Radionuclide probes-targeted prostate-specific membrane antigen (PSMA) is used in diagnosis and treatment of prostate cancer (PCa). Recent studies have shown that PSMA is expressed in the tumor neovascular endothelium, such as in malignant liver tumors. We report a case of PCa with incidental intrahepatic cholangiocarcinoma (ICC) detection using 18F-PSMA-1007 and 18F-fluorodeoxyglucose (FDG) positron emission topography (PET)/MRI.18F-PSMA-1007 PET/MRI of our patient with PCa showed that one liver lesion had high PSMA uptake. 18F-FDG PET/MRI revealed minimal FDG uptake in the liver lesion. Histopathological examination revealed that the liver lesion was moderately to poorly differentiated cholangiocarcinoma. Our studies, along with others, demonstrated that malignant liver tumors, such as ICC, hepatocellular carcinoma (HCC), and combined hepatocellular-cholangiocarcinoma (CHC), and benign lesions, such as benign liver hemangioma, focal nodular hyperplasia, focal inflammation and steatosis, vascular malformation, and fatty sparing, exhibited elevated PSMA uptake. Moreover, PSMA-PET was superior to FDG-PET in detecting ICC and HCC, indicating that PSMA-PET may be used as alternative staging and to identify patients for PSMA-targeted therapy.

Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of multiple solid tumors, including renal cell carcinoma (RCC). Studies have demonstrated promising results on the utility of PSMA-targeted PET/CT imaging in RCC. This report aims to provide a systematic review and metaanalysis on the utility and detection rate of PSMA PET/CT imaging in staging or evaluation of primary RCC and restaging of metastatic or recurrent RCC. Methods: Searches were performed in PubMed, Embase, and abstract proceedings (last updated, August 2023). Studies that provided a lesion-level detection rate of PSMA radiotracers in staging or restaging of RCC were included in the metaanalysis. The overall pooled detection rate with a 95% CI was estimated, and subgroup analysis was performed when feasible. Results: Nine studies comprising 152 patients (133 clear cell RCC [ccRCC], 19 other RCC subtypes) were included in the metaanalysis. The pooled detection rate of PSMA PET/CT in evaluation of primary or metastatic RCC was estimated to be 0.83 (95% CI, 0.67-0.92). Subgroup analysis showed a pooled PSMA detection rate of 0.74 (95% CI, 0.57-0.86) in staging or evaluation of primary RCC lesions and 0.87 (95% CI, 0.73-0.95) in restaging of metastatic or recurrent RCC. Analysis based on the type of radiotracer showed a pooled detection rate of 0.85 (95% CI, 0.62-0.95) for 68Ga-based PSMA tracers and 0.92 (95% CI, 0.76-0.97) for 18F-DCFPyL PET/CT. Furthermore, in metastatic ccRCC, the available data support a significantly higher detection rate for 18F-DCFPyL PET/CT than for conventional imaging modalities (2 studies). Conclusion: Our preliminary results show that PSMA PET/CT could be a promising alternative imaging modality for evaluating RCC, particularly metastatic ccRCC. Large prospective studies are warranted to confirm clinical utility in the staging and restaging of RCC.

BACKGROUND: active surveillance (AS) is a suitable strategy for patients with prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging is an established tool used to assess PCa. The aim of this review was to evaluate the role of PSMA imaging to guide correct risk-based classification and the AS approach in PCa patients.
METHODS: The Scopus, Embase, Web of Science, Cochrane Library, and PubMed/MEDLINE databases were screened to find relevant published articles.
RESULTS: 1774 articles were revealed with the literature search. A total of 1764 articles were excluded after applying exclusion criteria (data not within the field of interest, preclinical papers, conference proceedings, reviews, or editorials). Ten studies were finally included in the review, revealing that PSMA PET could have the ability to guide risk-based classification of PCa and the choice of AS, and to guide the execution of biopsies for the research of high-grade PCa, therefore precluding AS.
CONCLUSIONS: this systematic review underlined a possible role of PSMA PET imaging in patients with PCa by correctly re-classifying them on the basis of their risk and guiding AS.

Prostate cancer accounts for a significant proportion of cancer diagnoses in Canadian men. Over the past decade, the therapeutic landscape for the management of metastatic prostate cancer has undergone rapid changes. Novel strategies use hormonal agents, chemotherapy, homologous recombination repair inhibitors, and radioligand therapy or combination strategies in addition to androgen deprivation therapy. In this review, we summarize the available data addressing key therapeutic areas along the disease continuum and focus on practical aspects for general practitioners in oncology managing patients with metastatic prostate cancer.

Fluoro-deoxy glucose positron emission tomography/computed tomography (PET/CT), the workhorse of nuclear medicine, has limited utility for renal cell carcinoma (RCC), particularly clear cell variant. Thus, various other tracers have been tried for evaluation of RCC. One of the most promising targets for radiotracers is prostate-specific membrane antigen (PSMA) expressed in abundance in carcinoma-associated neo-vasculature. Thus, we tried to review and analyse the role of PSMA-targeted PET/CT in evaluation of RCC. Databases like PubMed, EMBASE and SCOPUS were searched for original studies published on PSMA-targeted PET/CT in RCC till 30 September 2023. Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist was used to assess the included studies. Pooled sensitivity and specificity were calculated and represented with 95% confidence intervals (95%CI). Heterogeneity in the studies was assessed by I-square index. Pooled sensitivity and specificity of PSMA-targeted PET/CT for detection of local disease estimates were 87.2% (95%CI: 77-94%) and 100% (95%CI: 92.9-100%), respectively. Pooled sensitivity and specificity for detection of local recurrent disease are 100% (95%CI: 71.5-100%) and 100% (95%CI: 89.4-100%), respectively. Pooled sensitivity and specificity for detection of metastatic disease are 92% (95%CI: 86.2-96%) and 96.9% (95%CI: 83.8-99.9%), respectively. Pooled sensitivity of PSMA-targeted PET/CT for detection of clear cell renal cell carcinoma (ccRCC) and non-ccRCC are 94.7% (95%CI: 88-98.3%) and 75% (95%CI: 35-96.8%), respectively. PSMA-targeted PET-CT demonstrated better diagnostic efficacy for the detection of recurrent RCC. Whilst for staging RCC, it had higher specificity but lower sensitivity. Thus, it can serve as a non-invasive adjuvant tool to conventional imaging in the evaluation of staging of RCC, particularly clear cell variant.

OBJECTIVE: The goal of this study was to evaluate the effectiveness of two diagnostic methods, 68Ga-PSMA-11 PET/CT and mpMRI, in detecting primary prostate cancer without limitations on the Gleason score.
METHODS: We conducted a comprehensive literature review, searching databases such as PubMed, Embase, and Web of Science until June 2023. Our objective was to identify studies that compared the efficacy of 68Ga-PSMA-11 PET/CT and mpMRI in detecting primary prostate cancer. To determine heterogeneity, the I2 statistic was used. Meta-regression analysis and leave-one-out sensitivity analysis were conducted to identify potential sources of heterogeneity.
RESULTS: Initially, 1286 publications were found, but after careful evaluation, only 16 studies involving 1227 patients were analyzed thoroughly. The results showed that the 68Ga-PSMA-11 PET/CT method had a pooled sensitivity and specificity of 0.87 (95 % CI: 0.80-0.92) and 0.80 (95 % CI: 0.69-0.89), respectively, for diagnosing prostatic cancer. Similarly, the values for mpMRI were determined as 0.84 (95 % CI: 0.75-0.92) and 0.74 (95 % CI: 0.61-0.86), respectively. There were no significant differences in diagnostic effectiveness observed when comparing two primary prostate cancer methodologies (pooled sensitivity P = 0.62, pooled specificity P = 0.50). Despite this, the funnel plots showed symmetry and the Egger test results (P values > 0.05) suggested there was no publication bias.
CONCLUSIONS: After an extensive meta-analysis, it was found that both 68Ga-PSMA-11 PET/CT and mpMRI demonstrate similar diagnostic effectiveness in detecting primary prostate cancer. Future larger prospective studies are warranted to investigate this issue further.

After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold.
The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2).
In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58-0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias.
A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.

BACKGROUND: Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown.
OBJECTIVE: To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC.
METHODS: Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians.
RESULTS: We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively.
CONCLUSIONS: Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence.
RESULTS: In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.

[18F]DCFPyL is increasingly used for prostate-specific membrane antigen (PSMA) mediated imaging of men with biochemically recurrent prostate cancer (BRPCa). In this meta-analysis, which is updated with the addition of multiple new studies, including the definitive phase III CONDOR trial, we discuss the detection efficiency of [18F]DCFPyL in BRPCa patients. PubMed was searched on 29 September 2022. Studies evaluating the diagnostic performance of [18F]DCFPyL among patients with BRPCa were included. The overall pooled detection rate with a 95% confidence interval (95% CI) was calculated among all included studies and stratified among patients with PSA ≥ 2 vs. <2 ng/mL and with PSA ≥ 0.5 vs. <0.5 ng/mL. The association of detection efficiency with pooled PSA doubling time from two studies was calculated. Seventeen manuscripts, including 2252 patients, met the inclusion criteria and were used for data extraction. A previous meta-analysis reported that the pooled detection rate was 0.81 (95% CI: 0.77-0.85), while our study showed a pooled overall detection rate of 0.73 (95% CI: 0.66-0.79). An increased proportion of positive scans were found in patients with PSA ≥ 2 vs. <2 ng/mL and PSA ≥ 0.5 vs. <0.5 ng/mL. No significant difference was found in detection efficiency between those with PSA doubling time ≥ 12 vs. <12 months. Detection efficiency is statistically related to serum PSA levels but not to PSA doubling time based on available data. The detection efficiency of [18F]DCFPyL in men with BRPCa has trended down since a previous meta-analysis, which may reflect increasingly stringent inclusion criteria for studies over time.

BACKGROUND: After initial treatment of prostate cancer, increases in prostate-specific antigen (PSA) levels commonly signify potential relapse or metastasis. 18F-labeled prostate-specific membrane antigen (PSMA) is considered a promising treatment due to its favorable physical properties.
OBJECTIVE: To investigate the diagnostic value of 18F-PSMA PET/CT for the recurrence and/or metastasis of biochemical recurrence of prostate cancer (BRPca).
METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library databases. Combined sensitivity and specificity values for the use of 18F-PSMA PET/CT in patients with BRPca were obtained. The quality of the studies was tested using the Diagnostic Accuracy Research Quality Assessment tool. Meta-analysis was performed using STATA 15 software, and heterogeneity was subsequently tested.
RESULTS: A total of 16 studies (1162 patients) were enrolled and had significant heterogeneity. The pooled sensitivity, specificity, and AUC values for 18F-PSMA PET/CT in the diagnosis of prostate recurrence and/or metastasis were 0.93 (0.89-0.95), 0.94 (0.85-0.98), and 0.96 (0,94-0.98), respectively. Meta-regression analyses showed that the sources of heterogeneity did not relate to ligands, study designs, or participants. The pooled sensitivity and specificity values of 18F-DCFPyL PET/CT were 0.90 (0.85-0.94) and 0.89 (0.85-0.93), respectively. The pooled sensitivity and specificity values of 18F-PSMA-1007 PET/CT were 0.89 (0.85-0.93) and 0.93 (0.70-0.99), respectively. The per-patient pooled sensitivity and specificity values were 0.92 (0.86-0.96) and 0.83 (0.41-0.97), respectively. The per-lesion pooled sensitivity and specificity values were 0.91 (0.86-0.94) and 0.91 (0.86-0.94), respectively.
CONCLUSIONS: According to our meta-analysis, 18F-PSMA PET/CT has the potential to be critical for the diagnosis of recurrence and/or metastasis in patients with BRPca.