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Introduction: This study aimed to evaluate the relationship between pathological and clinical risk classifications in newly diagnosed prostate cancer patients, and 68Ga-PSMA PET/CT data and serum Prostate Specific Antigen (PSA) values. Method: A total of 203 patients who were diagnosed with prostate cancer between 2019 and 2023, who had not yet received treatment and who underwent 68Ga-PSMA PET/CT for staging purposes were included in this study. Results: There was a substantial correlation between D’Amico risk classification, Gleason score, ISUP classification, and the presence or absence of metastasis (p < 0.0001). The median SUVmax value of the prostate gland and the D’Amico risk classification were statistically significantly correlated. (p < 0.0001). There was a statistically significant correlation between the ISUP classification and the PSA value and prostate gland SUVmax value (p < 0.0001). There was a significant correlation between the median SUVmax values of the prostate gland at the time of diagnosis and the patients with and without metastases (p < 0.0001). According to the data obtained from ROC analysis, patients with prostate gland SUVmax values of 8.75 and above were found to have a high probability of metastasis with a sensitivity of 78.9% and a specificity of 59.05%. Conclusion: Our study showed that 68Ga-PSMA PET/CT is a highly effective method for staging newly diagnosed high-risk prostate cancer. The probability of metastasis was found to be dramatically increased in Gleason 8 and above. According to D’Amico risk classification, metastasis was detected in at least half of high-risk patients. Since the sensitivity of metastasis was 78.9% in patients with prostate gland SUVmax value above 8.75, we think that these patients should be carefully reported in terms of metastasis.

Simple Summary: This study investigates the correlation between 68Ga-PSMA PET/CT imaging and histopathological grading in treatment-naive prostate cancer patients. We retrospectively analyzed 86 patients who underwent 68Ga-PSMA PET/CT scans for prostate cancer staging, with a subset of 40 patients also undergoing radical prostatectomy. The PET/CT results, specifically SUVmax values, were compared with Gleason scores and PSA levels to assess their association with cancer grades. Results indicated a significant positive correlation between SUVmax and ISUP grades, suggesting that higher SUVmax values correspond to more advanced prostate cancer stages. Furthermore, the analysis of biopsy and radical prostatectomy pathology reports revealed a substantial rate of grading changes, underscoring the limitations of biopsy alone for accurate staging. These findings highlight the potential utility of 68Ga-PSMA PET/CT as a diagnostic tool in stratifying prostate cancer risk and guiding treatment decisions. Future studies are recommended to validate these observations and explore further applications of this imaging modality. Objective: This study aimed to evaluate the correlation between 68Ga-PSMA uptake in PSMA PET/CT in primary prostate cancer (PC) and its histopathological grading (Gleason score and ISUP grade). Additionally, we compared preoperative biopsy histopathological findings with definitive pathology results in radical prostatectomy (RP) specimens. Methods: We retrospectively analyzed 86 patients who underwent 68Ga-PSMA PET/CT for primary PC staging, of which 40 patients later underwent radical prostatectomy. PET/CT results, including SUVmax values, were correlated with GS and PSA concentrations. Histopathology reports were analyzed and compared between biopsy and final pathology results following RP. Results: A significant positive correlation was observed between SUVmax and ISUP grades (Pearson's ρ = 0.34, p < 0.001), with higher SUVmax values associated with more advanced grades. A cut-off SUVmax value of 5.64 was determined to predict upstaging in patients, yielding a sensitivity of 76% and a specificity of 60% (AUC = 0.82, 95% CI: 0.70–0.94). Additionally, 57.5% of patients experienced a grade shift following RP, with a 35% upgrade and 22.5% downgrade in ISUP grades. Conclusion: 68Ga-PSMA PET/CT demonstrated high sensitivity in detecting high-risk prostate cancer, particularly in patients with GS > 7 or PSA levels ≥ 10 ng/mL. The findings suggest that this imaging modality may be less effective for the staging of patients with lower GS or PSA values, that is, low-risk PCa. Further prospective studies are necessary to validate these results. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the relationship between pathological and clinical risk classifications in newly diagnosed prostate cancer patients, and 68Ga-PSMA PET/CT data and serum Prostate Specific Antigen (PSA) values. Method: A total of 203 patients who were diagnosed with prostate cancer between 2019 and 2023, who had not yet received treatment and who underwent 68Ga-PSMA PET/CT for staging purposes were included in this study. Results: There was a substantial correlation between D'Amico risk classification, Gleason score, ISUP classification, and the presence or absence of metastasis (p < 0.0001). The median SUVmax value of the prostate gland and the D'Amico risk classification were statistically significantly correlated. (p < 0.0001). There was a statistically significant correlation between the ISUP classification and the PSA value and prostate gland SUVmax value (p < 0.0001). There was a significant correlation between the median SUVmax values of the prostate gland at the time of diagnosis and the patients with and without metastases (p < 0.0001). According to the data obtained from ROC analysis, patients with prostate gland SUVmax values of 8.75 and above were found to have a high probability of metastasis with a sensitivity of 78.9% and a specificity of 59.05%. Conclusion: Our study showed that 68Ga-PSMA PET/CT is a highly effective method for staging newly diagnosed high-risk prostate cancer. The probability of metastasis was found to be dramatically increased in Gleason 8 and above. According to D'Amico risk classification, metastasis was detected in at least half of high-risk patients. Since the sensitivity of metastasis was 78.9% in patients with prostate gland SUVmax value above 8.75, we think that these patients should be carefully reported in terms of metastasis. [ABSTRACT FROM AUTHOR]

Purpose: 68Ga-PSMA-11 is recommended for the selection of patients for treatment in the package insert for 177Lu-PSMA-617. We aimed to compare imaging properties and post-treatment outcomes from radioligand therapy (RLT) of patients selected with 68Ga-PSMA-11 and 18F-DCFPyL. Methods: We retrospectively evaluated 80 patients undergoing PSMA RLT, who had pretreatment imaging using either 68Ga-PSMA-11 or 18F-DCFPyL. For both groups, we compared the biodistribution and lesion uptake and the PSA response to treatment. Results: Both agents had comparable biodistribution. Patients initially imaged with 18F-DCFPyL had a higher PSA response (66% vs. 42%), and more patients had a PSA50 response (72% vs. 43%) compared to patients imaged with 68Ga-PSMA-11. Conclusion: 18F-DCFPyL and 68Ga-PSMA-11 had comparable biodistribution and lesion uptake. Patients imaged with 18F-DCFPyL demonstrated clinical benefit to PSMA RLT comparable to those imaged with 68Ga-PSMA-11, and either agent can be used for screening patients. [ABSTRACT FROM AUTHOR]

Background: 68Ga-PSMA PET/CT is superior to standard-of-care imaging for detecting regional and distant metastatic recurrent prostate cancer. The objective of our study was to evaluate the performance of 68Ga-PSMAPET/CT in our patient population, using the new PSMA-RADS version 2.0. Methods: A total of 128 patients scanned with 68Ga-PSMA PET/CT for detection of recurrence after RP were analyzed with PSMA-RADS version 2.0. For the analysis of the detection rate, categories PSMA-RADS 3 to 5 were considered as "positive for malignancy" and 1–2 as "negative". Results: According to PSMA-RADS v2.0, we classified patients as follows: 23 patients without PSMA-RADS because they were negative; PSMA-RADS 1: 10 patients; PSMA-RADS 2: 4 patients; PSMA-RADS 3A: 11 patients; PSMA-RADS 3B: 2 patients; PSMA-RADS 3C: 2 patients; PSMA-RADS 3D: 2 patients; PSMA-RADS 4: 13 patients; PSMA-RADS 5: 61 patients. Conclusions: The overall detection rate of 68Ga-PSMA PET/CT was 71%. By dividing the patients into fourgroups according to PSA level before examination, we obtained the following detection rates: PSA < 0.2 ng/mL 38%; 0.2 ≤ PSA < 0.5 ng/mL 57%; 0.5 ≤ PSA ≤ 1 ng/mL 77%; and PSA > 1 ng/mL 95%. Conclusion: Using PSMA-RADS version 2.0, we obtained detection rate values comparable with recent literature both in absolute terms and in relation to different PSA levels. [ABSTRACT FROM AUTHOR]

Objectives: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

We present the first study performed in Saudi Arabia to evaluate 68Ga-PSMA PET/CT in prostate cancer (PCa) initial diagnosis and its added value in bone metastases (BM) diagnosis in such patients. Twenty-six male patients underwent prostate histopathological examination and all imaging studies (68Ga-PSMA PET/CT and CT); all of them were confirmed with high-grade PCa. Patients' mean PSA levels and Gleason score were 5.12±1.12 and 7.0±0.9, respectively. 68Ga-PSMA PET/CT (20/26; sensitivity of 76.9%) was superior to traditional CT (18/26; sensitivity of 69.2%) in PCa detection. There was a non-significant association (P=0.206) between patients' age and BM. Based on bone scintigraphy (BS), in patients without BM (n=16), 68Ga-PSMA PET/CT detected metastasis-suspicious lesions in six patients (37.5%) and negative results in ten patients (62.5%). 68Ga-PSMA PET/CT showed no false-negative cases among patients with confirmed BM using BS. In conclusion, 68Ga-PSMA PET/CT performed well in PCa initial diagnosis in Saudi male patients with high-grade tumors. 68Ga-PSMA PET/CT also accurately detected BM in all PCa patients with confirmed BM by BS. Larger prospective studies are urgently required to compare 68Ga-PSMA PET/CT diagnostic performance with other standard modalities in PCa and BM diagnosis.

Objective: PSMA expression is seen in many solid tumours in addition to prostate cancer and several studies and case reports have shown PSMA expression and 68Ga-PSMA imaging of hepatocellular carcinoma (HCC). Our prospective study evaluates the role of 68Ga-PSMA in HCC patients and compares it to conventional imaging (CE-CT/MRI). Methods: Patients with radiologically and/or histopathologically confirmed HCC were included and all had undergone serum alpha-fetoprotein (S.AFP) assessment as well as CE-CT/MRI prior to PSMA PET/CT. Acquired whole-body PET/CTs were analysed both visually and quantitatively by two experienced nuclear medicine physicians. Results: Forty-one (41) patients (36 male; 5 female) with known HCC and a mean age of 53.9 ± 10.9 years underwent 68Ga-PSMA PET/CT. All patients had lesions on conventional imaging but only 38/41 patients showed 68Ga-PSMA uptake. Conventional imaging revealed 18 patients with single lesions, all of which were tracer avid. Twenty-three (23) of 41 patients had multifocal (> 2) hepatic lesions on CE-CT/MRI of which 3 patients showed no 68Ga-PSMA uptake, 7 showed tracer uptake in a single lesion only and 13 patients had multifocal tracer avid lesions. There was no correlation observed between S. AFP level and tumour SUVmax on 68Ga-PSMA PET/CT. Conclusion: 68Ga-PSMA PET/CT imaging of HCC may complement conventional imaging and identify patients for potential theranostic intervention. [ABSTRACT FROM AUTHOR]

Purpose68Ga-PSMA-11 is recommended for the selection of patients for treatment in the package insert for 177Lu-PSMA-617. We aimed to compare imaging properties and post-treatment outcomes from radioligand therapy (RLT) of patients selected with 68Ga-PSMA-11 and 18F-DCFPyL.MethodsWe retrospectively evaluated 80 patients undergoing PSMA RLT, who had pretreatment imaging using either 68Ga-PSMA-11 or 18F-DCFPyL. For both groups, we compared the biodistribution and lesion uptake and the PSA response to treatment.ResultsBoth agents had comparable biodistribution. Patients initially imaged with 18F-DCFPyL had a higher PSA response (66% vs. 42%), and more patients had a PSA50 response (72% vs. 43%) compared to patients imaged with 68Ga-PSMA-11.Conclusion18F-DCFPyL and 68Ga-PSMA-11 had comparable biodistribution and lesion uptake. Patients imaged with 18F-DCFPyL demonstrated clinical benefit to PSMA RLT comparable to those imaged with 68Ga-PSMA-11, and either agent can be used for screening patients.

In order to evaluate the diagnostic performance of 68Ga-PSMA PET-CT, we retrospectively analysed 100 patients with biochemically confirmed recurrence (BCR) of prostate cancer (PC). We compared positivity rates of PSMA PET scans with well-established disease indicators such as serum PSA levels, initial PSA (iPSA), PSAdt (PSA doubling time), elapsed time from prostatectomy, and Gleason score (GS). Of the 100 studies, 56 (56%) had lesions with pathological 68Ga-PSMA uptake. Positivity rate of PSMA PET studies was 50% (28/56) for PSA levels of 0.2-0.5 ng/mL, 47.83% (11/23) for PSA 0.51-1 ng/mL, 71.43% (10/14) for PSA 1.01-2 ng/mL, and 100% (7/7) for patients with PSA above 2.01 ng/mL. PSMA-PET/CT study positivity correlated with higher Gleason score (3+4 – 31.82%, 4+3 – 63.16%, 8 – 60%, and 9 – 85.71%). Local recurrence was found in 19.43% and lymph node metastases in 75% of studies with pathological tracer uptake, while bone metastases were found in 25% of PSMA-PET/CT positive studies. Regarding PSAdt, the PSMA-PET/ CT positivity rate was 66.67% (20/30) in cases with short PSAdt of less than 6 months, 57.14% (12/21) for PSAdt >6≤12 months, whereas only 23.53% (4/17) were positive in a group with very long PSAdt of >12 months. We have demonstrated that PSAdt may be considered the main positivity predictor of disease recurrence. Shorter PSAdt, even with low values of serum PSA, was linked with a higher positivity rate, while longer PSAdt was most often linked with negative scans. 68Ga-PSMA PET/CT is a sensitive PET method for the detection and localization of lesions in early biochemical recurrence of disease, even in cases with very low PSA serum values.

Objectives Patients and Methods Results Conclusions To compare the diagnostic performance and radiological staging impact of 68Ga‐prostate‐specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) compared to 99Tc whole‐body bone scan (WBBS) for the detection of skeletal metastasis in the primary staging of prostate cancer (PCa).A prospective institutional database was retrospectively examined for patients who underwent both PSMA PET and WBBS within a 1 week interval for PCa primary staging. Lesions were categorised as ‘negative’, ‘equivocal’, or ‘definite’ based on nuclear medicine physician interpretation. Metastatic burden was characterised for each imaging modality according to three groups: (i) local disease (no skeletal metastases), (ii) oligometastatic disease (three or fewer skeletal metastases), or (iii) polymetastatic disease (more than three skeletal metastases).There were 667 patients included. The median (interquartile range) prostate‐specific antigen level was 9.2 (6.2–16) ng/mL and 60% of patients were high risk according to a modified D'Amico risk classification. The overall distribution of skeletal metastasis detection changed across the two scans overall (P = 0.003), being maintained within high‐risk (P = 0.030) and low‐risk (P = 0.018) groups. PSMA PET/CT identified more definite skeletal metastases compared to WBBS overall (10.3% vs 7.3%), and according to risk grouping (high: 12% vs 9%, intermediate: 4% vs 1%). Upstaging was more common with PSMA PET/CT than WBBS (P = 0.001). The maximum standardised uptake value (SUVmax) of the primary tumour was associated with upstaging of skeletal metastases on PSMA PET/CT (P = 0.025), while age was associated with upstaging on WBBS (P = 0.021). The SUVmax of the primary tumour and metastases were both higher according to extent of metastatic disease (P = 0.001 and P < 0.001, respectively).More skeletal metastases were detected with PSMA PET/CT than WBBS, resulting in a higher upstaging rate mostly in high‐risk patients. The SUVmax of the primary tumour and metastases was associated with upstaging. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most common malignancy in men worldwide, with a good prognosis when is detected and treated in early stages, but, when it presents progression to castration-resistant metastatic prostate cancer, most of the cases will have bone metastasis, decreasing the quality of life and life expectancy. For the evaluation of the disease in the routinary clinical practice, 68Ga-PSMA PET/CT, among others is a valuable tool for the evaluation of the disease extension. 68Ga-PSMA PET/CT detects the presence of PSMA receptor in the tumoral tissue, but also has physiologic uptake in certain organs, such as liver, spleen, intestine, kidneys, lacrimal and salivary glands. Total or partial absence of uptake in those organs is rare and may be due to a high metastatic tumor burden, a phenomenon originally described in bone scintigraphy as super scan. We describe a case series of seven patients with prostate cancer from the National Institute of Cancerology in Colombia, in which a super scan pattern was found in the evaluation with 68Ga-PSMA PET/ CT, proposing the suppression of uptake in the intestine, liver, spleen, lacrimal and salivary glands as the main criteria for its definition, and showing that renal uptake persists in most cases, considering that, unlike the super scan in conventional bone scintigraphy, this is not a criterion necessary for its definition in the study with 68Ga-PSMA. [ABSTRACT FROM AUTHOR]

A 70-year-old man with high-risk prostate cancer (PCa) received radiation therapy and androgen deprivation therapy (ADT). The patient developed penile tenderness, compatible with Peyronie's disease upon physical examination. An ultrasound revealed a matching hypoechoic plaque and a thrombus in the vena dorsalis profunda, which were treated with anticoagulants. A follow-up ultrasound showed no abnormalities. Despite the use of analgesics, the patient suffered from persistent pain, later accompanied by an increasing PSA level of up to 7.5 ng/mL, despite ADT. 68Ga-PSMA PET/CT showed a PSMA uptake consistent with PCa penile metastasis. Due to severe pain and the presence of metastatic PCa, the patient was referred for penectomy. Histopathological analysis confirmed metastases originating from the PCa. This case underscores the importance of 68Ga-PSMA PET/CT in diagnosing PCa metastases and vigilance towards urogenital symptoms as potential indicators of metastases, despite the rarity of penile metastases. [ABSTRACT FROM AUTHOR]

Background: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test." Summary: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months.Key Messages: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background/Aim: To evaluate the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis and staging of prostate cancer (PCa). Patients and Methods: From January 2021 to December 2022, 160 men (median age: 66 years) with PCa (median PSA of 11.7 ng/ml) before prostate biopsy underwent 68Ga-PET/CT imaging examinations (Biograph 6; Siemens, Knoxville, TN, USA). The location of focal uptake on 68Ga-PSMA PET/TC and standardized uptake values (SUVmax) were reported on a per-lesion basis for each International Society of Urological Pathology (ISUP) grade group (GG) PCa. Results: Overall, the median intraprostatic 68Ga-PSMA SUVmax was 26.1 (range=2.7-164); in the 15 men with not clinically significant PCa (ISUP grade group 1) median SUVmax was 7.5 (range=2.7-12.5). In the 145 men with csPCa (ISUP GG=2) median SUVmax was 33 (range=7.8-164). A SUVmax cut-off of 8 demonstrated a diagnostic accuracy in the diagnosis of PCa equal to 87.7% vs. 89.3% vs. 100% in the presence of a GG1 vs. GG2 vs. GG=3 PCa, respectively. In addition, median SUVmax in the bone and node metastases was 52.7 (range=25.3-92.8) and 47 (range=24.5-65), respectively. Conclusion: 68GaPSMA PET/CT with a SUVmax cut-off of 8 demonstrated a good accuracy in the diagnosis of csPCa (100% in the presence of GG=3) showing a good cost-benefit ratio as a single procedure for the diagnosis and staging of high-risk PCa. [ABSTRACT FROM AUTHOR]

Recent studies have outlined the emerging role of 68Ga-PSMA-11 PET/CT in the diagnostic algorithm of clear cell renal cell carcinoma (ccRCC). We report a unique intra-patient comparison of bilateral primary ccRCC imaged with 68Ga-PSMA-11 PET/CT. Although both tumors resulted 68Ga-PSMA-11 avid, we found a remarkable discrepancy in uptake intensity between the high grade and the low grade ccRCC. This case confirms previous evidence reporting that SUVmax on 68Ga-PSMA-11 PET/CT could be used to discriminate aggressive high grade from more indolent low grade ccRCC, due to their different endothelial expression of PSMA. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the accuracy of 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis of clinically significant prostate cancer (csPCa: Grade Group ≥ 2) in men enrolled in Active Surveillance (AS) protocol. Materials and methods: From May 2013 to December 2021 200 men aged between 52 and 74 years (median age 63) with very low risk PCa were enrolled in an AS protocol study. During the follow up 48/200 (24%) men were upgraded and 10/200 (5%) decided to leave the AS protocol. After five years from confirmatory biopsy (range: 48-60 months) 40/142 (28.2%) consecutive patients were submitted to mpMRI and 68Ga-PSMA PET/CT imaging examinations before scheduled repeated biopsy. All the mpMRI (PI-RADS ≥ 3) and 68Ga-PET/TC standardized uptake value (SUVmax) ≥ 5 index lesions underwent targeted cores (mpMRI-TPBx and PSMA-TPBx) combined with transperineal saturation prostate biopsy (SPBx: median 20 cores). Results: Multiparametric MRI and 68Ga-PSMA PET/CT showed 18/40 (45%) and 9/40 (22.5%) lesions suspicious for PCa. In 3/40 (7.5%) men a csPCa (GG2) was found; 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. SPBx diagnosed 2/3 (66.6%) vs. 2/3 (66.6%) vs. 3/3 (100%) csPCa, respectively. In detail, mpMRI and 68Ga-PSMA PET/TC demonstrated 16/40 (40%) vs. 7/40 (17.5%) false positive and 1 (33.3%) vs. 1 (33.3%) false negative results. Conclusion: Although 68PSMA PET/CT did not improve the detection for csPCa of SPBx (1 false negative result equal to 33.3% of the cases), at the same time, would have spared 31/40 (77.5%) scheduled biopsies showing a better diagnostic accuracy in comparison with mpMRI (83.3% vs. 70.2%).

68Ga-PMSA imaging has revolutionized both diagnosis and radioligand therapy selection in patients with metastatic prostate cancer. We report a case of a 59-year-old recently diagnosed prostate cancer with high PSA level pf >2000ng/ml referred for 68Ga-PSMA PET/CT. 68Ga-PSMA PET/CT showed diffuse intense tracer uptake throughout the axial and appendicular skeleton with significantly lower uptake of 68Ga-PSMA in normal organs in a configuration of “tumour sink effect”. Findings are in keeping with diffuse skeletal infiltration and suspected marrow infiltration. Given the extensive nature of bone disease and pattern, 177Lu-PSMA-targetted radioligand therapy was thought to be more appropriate in a given situation with a favourable toxicity profile. Keywords: 68Ga-PSMA PET/CT; tumor sink effect; 177Lu-PSMA-RLT; PET/CT

Introduction: To evaluate the accuracy of 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis of clinically significant prostate cancer (csPCa: Grade Group = 2) in men enrolled in Active Surveillance (AS) protocol. Materials and methods: From May 2013 to December 2021 200 men aged between 52 and 74 years (median age 63) with very low risk PCa were enrolled in an AS protocol study. During the follow up 48/200 (24%) men were upgraded and 10/200 (5%) decided to leave the AS protocol. After five years from confirmatory biopsy (range: 48-60 months) 40/142 (28.2%) consecutive patients were submitted to mpMRI and 68Ga-PSMA PET/CT imaging examinations before scheduled repeated biopsy. All the mpMRI (PI-RADS = 3) and 68Ga-PET/TC standardized uptake value (SUVmax) = 5 index lesions underwent targeted cores (mpMRI-TPBx and PSMA-TPBx) combined with transperineal saturation prostate biopsy (SPBx: median 20 cores). Results: Multiparametric MRI and 68Ga-PSMA PET/CT showed 18/40 (45%) and 9/40 (22.5%) lesions suspicious for PCa. In 3/40 (7.5%) men a csPCa (GG2) was found; 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. SPBx diagnosed 2/3 (66.6%) vs. 2/3 (66.6%) vs. 3/3 (100%) csPCa, respectively. In detail, mpMRI and 68Ga-PSMA PET/TC demonstrated 16/40 (40%) vs. 7/40 (17.5%) false positive and 1 (33.3%) vs. 1 (33.3%) false negative results. Conclusion: Although 68PSMA PET/CT did not improve the detection for csPCa of SPBx (1 false negative result equal to 33.3% of the cases), at the same time, would have spared 31/40 (77.5%) scheduled biopsies showing a better diagnostic accuracy in comparison with mpMRI (83.3% vs. 70.2%). [ABSTRACT FROM AUTHOR]

BackgroundProstate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a promising yet not curative approach in castration-resistant (CR) prostate cancer (PC). Rational combination therapies may improve treatment efficacy. Here, we explored the effect of androgen receptor blockade (ARB) on PSMA expression visualized by PET and its potential additive effect when combined with 177Lu-PSMA RLT in a mouse model of prostate cancer.MethodsMice bearing human CRPC (C4-2 cells) xenografts were treated with 10 mg/kg enzalutamide (ENZ), with 50 mg/kg bicalutamide (BIC), or vehicle (control) for 21 days. PSMA expression was evaluated by 68Ga-PSMA11 PET/CT and quantified by flow cytometry of tumor fine needle aspirations before treatment and on days 23, 29, 34, and 39 post-therapy induction. For the RLT combination approach, mice bearing C4-2 tumors were treated with 10 mg/kg ENZ or vehicle for 21 days before receiving either 15 MBq (84 GBq/μmol) 177Lu-PSMA617 or vehicle. DNA damage was assessed as phospho-γH2A.X foci in tumor biopsies. Reduction of tumor volume on CT and survival were used as study endpoints.ResultsTumor growth was delayed by ARB while 68Ga-PSMA11 uptake increased up to 2.3-fold over time when compared to controls. ABR-induced upregulation of PSMA expression was confirmed by flow cytometry. Phospho-γH2A.X levels increased 1.8- and 3.4-fold at 48 h in response to single treatment ENZ or RLT and ENZ+RLT, respectively. Despite significantly greater DNA damage and persistent increase of PSMA expression at the time of RLT, no additional tumor growth retardation was observed in the ENZ+RLT group (vs. RLT only, p = 0.372 at day 81). Median survival did not improve significantly when ENZ was combined with RLT.ConclusionARB-mediated increases in PSMA expression in PC xenografts were evident by 68Ga-PSMA11 PET imaging and flow cytometry. 177Lu-PSMA617 effectively decreased C4-2 tumor size. However, while pre-treatment with ARB increased DNA damage significantly, it did not result in synergistic effects when combined with RLT.

Objective: 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.Materials and Methods: This retrospective study included 54 mCRPC patients, who underwent baseline 68Ga-PSMA PET/CT imaging within 1 month 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 12 weeks. Overall survival (OS) was measured from the start of the first-line treatment for mCRPC.Results: 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.Conclusion: The wbPSMA-TV may be a useful tool to reflect tumor burden and predict survival outcomes in patients with mCRPC. [ABSTRACT FROM AUTHOR]

To evaluate the clinical consequences of prostate specific membrane antigen (PSMA) PET/CT for primary staging in patients with ISUP grade 5 (Gleason score ≥9) prostate cancer (PCa), and no definitive distant metastases based on standard imaging. At our tertial referral center, PSMA PET/CT became standard of care from August 2018 for primary staging of prostate cancer given the following criteria: (1) no prior treatment for prostate cancer, (2) ISUP grade 5, (3) no definitive metastases on standard imaging (contrast enhanced CT and bone scintigraphy), and (4) deemed suitable for treatment with curative intent based on comorbidity and life expectancy. We present the preliminary results of first six months recruitment with 12 months of follow-up. Forty-eight patients (mean age 69 years, median PSA 13.0 ng/mL, 20 patients with locally advanced PCa) were included. CT was positive in pelvic lymph nodes in two patients, bone scintigraphy was equivocal in three patients. PSMA PET/CT showed pathological uptake outside the prostatic bed in 22 patients (46%) of which 13 patients (27%) showed lesions confined to regional lymph nodes, and nine patients (19%) showed nonregional lymph node metastases and/or bone metastases. PSMA PET/CT changed the treatment strategy from curatively intended treatment to palliative treatment in 18 patients (38%) PMSA PET/CT revealed pathological uptake in a large proportion of high-risk patients at primary staging among patients with no definite metastases on standard imaging leading to change of patient management in 38% of the patients. [ABSTRACT FROM AUTHOR]

A 78-year-old man with newly diagnosed high-risk prostate cancer underwent 68Ga-PSMA PET/CT for primary staging. This showed a single, very intense PSMA uptake in the vertebral body of Th2, without discrete morphological changes on low-dose CT. Thus, the patient was considered oligometastatic and underwent MRI of the spine for stereotactic radiotherapy planning. MRI demonstrated an atypical hemangioma in Th2. A bone algorithm CT scan confirmed the MRI findings. The treatment was changed, and the patient underwent a prostatectomy with no concomitant therapy. At three and six months after the prostatectomy, the patient had an unmeasurable PSA level, confirming the benign etiology of the lesion. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomog-raphy (PET/CT) vs. multiparametric magnetic resonance imag-ing (mpMRI) targeted biopsy (TPBx) in the diagnosis of clinical-ly significant prostate cancer (csPCa: Grade Group ≥ 2). Materials and methods: From January 2021 to June 2022, 100 patients (median age: 66 years) with negative digital rectal examination underwent transperineal prostate biopsy for abnor-mal PSA values (median 7.5 ng/ml). Before prostate biopsy, all patients underwent mpMRI and 68Ga-PET/CT examinations and mpMRI (PI-RADS version 2 ≥ 3) or 68Ga-PET/CT index lesions suspicious for cancer (SUVmax > 5 g/ml) underwent cognitive targeted cores (mpMRI-TPBx and PSMA-TPBx: four cores) com-bined with extended systematic prostate biopsy (eSPBx: median 18 cores). The procedure was performed transperineally using a tru-cut 18-gauge needle under sedation and antibiotic prophy-laxis. Results: PCa was found in 58/100 (58.0%) men; in detail, 44/58 (75.9%) were csPCa; mpMRI and 68Ga-PSMA showed 66/100 (66%) and 62/100 (60%) lesions suspicious for PCa, respective-ly. 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. eSPBx diagnosed 42 (95.4%) vs. 36 (81.8%) vs. 30 (68.2%) csPCa, respectively; mpMRI-TPBx vs. 68Ga-PSMA-TPBx showed a diagnostic accuracy of 76.9% vs. 84.9% in diagnosing csPCa. Conclusions: 68GaPSMA PET/CT TPBx demonstrated good accuracy in the diagnosis of csPCa, which was not inferior to mpMRI TPBx (84.9% vs. 76.9%) improving the detection rate for cancer of systematic biopsy.

Introduction: To evaluate the diagnostic accuracy of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) vs. multiparametric magnetic resonance imaging (mpMRI) targeted biopsy (TPBx) in the diagnosis of clinically significant prostate cancer (csPCa: Grade Group = 2). Materials and Methods: From January 2021 to June 2022, 100 patients (median age: 66 years) with negative digital rectal examination underwent transperineal prostate biopsy for abnormal PSA values (median 7.5 ng/ml). Before prostate biopsy, all patients underwent mpMRI and 68Ga-PET/CT examinations and mpMRI (PI-RADS version 2 ≥ 3) or 68Ga-PET/CT index lesions suspicious for cancer (SUVmax > 5 g/ml) underwent cognitive targeted cores (mpMRI-TPBx and PSMA-TPBx: four cores) combined with extended systematic prostate biopsy (eSPBx: median 18 cores). The procedure was performed transperineally using a tru-cut 18-gauge needle under sedation and antibiotic prophylaxis. Results: PCa was found in 58/100 (58.0%) men; in detail, 44/58 (75.9%) were csPCa; mpMRI and 68Ga-PSMA showed 66/100 (66%) and 62/100 (60%) lesions suspicious for PCa, respectively. 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. eSPBx diagnosed 42 (95.4%) vs. 36 (81.8%) vs. 30 (68.2%) csPCa, respectively; mpMRI-TPBx vs. 68Ga-PSMA-TPBx showed a diagnostic accuracy of 76.9% vs. 84.9% in diagnosing csPCa. Conclusions: 68GaPSMA PET/CT TPBx demonstrated good accuracy in the diagnosis of csPCa, which was not inferior to mpMRI TPBx (84.9% vs. 76.9%) improving the detection rate for cancer of systematic biopsy. [ABSTRACT FROM AUTHOR]

Background: To evaluate the accuracy of 68Ga-prostate specific membrane antigen (PSMA) PET/CT in the diagnosis of clinically significant prostate cancer (csPCa) (Grade Group > 2) in men enrolled in Active Surveillance (AS) protocol. Methods: From May 2013 to May 2021, 173 men with very low-risk PCa were enrolled in an AS protocol study. During the follow-up, 38/173 (22%) men were upgraded and 8/173 (4.6%) decided to leave the AS protocol. After four years from confirmatory biopsy (range: 48–52 months), 30/127 (23.6%) consecutive patients were submitted to mpMRI and 68Ga-PSMA PET/CT scan before scheduled repeated biopsy. All the mpMRI (PI-RADS > 3) and 68Ga-PET/TC standardised uptake value (SUVmax) > 5 g/mL index lesions underwent targeted cores (mpMRI-TPBx and PSMA-TPBx) combined with transperineal saturation prostate biopsy (SPBx: median 20 cores). Results: mpMRI and 68Ga-PSMA PET/CT showed 14/30 (46.6%) and 6/30 (20%) lesions suspicious for PCa. In 2/30 (6.6%) men, a csPCa was found; 68Ga-PSMA-TPBx vs. mpMRI-TPBx vs. SPBx diagnosed 1/2 (50%) vs. 1/2 (50%) vs. 2/2 (100%) csPCa, respectively. In detail, mpMRI and 68Ga-PSMA PET/TC demonstrated 13/30 (43.3%) vs. 5/30 (16.7%) false positive and 1 (50%) vs. 1 (50%) false negative results. Conclusion: 68Ga-PSMA PET/CT did not improve the detection for csPCa of SPBx but would have spared 24/30 (80%) scheduled biopsies showing a lower false positive rate in comparison with mpMRI (20% vs. 43.3%) and a negative predictive value of 85.7% vs. 57.1%, respectively. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer diagnosis is shifting towards a minimally invasive approach, maintaining accuracy and efficacy while reducing morbidity. We aimed to assess if PSMA–Ga68 PET/CT can accurately grade and localise prostatic malignancy using objective methods, compared with pathology and MRI. Methods: Retrospective analysis on 114 consecutive patients undergoing staging PSMA PET/CT scans over 12 months was carried out. The SUVmax and site of highest PSMA activity within the prostate gland were recorded. Pathology/biopsy review assessed maximum Gleason score (and location). MRI analysis assessed the highest PIRADS score and location. The grade, location and size of malignant tissue on biopsy, and PSA, were correlated with the SUVmax and the PIRADS score. Results: SUVmax was significantly elevated in cases with PSA ≥10 (P = 0.003) and Gleason score ≥8 (P = 0.0002). SUVmax demonstrated equivalent sensitivity to MRI‐PIRADS in predicting Gleason ≥8 disease, with higher specificity when tested under a high‐specificity regime (SUVmax ≥10, PIRADS = 5, P = 0.002). Furthermore, the region of highest SUVmax was superior to MRI‐PIRADS for localising the highest grade tumour region, correctly identifying 71% of highest grade regions compared to 54% with MRI (P = 0.015). Conclusion: PSMA PET/CT is as effective as MRI in identifying high‐grade prostate malignancy. Our findings also support previous studies in showing a significant relationship between SUVmax and Gleason grade. These benefits, along with the known advantage in identifying distant metastases and the reduced cost, further support the argument that PSMA PET/CT should be offered as an initial investigation in the workup of prostate cancer. [ABSTRACT FROM AUTHOR]

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the diagnostic power of 68Ga-PSMA PET/CT in the detection of metastatic spread of newly diagnosed PCa, and evaluate the relationship with modified D'Amico risk classification. Methods: We evaluated newly diagnosed PCa patients who underwent 68Ga-PSMA PET/CT prior to therapy. All images were interpreted retrospectively and areas of abnormally increased tracer uptake were documented according to PSMA-RADS version 1.0 system. Patients were divided into risk groups as low, intermediate, or high risk, according to a modification in D'Amico classification system as ISUP grade 3 tumors were included to high-risk group. 68Ga-PSMA PET/CT findings were compared among risk groups as well as PSA levels, clinical T stages, and ISUP grades. Results: A total of 356 patients were included to the study with a median PSA level was 16.42 (1.29–7013) ng/ml and median Gleason score was 8 (range: 6–10). Of these, 13(3.7%), 54 (15.1%), and 289 (81.2%) were in the low-, intermediate-, and high-risk groups, respectively. Lymph node metastases were detected in 125 (35.1%) patients, and in 48 of them, metastasis was limited to pelvic lymph nodes (PLN). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated as 71.4%, 100%, 95.9%, 100%, and 95.4%, respectively for the detection of PLN, based on histopathological results of 49 patients. Overall, any metastasis was detected in 47.7% of high-risk patients, while only PLN metastases were defined in 3.7% intermediate-risk patients and none of low-risk patients had any kind of metastasis. Conclusion: This study revealed that 68Ga-PSMA PET/CT should be routinely used in newly diagnosed high-risk PCa patients; whereas it seems to be of limited use for intermediate-risk group and useless for the low-risk group. [ABSTRACT FROM AUTHOR]

Objectives: Prostate cancer metastasizing to the brain is remarkably uncommon, with the incidence never having been described in the modern setting. The objective of this study was to determine the incidence and imaging pattern of intracranial metastasis from prostate cancer in a large cohort of Australian men with prostate cancer. Material and Methods: Retrospective review was undertaken of imaging reports for all known prostate cancer patients, who underwent an imaging examination inclusive of the brain, between July 1, 2014, and July 1, 2020. Once an intracranial lesion was identified, all available imaging and clinical notes were reviewed. Results: A total of 5644 imaging examinations which included the brain were identified in 4341 prostate cancer patients. The majority (92.1%) of examinations were 68-Gallium-labeled prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT). Eight patients were identified as having an intracranial metastasis from prostate cancer, yielding an incidence of 0.18%. All patients had a Gleason score of 9 (where known), and the majority of patients (5/8) had a non-acinar variant of prostate cancer. At the time of diagnosis of intracranial metastasis, all patients had extensive metastatic disease. Imaging characteristics of the intracranial lesions were highly variable. Conclusion: The incidence of intracranial metastasis in prostate cancer patients has never been well-established. In this study, we determined the incidence as being 0.18%. Given the majority of metastasis constituted unexpected findings on routine restaging 68Ga-PSMA PET/CT, the incidence determined in our study is arguably the most accurate and clinically relevant described to date. [ABSTRACT FROM AUTHOR]

Purpose: 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is valuable for detecting primary and recurrent prostatic lesions. This study aimed to evaluate the efficacy of 68Ga-PSMA-11 PET/CT as a triage tool for prostate biopsy (PSMA-TB) and compare with transrectal ultrasound-guided biopsy (TRUS-GB) for the diagnosis of clinically significant prostate cancer (csPCa). Methods: This single-centre study randomly allocated 120 patients with elevated serum prostate-specific antigen (PSA) levels (> 4 ng/ml) to PSMA-PET or TRUS group. Patients with PSMA-avid lesions (SUVmax ≥ 8.0) underwent PSMA-TB via a single-puncture percutaneous transgluteal approach (n = 25), whilst patients with negative PSMA-PET underwent systematic TRUS-GB (n = 35). All patients in the TRUS group underwent TRUS-GB directly (n = 60). Results: PCa and csPCa were detected in 26/60 (43.3%) and 24/60 (40.0%) patients in the PSMA-PET group and 19/60 (31.6%) and 15/60 (25.0%) in the TRUS group, respectively. In the PSMA-PET group, the detection rate of PCa and csPCa were significantly higher in PSMA-PET-positive than negative patients (PCa, 23/25 (92.0%) vs 3/35 (8.6%), P < 0.01; csPCa, 22/25 (88.0%) vs 2/35 (5.7%), P < 0.01). PSMA-TB detected significantly more PCa and csPCa than TRUS-GB in the TRUS controls (PCa, 21/25 (84.0%) vs 19/60 (31.6%), P < 0.01; csPCa, 20/25 (80.0%) vs 15/60 (25.0%), P < 0.01). PSMA-PET detected significantly more cases of csPCa amongst patients with PSA 4.0–20.0 ng/ml than TRUS (27.02% vs 8.82%, P < 0.05). No haematuria, urinary retention or pelvic infection was observed after PSMA-TB compare with TRUS-GB. Conclusions: 68Ga-PSMA-11 PET/CT is a feasible imaging technique that may serve as a triage tool for prostate biopsy, and may improve the detection rate of csPCa compared with TRUS-GB, especially in patients with serum PSA 4.0–20.0 ng/ml. [ABSTRACT FROM AUTHOR]

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings.

Abstract Background Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a promising yet not curative approach in castration-resistant (CR) prostate cancer (PC). Rational combination therapies may improve treatment efficacy. Here, we explored the effect of androgen receptor blockade (ARB) on PSMA expression visualized by PET and its potential additive effect when combined with 177Lu-PSMA RLT in a mouse model of prostate cancer. Methods Mice bearing human CRPC (C4-2 cells) xenografts were treated with 10 mg/kg enzalutamide (ENZ), with 50 mg/kg bicalutamide (BIC), or vehicle (control) for 21 days. PSMA expression was evaluated by 68Ga-PSMA11 PET/CT and quantified by flow cytometry of tumor fine needle aspirations before treatment and on days 23, 29, 34, and 39 post-therapy induction. For the RLT combination approach, mice bearing C4-2 tumors were treated with 10 mg/kg ENZ or vehicle for 21 days before receiving either 15 MBq (84 GBq/μmol) 177Lu-PSMA617 or vehicle. DNA damage was assessed as phospho-γH2A.X foci in tumor biopsies. Reduction of tumor volume on CT and survival were used as study endpoints. Results Tumor growth was delayed by ARB while 68Ga-PSMA11 uptake increased up to 2.3-fold over time when compared to controls. ABR-induced upregulation of PSMA expression was confirmed by flow cytometry. Phospho-γH2A.X levels increased 1.8- and 3.4-fold at 48 h in response to single treatment ENZ or RLT and ENZ+RLT, respectively. Despite significantly greater DNA damage and persistent increase of PSMA expression at the time of RLT, no additional tumor growth retardation was observed in the ENZ+RLT group (vs. RLT only, p = 0.372 at day 81). Median survival did not improve significantly when ENZ was combined with RLT. Conclusion ARB-mediated increases in PSMA expression in PC xenografts were evident by 68Ga-PSMA11 PET imaging and flow cytometry. 177Lu-PSMA617 effectively decreased C4-2 tumor size. However, while pre-treatment with ARB increased DNA damage significantly, it did not result in synergistic effects when combined with RLT.

Objective: We evaluated the impact of 68Ga-PSMA PET/CT (PSMA PET) on therapy management of newly diagnosed highrisk prostate cancer (PCa). Material and Method: Patients who underwent a PSMA PET for primary staging of high-risk PCa were evaluated retrospectively. Patients had abdominopelvic CT (n=126), pelvic MRI (n=42) and bone scintigraphy (BS) (n=40) prior to PSMA PET. All clinical, biochemical, and imaging data were documented. Increased PSMA uptakes related to PCa were documented according to previously described PSMA-RADS version 1.0 based on a fivepoint scale. The impact of PSMA PET on patient management was evaluated through pre and post PET/CT questionnaires, retrospectively. Management changes were categorized as inter or intramodality change, based on PSMA PET results. Paired samples t-test was used to compare subgroups in SPSS version 24.0 software. A p-value <0.05 was considered significant. Results: A total of 126 patients were included in the study. The median PSA level was 30.8 ng/ml (95%CI: 2.1-268.6 ng/ml) and median GS was 8 (range: 6-10). Based on the PSMA PET findings, 41 patients (32.5%) had more extensive disease and 2 patients (1.6%) had less extensive disease. Overall, therapy management was changed in 38 patients (30.1%). Intermodality changes occurred in 29 patients (23%), and intramodality changes occurred in 9 patients (7.1%). The change in management was similar in patients with BS and without BS, 30% vs. 30.2%. Conclusion: PSMA PET impacted the therapy management in almost one-third of patients in high-risk PCa even though they had already been staged with standard imaging modalities. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical value of 68Ga-PSMA PET/CT negativity in patients with biochemical recurrent prostate cancer (BCR). Methods: One hundred three BCR patients (median age, 70 years; median PSA, 0.47 ng/mL) with negative 68Ga-PSMA PET/CT, followed up for at least 1 year, were retrospectively identified in a database of 1003 consecutive patients undergoing 68Ga-PSMA PET/CT for BCR. Clinical recurrence (CR) was determined or excluded on follow-up imaging selected as per clinical practice. Clinical recurrence-free survival (CRFS) was computed from the date of negative 68Ga-PSMA PET/CT to the date of evident disease; frequencies of CRFS were described as per ISUP patient subset (subset 1: ISUP grades 1 and 2; subset 2: ISUP grade 3; subset 3: ISUP grades 4 and 5) and other conventional variables. Results: In 57 patients out of 103 (55.3%), CR was detected in the prostatic fossa (45.6%), nodes (38.6%), and bone (15.8%). The median CRFS was 15.4 months (range, 12.1–20.5), with a CRFS at 12 months in 61.4% of cases (range, 50.9–70.4) whereas the 24-month CRFS was 34.8% (range, 24–45.8). ISUP subset 1 benefited from significantly longer CRFS compared to subset 2 and subset 3 (median CRFS, 20.5 months, 12.6 months, and 12.1 months, respectively). ISUP subset 3 had significantly poorer 24-month CRFS (9.3%) compared to subset 1 (47.8%) and subset 2 (33.5%). At the univariate and multivariate analyses, the ISUP subset was the only significant risk factor for clinical relapse; ISUP subset 3 and subset 2 patients held a higher risk of CR compared to subset 1 patients (HR of 2.75 [1.35–5.57] for subset 3 versus subset 1; HR of 2.08 [1.11–3.88] for subset 2 versus subset 1). Conclusion: 68Ga-PSMA PET/CT negativity in early BCR patients (PSA < 0.5 ng/mL) with low-grade primary prostate cancer (ISUP1 and 2) may support the exploration of a clinical surveillance approach in future prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic performance of 68Ga-PSMA PET/TC with PRI-MUS (prostate risk identification using micro-ultrasound) in the primary diagnosis of prostate cancer (PCa). Methods: From September till December 2018, we prospectively enrolled 25 candidates to 68Ga-PSMA PET/TRUS (transrectal ultrasound) fusion biopsy and compared them with PRI-MUS. This included patients with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, with either negative or contraindication to mpMRI, and at least one negative biopsy. The diagnostic performance of the two modalities was calculated based on pathology results. Results: Overall, 20 patients were addressed to 68Ga-PSMA PET/TRUS fusion biopsy. Mean SUVmax and SUVratio for PCa lesions resulted significantly higher than in benign lesions (p = 0.041 and 0.011, respectively). Using optimal cut-off points, 68Ga-PSMA PET/CT demonstrated an overall accuracy of 83% for SUVmax ≥ 5.4 and 94% for SUVratio ≥ 2.2 in the detection of clinically significant PCa (GS ≥ 7). On counterpart, PRI-MUS results were: score 3 in nine patients (45%), score 4 in ten patients (50%), and one patient with score 5. PRI-MUS score 4 and 5 demonstrated an overall accuracy of 61% in detecting clinically significant PCa. Conclusion: In this highly-selected patient population, in comparison to PRI-MUS, 68Ga-PSMA PET/CT shows a higher diagnostic performance. [ABSTRACT FROM AUTHOR]

Objective: The objective of this research was to examine the prostate-specific membrane antigen (PSMA)-positive secondary tumor incidence in 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) imaging in patients with prostate cancer (PCa). Methods: Data from 605 68Ga-PSMA PET/CT images of 506 PCa patients used for staging or restaging were analyzed retrospectively. Further, documented separately, PSMA-positive lesions were found not to be PCa-related and were then suspected as secondary tumors. The results were analyzed from those lesions that were histopathologically verified. Results: Nine patients (1.8%) had a PSMA-positive lesion that was believed to be a secondary tumor. Of these lesions, five (1%) were histopathologically confirmed, and secondary tumors were diagnosed (namely, squamous cell non-small cell lung cancer, papillary thyroid cancer (TCa) lymph node metastasis, minimally invasive TCa, colon cancer and liver metastases, and fibrohistiocytic tumor). The mean serum PSA value for patients diagnosed with secondary tumor was 29.42 (0.01-142.22) ng/mL. For PSMA-positive secondary tumor lesions, the mean maximum standard unit value was 9.74 (3.9-15). Conclusion: Especially in the presence of atypical location and insufficient serum PSA values, PSMA-positive lesions should be considered secondary tumors, and differential diagnostic studies should be conducted. [ABSTRACT FROM AUTHOR]

Although prostate cancer can metastasize to any part of the body, isolated testicular metastasis is very rare and only few cases have been reported so far. Here we present a case of 65-year-old male patient, known case of prostate adenocarcinoma, referred for 68Ga-PSMA PET/CT scan, post radiotherapy, and androgen deprivation therapy, for rising serum PSA levels. He was found to have an isolated testicular metastasis on the scan. This report highlights the importance of 68Ga-PSMA PET-CT scan in detecting these unusual and rare sites of metastasis from prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer commonly metastasises to bone and regional lymphatics and more rarely to locations such as the brain, skin and penis. Gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has widely become the routine imaging modality for prostate cancer staging and re-staging in Australia. The aim of this study was to retrospectively review all 68 Ga-PSMA PET/CT examinations performed to date at our institution to determine the frequency of penile metastases.Methods: A total of 4860 68 Ga-PSMA PET/CT examinations were performed between 16/07/2014 and 31/10/2019. Radiology reports for each examination were filtered to identify those with the words 'penis' or 'penile'. Once identified, relevant reports and images were individually reviewed to confirm the presence of a PSMA-avid penile lesion.Results: The incidence of penile metastasis of prostate cancer observed in this study was 0.1% with six examinations identified as having PSMA-avid penile lesions in five prostate cancer patients (age range: 71-88 years). The patients had a 1-8 year history of prostate cancer with varying severity of disease. Appearance of PSMA-avidity varied between single focal lesion, multiple focal lesions and diffuse lesion.Conclusions: An incidence of 0.1% in our study confirms the rarity of penile metastases of prostate cancer. Although rare, identification of prostate cancer penile metastases is important for appropriate treatment management and symptom-relief. [ABSTRACT FROM AUTHOR]

Objectives: To examine the anatomical distribution of prostate cancer (PCa) recurrence on gallium‐68 prostate‐specific membrane antigen (68Ga‐PSMA) positron‐emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after undergoing radical prostatectomy (RP) with pathological lymph node metastasis (pN1) in their extended pelvic lymph node dissection (ePLND), and to compare the location of PCa recurrence with the location of the initial lymph node metastasis at ePLND. Materials and Methods: We retrospectively reviewed 100 patients with BCR (PSA 0.05–5.00 ng/mL) after RP with pN1 ePLND who underwent 68Ga‐PSMA PET/CT to guide salvage therapy. Clinical and pathological features and anatomical locations of PCa recurrence on 68Ga‐PSMA PET/CT were obtained, and management impact was recorded. Results: In all, 68 patients (68%) had a positive and 32 patients (32%) had a negative 68Ga‐PSMA PET/CT result. Of the 68 patients with a positive 68Ga‐PSMA PET/CT, 44 (65%) showed abnormal uptake only in the pelvic area, seven (10%) only outside the pelvic area, and 17 (25%) both within and outside the pelvic area. 68Ga‐PSMA PET/CT‐positive pelvic lymph nodes were often (84%) detected on the same side as the lymph node metastasis diagnosed at ePLND. Based on the outcomes of the 68Ga‐PSMA PET/CT, change of management was noted in 68% of the patients. Conclusion: Recurrence of PCa on 68Ga‐PSMA PET/CT was limited to the pelvis in the majority of patients with BCR after RP with pN1 ePLND. Moreover, recurrence was often detected on the same side as the lymph node metastasis at ePLND. The results confirm the diagnostic value of 68Ga‐PSMA PET/CT in patients with BCR after RP with pN1 ePLND. Prospective studies are needed to support the long‐term benefit of 68Ga‐PSMA PET/CT‐dictated management changes. [ABSTRACT FROM AUTHOR]

Objectives: To review the literature to determine the sensitivity and specificity of gallium‐68 prostate‐specific membrane antigen (68Ga‐PSMA) positron‐emission tomography (PET) for detecting pelvic lymph node metastases in patients with primary prostate cancer (PCa), and the positive predictive value in patients with biochemical recurrence (BCR) after initial curative treatment, and, in addition, to determine the detection rate and management impact of 68Ga‐PSMA PET in patients with BCR after radical prostatectomy (RP). Materials and Methods: We performed a comprehensive literature search. Search terms used in MEDLINE, EMBASE and Science Direct were '(PSMA, 68Ga‐PSMA, 68Gallium‐PSMA, Ga‐68‐PSMA or prostate‐specific membrane antigen)' and '(histology, lymph node, staging, sensitivity, specificity, positive predictive value, recurrence, recurrent or detection)'. Relevant abstracts were reviewed and full‐text articles obtained where possible. References to and from obtained articles were searched to identify further relevant articles. Results: Nine retrospective and two prospective studies described the sensitivity and specificity of 68Ga‐PSMA PET for detecting pelvic lymph node metastases before initial treatment, which ranged from 33.3% to 100% and 80% to 100%, respectively. In eight retrospective studies, the positive predictive value of 68Ga‐PSMA PET in patients with BCR before salvage lymph node dissection ranged from 70% to 100%. The detection rate of 68Ga‐PSMA PET in patients with BCR after RP in the PSA subgroups <0.2 ng/mL, 0.2–0.49 ng/mL and 0.5 to <1.0 ng/mL ranged from 11.3% to 50.0%, 20.0% to 72.7% and 25.0% to 87.5%, respectively. Conclusion: The review results showed that 68Ga‐PSMA PET had a high specificity for the detection of pelvic lymph node metastases in primary PCa. Furthermore, 68Ga‐PSMA PET had a very high positive predictive value in detecting lymph node metastases in patients with BCR. By contrast, sensitivity was only moderate; therefore, based on the currently available literature, 68Ga‐PSMA PET cannot yet replace pelvic lymph node dissection to exclude lymph node metastases. In the salvage phase, 68Ga‐PSMA PET had both a high detection rate and impact on radiotherapy planning in early BCR after RP. [ABSTRACT FROM AUTHOR]

Abstract Background To determine the potential role of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in radiotherapy (RT) planning for prostate cancer (PCa). Methods One hundred twenty-nine patients (pts) with 68Ga-PSMA PET/CT were retrospectively analysed. Potentially influencing factors (androgen deprivation therapy, amount of 68Ga-PSMA-HBED-CC, PSA doubling time ≤/> 10 months, PSA before PET/CT, T−/N-category and Gleason score) were evaluated by logistic regression analysis. The detection rate of PSMA PET/CT was compared to contrast enhanced CT and its impact on RT management analysed. Results One hundred twenty-nine patients (pts) (20 at initial diagnosis, 49 with PSA relapse and 60 with PSA persistence after radical prostatectomy) received PSMA PET/CT prior to RT. The majority of pts. (71.3%) had PET-positive findings (55.1% of pts. with PSA recurrence, 75% of pts. with PSA persistence and 100% of newly diagnosed pts). Median PSA before PET/CT in pts. with pathological findings (n = 92) was 1.90 ng/ml and without (n = 37) 0.30 ng/ml. PSA level at time of PET/CT was the only factor associated with PET-positivity. In pts. with a PSA ≤ 0.2 ng/ml, the detection rate of any lesion was 33.3%, with a PSA of 0.21–0.5 ng/ml 41.2% and with a PSA of 0.51–1.0 ng/ml 69.2%, respectively. Regarding the anatomic distribution of lesions, 42.2% and 14.7% of pts. with relapse or persistence had pelvic lymph node and distant metastases. In pts. at initial diagnosis the detection rate of pelvic lymph nodes and distant metastases was 20% and 10%. 68Ga-PSMA PET/CT had a high detection rate of PCa recurrence outside the prostatic fossa in pts. being considered for salvage RT (22.4% PET-positive pelvic lymph nodes and 4.1% distant metastases). Compared to CT, PSMA PET/CT had a significantly higher sensitivity in diagnosing rates of local recurrence/primary tumour (10.1% vs. 38%), lymph nodes (15.5% vs. 38.8%) and distant metastases (5.4% vs. 14.0%). This resulted in a modification of RT treatment in 56.6% of pts. Conclusions The detection of PCa is strongly associated with PSA level at time of 68Ga-PSMA PET/CT. PSMA PET/CT differentiates between local, regional and distant metastatic disease with implications for disease management. PSMA PET/CT allows for tumour detection in post-prostatectomy pts. with PSA ≤ 0.5 ng/ml considered for salvage RT.

In this systematic review and meta-analysis, the diagnostic performance of 68 Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of 18 F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of 18 F-DCFPyL PET and 68 Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of 18 F-DCFPyL PET and 68 Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of 18 F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For 68 Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. 18 F-DCFPyL PET and 68 Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for 18 F-DCFPyL PET and 68 Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for 18 F-DCFPyL PET and 68 Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Jiang et al.)