Development and validation of [18 F]-PSMA-1007 PET-based radiomics model to predict biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: Biochemical recurrence (BCR) following radical prostatectomy (RP) is a significant concern for patients with prostate cancer. Reliable prediction models are needed to identify patients at risk for BCR and facilitate appropriate management. This study aimed to develop and validate a clinical-radiomics model based on preoperative [18 F]PSMA-1007 PET for predicting BCR-free survival (BRFS) in patients who underwent RP for prostate cancer. MATERIALS AND METHODS: A total of 236 patients with histologically confirmed prostate cancer who underwent RP were retrospectively analyzed. All patients had a preoperative [18 F]PSMA-1007 PET/CT scan. Radiomics features were extracted from the primary tumor region on PET images. A radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The performance of the radiomics signature in predicting BRFS was assessed using Harrell's concordance index (C-index). The clinical-radiomics nomogram was constructed using the radiomics signature and clinical features. The model was externally validated in an independent cohort of 98 patients. RESULTS: The radiomics signature comprised three features and demonstrated a C-index of 0.76 (95% CI: 0.60-0.91) in the training cohort and 0.71 (95% CI: 0.63-0.79) in the validation cohort. The radiomics signature remained an independent predictor of BRFS in multivariable analysis (HR: 2.48, 95% CI: 1.47-4.17, p < 0.001). The clinical-radiomics nomogram significantly improved the prediction performance (C-index: 0.81, 95% CI: 0.66-0.95, p = 0.007) in the training cohort and (C-index: 0.78 95% CI: 0.63-0.89, p < 0.001) in the validation cohort. CONCLUSION: We developed and validated a novel [18 F]PSMA-1007 PET-based clinical-radiomics model that can predict BRFS following RP in prostate cancer patients. This model may be useful in identifying patients with a higher risk of BCR, thus enabling personalized risk stratification and tailored management strategies.

Multimodal radiomics based on 18F-Prostate-specific membrane antigen-1007 PET/CT and multiparametric MRI for prostate cancer extracapsular extension prediction.

OBJECTIVES: To compare the performance of the multiparametric magnetic resonance imaging (mpMRI) radiomics and 18F-Prostate-specific membrane antigen (PSMA)-1007 PET/CT radiomics model in diagnosing extracapsular extension (EPE) in prostate cancer (PCa), and to evaluate the performance of a multimodal radiomics model combining mpMRI and PET/CT in predicting EPE. METHODS: We included 197 patients with PCa who underwent preoperative mpMRI and PET/CT before surgery. mpMRI and PET/CT images were segmented to delineate the regions of interest and extract radiomics features. PET/CT, mpMRI, and multimodal radiomics models were constructed based on maximum correlation, minimum redundancy, and logistic regression analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and indices derived from the confusion matrix. RESULTS: AUC values for the mpMRI, PET/CT, and multimodal radiomics models were 0.85 (95% CI, 0.78-0.90), 0.73 (0.64-0.80), and 0.83 (0.75-0.89), respectively, in the training cohort and 0.74 (0.61-0.85), 0.62 (0.48-0.74), and 0.77 (0.64-0.87), respectively, in the testing cohort. The net reclassification improvement demonstrated that the mpMRI radiomics model outperformed the PET/CT one in predicting EPE, with better clinical benefits. The multimodal radiomics model performed better than the single PET/CT radiomics model (P < .05). CONCLUSION: The mpMRI and 18F-PSMA-PET/CT combination enhanced the predictive power of EPE in patients with PCa. The multimodal radiomics model will become a reliable and robust tool to assist urologists and radiologists in making preoperative decisions. ADVANCES IN KNOWLEDGE: This study presents the first application of multimodal radiomics based on PET/CT and MRI for predicting EPE.

Combination of [18F]FDG and [18F]PSMA-1007 PET/CT predicts tumour aggressiveness at staging and biochemical failure postoperatively in patients with prostate cancer.

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.

Impact of non-regional lymph node metastases accurately revealed on 18F-PSMA-1007 PET/CT in the clinical management of metastatic hormone-sensitive prostate cancer.

BACKGROUND: Non-regional lymph node (NRLN) metastases has shown increasing importance in the prognosis evaluation and clinical management of primary metastatic hormone-sensitive prostate cancer (mHSPC). Hence, this study aimed to investigate the concordance rates between 18F-PSMA-1007 PET/CT and conventional imaging (CI) in revealing NRLN metastases, and explore the impact of NRLN metastases on the management of primary mHSPC. METHODS: The medical records of 224 patients with primary mHSPC were retrospectively reviewed, including 101 patients (45.1%) only received CI for TNM classification, 24 patients (10.7%) only received 18F-PSMA-1007 PET/CT, and 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI. Among patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rates between 18F-PSMA-1007 PET/CT and CI were analyzed. The high-volume disease was defined as the presence of visceral metastases and/or ≥ 4 bone metastases (≥ 1 beyond the vertebral bodies or the pelvis) based on the findings of 18F-PSMA-1007 PET/CT and/or CI. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore independent predictors of PFS. RESULTS: A total of 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI, the concordance rate in revealing NRLN metastases between 18F-PSMA-1007 PET/CT and CI was only 61.62%, and Cohen's kappa coefficient was as low as 0.092. Moreover, 18F-PSMA-1007 PET/CT detected an additional 37 of 94 (39.4%) patients with positive NRLNs who were negative on CI. Cox regression revealed that androgen deprivation therapy (ADT), N1, high-volume, NRLN and visceral metastases were associated with worse PFS (all P < 0.05) in 224 patients. Furthermore, in patients with low-volume disease, the median PFS of patients with NRLN metastases was significantly shorter than that of patients without NRLN metastases (19.5 vs. 27.5 months, P = 0.01), while the difference between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P = 0.55). Moreover, early docetaxel chemotherapy significantly prolonged the PFS of these patients compared with ADT alone (20.7 vs. 12.3 months, P = 0.008). CONCLUSION: NRLN metastases could be accurately revealed by 18F-PSMA-1007 PET/CT, which should be considered a high-volume feature, especially concomitant with bone metastases. Furthermore, patients with low-volume plus NRLN metastases may be suitable for more intensive treatment, such as early docetaxel chemotherapy.

The prognostic value of 18F-PSMA-1007 PET/CT in predicting pathological upgrading of newly diagnosed prostate cancer from systematic biopsy to radical prostatectomy.

Objective: This study aimed to evaluate predictors for upgrading of newly diagnosed prostate cancer from systematic biopsy (SB) to radical prostatectomy (RP) using fluorine-18 prostate-specific membrane antigen 1007 (18F-PSMA-1007) positron emission tomography/computed tomography (PET/CT) and association with clinical parameters. Materials and methods: We retrospectively collected data from biopsy-confirmed prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT prior to RP from July 2019 and October 2022. Imaging characteristics derived from 18F-PSMA-1007 PET/CT and clinical parameters were compared in patients of pathological upgrading and concordance subgroups. Univariable and multivariable logistic regressions were performed to analyze factors predicting histopathological upgrading from SB to RP specimens. Discrimination ability of independent predictors was further evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC). Results: Pathological upgrading occurred in 26.97% (41/152) PCa patients, and 23.03% (35/152) of all patients experienced pathological downgrading. Concordance rate reached 50% (76/152). International Society of Urological Pathology grade group (ISUP GG) 1(77.78%) and ISUP GG 2 (65.22%) biopsies were related with the highest rate of upgrading. Multivariable logistic regression analyses showed that prostate volume (OR= 0.933; 95% CI, 0.887-0.982; p = 0.008), ISUP GG 1 vs. 4 (OR= 13.856; 95% CI: 2.467-77.831; p = 0.003), and total uptake of PSMA-avid lesions (PSMA-TL) (OR = 1.003; 95% CI, 1.000-1.006; p = 0.029) were found to be independent risk factors of pathological upgrading after RP. The AUCs and corresponding sensitivity and specificity of the independent predictors of synthesis for upgrading were 0.839, 78.00%, and 83.30% respectively, which showed good discrimination capacity. Conclusion: 18F-PSMA-1007 PET/CT may help to predict pathological upgrading between biopsy and RP specimens, particularly for ISUP GG 1 and ISUP GG 2 patients with higher PSMA-TL and smaller prostate volume.

Flare on [18F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naïve metastatic prostate cancer patients.

PURPOSE: Short-term androgen deprivation therapy (ADT) is known to increase heterogeneously prostate-specific membrane antigen (PSMA) expression. This phenomenon might indicate the potential of cancer lesions to respond to ADT. In this prospective study, we evaluated the flare on [18F]PSMA-1007 PET/CT after ADT in metastatic prostate cancer (PCa). Given that aggressive PCa tends to display FDG uptake, we particularly investigated whether the changes in PSMA uptake might correlate with glucose metabolism. METHODS: Twenty-five men with newly diagnosed treatment-naïve metastatic PCa were enrolled in this prospective registered clinical trial. All the patients underwent [18F]PSMA-1007 PET/CT immediately before and 3-4 weeks after ADT initiation (degarelix). Before ADT, [18F]FDG PET/CT was also performed. Standardized uptake values (SUV)max of primary and metastatic lesions were calculated in all PET scans. Serum PSA and testosterone blood samples were collected before the two PSMA PET scans. The changes in PSMA uptake after ADT were represented as ΔSUVmax. RESULTS: All the patients reached castration levels of testosterone at the time of the second [18F]PSMA-1007 PET/CT. Overall, 57 prostate, 314 lymph nodes (LN), and 406 bone lesions were analyzed. After ADT, 104 (26%) bone, 33 (11%) LN, and 6 (11%) prostate lesions showed an increase (≥ 20%) in PSMA uptake, with a median ΔSUVmax of + 50%, + 60%, and + 45%, respectively. Among the lesions detected at the baseline [18F]PSMA-1007 PET/CT, 63% bone and 46% LN were FDG-positive. In these metastases, a negative correlation was observed between the PSMA ΔSUVmax and FDG SUVmax (p < 0.0001). Moreover, a negative correlation between the ΔSUVmax and the decrease in serum PSA after ADT was noted (p < 0.0001). CONCLUSIONS: A heterogeneous increase in PSMA uptake after ADT was detected, most evidently in bone metastases. We observed a negative correlation between the PSMA flare and the intensity of glucose uptake as well as the decrease of serum PSA, suggesting that lesions presenting with such flare might potentially be less aggressive. TRIAL REGISTRATION: NCT03876912, registered 15 March 2019.

Adjunctive role of dual time point imaging in evaluating bone lesions with increased 18F-PSMA-1007 uptake

Background@#Non-specific focal uptake in the skeleton is a diagnostic pitfall on 18F-PSMA-1007 PET/CT, but adjunctive measures to aid interpretation of these lesions are currently lacking. We present two cases where dual time point imaging provided additional information. @*Case Presentation@#The first patient had a PI-RADS 3 lesion on MRI. No PSMA-avid abnormality was seen on PET, save for focal uptake in the right pubis with no anatomic correlate. Additional imaging showed a decrease in lesion SUV, and this was interpreted as benign. Another patient, diagnosed with prostate cancer, had multiple PSMA-avid pelvic foci. Two suspiciously malignant bone lesions had increasing SUV trend after dual time point imaging despite only faint sclerosis on CT. In contrast, one faint PSMA-avid lesion with no anatomic abnormality was read as benign after a decrease in SUV. A decrease in lesion SUV may point to a benign etiology, while an increase would heighten suspicion for malignancy. One possible molecular explanation is that a true PSMA-overexpressing lesion would bind to the tracer for a longer period than a false positive.@*Conclusion@#Dual time point imaging provides additional information that may be useful in the interpretation of non-specificskeletal lesions with increased 18F-PSMA-1007 uptake.

Evaluation of a radiomics nomogram derived from Fluoride-18 PSMA-1007 PET/CT for risk stratification in newly diagnosed prostate cancer.

Objective: The aim of this study was to evaluate the performance of Fluoride-18 (18F)-PSMA-1007-PET/CT radiomics for the tumor malignancy and clinical risk stratification in primary prostate cancer (PCa). Materials and Methods: A total of 161 pathological proven PCa patients in a single center were retrospectively analyzed. Prostate-specific antigen (PSA), Gleason Score (GS) and PET/CT indexes (SUVmin, SUVmax, and SUVmean) were compared according to risk stratification. Radiomics features were extracted from PCa 18F-PSMA-1007-PET/CT imaging. The radiomics score integrating all selected parameters and clinicopathologic characteristics was used to construct a binary logistic regression and nomogram classifier. Predictors contained in the individualized prediction nomogram included radiomics score, PSA level and metastasis status. Results: The radiomics signature, which consisted of 30 selected features, was significantly associated with PSA level and Gleason score (P < 0.001 for both primary and validation cohorts). Predictors contained in the individualized prediction nomogram included radiomics score, PSA level and metastasis status. The model showed good discrimination with an area under the ROC curve of 0.719 for the GS. Combined clinical-radiomic score nomogram had a similar benefit to utilizing the PET/CT radiomic features alone for GS discrimination. Conclusion: The 18F-PSMA-1007-PET/CT radiomics signature can be used to facilitate preoperative individualized prediction of GS; incorporating the radiomics signature, PSA level, and metastasis status had similar benefits to those of utilizing the PET/CT radiomics features alone.

Isolated Rectal Metastases from Locally Advanced Carcinoma Prostate Detected by 18 F-PSMA-1007 PET/CT.

Rectal involvement by prostate carcinoma is rare and isolated rectal metastases are even rarer with only a few cases having been reported in the literature. In our knowledge, no case of isolated rectal metastases diagnosed on prostate specific membrane antigen positron emission tomography/computed tomography has been reported to date. We present a case of a 66-year-old patient who presented with rectal bleeding and passage of urine from anal region and was diagnosed with carcinoma prostate infiltrating the rectum along with solitary rectal metastases.

The 18F-PSMA-1007 PET/CT performance on metastasis status and therapy assessment in oligo-metastasis prostate cancer.

Objective: The prostate-specific membrane antigen (PSMA) PET/CT is potentially identifying patients with oligo-metastasis who would be deemed to only have localized disease in the traditional approaches. However, the best selected oligo-metastasis prostate cancer (PCa) patients most likely to benefit from system androgen deprivation therapy (ADT) are still unknown. The aim of this study was to explore the potential 18F-PSMA-1007 PET/CT parameters and clinicopathologic characteristics for oligo-metastasis PCa discrimination and follow-up evaluation. Materials and methods: A total of 180 retrospective patients with different metastasis burdens (PCa of none-metastases, oligo-metastases, and poly-metastases), different metastasis status (untreated and recurrent oligo-metastases), and follow-up ADT were included respectively. A one-way analysis of variance was used to evaluate whether PET/CT parameters and clinicopathologic characteristics were different and univariate/multivariate logistic regression models were applied to assess independent predictors in the metastasis burdens group (89/180). Selected predictors were further compared between different metastasis statuses to test the diagnostic accuracy (69/180). The predictor efficiency was evaluated by the ROC and the cut-off value was used to test the ADT response-to-treatment with a longitudinal cohort (22/180) from untreated baseline to 3-15 months. Results: The significant group differences were observed on SUVmax (P = 0.012), International Society of Urologic Pathologists (ISUP, P<0.001) and Gleason Score (P<0.001). Poly-Metastases patients had higher SUVmax, ISUP and Gleason Score compared to Non-Metastases and Oligo-Metastases patients, respectively (P<0.05, all), and no difference between Non-Metastases and Oligo-Metastases. The SUVmax, ISUP and Gleason Score were independent predictors for metastasis burdens discrimination. The untreated and recurrent oligo-metastases lesions SUVmax were also different (P = 0.036). The AUC of ROC for oligo-metastasis prediction was 0.658 (P = 0.039) when the primary prostatic carcinoma focus SUVmax was higher than 28.22, ADT response-to-treatment patients (5/5 in 22) were all progress in a follow-up test. Conclusion: The SUVmax can discriminate PCa metastasis degree and oligo-metastasis status. The ADT-treated oligo-metastasis patient may still have disease progression when the primary prostatic carcinoma focus SUVmax is greater than 28.22.

False Positive Findings of [18F]PSMA-1007 PET/CT in Patients After Radical Prostatectomy with Undetectable Serum PSA Levels.

Background: PET-CT using prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals labeled with 68Ga or 18F has emerged as the most sensitive staging tool in prostate cancer (PC). Nonetheless, the occurrence of false positive (FP) findings presents a major concern of this approach. In this prospective study, we investigated the frequency and pattern of false-positive findings of [18F]PSMA-1007 PET/CT in patients after radical prostatectomy with undetectable serum PSA levels. Any discrete non-physiological accumulation of [18F]PSMA-1007 in this population is by definition FP. Methods: Seventeen men after radical prostatectomy, whose serum PSA levels were <0.05 ng/mL at 2-24 months after surgery were prospectively recruited. PET/CT was acquired at both 1 and 2 h after injection of [18F]PSMA-1007. Findings: Three studies (18%) were interpreted as completely normal. Thirty-five foci of "non-physiological" uptake were observed in the remaining 14 (82%) patients, including a single skeletal focus in four patients, multiple skeletal foci in five patients and soft tissue uptake in eight, including in a desmoid tumor and in pelvic lymphocele. The SUVmax of all lesions was in the range of 1-7, except for the desmoid tumor which measured 12.7. All foci were visible in both the 1- and the 2 h studies, presenting a minor (<10%), statistically insignificant increase of SUVmax during this time-interval. Interpretation: FP [18F]PSMA-1007-avid foci are found in about 80% of patients with undetectable serum PSA levels. Thus, focal uptake of [18F]PSMA-1007 outside its physiological distribution is not a categorical sign of metastasis and can arise from non-specific uptake of the ligand. The interpretation of [18F]PSMA-1007 PET/CT studies should always consider the clinical context, and lesions with SUVmax < 7 are suspicious for FP.

Case Report: 18F-PSMA-1007 PET/CT Avid Solitary Penile Metastasis of Castration-Resistant Prostate Cancer With a PSA of 0.072 ng/ml.

Penile metastasis of prostate cancer is rare, with a poor prognosis, and only a limited number of relevant cases have been reported so far. With the application of 18F-PSMA-1007 PET/CT, the biochemical recurrence of prostate cancer can be detected at an early stage for providing important evidence, facilitating clinical decision-making. Here, we have reported a case of solitary penile metastatic recurrence in the context of mild PSA progression (PSA: 0.072 ng/ml). This case highlights the preferable sensitivity of 18F-PSMA-1007 PET/CT imaging in prostate cancer.

Comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 PET/CT in Restaging of Prostate Cancer Patients with PSA Relapse.

This study aimed to compare the diagnostic performance of [18F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (18F-PSMA) and [68Ga]Ga-PSMA-11 PET/CT (68Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and to compare both methods. Retrospectively, the study included 264 patients. The performances of 18F-PSMA and 68Ga-PSMA in relation to the pre-scan PSA were assessed by receiver operating characteristic (ROC) curve. 18F-PSMA showed PC-lesions in 87.5% (112/128 patients), while 68Ga-PSMA identified them in 88.9% (121/136). For 18F-PSMA biochemical recurrent (BCR) patients treated with radical prostatectomy (78/128, patient group: F-RP), a PSA of 1.08 ng/mL was found to be the optimal cut-off level for predicting positive and negative scans (AUC = 0.821; 95%, CI: 0.710−0.932), while for prostatectomized 68Ga-PSMA BCR-patients (89/136, patient group: Ga-RP), the cut-off was 1.84 ng/mL (AUC = 0.588; 95%, CI: 0.410−0.766). In patients with PSA < 1.08 ng/mL (F-RP) 76.3% and <1.84 ng/mL (Ga-RP) 78.6% scans were positive, whereas patients with PSA ≥ 1.08 ng/mL (F-RP) or 1.84 ng/mL (Ga-RP) had positive scan results in 100% and 91.5% (p < 0.001/p = 0.085). The identified PSA thresholds for PSMA-mappable PC lesions in BCR-patients (RP) showed a better separation for 18F-PSMA with regard to the distinguishing of positive and negative PC-lesions compared to 68Ga-PSMA. However, the two PSMA PET/CT tracers gave similar overall findings.

Role of early dynamic PET/CT scan imaging with 18F-PSMA-1007 in staging and restaging prostate cancer in a tertiary private hospital

Introduction@#18F-PSMA-1007 is a novel prostate-specific membrane antigen (PSMA)-based radiopharmaceutical for imaging prostate cancer. The recommended imaging time is 60 minutes post-injection of the radiotracer. However, during this time there is a physiologic accumulation of the radiotracer in the urinary bladder which sometimes may obscure lesions adjacent to it. @*Objective@#This study aims to determine if early dynamic imaging in addition to the recommended 60-minute postinjection static imaging can improve the detection of PSMA-avid lesions in the staging and restaging of prostate cancer. @*Methods@#This is a retrospective cross-sectional study of the detection rate of early dynamic and static imaging using 18F-PSMA-1007 PET/CT scan in patients with prostate cancer (PCa) who were referred for initial staging or restaging. The McNemar test was used to compare the detection rate between the two imaging. Spearman correlation was used to determine the correlation of Gleason score (GS), PSA, and SUVmax values.@*Results@#18F-PSMA-1007 PET/CT scans of 53 patients with prostate cancer, were referred for either staging (22/53) or restaging (31/53), all of whom had undergone both early dynamic and static imaging. Among the 53 patients, 5 had 2 lesions each, for a total of 58 lesions were included in the analysis. There were 48/58 lesions detected on both early dynamic and static imaging, 2/58 lesions were only detected in the early imaging, 1/58 lesions was only detected in the static imaging, and 7/58 were not detected on both imaging. McNemar the test was not statistically significant (p = 1.000) in the detection rate of the two methods. There is a positive correlation between serum PSA levels and SUVmax measurements for all the patients. Only the correlation between the GS and SUVmax in the static imaging of the staging group was statistically significant. @*Conclusion@#Early dynamic imaging may be an adjunctive procedure in detecting PSMA-avid lesions, particularly in the basal segment of the prostate gland near the urinary bladder. However, it is not recommended as a standard component of the comprehensive protocol for imaging using 18F-PSMA-1007 PET/CT in patients with PCa.

Risk of metastatic disease using [18F]PSMA-1007 PET/CT for primary prostate cancer staging.

BACKGROUND: Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [68Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [18F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [18F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis. RESULTS: The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease. CONCLUSION: Metastatic disease according to [18F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [18F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax.

18F-PSMA-1007 PET/CT Performance on Risk Stratification Discrimination and Distant Metastases Prediction in Newly Diagnosed Prostate Cancer.

OBJECTIVE: To evaluate the prediction performance of 18F-PSMA-1007 PET/CT and clinicopathologic characteristics on prostate cancer (PCa) risk stratification and distant metastatic prediction. MATERIALS AND METHODS: A retrospective analysis was performed on 101 consecutively patients with biopsy or radical prostatectomy proved PCa who underwent 18F-PSMA-1007 PET/CT. The semi-quantitative analysis provided minimum, maximum and mean standardized uptake (SUVmin, SUVmax and SUVmean) of PCa. Association between clinicopathologic characteristics (total prostate-specific antigen, tPSA and Gleason Score, GS) and PET/CT indexes were analyzed. The diagnostic performance of distant metastatic on PET/CT parameters, tPSA and GS was evaluated using logistic regression analyses. A path analysis was conducted to evaluate the mediating effect of tPSA level on the relation between semi-quantitative parameters of primary tumors and metastatic lesions. RESULTS: The PET/CT parameters were all higher in high risk stratification subgroups (tPSA>20 ng/mL, GS ≥ 8, and tPSA>20 ng/mL and/or GS ≥ 8, respectively) with high sensitivity (86.89%, 90.16% and 83.61%, respectively). The SUVmax, tPSA and GS could effectively predict distant metastatic with high sensitivity of SUVmax (90.50%) compared with tPSA (57.14%) and GS (55.61%). With a cutoff value of 29.01ng/mL for tPSA, the detection rate of distant metastasis between low and high prediction tPSA group had statistical differences (50.00% vs. 76.60%, respectively; P = 0.006) which was not found on guideline tPSA level (P>0.05). 6/15 (40%) patients tPSA between 20ng/mL to 29.01ng/mL without distant metastases may change the risk stratification. Finally, tPSA had a partial mediating effect on SUVmax of primary tumors and metastases lesions. CONCLUSION: The 18F-PSMA-1007 PET/CT SUVmax has a higher sensitivity and can be an "imaging biomarker" for primary PCa risk stratification. The prediction tPSA level (29.01 ng/mL) is more conducive to the assessment of distant metastasis and avoid unnecessary biopsy.

Diagnostic scope of 18F-PSMA-1007 PET/CT: comparison with multiparametric MRI and bone scintigraphy for the assessment of early prostate cancer recurrence.

The aim of this study was to compare the diagnostic tools-18F-PSMA-1007 positron emission tomography (PET/CT), magnetic resonance imaging (MRI) and bone scintigraphy for the evaluation of local recurrence, regional lymph nodes and bone metastases of recurrent prostate cancer (PCa). 28 PCa patients after radical prostatectomy and/or radiation therapy and with biochemical relapse were enrolled in this study. The evaluation of local recurrence and regional lymph node metastases was based on results of PET/CT and MRI. Local recurrent disease in 28 patients was detected by PET/CT in 36% (10/28) and by MRI in 32% (9/28) with sensitivity, specificity, accuracy of 90.9%, 100%, 96.4% and 81.8%, 100%, 92.9%, respectively (kappa 0.92, P<0.001). Nodal involvement was confirmed by PET/CT and MRI in 46% (13/28) and 25% (7/28) with sensitivity, specificity and accuracy for PET/CT 92.3%, 93.3%, 92.9% and for MRI-53.8%, 100%, 78.6%, respectively (kappa 0.57, P<0.001). The evaluation of skeletal metastases was based on PET/CT and bone scintigraphy. Bone metastases were seen on PET/CT and bone scintigraphy in 21% (6/28) and 20% (5/25) with sensitivity, specificity and accuracy of 100%; 91.7%; 92.9% and 50.0%; 85.7%; 80.0%, respectively (kappa 0.41, P<0.01). In conclusion, our comparative study demonstrates advantages of 18F-PSMA-1007 PET/CT compared to MRI and scintigraphy for the evaluation of recurrent prostate cancer. Both methods, 18F-PSMA-1007 PET/CT and MRI, detect local recurrence with high accuracy and excellent agreement, which may be attributed to the low urinary background clearance of 18F-PSMA-1007.

Parameters predicting [18F]PSMA-1007 scan positivity and type and number of detected lesions in patients with biochemical recurrence of prostate cancer.

BACKGROUND: Detection of the site of recurrence using PSMA-PET/CT is important to guide treatment in patients with biochemical recurrence of prostate cancer (PCa). The aim of this study was to evaluate the positivity rate of [18F]PSMA-1007-PET/CT in patients with biochemically recurrent PCa and identify parameters that predict scan positivity as well as the type and number of detected lesions. This monocentric retrospective study included 137 PCa patients with biochemical recurrence who underwent one or more [18F]PSMA-1007-PET/CT scans between August 2018 and June 2019. PET-positive malignant lesions were classified as local recurrence, lymph node (LN), bone or soft tissue lesions. The association between biochemical/paraclinical parameters, as PSA value, PSA doubling time, PSA velocity, Gleason score (GS) and androgen deprivation therapy (ADT), and scan positivity as well as type and number of detected lesions was evaluated using logistic regression analysis (binary outcomes) and Poisson models (count-type outcomes). RESULTS: We included 175 [18F]PSMA-1007-PET/CT scans after radical prostatectomy (78%), external beam radiation therapy (8.8%), ADT (7.3%), brachytherapy (5.1%) and high intensity focused ultrasound (0.7%) as primary treatment (median PSA value 1.6 ng/ml). Positivity rate was 80%. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence of bone and soft tissue lesions and number of bone, LN and soft tissue lesions, both in uni- and/or multivariable analysis. Multivariable analysis also showed prior ADT as predictor of bone and soft tissue lesions, GS as predictor of the number of bone lesions and ongoing ADT as predictor of the number of LN lesions. CONCLUSION: [18F]PSMA-1007-PET/CT showed a high positivity rate in patients with biochemically recurrent PCa. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence and number of bone and soft tissue lesions and the number of LN lesions. Our findings can guide clinicians in optimal patient selection for [18F]PSMA-1007-PET/CT and support further research leading to the development of a prediction nomogram.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

PURPOSE: To prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). METHODS: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. RESULTS: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. CONCLUSION: 18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391.

Diagnostic Accuracy of 18F-PSMA-1007 PET/CT Imaging for Lymph Node Staging of Prostate Carcinoma in Primary and Biochemical Recurrence.

Prostate-specific membrane antigen (PSMA)-ligand PET/CT is performed on patients with prostate cancer to stage the disease initially or to identify sites of recurrence after definitive therapy. On the basis of clinical results, 18F-PSMA-1007 is a promising PSMA PET tracer, but detailed histologic confirmation has been lacking. Methods: Ninety-six patients with prostate cancer underwent 18F-PSMA-1007 PET/CT followed by either radical prostatectomy with lymphadenectomy or salvage lymphadenectomy. The histologic findings of PSMA PET-positive nodes were analyzed retrospectively. A lesion-based and patient-based analysis was performed comparing all positive lesions and only lesions larger than 3 mm on histopathology. Results: Of the patients, 90.6% received 18F-PSMA-1007 PET/CT for staging before the primary treatment, whereas 9.4% underwent imaging for biochemical recurrence. In 34.4% of the cohort, positive lymph nodes were present on imaging. In total, 1,746 lymph nodes were dissected in 96 patients. 18F-PSMA-1007 PET had a lesion-based sensitivity of 81.7%, a specificity of 99.6%, a positive predictive value of 92.4%, and a negative predictive value of 98.9% for detecting positive lymph nodes larger than 3 mm. In the analysis of all malignant nodes regardless of size, the overall sensitivity, specificity, positive predictive value, and negative predictive value on lesion-based analysis were 71.2%, 99.5%, 91.3%, and 97.9%, respectively. The patient-based analysis showed a sensitivity of 85.9% and a specificity of 99.5% for lymph nodes larger than 3 mm. Conclusion:18F-PSMA-1007 PET/CT reliably detects malignant lymph nodes and has an exceptional specificity of more than 99% for nodal metastases.