Utility of PSMA PET/CT in Staging and Restaging of Renal Cell Carcinoma: A Systematic Review and Metaanalysis.

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.

Rare genetic variation in VE-PTP is associated with central serous chorioretinopathy, venous dysfunction and glaucoma.

Central serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10-9). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0×10-4) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3×10-11) and glaucoma (OR=0.82, P=6.9×10-9). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases.

Interassay Variability and Clinical Implications of Five Different Prostate-specific Antigen Assays.

Background and objective: Prostate-specific antigen (PSA) remains a critical marker for prostate cancer (PCa) detection and monitoring. Recognising historical variability in PSA assays and the evolution of assay technology and calibration, this study aims to reassess interassay variability using the latest generation of five assays in a contemporary cohort of men undergoing prostate biopsy. Methods: Five different commercially available PSA assays were tested in a blood sample of 76 men before undergoing a prostate biopsy. Total PSA (tPSA) and free-to-total PSA ratio (%fPSA) were compared across assays, using Roche (Basel, Switzerland) as the benchmark, and correlated with biopsy outcome to analyse the impact on PCa diagnosis. The statistical analysis included Passing-Bablok regression and Bland-Altman plots, with a p value threshold of <0.05 for significance. Key findings and limitations: Among the 76 men, 28 (36.8%) were diagnosed with significant PCa (defined as International Society of Urological Pathology grade ≥2). A high correlation was observed between tPSA and %fPSA values among the different PSA assays tested (r2 ≥ 0.9). The Passing-Bablok analysis showed that tPSA results varied substantially among the assays, with slopes ranging between 0.78 and 1.04. Compared with the tPSA of Roche, tPSA values were on average 20.7% lower by Beckman (Oststeinbeck, Germany), 15.2% lower by Abbott (Chicago, IL, USA), 6.1% lower by Diasorin (Saluggia, Italy), and 9.6% higher by Brahms (Hennigsdorf, Germany; p < 0.001 for all). The %fPSA values by Abbott and Brahms were higher at 15.7% and 10.6%, respectively (p < 0.001), while the Beckman and Diasorin values had minimal differences of -0.3% and 2.3%, respectively (p > 0.05). The variability across assays would have resulted in discrepancies in both the sensitivity and the specificity for tPSA and %fPSA by at least 14%, depending on the cut-offs applied. Conclusions and clinical implications: Despite the use of the latest PSA assays, relevant variability of tPSA and %fPSA results can be observed among different assays. There is an urgent need for standardised calibration methods and greater awareness among practitioners concerning interassay variability. Clinicians should acknowledge that clinically relevant thresholds may depend on the specific PSA assay and that ideally the same assay is applied over time for better clinical decision-making. Patient summary: Prostate-specific antigen (PSA) is a critical marker for prostate cancer (PCa) detection and monitoring. However, significant variations were observed in the results of the latest PSA assays. Thus, standardised calibration methods and greater awareness among practitioners concerning interassay variability are needed.

Comparative analysis of in-silico tools in identifying pathogenic variants in dominant inherited retinal diseases.

Inherited retinal diseases (IRDs) are a group of rare genetic eye conditions that cause blindness. Despite progress in identifying genes associated with IRDs, improvements are necessary for classifying rare autosomal dominant (AD) disorders. AD diseases are highly heterogenous, with causal variants being restricted to specific amino acid changes within certain protein domains, making AD conditions difficult to classify. Here, we aim to determine the top-performing in-silico tools for predicting the pathogenicity of AD IRD variants. We annotated variants from ClinVar and benchmarked 39 variant classifier tools on IRD genes, split by inheritance pattern. Using area-under-the-curve (AUC) analysis, we determined the top-performing tools and defined thresholds for variant pathogenicity. Top-performing tools were assessed using genome sequencing on a cohort of participants with IRDs of unknown etiology. MutScore achieved the highest accuracy within AD genes, yielding an AUC of 0.969. When filtering for AD gain-of-function and dominant negative variants, BayesDel had the highest accuracy with an AUC of 0.997. Five participants with variants in NR2E3, RHO, GUCA1A, and GUCY2D were confirmed to have dominantly inherited disease based on pedigree, phenotype, and segregation analysis. We identified two uncharacterized variants in GUCA1A (c.428T>A, p.Ile143Thr) and RHO (c.631C>G, p.His211Asp) in three participants. Our findings support using a multi-classifier approach comprised of new missense classifier tools to identify pathogenic variants in participants with AD IRDs. Our results provide a foundation for improved genetic diagnosis for people with IRDs.

Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.

Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.

Evaluation of Proclarix in the diagnostic work-up of prostate cancer.

Objectives: The use of multiparametric magnetic resonance imaging (mpMRI) has been widely adopted in the diagnostic work-up for suspicious prostate cancer (PCa) and is recommended in most current guidelines. However, mpMRI lesions are often indeterminate and/or turn out to be false-positive on prostate biopsy. The aim of this work was to evaluate Proclarix, a biomarker test for the detection of relevant PCa, regarding its diagnostic value in all men before biopsy and in men with indeterminate lesions on mpMRI (PI-RADS 3) during work-up for PCa. Materials and Methods: Men undergoing mpMRI-targeted and systematic biopsy of the prostate were prospectively enrolled. The Proclarix test was evaluated for the detection accuracy of clinically significant PCa (csPCa) defined as Grade Group ≥ 2 and its association to mpMRI results. Further, Proclarix's performance was also tested when adapted to prostate volume (Proclarix density) and performance compared to PSA density (PSAD). Results: A total of 150 men with a median age of 65 years and median PSA of 5.8 ng/mL were included in this study. CsPCa was diagnosed in 65 (43%) men. Proclarix was significantly associated with csPCa and higher PI-RADS score (p < 0.001). At the pre-defined cut-off of 10%, Proclarix's sensitivity for csPCa was 94%, specificity 19%, negative predictive value 80% and positive predictive value 47%. Proclarix density showed the highest AUC for the detection of csPCa of 0.77 (95%CI: 0.69-0.85) compared to PSA, PSAD and Proclarix alone. Proclarix was able to identify all six csPCa in men with PI-RADS 3 lesions (n = 28), whereas PSAD missed two out of six. At optimized cut-offs, Proclarix density outperformed PSAD by potentially avoiding 41% of unnecessary biopsies. Conclusion: Proclarix demonstrates high sensitivity in detecting csPCa but may still result in unnecessary biopsies. However, Proclarix density was able to outperform PSAD and Proclarix and was found to be useful in men with PI-RADS 3 findings by safely avoiding unnecessary biopsies without missing csPCa.

Validation of a Zero-shot Learning Natural Language Processing Tool to Facilitate Data Abstraction for Urologic Research.

BACKGROUND: Urologic research often requires data abstraction from unstructured text contained within the electronic health record. A number of natural language processing (NLP) tools have been developed to aid with this time-consuming task; however, the generalizability of these tools is typically limited by the need for task-specific training. OBJECTIVE: To describe the development and validation of a zero-shot learning NLP tool to facilitate data abstraction from unstructured text for use in downstream urologic research. DESIGN, SETTING, AND PARTICIPANTS: An NLP tool based on the GPT-3.5 model from OpenAI was developed and compared with three physicians for time to task completion and accuracy for abstracting 14 unique variables from a set of 199 deidentified radical prostatectomy pathology reports. The reports were processed in vectorized and scanned formats to establish the impact of optical character recognition on data abstraction. INTERVENTION: A zero-shot learning NLP tool for data abstraction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The tool was compared with the human abstractors in terms of superiority for data abstraction speed and noninferiority for accuracy. RESULTS AND LIMITATIONS: The human abstractors required a median (interquartile range) of 93 s (72-122 s) per report for data abstraction, whereas the software required a median of 12 s (10-15 s) for the vectorized reports and 15 s (13-17 s) for the scanned reports (p < 0.001 for all paired comparisons). The accuracies of the three human abstractors were 94.7% (95% confidence interval [CI], 93.8-95.5%), 97.8% (95% CI, 97.2-98.3%), and 96.4% (95% CI, 95.6-97%) for the combined set of 2786 data points. The tool had accuracy of 94.2% (95% CI, 93.3-94.9%) for the vectorized reports and was noninferior to the human abstractors at a margin of -10% (α = 0.025). The tool had slightly lower accuracy of 88.7% (95% CI 87.5-89.9%) for the scanned reports, making it noninferior to two of three human abstractors. CONCLUSIONS: The developed zero-shot learning NLP tool offers urologic researchers a highly generalizable and accurate method for data abstraction from unstructured text. An open access version of the tool is available for immediate use by the urologic community. PATIENT SUMMARY: In this report, we describe the design and validation of an artificial intelligence tool for abstracting discrete data from unstructured notes contained within the electronic medical record. This freely available tool, which is based on the GPT-3.5 technology from OpenAI, is intended to facilitate research and scientific discovery by the urologic community.

Immunomodulatory response to neoadjuvant nivolumab in non-metastatic clear cell renal cell carcinoma.

Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.

PET/Computed Tomography Transformation of Oncology: Kidney and Urinary Tract Cancers.

Renal cell carcinoma (RCC) and urothelial carcinoma (UC) are two of the most common genitourinary malignancies. 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) can play an important role in the evaluation of patients with RCC and UC. In addition to the clinical utility of 18F-FDG PET to evaluate for metastatic RCC or UC, the shift in molecular imaging to focus on specific ligand-receptor interactions should provide novel diagnostic and therapeutic opportunities in genitourinary malignancies. In combination with the rise of artificial intelligence, our ability to derive imaging biomarkers that are associated with treatment selection, response assessment, and overall patient prognostication will only improve.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial.

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.

Defining the Role of Large Language Models in Urologic Care and Research.

Large language models such as ChatGPT are poised to transform health care. We envision them being used in the future in urology, albeit with appropriate supervision, to educate patients, guide clinicians and scientists, and automate complex tasks.

Applications of artificial intelligence in prostate cancer histopathology.

The diagnosis of prostate cancer (PCa) depends on the evaluation of core needle biopsies by trained pathologists. Artificial intelligence (AI) derived models have been created to address the challenges posed by pathologists' increasing workload, workforce shortages, and variability in histopathology assessment. These models with histopathological parameters integrated into sophisticated neural networks demonstrate remarkable ability to identify, grade, and predict outcomes for PCa. Though the fully autonomous diagnosis of PCa remains elusive, recently published data suggests that AI has begun to serve as an initial screening tool, an assistant in the form of a real-time interactive interface during histological analysis, and as a second read system to detect false negative diagnoses. Our article aims to describe recent advances and future opportunities for AI in PCa histopathology.

Consensus Guidelines for Ocular Surveillance of von Hippel-Lindau Disease.

PURPOSE: To develop guidelines for ocular surveillance and early intervention for individuals with von Hippel-Lindau (VHL) disease. DESIGN: Systematic review of the literature. PARTICIPANTS: Expert panel of retina specialists and ocular oncologists. METHODS: A consortium of experts on clinical management of all-organ aspects of VHL disease was convened. Working groups with expertise in organ-specific features of VHL disease were tasked with development of evidence-based guidelines for each organ system. The ophthalmology subcommittee formulated questions for consideration and performed a systematic literature review. Evidence was graded for topic quality and relevance and the strength of each recommendation, and guideline recommendations were developed. RESULTS: The quality of evidence was limited, and no controlled clinical trial data were available. Consensus guidelines included: (1) individuals with known or suspected VHL disease should undergo periodic ocular screening (evidence type, III; evidence strength, C; degree of consensus, 2A); (2) patients at risk of VHL disease, including first-degree relatives of patients with known VHL disease, or any patient with single or multifocal retinal hemangioblastomas (RHs), should undergo genetic testing for pathologic VHL disease gene variants as part of an appropriate medical evaluation (III/C/2A); (3) ocular screening should begin within 12 months after birth and continue throughout life (III/C/2A); (4) ocular screening should occur approximately every 6 to 12 months until 30 years of age and then at least yearly thereafter (III/C-D/2A); (5) ocular screening should be performed before a planned pregnancy and every 6 to 12 months during pregnancy (IV/D/2A); (6) ultra-widefield color fundus photography may be helpful in certain circumstances to monitor RHs, and ultra-widefield fluorescein angiography may be helpful in certain circumstances to detect small RHs (IV/D/2A); (7) patients should be managed, whenever possible, by those with subspecialty training, with experience with VHL disease or RHs, or with both and ideally within the context of a multidisciplinary center capable of providing multiorgan surveillance and access to genetic testing (IV/D/2A); (8) extramacular or extrapapillary RHs should be treated promptly (III/C/2A). CONCLUSIONS: Based on available evidence from observational studies, broad agreement was reached for a strategy of lifelong surveillance and early treatment for ocular VHL disease. These guidelines were endorsed by the VHL Alliance and the International Society of Ocular Oncology and were approved by the American Academy of Ophthalmology Board of Trustees. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of Multiple Segmentation Methods for Volumetric Delineation of Primary Prostate Cancer with Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT.

This study aimed to assess the accuracy of intraprostatic tumor volume measurements on prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT made with various segmentation methods. An accurate understanding of tumor volumes versus segmentation techniques is critical for therapy planning, such as radiation dose volume determination and response assessment. Methods: Twenty-five men with clinically localized, high-risk prostate cancer were imaged with 18F-DCFPyL PET/CT before radical prostatectomy. The tumor volumes and tumor-to-prostate ratios (TPRs) of dominant intraprostatic foci of uptake were determined using semiautomatic segmentation (applying SUVmax percentage [SUV%] thresholds of SUV30%-SUV70%), adaptive segmentation (using adaptive segmentation percentage [A%] thresholds of A30%-A70%), and manual contouring. The histopathologic tumor volume (TV-Histo) served as the reference standard. The significance of differences between TV-Histo and PET-based tumor volume were assessed using the paired-sample Wilcoxon signed-rank test. The Spearman correlation coefficient was used to establish the strength of the association between TV-Histo and PET-derived tumor volume. Results: Median TV-Histo was 2.03 cm3 (interquartile ratio [IQR], 1.16-3.36 cm3), and median TPR was 10.16%. The adaptive method with an A40% threshold most closely determined the tumor volume, with a median difference of +0.19 (IQR, -0.71 to +2.01) and a median relative difference of +7.6%. The paired-sample Wilcoxon test showed no significant difference in PET-derived tumor volume and TV-Histo using A40%, A50%, SUV40%, and SUV50% threshold segmentation algorithms (P > 0.05). For both threshold-based segmentation methods, use of higher thresholds (e.g., SUV60% or SUV70% and A50%-A70%) resulted in underestimation of tumor volumes, and use of lower thresholds (e.g., SUV30% or SUV40% and A30%) resulted in overestimation of tumor volumes relative to TV-Histo and TPR. Manual segmentation overestimated the tumor volume, with a median difference of +2.49 (IQR, 0.42-4.11) and a median relative difference of +130%. Conclusion: Segmentation of intraprostatic tumor volume and TPR with an adaptive segmentation approach most closely approximates TV-Histo. This information might be used to guide the primary treatment of men with clinically localized, high-risk prostate cancer.

Saline-assisted fascial exposure (SAFE) technique to improve nerve-sparing in robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To provide a summary of our initial experience and assess the impact of the Saline-Assisted Fascial Exposure (SAFE) technique on erectile function (EF), urinary continence, and oncological outcomes after Robot-Assisted Laparoscopic Radical Prostatectomy (RALP). PATIENTS AND METHODS: From January 2021 to July 2022, we included patients with a baseline Sexual Health Inventory for Men (SHIM) score of ≥17 and a high probability of extracapsular extension (ECE), ranging from 21% to 73%, as per the Martini et al. nomogram. A propensity score matching was carried out at a ratio of 1:2 between patients who underwent RALP + SAFE (33) and RALP alone (66). The descriptive statistical analysis is presented. The SAFE technique was performed using two approaches, transrectal guided by micro-ultrasound or transperitoneal. Its principle entails a low-pressure injection of saline solution in the periprostatic fascia to achieve an atraumatic dissection of the neural hammock. Potency was defined as a SHIM score of ≥17 and continence as no pads per day. RESULTS: At follow-up intervals of 6, 13, 26, and 52 weeks, the SHIM score differed significantly between the two groups, favouring the RALP + SAFE (P = 0.01, P < 0.001, P < 0.001, and P = 0.01, respectively). These results remained significant when the mean SHIM score was assessed. As shown by the cumulative incidence curve, EF rates were higher in the RALP + SAFE compared to the RALP alone group (log-rank P < 0.001). The baseline SHIM and use of the SAFE technique were independent predictors of EF recovery. CONCLUSIONS: The use of the SAFE technique led to better SHIM scores at 6, 13, 26, and 52 weeks after RALP in patients at high risk of ECE who underwent a partial NS procedure.

Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

OBJECTIVE: To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. PATIENTS AND METHODS: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. RESULTS: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. CONCLUSIONS: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.

A Practical Guide to the Pearls and Pitfalls of PSMA PET Imaging.

Prostate-specific membrane antigen (PSMA)-targeted PET agents have revolutionized the care of patients with prostate cancer, supplanting traditional methods of imaging prostate cancer, and improving the selection and delivery of therapies. This has led to a rapid expansion in both the number of PSMA PET scans performed and the imaging specialists required to interpret those scans. To aid those imagers and clinicians who are new to the interpretation of PSMA PET, this review provides an overview of the interpretation of PSMA PET/CT imaging and pearls for overcoming commonly encountered pitfalls. We discuss the physiologic distribution of the clinically available PSMA-targeted radiotracers, the commonly encountered patterns of prostate cancer spread, as well as the benign and malignant mimics of prostate cancer. Additionally, we review the standardized PSMA PET reporting systems and the role of PSMA in selecting appropriate patients for PSMA-targeted therapies.

Management of Patients With a Negative Multiparametric Prostate MRI Examination: AJR Expert Panel Narrative Review.

Multiparametric prostate MRI (mpMRI) aids risk stratification of patients with elevated PSA levels. While most clinically significant prostate cancers are detected by mpMRI, insignificant cancers are less evident. Thus, multiple international prostate cancer guidelines now endorse routine use of prostate MRI as a secondary screening test before prostate biopsy. Nonetheless, management of patients with negative mpMRI results (defined as PI-RADS category 1 or 2) remains unclear. This AJR Expert Panel Narrative Review summarizes the available literature on patients with an elevated screening PSA level and a negative prostate mpMRI, and provides guidance for these patients' management. Systematic biopsy should not be routinely performed after a negative mpMRI in patients at average risk but should be considered in patients at high risk. In patients who undergo PSA screening rather than systematic biopsy after negative mpMRI, clear triggers should be established for when to perform a repeat MRI. Patients with negative MRI followed by negative biopsy should follow their healthcare practitioners' preferred guidelines concerning subsequent PSA screening for the patient's risk level. Insufficient high-level data exist to support routine use of adjunctive serum or urine biomarkers, artificial intelligence, or PSMA PET to determine the need for prostate biopsy after negative mpMRI.