Biopsy-proven Prostate Cancer Research Articles

Can PSMA PET detect intratumour heterogeneity in histological PSMA expression of primary prostate cancer? Analysis of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007.

Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [68Ga]Ga-PSMA-11 or [18F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression. Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [68Ga]Ga-PSMA-11 (cohort I, 20 patients) or [18F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman's coefficients of PSMA expression to mean and maximum standardized uptake value (SUVmean and SUVmax) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed. Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUVmean and SUVmax (p < 0.001, p = 0.001). An approximate linear correlation between H-Score and SUVmean / SUVmax was found for tumour areas larger than 400μm² in histology (p < 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (p < 0.01). No significant differences were found between the two tracer cohorts (p = 0.72). PSMA PET with both [68Ga]Ga-PSMA-11 or [18F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.

In-field prostate cancer recurrence following radical prostatectomy and salvage radiation.

To define the natural history, patterns of recurrence and treatment modalities for local prostate cancer (PCa) recurrence following radical prostatectomy (RP) and radiation therapy (RT), and to investigate factors that could predict metastasis-free survival (MFS) in this unique patient population. We queried a prospectively maintained PCa registry to identify men developing in-field recurrence (IFR) following RP and RT from 2008 to 2021 at a single institution. IFR was defined as biopsy-proven recurrent PCa or the presence of persistent positron emission tomography-avid lesions in the prior radiation field without evidence of metastasis. Cox regression was conducted to determine predictors of MFS. Kaplan-Meier methods were used to calculate MFS, cancer-specific survival (CSS) and overall survival (OS) for patients in three primary therapy categories: cryoablation, androgen deprivation therapy (ADT) alone, and surveillance. Of 4575 patients from our registry, 108 (2.3%) with IFR were identified. The median (interquartile range [IQR]) time to IFR from salvage treatment was 78 (50-126) months. A total of 29 patients (26%) were managed with cryoablation, 23 (21%) with ADT, and 28 (25%) with surveillance. The median (IQR) follow-up was 76 (48-100) months. There were no statistically significant differences in MFS (P = 0.67) or OS (P = 0.07) among the three primary treatment cohorts. Patients treated with ADT or cryoablation had longer CSS compared to patients managed with surveillance (P = 0.047). We found that IFR may present years after completion of primary treatment for PCa. While curative management strategies may be attempted, local and distant metastatic recurrence is common and often requires systemic therapy.

P003 Defining the ExoDx Prostate (EPI) score for biopsy proven prostate cancer after MRI prostate

P003 Defining the ExoDx Prostate (EPI) score for biopsy proven prostate cancer after MRI prostate

Personalized dosimetry assessment of [177Lu]Lu-PSMA-617 radioligand therapy in the management of metastatic castration-resistant prostate cancer

Introduction Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is revolutionizing the treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) patients. This study aimed to establish patient-specific radiation dosimetry for [177Lu]Lu-PSMA-617 RLT in Iranian patients with mCRPC. Method Twelve biopsy-proven prostate cancer patients (aged 68.73 ± 5.26 yr) underwent 6.62 ± 0.36 GBq [177Lu]Lu-PSMA-617 RLT. Post-therapy whole-body planar scans were acquired approximately at 4, 48, and 72 h post-administration, alongside a single SPECT/CT around 48 h using Siemens Symbia T2 to obtain cumulated activity. An imaging protocol and dosimetry approach were designed to balance between time efficacy and accuracy in post-therapeutic dosimetry. Using accurate activity calibration, S-values were calculated by importing SPECT/CT images as the source/geometry into the Geant4 application for the tomographic emission (GATE) Monte Carlo (MC) toolkit. The Medical Internal Radiation Dose (MIRD) scheme was followed for subsequent absorbed dose (AD) calculations in organs at risk (OAR) and tumoral lesions using the dose actor and accumulated activities for precise dose estimations. Results Using the MC approach, the mean ADs to the liver, spleen, right and left kidneys, and tumor lesions were 0.11 ± 0.04 Gy/GBq, 0.08 ± 0.03 Gy/GBq, 0.34 ± 0.09 Gy/GBq, 0.34 ± 0.10 Gy/GBq, and 0.83 ± 0.54 Gy/GBq, respectively. Notably, tumoral lesions demonstrated significantly higher ADs, indicating enhanced uptake of radiopharmaceuticals by malignant cells. Conclusions This study indicates that the ADs of OARs and tumoral lesions from [177Lu]Lu-PSMA-617 RLT in patients with mCRPC are consistent with existing literature. The dosimetry findings suggest that increasing the administered activity of [177Lu]Lu-PSMA-617 RLT is feasible and does not pose a significant risk of adverse effects on OARs, as supported by our data. However, to validate the safety and efficacy of higher doses, further clinical follow-up studies are recommended.

A single-center retrospective review of metastatic prostate cancer on PSMA position emission tomography/computed tomography: Beyond lymph nodes and bones.

Prostate-specific membrane antigen (PSMA) Positron emission tomography/computed tomography (PET/CT) has become a crucial imaging modality for the staging of patients with prostate cancer. The purpose of this study is to retrospectively determine the frequency, anatomical distribution, and clinical-pathologic correlates of extra-nodal and extra-osseous metastatic prostate cancer detected on PSMA PET/CT. All available 650 PSMA PET/CT performed in patients with biopsy-proved prostate cancer in our institution between September 2021 and December 2023 were reviewed for the presence of extra-nodal and extra-osseous metastatic disease (M1C disease). Thirty-four patients with M1C disease were identified. The most frequent sites of visceral/soft tissue metastases were the lungs (58.8%), liver (23.5%) and adrenal glands (20.6%). 75% of patients with lung metastases detected on PSMA PET/CT had concurrent intrathoracic lymph node involvement. A higher frequency of patients with M1C disease (55.9%) had a high Gleason score. The median prostate-specific antigen (PSA) level at the time of the PSMA scan was 20.16 ng/mL. There was a statistically significant association between PSA level and osseous disease (p = 0.004), as well as PSA level and nodal disease (p = 0.008). While a large number of patients had concurrent osseous and nodal disease (82.4% and 79.4%, respectively), no visceral/soft tissue sites demonstrated a significant association with the presence of osseous or nodal involvement. Given the increasing utilization of PSMA PET/CT, increased knowledge of the location and pattern of distribution of visceral/soft tissue metastatic sites is crucial not only for staging but also to better understand patterns of therapeutic response. We identified the lungs, liver and adrenal glands as the most common visceral/soft tissue metastatic sites from prostate cancer. We found that higher PSA levels at the time of PSMA PET/CT imaging were positively associated with concurrent osseous and nodal involvement.

Different sodium concentrations of noncancerous and cancerous prostate tissue seen on MRI using an external coil.

Sodium (23Na) MRI of prostate cancer (PCa) is a novel but underdocumented technique conventionally acquired using an endorectal coil. These endorectal coils are associated with challenges (e.g., a nonuniform sensitivity profile, limited prostate coverage, patient discomfort) that could be mitigated with an external 23Na MRI coil. To quantify tissue sodium concentration (TSC) differences within the prostate of participants with PCa and healthy volunteers using an external 23Na MRI radiofrequency coil at 3 T. A prospective study was conducted from January 2022 to June 2024 in healthy volunteers and participants with biopsy-proven PCa. Prostate 23Na MRI was acquired on a 3-T PET/MRI scanner using a custom-built 2-loop (diameter, 18 cm) butterfly surface coil tuned for the 23Na frequency (32.6 MHz). The percent difference in TSC (ΔTSC) between prostate cancer lesions and surrounding noncancerous prostate tissue of the peripheral zone (PZ) and transition zone (TZ) was evaluated using a 1-sample t-test. TSC was compared to apparent diffusion coefficient (ADC) measurements as a clinical reference. Six healthy volunteers (mean age, 54.5 years ± 12.7) and 20 participants with PCa (mean age, 70.7 years ± 8.3) were evaluated. A total of 31 lesions were detected (21 PZ, 10 TZ) across PCa participants. Compared to noncancerous prostate tissue, prostate cancer lesions had significantly lower TSC (ΔTSC, -14.1% ± 18.2, P = .0002) and ADC (ΔADC, -26.6% ± 18.7, P < .0001). We used an external 23Na MRI coil for whole-gland comparison of TSC in PCa and noncancerous prostate tissue at 3 T. PCa lesions presented with lower TSC compared to surrounding noncancerous PZ and TZ tissue. These findings demonstrate the feasibility of an external 23Na MRI coil to quantify TSC in the prostate and offer a promising, noninvasive approach to PCa diagnosis and management.

Methylated DNA Markers in Voided Urine for the Identification of Clinically Significant Prostate Cancer.

Non-invasive assays are needed to better discriminate patients with prostate cancer (PCa) to avoid over-treatment of indolent disease. We analyzed 14 methylated DNA markers (MDMs) from urine samples of patients with biopsy-proven PCa relative to healthy controls and further studied discrimination of clinically significant PCa (csPCa) from healthy controls and Gleason 6 cancers. To evaluate the panel, urine from 24 healthy male volunteers with no clinical suspicion for PCa and 24 men with biopsy-confirmed disease across all Gleason scores was collected. Blinded to clinical status, DNA from the supernatant was analyzed for methylation signal within specific DNA sequences across 14 genes (HES5, ZNF655, ITPRIPL1, MAX.chr3.6187, SLCO3A1, CHST11, SERPINB9, WNT3A, KCNB2, GAS6, AKR1B1, MAX.chr3.8028, GRASP, ST6GALNAC2) by target enrichment long-probe quantitative-amplified signal assays. Utilizing an overall specificity cut-off of 100% for discriminating normal controls from PCa cases across the MDM panel resulted in 71% sensitivity (95% CI: 49-87%) for PCa detection (4/7 Gleason 6, 8/12 Gleason 7, 5/5 Gleason 8+) and 76% (50-92%) for csPCa (Gleason ≥ 7). At 100% specificity for controls and Gleason 6 patients combined, MDM panel sensitivity was 59% (33-81%) for csPCa (5/12 Gleason 7, 5/5 Gleason 8+). MDMs assayed in urine offer high sensitivity and specificity for detection of clinically significant prostate cancer. Prospective evaluation is necessary to estimate discrimination of patients as first-line screening and as an adjunct to prostate-specific antigen (PSA) testing.

Incidence of exclusive extrapelvic skeletal metastasis in prostate carcinoma on bone scintigraphy.

Bone is one of the common sites of metastasis from prostate carcinoma. Bone scintigraphy (BS) is one of the most sensitive imaging modalities currently used for bone metastatic work-up. Skeletal metastasis in prostate carcinoma commonly involves pelvic bones but rarely involves extrapelvic-extraspinal sites. To retrospectively analyze the BS data to determine the pattern of skeletal metastases in the prostate carcinoma. This retrospective observational study involves patients with biopsy-proven prostate carcinoma referred for BS for staging assessment. Patients with abnormal BS were evaluated for the pattern of skeletal involvement and data were presented in descriptive format in the form of percentages. A total of 150 patients with biopsy-proven prostate cancer who were referred for staging were included in the study. Thirteen of 150 patients (8.67%) had no abnormal uptake on planar images, ruling out metastatic disease. Twenty-four patients (16%) had heterogeneous uptake in the spine with distribution characteristic of degenerative disease and no scan pattern of metastatic disease. Thirty patients (20%) had multifocal uptake involving both pelvic and extra pelvic bones on planar images typical for skeletal metastasis and were considered metastatic. Eighty-three out of 150 patients (55.3%) had increased tracer uptake, which was indeterminate, thus, single photon emission computed tomography-computed tomography (SPECT-CT) was acquired, which showed 51 with metastatic disease, 31 benign lesions, and one indeterminate finding. Seven of 150 patients had exclusive pelvic bone uptake, which was found to be metastatic in 4/7 patients in SPECT-CT. Fifty six out of 150 patients showed exclusive extrapelvic tracer uptake, of which only 3 had vertebral metastatic disease. None of the patients with increased uptake exclusively in the extrapelvic-extraspinal location was metastatic. The incidence of exclusive extrapelvic skeletal metastatic disease in prostate carcinoma is 2% (excluding one patient with indeterminate findings). Further, none of the patients in the current study had exclusive extrapelvic-extraspinal metastasis. Thus, exclusive extrapelvic-extraspinal focal abnormality on planar BS carries a very low probability of metastatic disease and hence, further imaging or SPECT-CT can be safely avoided in such cases.

Advancing Prostate Cancer Staging: A Single-Step Approach With Bi-parametric and Whole-Body Diffusion MRI in an African Cohort.

To document our initial experience using whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) and bi-parametric magnetic resonance imaging (bpMRI) as a single exam in the staging of biopsy-proven prostate cancers. This retrospective study involved 120 African men with biopsy-confirmed prostate cancer (PCa). All the participants had a single exam that included both a bpMRI and a WB-DWI/MRI. The results were analyzed based on the American Urological Association's risk stratification system and evaluated using descriptive statistics. The combined imaging approach confirmed PCa in all cases, identifying pelvic lymph node metastases in 21 (17.5%) patients. Among 72 high-risk patients, bpMRI+WB-DWI/MRI detected pelvic lymph node metastases in 18 (25.0%), bone metastases in 15 (20.8%),retroperitoneal lymph node metastases in six (8.3%), and extraprostatic extension in 18 (25%), with no solid organ metastases observed. The combination of WB-DWI/MRI and bpMRI in a single-step approach demonstrates diagnostic potential in primary prostate cancer staging for high-risk groups, with the added advantage of shorter examination times, lowerpatients' costs, and elimination of the risks of adverse events associated with the use of contrast agents and exposure to radiation.

Robot-Assisted Radical Prostatectomy Performed with the Novel Surgical Robotic Platform Hugo™ RAS: Monocentric First Series of 132 Cases Reporting Surgical, and Early Functional and Oncological Outcomes at a Tertiary Referral Robotic Center.

Robotic-assisted surgery is the gold standard for performing radical prostatectomy (RARP), with new robotic devices such as HugoTM RAS gaining prominence worldwide. We report the surgical, perioperative, and early postoperative outcomes of RARP using HugoTM RAS. Between April 2022 and October 2023, we performed 132 procedures using the Montsouris technique with a four-robotic-arm configuration in patients with biopsy-proven prostate cancer (PCa). We collected intraoperative and perioperative data during hospitalization, along with follow-up data at predefined postoperative intervals of 3 and 6 months. Lymphadenectomy was performed in 25 procedures, with a bilateral nerve-sparing technique in 33 and a monolateral nerve-sparing technique in 33 cases. The mean total surgery time was 242 (±57) min, the mean console time was 124 (±48) min, and the mean docking time was 10 (±2) min. We identified 17 system errors related to robotic arm failures, 9 robotic instrument breakdowns, and 8 significant conflicts between robotic arms. One post-operative complication was classified as Clavien-Dindo 3b. None of the adverse events, whether singular or combined, increased the operative time. Positive margins (pR1) were found in 54 (40.9%) histological specimens, 37 (28.0%) of which were clinically significant. At 3 and 6 months post-surgery, the PSA levels were undetectable in 94.6% and 92.1% of patients, respectively. Social urinary continence was regained in 86% after 6 months. Limitations of our study include its observational monocentric case-series design and the short follow-up data for functional and oncological outcomes. Our initial experience highlights the reliability of the HugoTM RAS system in performing RARP. Additionally, we also list problems and solutions found in our daily work.

Machine learning-based analysis of 68Ga-PSMA-11 PET/CT images for estimation of prostate tumor grade.

Early diagnosis of prostate cancer, the most common malignancy in men, can improve patient outcomes. Since the tissue sampling procedures are invasive and sometimes inconclusive, an alternative image-based method can prevent possible complications and facilitate treatment management. We aim to propose a machine-learning model for tumor grade estimation based on 68Ga-PSMA-11 PET/CT images in prostate cancer patients. This study included 90 eligible participants out of 244 biopsy-proven prostate cancer patients who underwent staging 68Ga-PSMA-11 PET/CT imaging. The patients were divided into high and low-intermediate groups based on their Gleason scores. The PET-only images were manually segmented, both lesion-based and whole prostate, by two experienced nuclear medicine physicians. Four feature selection algorithms and five classifiers were applied to Combat-harmonized and non-harmonized datasets. To evaluate the model's generalizability across different institutions, we performed leave-one-center-out cross-validation (LOOCV). The metrics derived from the receiver operating characteristic curve were used to assess model performance. In the whole prostate segmentation, combining the ANOVA algorithm as the feature selector withRandom Forest (RF) and Extra Trees (ET) classifiers resulted in the highest performance among the models, with an AUC of 0.78 and 083, respectively. In the lesion-based segmentation, the highest AUC was achieved byMRMR feature selector + Linear Discriminant Analysis (LDA) andLogistic Regression (LR) classifiers (0.76 and 0.79, respectively). The LOOCV results revealed that both the RF_ANOVA and ET_ANOVA models showed high levels of accuracy and generalizability across different centers, with an average AUC value of 0.87 for the ET_ANOVA combination. Machine learning-based analysis of radiomics features extracted from 68Ga-PSMA-11 PET/CT scans can accurately classify prostate tumors into low-risk and intermediate- to high-risk groups.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

A comparison study of 68gallium-prostate-specific membrane antigen positron emission tomography-computed tomography and multiparametric magnetic resonance imaging for locoregional staging of prostate cancer.

Prostate cancer (PCa) is the most common malignancy in men aged 50 years and older and the second cause of cancer death among men. Accurate staging of PCa preoperatively is of high importance for treatment decisions and patient management. Conventional imaging modalities (ultrasound, computed tomography [CT], and magnetic resonance imaging) are inaccurate for the staging of PCa. Newer modality multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan show promising results for the staging of PCa. Only fewer studies are available for comparison of these modalities with histopathology as reference. The objective of our study is to evaluate the diagnostic accuracy of independent 68gallium PSMA (68Ga-PSMA) PET-CT compared with mpMRI for preoperative staging of PCa, using histopathology as the reference standard. From August 2021 to December 2022, 30 patients of biopsy-proven PCa were prospectively enrolled as per eligibility criteria. Preoperatively, 68Ga-PSMA PET scan and mpMRI were done in all the patients. Extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node metastasis (LNM) were investigated separately. Subsequently, the patients underwent robotic-assisted radical prostatectomy with bilateral pelvic lymph node dissection. mpMRI prostate was more sensitive (66.66%) but less specific than PSMA PET-CT (55.55%) for ECE. mpMRI and PSMA PET-CT both had similar sensitivity (83.3%) and specificity (87.5%) for SVI. PSMA PET-CT was more sensitive (85.71%) and specific (95.6%) than mpMRI prostate (62.5% and 91.30%, respectively) for LNM. PSMA PET-CT is more specific for the detection of ECE and more sensitive and specific for the detection of LNM than mpMRI, and similar for the detection of SVI. mpMRI provides only local staging, while PSMA PET-CT provides information about local, regional, and distal staging. Overall, PSMA PET-CT is superior to mpMRI for locoregional staging of PCa.

Convoluted Neural Network for Detection of Clinically Significant Prostate Cancer on 68Ga PSMA PET/CT Delayed Imaging by Analyzing Radiomic Features.

To assess the utility of convoluted neural network (CNN) in differentiating clinically significant and insignificant prostate cancer in patients with 68Ga PSMA PET/CT-targeted prostate biopsy-proven prostate cancer. In this retrospective study, 142 patients with clinical suspicion of prostate cancer were evaluated who underwent 68Ga-PSMA PET/CT imaging followed by 68Ga-PSMA PET/CT-targeted prostate biopsy from the PSMA-avid prostate lesion. Twenty patients with no PSMA-avid lesions were excluded. Local Image Features Extraction (LifeX) software was used to extract radiomic features (RF) from delayed 68Ga-PSMA PET/CT images of 122 patients. LifeX failed to extract radiomic features in 24 patients, and the remaining 98 were evaluated. RFs were fed to an in-built CNN of the software for computation and results were achieved. Patients with Gleason Score ≥ 7 on histopathology were labeled clinically significant prostate cancer (csPCa). The diagnostic values of radiomic features were evaluated. The csPCa was revealed in 69/98 (70.4%) patients, and insignificant PCa was noticed in 29/98 (29.6%) patients. The software extracted 124 RF from the delayed 68Ga-PSMA PET/CT images. The accuracy of the CNN was 80.7% to differentiate clinically significant and clinically insignificant prostate cancer, with an error percentage (E %) of 19.3%. The sensitivity, specificity, positive predictive, and negative predictive values were 90.3%, 57.7%, 83.6%, and 71.4%, respectively, to detect csPCa. CNN is a feasible pre-biopsy screening tool for identifying clinically significant prostate cancer and can be used as an adjunct in the initial diagnosis and early treatment planning. The online version contains supplementary material available at 10.1007/s13139-023-00832-3.

Safety of high-dose-rate brachytherapy in patients with prostate cancer and inflammatory bowel disease: A case series.

Inflammatory bowel disease (IBD) is a relative contraindication to external beam radiation therapy (EBRT) for prostate cancer patients due to fear of increased risk of gastrointestinal (GI) toxicity. High-dose-rate (HDR) brachytherapy, capable of minimizing radiation dose to surrounding tissues, is a feasible alternative. Given limited data, this study examined the safety profile of HDR brachytherapy in this setting. We conducted a retrospective review of patients with localized prostate cancer and IBD treated with HDR brachytherapy at the University of California San Francisco (UCSF), between 2010 and 2022. Eligibility criteria included biopsy-proven prostate cancer, no distant metastases, absence of prior pelvic radiotherapy, IBD diagnosis, and at least one follow-up visit post-treatment. Eleven patients were included, with a median follow-up of 28.7 months. The median dose administered was 2700 cGy (range, 1500-3150 cGy) over 2 fractions (range, 1-3 fractions). Two patients also received EBRT. Rectal spacers (SpaceOAR) were applied in seven patients. All patients experienced acute genitourinary (GU) toxicity, ten of which were grade 1 and one was grade 2. Eight patients experienced late grade 1 GU toxicity, and three patients had late grade 2 GU toxicity. GI toxicities were similarly low-grade, with six grade 1 acute toxicity, no grade 2 or higher acute toxicity, six grade 1 late toxicity, and one late grade 2 GI toxicity. No grade 3 or higher acute or late GI or GU toxicities were reported. HDR brachytherapy appears to be a safe and tolerable treatment modality for patients with prostate cancer and IBD, with minimal acute and late GI and GU toxicity. These findings warrant multi-institutional validation due to small sample size.

Role of non-contrast CT component of prostate-specific membrane antigen PET/CT scan in the detection of peripheral zone prostate cancer.

The aim of this study was to look for feasibility of non-contrast CT (NCCT) in detecting peripheral zone prostate cancer (PCa). A retrospective analysis included 50 biopsy-proven PCa patients between April 2019 and March 2022 who underwent staging whole body prostate-specific membrane antigen (PSMA)/CT prior to treatment. The control subjects were 50 randomly selected adult male patients who underwent PET/CT for non-prostate malignancy during the same time period. Two readers independently calculated the Hounsfield unit (HU) of normal peripheral zone, central zone, and corresponding PSMA avid focus in cases. No significant difference was seen in the mean HU value of normal peripheral zone between cases and controls. Significant difference in the mean HU was seen between the PSMA avid focus in cases (40.1 ± 6.2) and normal peripheral zone of cases (28.2 ± 7.0) and controls (27.7 ± 5.8). No significant difference was found between the mean HU values of high-grade PCa and non-high-grade PCa. Receiver operating characteristic (ROC) curve analysis revealed a mean HU cut-off of ≥35 for detecting PCa with a sensitivity and specificity of 86% and 90%, respectively, between cases and controls (AUC 0.88). Detection of clinically significant PCa is possible on routinely performed NCCT scans. Radiologists should routinely look for and convey these findings to facilitate further work-up and early detection of PCa. Our study adds to the knowledge that NCCT scans performed for unrelated indications can serve as a screening tool for clinically significant PCa.

The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography

BackgroundMultiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.MethodsWe analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsWe find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.ConclusionsBy co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.

Ethnic differences in prostate cancer presentation: a time for testing advocacy.

It is recognised that there are ethnic variations in prostate cancer (PCa) epidemiology, affecting outcomes. South Asians (SA) are less likely to be diagnosed with PCa than others, although recent evidence shows PCa is rising amongst SA. This study examines the differences between ethnicities in PCa presentation, progression risk and prostate-specific antigen (PSA) testing use. This retrospective study is on biopsy-diagnosed PCa patients from a multi-ethnic area in London. We grouped ethnicities as SA, White, Black and others, compared presenting symptoms, PSA, Gleason score (GS), and clinical stage, and estimated the D'Amico risk across ethnicities. We also evaluated if the presentation was due to symptoms or an elevated PSA. We studied 1176 patients with biopsy-proven PCa. Black patients were diagnosed about 3years before others (65 ± 8.8years, p = < 0.001). There was no significant difference between ethnicities in presenting PSAs. At presentation, 65-71% were in the high-risk D'Amico category across all ethnicities. SA were least likely to have PSA test-detected cancers (38%, p = 0.001) and had the highest proportion with advanced GS (30.6%). There was no significant difference in the risk of disease progression between groups. Black men were diagnosed youngest. SA had the highest proportion with advanced GS. Most ethnicities had a high risk of progression. SA had the least PSA test-detected cases. The significance of the study lies in understanding ethnic variations in PCa, which could direct targeted prevention and management. We recommend further ethnicity studies and interventions encouraging SA men to embrace PSA testing.

Delta radiomic patterns on serial bi-parametric MRI are associated with pathologic upgrading in prostate cancer patients on active surveillance: preliminary findings.

The aim of this study was to quantify radiomic changes in prostate cancer (PCa) progression on serial MRI among patients on active surveillance (AS) and evaluate their association with pathologic progression on biopsy. This retrospective study comprised N = 121 biopsy-proven PCa patients on AS at a single institution, of whom N = 50 at baseline conformed to the inclusion criteria. ISUP Gleason Grade Groups (GGG) were obtained from 12-core TRUS-guided systematic biopsies at baseline and follow-up. A biopsy upgrade (AS+) was defined as an increase in GGG (or in number of positive cores) and no upgrade (AS-) was defined when GGG remained the same during a median period of 18 months. Of N = 50 patients at baseline, N = 30 had MRI scans available at follow-up (median interval = 18 months) and were included for delta radiomic analysis. A total of 252 radiomic features were extracted from the PCa region of interest identified by board-certified radiologists on 3T bi-parametric MRI [T2-weighted (T2W) and apparent diffusion coefficient (ADC)]. Delta radiomic features were computed as the difference of radiomic feature between baseline and follow-up scans. The association of AS+ with age, prostate-specific antigen (PSA), Prostate Imaging Reporting and Data System (PIRADS v2.1) score, and tumor size was evaluated at baseline and follow-up. Various prediction models were built using random forest (RF) classifier within a threefold cross-validation framework leveraging baseline radiomics (Cbr), baseline radiomics + baseline clinical (Cbrbcl), delta radiomics (CΔr), delta radiomics + baseline clinical (CΔrbcl), and delta radiomics + delta clinical (CΔrΔcl). An AUC of 0.64 ± 0.09 was obtained for Cbr, which increased to 0.70 ± 0.18 with the integration of clinical variables (Cbrbcl). CΔr yielded an AUC of 0.74 ± 0.15. Integrating delta radiomics with baseline clinical variables yielded an AUC of 0.77 ± 0.23. CΔrΔclresulted in the best AUC of 0.84 ± 0.20 (p < 0.05) among all combinations. Our preliminary findings suggest that delta radiomics were more strongly associated with upgrade events compared to PIRADS and other clinical variables. Delta radiomics on serial MRI in combination with changes in clinical variables (PSA and tumor volume) between baseline and follow-up showed the strongest association with biopsy upgrade in PCa patients on AS. Further independent multi-site validation of these preliminary findings is warranted.

Head-to-head comparison of 68Ga-PSMA-11 PET with 99mTc-MDP bone scan for detection of bone disease in patients with prostate cancer with biochemical progression during ADT: A single center prospective study.

e17072 Background: 68Ga-PSMA-11 PET/CT (PSMA-PET) was approved by the U.S. Food and Drug Administration in patients with prostate cancer (PCa) at primary staging or biochemical recurrence. A head-to-head comparison between PSMA-PET and conventional imaging (99mTc-MDP bone scan [BS] and CT) in men with advanced prostate cancer was not performed. We aimed to compare the detection rate of bone disease for PSMA-PET vs BS in men with PCa and with biochemical progression during androgen deprivation therapy (ADT). Methods: This was a prospective single-center, open-label, single-arm, head-to-head comparison, prospective phase 2 study (NCT04928820). A sample size of 102 men was required to achieve an 80.3% power to detect a difference of 12% positivity rate of bone disease in favor of PSMA-PET vs BS (35% vs 23%). Men with i) biopsy-proved PCa, ii) who had rising PSA levels on 2 successive occasions ≥1 week apart, iii) were receiving treatment with hormonal therapy, iii) and had an absolute PSA value ≥1 ng/ml were eligible. Men who were enrolled received PSMA-PET and bone scan within 30 days. The primary endpoint was detection rate of bone disease for PSMA-PET vs BS. Secondary endpoint was the number of bone lesions detected by PSMA-PET vs BS. Number of lesions was categorized into: 0 vs 1 vs 2 vs 3 vs 4 vs 5 vs &gt; 5. A p value &lt; 0.05 was considered statistically significant. Results: 22 men were enrolled between July 8, 2021 and June 9, 2022. The median patients age was 71 years (range: 56-94). The median time between scans was 12 days (range: 1-29). The median PSA value was 9.5 ng/ml (range: 1.2 – 1717). 11/22 (11%) patients had hormone-sensitive PCa, while 11/22 (50%) had castration-resistant PCa prior to receiving the scans. The positivity rate for bone disease was equal for PSMA-PET and BS in all cases: 7/22 (32%) patients had negative scans on both imaging modalities and 15 (68%) had ≥1 bone lesion detected on both imaging modalities (p = 1.00). In 15/22 (68%) men, both imaging modalities showed equal number of bone lesions: 0 lesions in 7/22 (32%) men and &gt; 5 lesions in 8/22 (36%) men. In 3/22 (14%) men BS showed higher number of lesions, while in 4/22 (18%) men PSMA-PET showed higher number of lesions. No statistical difference was noticed between PSMA-PET and BS in number of bone lesions detected (p &gt; 0.05). The trial was terminated early since these preliminary results gave already a 95% confidence interval of 81-100% for equivalent positivity rate of bone disease between PSMA-PET and BS. Conclusions: In this prospective study of patients with prostate cancer with rising PSA levels under hormonal therapy, 68Ga-PSMA-11 PET and 99mTc-MDP bone scan had similar detection rate for bone disease. Further studies investigating similar comparison between PSMA-PET and BS in clinically-relevant selected patient population are warranted. Clinical trial information: NCT04928820 .