistically. Primary prostate tumor maximum standardized uptake value (SUVmax) and GS were significantly related to serum PSA levels (p<0.05). PSA levels and SUVmax values were significantly higher in patients with lymph node metastases than in those without. GS was found to be significantly increased in metastatic patients. PSMA-derived tumor volume (PSMA-TV) and total lesion PSMA of the primary lesion had a significant relationship with PSA value, GS, and regional lymph node metastases. Receiver operating characteristic analysis, conducted in patients with metastatic and localized disease, identified the cutoff value for SUVmax as 10.85. According to the results of the logistic regression analysis, PSMA-TV was found to be a predictive factor for progression despite treatment. 68Ga-PSMA PET/CT remains an invaluable imaging modality that should be considered first in PCa staging because of its superior compatibility with clinical and histopathologic data. The importance of this method goes beyond diagnostic accuracy; it also extends into the predictive domain, where the PSMA-TV value of primary prostate lesions is a potential predictor of treatment efficacy. This information is valuable for personalizing patient treatment, improving prognostic accuracy, and predicting clinical outcomes.

Utility of PSMA-PET derived volumetric parameters in initial risk stratification and prediction of prostate cancer metastasis - a head-to-head comparison of the radiotracers 18F-PSMA-1007 and 68Ga-PSMA-11.

This study aimed to explore and compare the utility of baseline 18F-PSMA-1007 and 68Ga-PSMA-11 PET/computed tomography (CT) derived volumetric parameters in initial risk stratification and prediction of prostate cancer (PCa) metastasis. Forty treatment-naïve, biopsy-proven intermediate-/high-risk PCa patients were prospectively recruited. Each patient underwent PET/CT with 68Ga-PSMA-11 and 18F-PSMA-1007 (within 2 weeks). The maximum and mean standardized uptake values (SUVmax and SUVmean) of primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) were measured. PSMA-TVp and TL-PSMAp (with both radiotracers) mostly exhibited moderate-to-strong correlation with Gleason score, serum prostate-specific antigen level and clinical tumor stage (Spearman ρ = 0.361-0.783, P-values ≤0.022). Primary tumor SUVmax values were similar across initial risk categories. PSMA-TVp and TL-PSMAp, however, were significantly higher in high-risk PCa compared to intermediate-risk PCa (P-values ≤0.001). Receiver operating characteristic (ROC) curve analysis revealed that F-PSMA-TVp, Ga-PSMA-TVp, F-TL-PSMAp, and Ga-TL-PSMAp (optimal cutoff values of 20.9, 23.4, 142.5, and 144.8, respectively) could effectively differentiate high-risk from intermediate-risk PCa [area under the ROC curve (AUCs) 0.859-0.898, P-values <0.001] with high sensitivity (~68.8-75%) and excellent specificity (100%). PSMA-TVp and TL-PSMAp (with both radiotracers) could predict presence of regional and extraregional nodal metastasis (AUCs 0.703-0.801, P-values ≤0.03) with moderate sensitivity (~47.8-70.6%) and excellent specificity (~82.6-94.1%). Our results suggest that baseline PSMA-PET primary tumor volumetric parameters provide a noninvasive, objective, and accurate index for initial risk stratification and can predict presence of regional and extraregional nodal metastasis in PCa patients. Larger studies are warranted to evaluate their incremental role over conventional parameters.

Baseline Ga-68 PSMA PET-Derived Primary Tumor Parameters in Patients with Prostate Cancer and Their Association with Clinical Risk Stratification and Clinicopathologic Features

Abstract Aim This article evaluates whether parameters derived from the gallium-68-labeled prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging studies of primary prostate cancer (PCa) lesions were associated with Gleason score (GS), D'Amico risk class, Candiolo nomograms, and the metastatic status of the disease. Methods We retrospectively evaluated newly diagnosed PCa patients who underwent 68Ga-PSMA PET/CT before therapy. Age, baseline serum prostate-specific antigen (PSA), and metastatic status were recorded. Maximal standardized uptake value (SUVmax), mean SUV (SUVmean), total lesion PSMA (TL-PSMA), and PSMA-derived tumor volume (PSMA-TV) were analyzed. The patients were grouped according to GS (GS ≤ 7 and GS ≥ 8), D'Amico risk classes (low intermediate and high-risk), and also based on their results with the Candiolo nomogram which normally creates five risk classes. For Candiolo classes, very-low risk and low-risk patients were pooled into the low-risk Candiolo (LRC) group, high and very high-risk patients were pooled into the high-risk Candiolo (HRC) group. The intermediate-risk Candiolo group was utilized as-is (IRC). Results Mean age was 67 ± 8 years, median PSA value was 14.3 (3–211). There were 82 patients with GS ≤ 7 and 38 patients with GS ≥ 8; intermediate D'Amico class comprised 32 patients, while the high D'Amico class comprised 88 patients. For Candiolo, there were 23 LRC, 40 IRC, and 57 HRC patients. PSMA-positive metastases were detected in 44 (36.7%) patients. The SUVmean, SUVmax, PSMA-TV, and TL-PSMA values of the primary tumor demonstrated significant differences when compared according to classifications for GS, D'Amico, LRC versus HRC, and metastatic versus nonmetastatic patients. Of note, TL-PSMA was the only parameter that varied significantly among all risk groups. Conclusion Primary tumor parameters obtained from baseline 68Ga-PSMA PET/CT are useful to distinguish PCa patients in terms of GS, D'Amico, Candiolo nomogram, and metastatic states. TL-PSMA appears to be the best parameter as it is the only parameter that can distinguish all risk groups from each other.

Towards improved diagnosis: radiomics and quantitative biomarkers in 18 F-PSMA-1007 and 18 F-fluorocholine PET/CT for prostate cancer recurrence.

This study compared the radiomic features and quantitative biomarkers of 18 F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18 F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUV mean , PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUV max value was significantly higher for 18 F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P < 0.001). There were statistically significant differences in median SUV mean , TL-PSMA/FCH, and PSMA/FCH-TV between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P < 0.001). The correlation between SUV mean /SUV max and PSA level was moderate, both for 18 F-PSMA ( r = 0.44, P < 0.001; r = 0.44, P < 0.001) and FCH ( r = 0.35, P < 0.001; r = 0.41, P < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18 F-PSMA ( r = 0.56, P < 0.001; r = 0.57, P < 0.001) and FCH ( r = 0.49, P < 0.001; r = 0.51, P < 0.001). While patients who received hormone therapy showed higher median SUV max values for both radiotracers compared with those who did not, the difference was statistically significant only for 18 F-PSMA ( P < 0.05). Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18 F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.

Baseline PSMA PET/CT as a predictive biomarker for toxicity and patient-reported outcomes in mCRPC patients undergoing 177Lu-PSMA radioligand therapy.

e17058 Background: The phase III VISION trial demonstrated that 177Lu-PSMA-617 (PSMA-RLT) prolonged overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Common side effects of PSMA-RLT include xerostomia, bone pain, and myelosuppression. The objective of this study is to evaluate the role of baseline PSMA PET/CT (bPET) in predicting hematologic toxicity and patient-reported outcomes in mCRPC patients undergoing PSMA-RLT. Methods: Patients treated with 177Lu-PSMA-617 in the Expanded Access Program at UCLA with available bPET, toxicity data, and patient-reported outcomes (BPI, FACT-P, and Xerostomia Questionnaire) were included in this retrospective analysis. TRAQinform IQ technology (AIQ Solutions-Madison, WI) was used to conduct region of interest (ROI)-based analyses at bPET. SUVmean, SUVmax, volume (cm3), and total lesion PSMA (TLP; SUVmean x volume) of the whole-body tumor burden, healthy bone, and the salivary glands were extracted. We evaluated the following associations: 1) Whole-body tumor parameters on bPET with time to worsening of FACT-P scores (defined as a decrease of &gt;10 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 2) Healthy bone parameters on bPET with time to worsening of BPI Pain Severity and Pain Interference scores (defined as a 30% increase or at least 2 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 3) Salivary gland parameters on bPET with Xerostomia Questionnaire scores (Mixed-effect linear regression model). Results: 61 mCRPC patients were included. When evaluating associations between healthy bone SUVmean, SUVmax, and TLP with time to first occurrence of Grade 3 or 4 hematologic toxicity, baseline hemoglobin was associated with a longer time to first occurrence (HR = 0.61, p = 0.005; HR = 0.59, p = 0.002; HR = 0.62, p = 0.005 respectively). When evaluating associations between bPET and time to worsening of FACT-P scores, whole-body tumor SUVmean, SUVmax, and TLP were associated with a longer time to worsening (HR = 0.74, p = 0.033; HR = 0.82, p = 0.01; HR = 0.91, p = 0.028 respectively). When evaluating associations between salivary gland SUVmean, volume, SUVmax, and TLP with Xerostomia Questionnaire scores, the number of cycles was associated with higher scores (mean estimate: 0.63, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.63, p = 0.003 respectively). Conclusions: In this retrospective analysis of 61 mCRPC patients treated with PSMA-RLT, bPET parameters were generally not predictive of hematologic toxicity or patient-reported outcomes. Of note, whole-body tumor SUV was associated with a longer time to worsening of FACT-P scores. Validation in a larger, prospective cohort is warranted.

Prostate-specific membrane antigen-PET/CT may result in stage migration in prostate cancer: performances, quantitative analysis, and potential criticism in the clinical practice.

The early detection of prostate cancer (PCa) metastatic disease with PET imaging leads to stage migration and change of disease management. We aimed to assess the impact on clinical management deriving from prostate-specific membrane antigen (PSMA) imaging with a digital PET/CT during the routine application in the staging and restaging process of PCa. Eighty consecutive PCa patients underwent 18F-PSMA-1007. Digital PET/CT were retrospectively evaluated and discussed with oncologists to evaluate the impact on clinical management. Performances analysis, correlation among variables also considering semiquantitative parameters have been conducted. In the whole group of 80 patients at staging (N = 31) and restaging (N = 49), the detection rate of PSMA PET was 85% for all lesions. At staging, the performance analysis resulted in sensitivity 77.6%, specificity 89.5%, negative predictive value (NPV) 77.6%, positive predictive value (PPV) 89.5%, accuracy 85.7%, and area under curve (AUC) 0.87%. The performance of restaging PET in the group of patients with PSA values <1 ng/ml resulted in the following values: sensitivity 66.7%, specificity 92.9%, NPV 85.7%, PPV 81.3%, accuracy 82.6%, and AUC 0.79. Semiquantitative analysis revealed a mean value of SUVmax, metabolic tumor volume, and total lesion PSMA expression with differences in patients with high risk compared to low intermediate. At restaging PET, semiquantitative values of patients with total prostate specific antigen (tPSA) ≤ 1 ng/ml were significantly less than those of the tPSA > 1 ng/ml. A significant impact on clinical management was reported in 46/80 patients (57.5%) based on PSMA PET findings at staging and restaging. Although PSMA-PET provides optimal performances, its current role in redefining a better staging should be translated in the current clinical scenario about potential improvement in clinical/survival outcomes.

Predictive significance of intraprostatic volumetric parameters derived from early and standard time 68Ga-PSMA PET/CT images in newly diagnosed prostate cancer patients.

To investigate the relationship between intraprostatic 68Ga-prostate-specific membrane antigen (PSMA) uptake values and volumetric parameters derived from early pelvic and standard-time whole-body 68Ga-PSMA PET/computed tomography (CT) images in untreated prostate cancer (PCa) patients, and to assess the predictive significance of these data in relation to disease prognosis, comparing them with the Gleason score, clinical risk classification and the presence of metastatic disease detected in 68Ga-PSMA PET/CT imaging. Eighty-one newly diagnosed PCa patients underwent early phase pelvic imaging at the 5th minute and standard time whole-body imaging at the 60th minute. Various threshold values were used in intraprostatic delineations to compute maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), intraprostatic PSMA tumor volume and intraprostatic total lesion PSMA uptake. Correlations between early and standard time measurements, as well as changes in SUV parameters over time, were examined. The association of these values with Gleason score, clinical risk status (National Comprehensive Cancer Network), and metastatic disease was explored. SUVmax measurements from both early and standard time images distinguished all three groups (clinical risk scores, Gleason score and metastatic group), with standard imaging demonstrating statistical superiority in receiver operating characteristic analyses. Strong correlations were observed between early and standard-time PET parameters. Changes in intraprostatic SUVmax and SUVmean values over time did not exhibit predictive value. Although intraprostatic PSMA PET parameters generally aligned at both early and standard times, parameters obtained from standard time images showed more robust correlations with clinical risk scores, Gleason score and metastasis status in newly diagnosed, untreated PCa patients.

Prognostic Performance of RECIP 1.0 Based on [18F]PSMA-1007 PET in Prostate Cancer Patients Treated with [177Lu]Lu-PSMA I&T.

In metastatic castration-resistant prostate cancer (mCRPC) patients treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), the recently proposed criteria for evaluating response to PSMA PET (RECIP 1.0) based on 68Ga- and 18F-labeled PET agents provided prognostic information in addition to changes in prostate-specific antigen (PSA) levels. Our aim was to evaluate the prognostic performance of this framework for overall survival (OS) in patients undergoing RLT and imaged with [18F]PSMA-1007 PET/CT and compare the prognostic performance with the PSA-based response assessment. Methods: In total, 73 patients with mCRPC who were scanned with [18F]PSMA-1007 PET/CT before and after 2 cycles of RLT were retrospectively analyzed. We calculated the changes in serum PSA levels (ΔPSA) and quantitative PET parameters for the whole-body tumor burden (SUVmean, SUVmax, PSMA tumor volume, and total lesion PSMA). Men were also classified following the Prostate Cancer Working Group 3 (PCWG3) criteria for ΔPSA and RECIP 1.0 for PET imaging response. We performed univariable Cox regression analysis, followed by multivariable and Kaplan-Meier analyses. Results: Median OS was 15 mo with a median follow-up time of 14 mo. Univariable Cox regression analysis provided significant associations with OS for ΔPSA (per percentage, hazard ratio [HR], 1.004; 95% CI, 1.002-1.007; P < 0.001) and PSMA tumor volume (per unit, HR, 1.003; 95% CI, 1.000-1.005; P = 0.03). Multivariable Cox regression analysis confirmed ΔPSA (per percentage, HR, 1.004; 95% CI, 1.001-1.006; P = 0.006) as an independent prognosticator for OS. Kaplan-Meier analyses provided significant segregation between individuals with versus those without any PSA response (19 mo vs. 14 mo; HR, 2.00; 95% CI, 0.95-4.18; P = 0.04). Differentiation between patients with or without progressive disease (PD) was also feasible when applying PSA-based PCWG3 (19 mo vs. 9 mo for non-PD and PD, respectively; HR, 2.29; 95% CI, 1.03-5.09; P = 0.01) but slightly failed when applying RECIP 1.0 (P = 0.08). A combination of both response systems (PCWG3 and RECIP 1.0), however, yielded the best discrimination between individuals without versus those with PD (19 mo vs. 8 mo; HR, 2.78; 95% CI, 1.32-5.86; P = 0.002). Conclusion: In patients with mCRPC treated with RLT and imaged with [18F]PSMA-1007, frameworks integrating both the biochemical (PCWG3) and PET-based response (RECIP 1.0) may best assist in identifying subjects prone to disease progression.

Predictive value of volumetric parameters based on 18F-PSMA-1007 PET/CT for prostate cancer metastasis.

To explore the value of 18F-labeled prostate-specific membrane antigen (PSMA-1007) positron emission tomography (PET)/computed tomography (CT), the maximum standardized uptake value (SUVmax) of the primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) for predicting prostate cancer (PCa) metastasis and follow-up evaluation in primary PCa lesions. 18F-PSMA-1007 PET/CT data of 110 consecutive newly diagnosed PCa patients were retrospectively analyzed. Patients were divided into non-metastatic, oligometastatic, and extensive metastatic groups. The predictive power was assessed using the receiver operating characteristic curve. Multi-group one-way analysis of variance and post-hoc tests were used to compare the groups. Patients were monitored post-therapy to evaluate treatment effectiveness. Among the 110 patients, 66.4% (73) had metastasis (29 oligometastatic, 44 extensive metastasis). AUCs for Gleason score (GS), total prostate-specific antigen(TPSA), SUVmax, TL-PSMAp, and PSMA-TVp were 0.851, 0.916, 0.834, 0.938, and 0.923, respectively. GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp were significantly different among the groups. In the post-hoc tests, differences in GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp between the non-metastatic and oligometastatic groups and non-metastatic and extensive metastatic groups were significant (P<0.010). Differences in TL-PSMAp and PSMA-TVp between oligometastatic and extensive metastatic groups were significant (P=0.039 and 0.015, respectively), while those among GS, TPSA, and SUVmax were not. TL-PSMAp and PSMA-TVp distinguished between oligometastatic and extensive metastases, but GS, TPSA, and SUVmax did not. In individuals with oligometastasis, the implementation of active treatment for both primary and metastatic lesions may result in a more favorable prognosis. 18F-PSMA-1007 PET/CT volumetric parameters PSMA-TVp and TL-PSMAp can predict PCa oligometastasis.

Pre-treatment 68 Ga-PSMA-11 PET/CT Prognostic Value in Predicting Response to 177Lu-PSMA-I&T Therapy and Patient Survival

PurposeTo assess the prognostic value of pre-treatment [68Ga]Ga-PSMA-11 PET/CT and other baseline clinical characteristics in predicting prostate cancer (PCa) patients response to [177Lu]Lu-PSMA (PSMA-I&T), as well as patient survival.ProceduresIn this retrospective study, 81 patients who received [177Lu]Lu-PSMA-I&T between October 2018 and January 2023 were reviewed. Eligible patients had metastatic castration-resistant PCa, underwent pre-treatment [68Ga]Ga-PSMA-11 PET/CT, and had serum prostate-specific antigen (PSA) levels available. On PET/CT images, SUVmax, SULmax, SUVpeak, and SULpeak of the most-avid tumoral lesion, as well as SUVmean of the parotid gland (P-SUVmean) and liver (L-SUVmean), were measured. Also, whole-body PSMA tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were calculated. To interpret treatment response after [177Lu]Lu-PSMA-I&T, a composite of PSA values and [68Ga]Ga-PSMA-11 PET/CT findings were considered. The outcomes were dichotomised into progressive versus controlled (stable disease or partial response) disease. Then, the association of baseline parameters with patient response was evaluated. Also, survival analyses were performed to assess baseline parameters in predicting overall survival.ResultsSixty patients (age:73 ± 8, PSA:185 ± 371) were included. Patients received at least one cycle of [177Lu]Lu-PSMA therapy (median = 4). Overall, half of the patients showed disease progression. In the progressive versus controlled disease evaluation, the highest SULmax, as well as SUVmax and SULmax to both backgrounds (L-SUVmean and P-SUVmean), were significantly correlated with the outcome (p-values < 0.05). In the multivariate analysis, only SULmax to the L-SUVmean remained significant (p-value = 0.038). The best cut-off was 8 (AUC = 0.71). With a median follow-up of 360 days, 11 mortal events were documented. In the multivariate survival analysis, only SULmax to P-SUVmean (cut-off = 2.4; p-value = 0.043) retained significance (hazard ratio = 4.0).ConclusionsA greater level of PSMA uptake, specifically higher tumour-to-background uptake in the hottest lesion, may hold substantial prognostic significance, considering both [177Lu]Lu-PSMA-I&T response and patient survival. These ratios may have the potential to be used for PCa patient selection for radioligand therapy.

Change of glucometabolic activity per PSMA expression predicts survival in mCRPC patients non-responding to PSMA radioligand therapy: introducing a novel dual imaging biomarker.

The value of [18F]fluorodeoxyglucose ([18F]FDG) PET/CT in monitoring prostate-specific membrane antigen (PSMA) targeted radioligand therapy (RLT) is still unclear. The aim of this study was to identify appropriate prognostic dynamic parameters derived from baseline and follow-up [18F]FDG and dual [18F]FDG/[68Ga]Ga-PSMA-11 PET/CT for monitoring early non-responding mCRPC patients undergoing PSMA-RLT. Twenty-three mCRPC patients of a prospective registry (NCT04833517), who were treated with [177Lu]Lu-PSMA-617 RLT and classified as early non-responders were included in this study. All patients received dual PET/CT imaging with [18F]FDG and [68Ga]Ga-PSMA-11 at baseline and after median two cycles of RLT. We tested potential biomarkers representing the "change of glucometabolic activity (cGA)" and "change of glucometabolic activity in relation to PSMA expression (cGAP)" composed of established parameters on [18F]FDG PET/CT as SUVmax, cumulative SUV of five lesions (SUV5), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) and its corresponding parameters on [68Ga]Ga-PSMA-11 PET/CT, respectively, for association with overall survival (OS). Kaplan-Meier analyses showed no significant association with OS for each tested cGA (cGASUVmaxp = 0.904, cGASUV5, p = 0.747 cGAMTVp = 0.682 and cGATLGp = 0.700), likewise the dual imaging biomarkers cGAPSUVmax (p = 0.136), cGAPSUV5 (p = 0.097), and cGAPTV (p = 0.113) failed significance. In contrast, cGAPTL, which is based on TLG and total lesion PSMA (TLP) showed a significant association with OS (p = 0.004). Low cGAPTL (cut-off 0.7) was associated with significant longer survival (17.6 vs. 12.9 months). The novel biomarker cGAPTL, which represents the temporal change of whole-body TLG normalized by TLP, predicts overall survival in the challenging cohort of patients non-responding to PSMA-RLT.

Potential role of 68Ga-PSMA PET/CT in metastatic renal cell cancer: A prospective study

PurposeProstate-specific membrane antigen (PSMA), in addition to its utility in prostate cancer, is also an angiogenic imaging marker for hypervascular tumors like renal cell carcinoma (RCC). Our study aims to assess the potential role of 68Ga-PSMA-11 positron emission tomography (PET)/CT in metastatic RCC and compare it with contrast-enhanced computed tomography (CECT). MethodsBiopsy-proven RCC patients with known or suspected distant metastases who underwent 68Ga-PSMA-11 PET/CT for staging/restaging were prospectively recruited. Those patients who had undergone 18F-FDG PET/CT within six weeks of 68Ga-PSMA PET/CT were also included retrospectively for comparative analysis. A patient-based and lesion-based analysis was done to compare the lesion detection rates of CECT, 68Ga-PSMA-11 PET and 18F-FDG PET. PET-based quantitative parameters were also compared between both the PET modalities. Impact of baseline parameters on survival was assessed using Cox regression analysis. A p-value of < 0.05 was considered significant. ResultsThirty-seven patients with median age 60 years ± 13 years (range = 26–76 years) were included in the study. Twenty-seven patients had clear cell (cc) RCC, six had papillary RCC (pRCC), and one each had an eosinophilic variant of ccRCC, collecting duct RCC, translocation RCC and poorly differentiated RCC. 68Ga-PSMA-11 PET performed better in detecting marrow and equivocal bone lesions and worse in detecting liver lesions compared to CECT. 68Ga-PSMA-11 PET-based angiogenic tumor burden estimation using Total Lesion-PSMA (TL-PSMA) and PSMA-Total volume (PSMA-TV) had a prognostic impact on the survival of patients. 68Ga-PSMA-11 PET also detected more lesions and showed significantly higher SUVmax than 18F-FDG PET. Conclusion68Ga-PSMA-11 PET/CT performs better than CECT and 18F-FDG PET/CT in metastatic evaluation and has prognostic value in the management of clear cell RCC.

Change in total lesion PSMA (TLP) during [177Lu]Lu-PSMA-617 radioligand therapy predicts overall survival in patients with mCRPC: monocentric evaluation of a prospective registry

PurposeThis study investigates imaging response of [177Lu]Lu-PSMA-617 radioligand therapy (RLT) based on the whole-body parameter total lesion PSMA (TLP), derived by PSMA-PET/CT and reflecting the total tumor burden, in patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a prospective registry (NCT 04833517).MethodsA total of n = 102 mCRPC patients received a [68Ga]Ga-PSMA-11 PET/CT at baseline and after two cycles of PSMA-RLT, in which TLP was measured by using a semi-automated tumor segmentation. TLP was defined as the summed products of volume and uptake (∑ Volume × SUVmean) of all tumor lesions. The Kaplan-Meier method was used to determine the most appropriate ∆TLP thresholds for classification into partial remission (PR), stable disease (SD), and progressive disease (PD) regarding overall survival (OS). Furthermore, we analyzed criteria that are also frequently used in established response frameworks, such as the occurrence of new metastases as independent criterion (I) or in combination with change in tumor burden (II), and the change in PSA serum value (III).ResultsFor the ∆TLP thresholds −30%/+30% (and also for higher thresholds, −40%/+40% or −50%/+50%), significant differences between all three response categories became apparent (PR/PD: p = 0.001; PR/SD: p = 0.001; SD/PD: p = 0.018). Including the development of new metastases as independent criterion of PD, there was no significant difference in OS between SD and PD (p = 0.455), neither when applied in combination with TLP (p = 0.191). Similarly, significant differentiation between SD and PD was not achieved by PSA serum value (p = 0.973).ConclusionIn the largest monocentric study to date, TLP is shown to be a qualified prognostic biomarker, applying ∆TLP thresholds of −30%/+30%. It significantly differentiated between PR, SD, and PD, whereas other response criteria did not differentiate SD vs. PD. Using TLP, the development of new metastases is not a required information for predicting OS.

A Phase I Trial of Focal Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer.

Locally recurrent prostate cancer after radiotherapy (RT) is an increasingly recognized entity with no standard management. NCT03253744 was a phase I trial with a primary objective of identifying the maximally tolerated dose (MTD) of a course of image-guided, focal, salvage stereotactic body radiotherapy (SBRT) for patients with local recurrence after prior definitive RT. Additional objectives included biochemical control and imaging response on mpMRI and 18F-DCFPyL (PSMA) PET/CT. SBRT was prescribed to three dose levels (DLs): 40Gy (DL1), 42.5Gy (DL2), and 45Gy (DL3) in 5 fractions. The prescription dose was delivered to a PTV defined by mpMRI and PSMA imaging and biopsy confirmed tumor volume. Dose escalation followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities above baseline were scored using CTCAE v5.0 criteria for two years after completion of SBRT. Escalation was halted if 2 dose limiting toxicities (DLTs) were observed. DLTs were defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT, and any grade 3 GU or grade 4 GI toxicity thereafter. Imaging response was compared between baseline and 6-months by the Wilcoxon signed rank test. Between 08/2018 and 05/2022, 8 patients underwent salvage SBRT to 11 intraprostatic lesions with a median follow-up of 27 months. No DLTs were observed on DL1. Two patients were enrolled on DL2 and both experienced grade 3 GU toxicities, prompting de-escalation and expansion (n = 6) on DL1, the MTD. The most common toxicities were grade 2 GU toxicities: acute urinary urgency/frequency, acute weak urinary stream, and noninfective cystitis. One patient at DL1 had a self-limited episode of grade 2 GI toxicity (proctitis). No grade 3 GI toxicities were observed. All but two patients achieved an undetectable PSA nadir. Only one of these experienced biochemical failure (nadir + 2.0) at 33 months with suspicion of distant metastatic failure on restaging PET/CT. Imaging response was demonstrated by MRI in all lesions with heterogeneity in volumetric response (6% to 100%). A significant (p<0.01) response on PSMA PET/CT was observed for all measured parameters (SUVMax, SUVMean, GTVPSMA, Total Lesion PSMA [SUVMean × GTVPSMA]). Of the 11 lesions, 1 (9%) demonstrated a complete response (CR) by MRI and 9 (82%) by PSMA PET/CT. A single lesion increased in volume by 0.06 cc (16%) at 6-month PSMA PET/CT compared to baseline in the only patient who did not achieve an undetectable PSA nadir and did not have imaging suggestive of distant failure. On this phase I dose escalation study of salvage SBRT for isolated intraprostatic local failure after definitive RT, the MTD was 40Gy in 5 fractions. producing a 100% 24-month bPFS, with one late failure at 33 months occurring after the 24-month study period. The most frequent clinically significant toxicity was late grade 2 GU toxicity. Imaging response was demonstrated in all lesions on MRI and PSMA PET/CT with exception of a single lesion.

Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients

PurposeThe aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival.MethodsThis retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2–9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP).ResultsAfter one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1–5) and 2 (1–6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09).ConclusionIn this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.

18F-PSMA-1007 PET/CT-derived semi-quantitative parameters for risk stratification of newly diagnosed prostate cancer.

This study aimed to assess the value of 18F-PSMA-1007 positron emission tomography/computed tomography (PET/CT)-derived semi-quantitative parameters of primary tumor for risk stratification of newly diagnosed prostate cancer (PCa). Sixty patients referred for 18F-PSMA-1007 PET/CT imaging for primary PCa were retrospectively analyzed and classified into the low-intermediate-risk (LIR) or high-risk (HR) group. The maximum standardized uptake value (SUVmax) of primary tumor, prostate total lesion PSMA (TL-PSMAp), and prostate PSMA-tumor volume (PSMA-TVp) were measured, and group differences were evaluated using the Mann-Whitney U test. Spearman's correlation was performed to assess the correlation between the above parameters with prostate-specific antigen (PSA) levels and Gleason score (GS). Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for SUVmax, TL-PSMAp, and PSMA-TVp to identify high-risk PCa and compare diagnostic efficacy. Among 60 patients, 46 were assigned to the HR group and 16 to the LIR group. In all patients, SUVmax, TL-PSMAp, and PSMA-TVp were moderately correlated with pre-treatment PSA values (r = 0.411, p = 0.001; r = 0.663, p < 0.001; and r = 0.549, p < 0.001, respectively). SUVmax and TL-PSMAp were moderately correlated with GS (r = 0.457 and r = 0.448, respectively; p < 0.001), while PSMA-TVp was weakly correlated with GS (r = 0.285, p = 0.027). In the ROC curve analysis, the optimal cut-off values of SUVmax, TL-PSMAp, and PSMA-TVp for identifying high-risk PCa were 9.61, 59.62, and 10.27, respectively, and the areas under the operating curve were 0.828, 0.901, and 0.809, respectively. The sensitivities of SUVmax, TL-PSMAp, and PSMA-TVp were 91.03%, 71.74%, and 63.04%, respectively, and the specificities were 71.43%, 100.00%, and 92.86%, respectively. TL-PSMAp had a superior ability to identify high-risk PCa. The semi-quantitative parameters of primary tumor on 18F-PSMA-1007 PET/CT imaging can be an objective imaging reference index to determine PCa risk stratification.

Predictive Value of Ga68-PSMA PETCT-Based Response to Neoadjuvant Androgen Deprivation Therapy in Node Positive Prostate Cancer Treated with Radical Radiotherapy

<h3>Purpose/Objective(s)</h3> To evaluate the utility of Ga68-PSMA PETCT based response to neoadjuvant androgen deprivation therapy (ADT) as a predictive biomarker in patients with node positive prostate cancer treated with definitive radiotherapy <h3>Materials/Methods</h3> Patients with newly diagnosed non-metastatic adenocarcinoma prostate with regional nodal involvement on index Ga68-PSMA PETCT scan were identified from prospectively maintained institutional database. All patients were started on neoadjuvant ADT and treated with definitive image-guided conformal radiotherapy with long term ADT. Eligible patients also had a response assessment Ga68-PSMA PETCT scan prior to radiotherapy. Patients who had a single PSMA PETCT scan, or who received prior or concurrent abiraterone ordocetaxel were excluded. Imaging parameters including maximum standardized uptake values (SUV_max), PSMA tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA) were calculated separately for prostate and pelvic nodes in the paired Ga68-PSMA PETCT scans done pre-ADT and pre-radiotherapy. Absolute and relative response for these parameters was calculated. Biochemical failure (BCF) was defined by the Phoenix criteria and its association with absolute and relative response in Ga68-PSMA PETCT parameters was tested using the logistic regression analysis. <h3>Results</h3> Total 93 patients were eligible for analysis. Median duration of neoadjuvant ADT was 6 months. Response observed in the paired Ga68-PSMA PETCT scans is detailed in Table 1. Complete metabolic response was observed in 62% patients for pelvic nodes and 7% for prostate. Partial metabolic response was observed in 23% for pelvic nodes and 55% for prostate, while stable disease was seen in 11% and 18% for pelvic nodes and prostate respectively. Progressive disease was observed in 4% for pelvic nodes and 14% for prostate. At a median follow up of 37 months, 15 patients (16%) experienced BCF. Median absolute and relative decline in SUV_max for pelvic nodes was 8.29 (IQR:3.5-20.3) and 100% (IQR:61.3-100) respectively. Both the absolute and the relative decline in SUV_max for pelvic nodes showed statistically significant association with BCF post treatment using logistic regression (p=0.05 each). No significant association was observed for other volumetric parameters. <h3>Conclusion</h3> A steeper decline in absolute and relative nodal SUV_max on Ga68-PSMA PETCT with neoadjuvant ADT is associated with lower probability of BCF post radiotherapy in node positive prostate cancer.

Role of baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters in predicting survival outcomes of metastatic castration-resistant prostate cancer patients receiving first-line treatment.

We aimed to evaluate whether baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters could be used as predictive biomarkers for survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line treatment. This retrospective study included 54 mCRPC patients, who underwent baseline 68Ga-PSMA PET/CT imaging within 1month before starting first-line treatment. Pre-treatment prostate-specific antigen (PSA) levels and treatments were recorded. SUVmax, SUVmean, whole-body PSMA-derived tumor volume (wbPSMA-TV), and whole-body total lesion PSMA (wbTL-PSMA) were calculated for all patients. PSA response was defined as a decline of ≥ 50% from pre-treatment value at 12weeks. Overall survival (OS) was measured from the start of the first-line treatment for mCRPC. Docetaxel and abiraterone/enzalutamide were administered to 32 and 22 patients in the first-line setting, respectively. wbPSMA-TV (rho = 0.582, p = 0.004) and wbTL-PSMA (rho = 0.564, p = 0.007) showed moderate positive correlations with PSA levels. Older age (p = 0.02), higher wbPSMA-TV (p = 0.007), higher PSA (p = 0.01), higher number of bone metastases (p = 0.02), and lack of PSA response (p = 0.03) were significantly associated with an increased risk of mortality. Multivariate analysis determined wbPSMA-TV (HR: 1.003, 95% CI 1.001-1.004, p = 0.001) and PSA response (HR: 2.241, 95% CI 1.189-4.222, p = 0.01) as independent predictors of OS. The wbPSMA-TV may be a useful tool to reflect tumor burden and predict survival outcomes in patients with mCRPC.