Biochemically recurrent prostate cancer in the era of EMBARK and PSMA PET imaging: everything has changed, except the patients.

PURPOSE OF REVIEW: Patients with biochemically recurrent prostate cancer (BCR) after unsuccessful curative therapies frequently have an indolent and asymptomatic disease course for years. There are no prospective data showing that treating BCR improves overall survival despite new imaging strategies and emerging therapeutic data. Managing BCR requires a unique perspective in oncology that balances toxicities and disease kinetics. RECENT FINDINGS: Prostate specific membrane antigen (PSMA) imaging is now widely available and can define subclinical disease in patients with BCR who otherwise have negative CT and bone scans, but limited data exists showing that treating PSMA-positive disease has long term impact. A phase 3 trial demonstrated that the androgen receptor pathway inhibitor enzalutamide either alone or with androgen deprivation therapy (ADT) was superior in delaying metastasis, relative to ADT alone. Survival benefits from this study remain unknown. SUMMARY: BCR is a heterogeneous population where overtreatment may present greater risk to patients than a disease course that is often indolent. Management of BCR should be individualized based on disease kinetics. Given the unique biology of BCR, future therapeutic research should emphasize an approach that alters disease trajectory without accompanying side effects and should explore options beyond ADT-based strategies.

Optimizing PSMA scintigraphy for resource limited settings - a retrospective comparative study.

BACKGROUND: PSMA PET/CT is the most sensitive molecular imaging modality for prostate cancer (PCa), yet much of the developing world has little or no access to PET/CT. [99mTc]Tc-PSMA scintigraphy (PS) is a cheaper and more accessible gamma camera-based alternative. However, many resource-constrained departments have only a single camera without tomographic or hybrid imaging functionality, and camera time is frequently in high demand. Simplifying imaging protocols by limiting the field of view (FOV) and omitting SPECT/CT or even SPECT may provide a partial solution. The aim was thus to determine the adequacy of PS planar-only and/or SPECT-only imaging protocols with a limited FOV. METHODS: The scans of 95 patients with histologically proven PCa who underwent PS with full-body planar and multi-FOV SPECT/CT were reviewed. The detection rates for uptake in the prostate gland/bed and in metastases were compared on planar, SPECT, and SPECT/CT. The agreement between modalities was calculated for the detection of metastases and for staging. The impact of imaging a limited FOV was determined. RESULTS: Pathological prostatic uptake was seen in all cases on SPECT/CT (excluding two post-prostatectomy patients), 90.3% of cases on SPECT, and 15.1% on planar images (p < 0.001). Eleven (11.7%) patients had seminal vesicle involvement on SPECT/CT, which was undetectable/indistinguishable on planar images and SPECT. The agreement between modalities was moderate to good (κ = 0.41 to 0.61) for the detection of nodal metastases, with detection rates that did not differ significantly (SPECT/CT = 11.6%, SPECT = 8.4%, planar = 5.3%). Detection rates for bone metastases were 14.7% (SPECT/CT) and 11.6% (SPECT and planar). Agreement between modalities for the detection of bone metastases was good (κ = 0.73 to 0.77). Three (3.1%) patients had visceral metastases on SPECT/CT, two of which were detected on SPECT and planar. There was good agreement between modalities for the TNM staging of patients (κ = 0.70 to 0.88). No metastatic lesions were missed on the limited FOV images. CONCLUSION: When PS scintigraphy is performed, SPECT/CT is recommended. However, the lack of SPECT/CT capabilities should not preclude the use of PS in the presence of limited resources, as both planar and SPECT imaging are adequate and will correctly stage most PCa patients. Furthermore, time-based optimisations are achievable by limiting the FOV to exclude the distal lower limbs.

Emerging Theranostics for Prostate Cancer and a Model of Prostate-specific Membrane Antigen Therapy.

There is increasing demand worldwide to develop diagnostic and therapeutic (theranostic) markers for prostate cancer. One target of interest is prostate-specific membrane antigen (PSMA), a protein which is overexpressed in prostate cancer cells. Over the past decade, a growing body of literature has demonstrated that radiolabeled ligands that target PSMA show favorable clinical response and survival outcomes in patients with advanced prostate cancer. This focused review provides background to the development of PSMA as a target, an overview of key studies informing our current approach to radioligand-based imaging and therapy for prostate cancer, and a model for real-world implementation of PSMA theranostics based on an Australian experience.

Prediction of false-positive PI-RADS 5 lesions on prostate multiparametric MRI: development and internal validation of a clinical-radiological characteristics based nomogram.

BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.

The effects of different positions on lower extremity hemodynamics during robot-assisted laparoscopic radical prostatectomy for prostate cancer.

PURPOSE: This study aimed to investigate the effects of two different positions on lower extremity hemodynamics during robot-assisted laparoscopic radical prostatectomy (RARP) for prostate cancer. METHODS: A total of 196 patients who underwent RARP in our hospital from February 2020 to March 2022 were included in this study. Among them, 98 patients who underwent surgery with the Trendelenburg position and split-leg position with calf reverse arch from March 2021 to March 2022 were assigned to the observation group, while 98 patients who underwent surgery with the Trendelenburg position and low lithotomy position from February 2020 to February 2021 were assigned to the control group. Using an ultrasound diagnostic instrument to detect the internal diameter, mean blood flow velocity, and mean blood flow volume of the left deep femoral vein at different times, such as the supine position (T0), after 5 minutes of placing the patient in the leg spilt or low lithotomy position (T1), after 5 minutes of pneumoperitoneum (T2), after 5 minutes of head-down tilt or head-down tilt and calf reverse arch (T3), 1.5 hours after the start of surgery (T4), before the removal of CO2 gas (T5), and before the patient left the operating room (T6). As well as the patency of deep venous blood flow in both lower extremities before leaving the operating room, RESULTS: After establishment of pneumoperitoneum, the internal diameter of the deep femoral vein increased significantly, while the mean blood flow velocity and mean blood flow volume decreased significantly in both groups(T0) (P<0.001). With the prolongation of surgical time, the impact on lower extremity hemodynamics in the observation group was smaller than that in the control group. From T2 to T6, the internal diameter of the femoral vein in the observation group was smaller than that in the control group, while the mean blood flow velocity and mean blood flow volume were increased compared to the control group (P<0.05). Before leaving the operating room, the patency of deep venous blood flow in the observation group was better than that in the control group (P=0.003). CONCLUSION: Placing patients in the Trendelenburg position and split-leg position with calf reverse arch during RARP for prostate cancer has a smaller impact on lower extremity hemodynamics than the low lithotomy position, and can relatively reduce the risk of postoperative deep vein thrombosis.

Clinical and Radiological Factors for Predicting Clinically Significant Prostate Cancer in Biopsy-Naive Patients With PI-RADS 3 Lesions.

OBJECTIVE: This study intends to examine the anticipatory power of clinical and radiological parameters in detecting clinically significant prostate cancer in patients demonstrating Prostate Imaging Reporting and Data System 3 lesions. METHODS: This was a retrospective study. The study included participation from 453 patients at the First Affiliated Hospital of Soochow University, sampled between September 2017 through August 2022. Each patient underwent a routine 12-core prostate biopsy followed by a 2 to 5 core fusion-targeted biopsy. We utilized both univariate and multivariate logistic regression analyses to identify the parameters that have a correlation with clinically significant prostate cancer. The predictive ability of these parameters was assessed using the receiver operating characteristic curve, leading to the creation of a nomogram. RESULTS: Clinically significant prostate cancer was detected in 68 out of 453 patients with Prostate Imaging Reporting and Data System 3 lesions (15.01%). Among Prostate Imaging Reporting and Data System 3a and 3b patients, 4.78% (3.09% of the total) and 33.75% (11.92% of the total), respectively, had clinically significant prostate cancer. Systematic biopsy improved prostate cancer and clinically significant prostate cancer detection rates by 7.72% and 3.09%, respectively, compared to targeted biopsy. Without systematic biopsy, there would be an undetected rate of 15% for prostate cancer and 8.13% for clinically significant prostate cancer in Prostate Imaging Reporting and Data System 3b patients. Several clinical parameters, including age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination, were statistically significant in the logistic regression analysis for clinically significant prostate cancer. The individual diagnostic accuracies of these parameters for clinically significant prostate cancer were 0.648, 0.645, 0.75, 0.763, and 0.7, respectively, but their combined accuracy improved to 0.866. A well-fit nomogram based on the identified risk factors was constructed (χ2 = 10.254, P = .248). CONCLUSION: The combination of age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination presented a higher diagnostic value for clinically significant prostate cancer than any single parameter in patients with Prostate Imaging Reporting and Data System 3 lesions. Systematic biopsy proved crucial for biopsy-naive patients with Prostate Imaging Reporting and Data System 3 lesions and should not be omitted.

Racial and Ethnic Variation in Receipt and Intensity of Active Surveillance for Older Patients With Localized Prostate Cancer.

INTRODUCTION: The use of active surveillance (AS) for prostate cancer is increasing, and racial disparities have been identified in its implementation. We investigated differences by race and ethnicity in the utilization and intensity of AS by race and ethnicity among older men with low- and favorable intermediate-risk prostate cancer, with particular focus on the integration of multiparametric MRI (mpMRI) into AS protocols. METHODS: Using the Surveillance, Epidemiology, and End Results and Medicare fee-for-service linked database, we identified a cohort of men diagnosed between 2010 and 2017 with low- or favorable intermediate-risk prostate cancer. The odds of receiving AS were compared by patient race and ethnicity using multivariable logistic regression models, while the rates of usage of PSA tests, biopsy, and mpMRI within 2 years of diagnosis among men on AS were assessed using multivariable Poisson regression models. RESULTS: Our cohort included 33,542 men. The proportion of men with low-risk disease who underwent AS increased from 29.5% in 2010 to 51.7% in 2017, while the proportion among men with favorable intermediate disease grew from 11.4% to 17.2%. Hispanic (odds ratio [OR] = 0.68, 95% CI 0.58-0.79) and non-Hispanic Black men (OR = 0.78, 95% CI 0.68-0.89) were less likely to receive AS than non-Hispanic White men for low-risk disease, while non-Hispanic Black men were more likely to receive AS for favorable intermediate disease (OR = 1.21, 95% CI 1.04-1.39). Non-Hispanic Black men receiving AS underwent prostate MRI at a lower rate compared to non-Hispanic White men, regardless of whether they had low-risk (incidence rate ratio = 0.77, 95% CI 0.61-0.97) or favorable intermediate-risk (incidence rate ratio = 0.61, 95% CI 0.44-0.83) disease, respectively. CONCLUSIONS: The overall adoption of AS for low-risk prostate cancer increased among Medicare fee-for-service beneficiaries. However, a significant disparity exists for non-Hispanic Black men, as they exhibit lower rates of AS utilization. Moreover, non-Hispanic Black men are less likely to have access to novel technologies, such as mpMRI, as part of their AS protocols.

FastMRI Prostate: A public, biparametric MRI dataset to advance machine learning for prostate cancer imaging.

Magnetic resonance imaging (MRI) has experienced remarkable advancements in the integration of artificial intelligence (AI) for image acquisition and reconstruction. The availability of raw k-space data is crucial for training AI models in such tasks, but public MRI datasets are mostly restricted to DICOM images only. To address this limitation, the fastMRI initiative released brain and knee k-space datasets, which have since seen vigorous use. In May 2023, fastMRI was expanded to include biparametric (T2- and diffusion-weighted) prostate MRI data from a clinical population. Biparametric MRI plays a vital role in the diagnosis and management of prostate cancer. Advances in imaging methods, such as reconstructing under-sampled data from accelerated acquisitions, can improve cost-effectiveness and accessibility of prostate MRI. Raw k-space data, reconstructed images and slice, volume and exam level annotations for likelihood of prostate cancer are provided in this dataset for 47468 slices corresponding to 1560 volumes from 312 patients. This dataset facilitates AI and algorithm development for prostate image reconstruction, with the ultimate goal of enhancing prostate cancer diagnosis.

Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study.

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.

Assessment of the accuracy of biparametric MRI/TRUS fusion-guided biopsy for index tumor evaluation using postoperative pathology specimens.

BACKGROUND: Multiparametric MRI (mpMRI) is widely used for the diagnosis, surveillance, and staging of prostate cancer. However, it has several limitations, including higher costs, longer examination times, and the use of gadolinium-based contrast agents. This study aimed to investigate the accuracy of preoperatively assessed index tumors (ITs) using biparametric MRI (bpMRI)/transrectal ultrasound (TRUS) fusion biopsy compared with radical prostatectomy (RP) specimens. METHODS: We included 113 patients diagnosed with prostate cancer through bpMRI/TRUS fusion-guided biopsies of lesions with a Prostate Imaging Reporting and Data System (PI-RADS) category ≥ 3. These patients underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our institution between July 2017 and March 2023. We examined the localization of preoperative and postoperative ITs, the highest Gleason score (GS), and tumor diameter in these patients. RESULTS: The preoperative cT stage matched the postoperative pT stage in 53 cases (47%), while 31 cases (27%) were upstaged, and 29 cases (26%) were downstaged (Weighted Kappa = 0.21). The preoperative and postoperative IT localizations were consistent in 97 cases (86%). The concordance rate between Gleason groups in targeted biopsies and RP specimens was 51%, with an upgrade in 25 cases (23%) and a downgrade in 27 cases (25%) (Weighted Kappa = 0.42). The maximum diameter of the IT and the maximum cancer core length on biopsy were correlated with the RP tumor's maximum diameter (p < 0.001 for both). CONCLUSION: The diagnostic accuracy of bpMRI/TRUS fusion biopsy is comparable to mpMRI, suggesting that it can be a cost-effective and time-saving alternative.

RAPHIA: A deep learning pipeline for the registration of MRI and whole-mount histopathology images of the prostate.

Image registration can map the ground truth extent of prostate cancer from histopathology images onto MRI, facilitating the development of machine learning methods for early prostate cancer detection. Here, we present RAdiology PatHology Image Alignment (RAPHIA), an end-to-end pipeline for efficient and accurate registration of MRI and histopathology images. RAPHIA automates several time-consuming manual steps in existing approaches including prostate segmentation, estimation of the rotation angle and horizontal flipping in histopathology images, and estimation of MRI-histopathology slice correspondences. By utilizing deep learning registration networks, RAPHIA substantially reduces computational time. Furthermore, RAPHIA obviates the need for a multimodal image similarity metric by transferring histopathology image representations to MRI image representations and vice versa. With the assistance of RAPHIA, novice users achieved expert-level performance, and their mean error in estimating histopathology rotation angle was reduced by 51% (12 degrees vs 8 degrees), their mean accuracy of estimating histopathology flipping was increased by 5% (95.3% vs 100%), and their mean error in estimating MRI-histopathology slice correspondences was reduced by 45% (1.12 slices vs 0.62 slices). When compared to a recent conventional registration approach and a deep learning registration approach, RAPHIA achieved better mapping of histopathology cancer labels, with an improved mean Dice coefficient of cancer regions outlined on MRI and the deformed histopathology (0.44 vs 0.48 vs 0.50), and a reduced mean per-case processing time (51 vs 11 vs 4.5 min). The improved performance by RAPHIA allows efficient processing of large datasets for the development of machine learning models for prostate cancer detection on MRI. Our code is publicly available at: https://github.com/pimed/RAPHIA.

Manual on the proper use of the 211At-labeled PSMA ligand ([211At]PSMA-5) for clinical trials of targeted alpha therapy (1st edition).

Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients' caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer.

TransVFS: A spatio-temporal local-global transformer for vision-based force sensing during ultrasound-guided prostate biopsy.

Robot-assisted prostate biopsy is a new technology to diagnose prostate cancer, but its safety is influenced by the inability of robots to sense the tool-tissue interaction force accurately during biopsy. Recently, vision based force sensing (VFS) provides a potential solution to this issue by utilizing image sequences to infer the interaction force. However, the existing mainstream VFS methods cannot realize the accurate force sensing due to the adoption of convolutional or recurrent neural network to learn deformation from the optical images and some of these methods are not efficient especially when the recurrent convolutional operations are involved. This paper has presented a Transformer based VFS (TransVFS) method by leveraging ultrasound volume sequences acquired during prostate biopsy. The TransVFS method uses a spatio-temporal local-global Transformer to capture the local image details and the global dependency simultaneously to learn prostate deformations for force estimation. Distinctively, our method explores both the spatial and temporal attention mechanisms for image feature learning, thereby addressing the influence of the low ultrasound image resolution and the unclear prostate boundary on the accurate force estimation. Meanwhile, the two efficient local-global attention modules are introduced to reduce 4D spatio-temporal computation burden by utilizing the factorized spatio-temporal processing strategy, thereby facilitating the fast force estimation. Experiments on prostate phantom and beagle dogs show that our method significantly outperforms existing VFS methods and other spatio-temporal Transformer models. The TransVFS method surpasses the most competitive compared method ResNet3dGRU by providing the mean absolute errors of force estimation, i.e., 70.4 ± 60.0 millinewton (mN) vs 123.7 ± 95.6 mN, on the transabdominal ultrasound dataset of dogs.

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.