Mimic Prostate Cancer Research Articles

Bacillus Calmette-Guérin Instillations May Mimic Prostate Cancer on Multiparametric Magnetic Resonance Imaging.

Granulomatous prostatitis (GP) is a rare and benign inflammatory condition of the prostate, often mimicking prostate cancer (PCa) in clinical and radiological evaluations. This study examines the characteristics and diagnostic challenges of GP in a cohort of 12 patients who received Bacillus Calmette-Guérin (BCG) therapy following treatment for non-muscle-invasive bladder urothelial carcinoma. In this case series, we analyze their clinical presentations, MRI findings, and histopathological results. Patients presented with elevated PSA levels and firm or nodular prostates on digital rectal examination, complicating the differentiation from PCa. Multiparametric MRI showed lesions with hypointensity on T2-weighted images, hypersignal on diffusion-weighted imaging and hyposignal on the apparent diffusion coefficient map, further mimicking malignancy. Histopathological examination remains the gold standard for diagnosing GP, distinguishing it from PCa through the identification of granulomas and associated inflammatory cells. This study underscores the importance of awareness and accurate diagnosis of GP to avoid unnecessary biopsies and treatments, highlighting the need for a multidisciplinary approach combining clinical, imaging, and pathological data.

Effect of Bacillus Calmette–Guerin Exposure on Prostate Cancer Detection Using Magnetic Resonance Imaging: A Cohort Study

BackgroundGranulomatous prostatitis is a medical condition that may mimic prostate cancer. PurposeGranulomatous prostatitis resulting from BCG-exposure can confound the diagnosis of prostate cancer based on prostate imaging and data system (PI-RADS) classification observed on multiparametric prostate magnetic resonance imaging (mpMRI). Study type, Population, Assessment and Statistical TestsA cohort study was conducted, enrolling consecutive males at risk for prostate cancer who underwent an mpMRI-targeted prostate biopsy between February 2016 and August 2023. The focus of the study was on prior BCG-exposure as adjuvant treatment for non–muscle-invasive urothelial carcinoma within the 3 years prior the magnetic resonance imaging (MRI). Exclusion criteria were a prior androgen deprivation therapy, prostate surgery or radiation, and BCG-exposure occurring more than 3 years and less than 3 months before the MRI. Chi-square, logistic-regression, statistical association, and homogeneity tests were used. ResultsTotal 712 patients, 899 biopsied lesions (218 PI-RADS 3, 521 PI-RADS 4 and 160 PI-RADS 5) and 20 patients with 30 lesions within the BCG-exposed cohort. Chi-square and logistic-regression tests showed an association between PI-RADS with malignancy and significant tumor (ST), considering PI-RADS3 as the reference (OR: 4.9 [95% CI, 3.4-7.1] for PI-RADS4 and OR: 21.7 [95% CI, 12.4-37.8] for PI-RADS5 for malignancy, and OR: 5.3 [95% CI, 3.2-8.7] for PI-RADS4 and OR: 16.5 [95% CI, 9.4-28.9] for PI-RADS5 regarding ST). A statistically significant negative association was demonstrated between malignancy and ST with respect to BCG-exposure (OR: 0.15 [95% CI, 0.06-0.39] and OR: 0.39 [95% CI, 0.15-1.0], respectively). Statistically significant risk-difference for malignancy in patients nonexposed to BCG regarding those exposed was 45% (61.6% vs. 16.7%) for PI-RADS4, and 68.5% (90.7% vs. 22.2%) and 42.7% (64.9% vs. 22.2%) concerning malignancy and ST for PI-RADS5, respectively. Data ConclusionsGranulomatous prostate reaction caused by BCG-exposure acts as confounding factor for prostate MRI interpretation. The risk of malignancy and significant tumor on targeted biopsy to PI-RADS 3, 4 and 5 is notably lower in exposed patients.

Abstract 688: Radium-223 in combination with darolutamide exhibits synergistic antitumor efficacy in LNCaP prostate cancer models

Abstract Radium-223 dichloride (radium-223) is a targeted alpha therapy that binds to newly formed abnormal bone in bone metastases and induces DNA double-strand breaks (DSBs) in cancer cells, osteoblasts and osteoclasts. Radium-223 is used for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Darolutamide is an androgen receptor inhibitor indicated for patients with metastatic hormone-sensitive prostate cancer or non-metastatic CRPC. We studied the antitumor effects of radium-223 in combination with darolutamide using LNCaP human prostate cancer cells in vitro and an intratibial LNCaP model mimicking prostate cancer metastasized to bone. The in vitro antiproliferative effects of radium-223 and darolutamide were determined using LNCaP cells. Gene set enrichment analysis (GSEA) was conducted on RNA sequencing data from LNCaP cells treated with the synthetic androgen R1881 alone or in combination with darolutamide. LNCaP cells were inoculated into the right tibia of male NOD.scid mice. The mice (n=7-9/group) were randomized based on serum prostate-specific antigen (PSA) and treated with vehicle, radium-223 (330 kBq/kg, Q4Wx2, i.v.), darolutamide (100 mg/kg, BID, p.o.), or with a combination of radium-223 and darolutamide, for 41 days. PSA and the bone turnover markers PINP and CTX-I were measured every second week in serum. Tumor-induced abnormal bone area, bone formation rate and radium-223 uptake in tumor-bearing tibiae were determined by X-ray, histomorphometry and gamma counter, respectively. The combination of radium-223 and darolutamide showed synergistic antiproliferative effects with combination indexes between 0.69-0.75 in vitro. GSEA demonstrated a prominent darolutamide-induced downregulation of DNA damage response (DDR) signaling pathways. In vivo, the combination treatment showed synergistic antitumor efficacy (p=0.04) as demonstrated by lower PSA concentrations when compared with the vehicle, radium-223 or darolutamide monotherapies (p=0.004, p=0.011 and p=0.002, respectively). In the vehicle and combination treatment groups, the mean serum PSA was 541% and 95.9% of the pre-treatment level, respectively. Furthermore, radium-223 alone or in combination with darolutamide inhibited increased bone turnover, tumor-induced abnormal bone growth and trabecular bone formation when compared to vehicle. Concurrent administration of darolutamide did not affect radium-223 uptake in tibiae. Radium-223 in combination with darolutamide exhibited synergistic antitumor efficacy both in vitro and in vivo. The synergistic effects could be due to the radiosensitization of cancer cells by darolutamide-induced downregulation of DDR pathways. Our results suggest that the combination of targeted alpha therapy with an androgen receptor inhibitor is a promising treatment strategy for mCRPC. Citation Format: Christoph A. Schatz, Mari I. Suominen, Andreas Schlicker, Matias Knuuttila, Esa Alhoniemi, Sanna-Maria Käkönen, Bernard Haendler, Urs B. Hagemann, Arne Scholz. Radium-223 in combination with darolutamide exhibits synergistic antitumor efficacy in LNCaP prostate cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 688.

Zoledronic Acid Prevents Bone Resorption Caused by the Combination of Radium-223, Abiraterone Acetate, and Prednisone in an Intratibial Prostate Cancer Mouse Model.

An increased risk of non-pathological fractures in patients with prostate cancer and bone metastases has been associated with combination treatment with radium-223, abiraterone, and prednisone/prednisolone in the absence of bone-protecting agents. Here, we investigated possible mechanisms leading to this outcome using an intratibial LNCaP model mimicking prostate cancer bone metastases. Male NOD.scid mice were inoculated intratibially with LNCaP prostate cancer cells and treated with vehicle, radium-223, abiraterone, prednisone, zoledronic acid, or their combinations for 28 days. Serum TRACP 5b and PSA levels were measured. Bone structure, quality, and formation rate of non-tumor-bearing and tumor-bearing tibiae were analyzed by microCT, 3-point bending assay, and dynamic histomorphometry, respectively. Radium-223 incorporation into bone was also measured. Radium-223/abiraterone/prednisone combination treatment induced a transient increase in bone resorption indicated by elevated TRACP 5b levels, which was inhibited by concurrent treatment with zoledronic acid. Furthermore, radium-223/abiraterone/prednisone combination reduced periosteal and trabecular new bone formation and the number of osteoblasts, but bone structure or biomechanical quality were not affected. The abiraterone/prednisone treatment decreased radium-223 incorporation into tumor-bearing bone, possibly explaining the lack of additional antitumor efficacy. In conclusion, radium-223/abiraterone/prednisone combination increased bone resorption, which may have been one of the mechanisms leading to an increased fracture risk in patients with mCRPC.

Dynamic modulation of matrix adhesiveness induces epithelial-to-mesenchymal transition in prostate cancer cells in 3D

Synthetic matrices with dynamic presentation of cell guidance cues are needed for the development of physiologically relevant in vitro tumor models. Towards the goal of mimicking prostate cancer progression and metastasis, we engineered a tunable hyaluronic acid-based hydrogel platform with protease degradable and cell adhesive properties employing bioorthogonal tetrazine ligation with strained alkenes. The synthetic matrix was first fabricated via a slow tetrazine-norbornene reaction, then temporally modified via a diffusion-controlled method using trans-cyclooctene, a fierce dienophile that reacts with tetrazine with an unusually fast rate. The encapsulated DU145 prostate cancer single cells spontaneously formed multicellular tumoroids after 7 days of culture. In situ modification of the synthetic matrix via covalent tagging of cell adhesive RGD peptide induced tumoroid decompaction and the development of cellular protrusions. RGD tagging did not compromise the overall cell viability, nor did it induce cell apoptosis. In response to increased matrix adhesiveness, DU145 cells dynamically loosen cell-cell adhesion and strengthen cell-matrix interactions to promote an invasive phenotype. Characterization of the 3D cultures by immunocytochemistry and gene expression analyses demonstrated that cells invaded into the matrix via a mesenchymal like migration, with upregulation of major mesenchymal markers, and down regulation of epithelial markers. The tumoroids formed cortactin positive invadopodia like structures, indicating active matrix remodeling. Overall, the engineered tumor model can be utilized to identify potential molecular targets and test pharmacological inhibitors, thereby accelerating the design of innovative strategies for cancer therapeutics.

Enhanced Antitumor Efficacy of Radium-223 and Enzalutamide in the Intratibial LNCaP Prostate Cancer Model.

Radium-223 dichloride and enzalutamide are indicated for metastatic castration-resistant prostate cancer and their combination is currently being investigated in a large phase 3 clinical trial. Here, we evaluated the antitumor efficacy of radium-223, enzalutamide, and their combination in the intratibial LNCaP model mimicking prostate cancer metastasized to bone. In vitro experiments revealed that the combination of radium-223 and enzalutamide inhibited LNCaP cell proliferation and showed synergistic efficacy. The combination of radium-223 and enzalutamide also demonstrated enhanced in vivo antitumor efficacy, as determined by measuring serum PSA levels in the intratibial LNCaP model. A decreasing trend in the total area of tumor-induced abnormal bone was associated with the combination treatment. The serum levels of the bone formation marker PINP and the bone resorption marker CTX-I were lowest in the combination treatment group and markedly decreased compared with vehicle group. Concurrent administration of enzalutamide did not impair radium-223 uptake in tumor-bearing bone or the ability of radium-223 to inhibit tumor-induced abnormal bone formation. In conclusion, combination treatment with radium-223 and enzalutamide demonstrated enhanced antitumor efficacy without compromising the integrity of healthy bone. The results support the ongoing phase 3 trial of this combination.

Hepatic Small Vessel Neoplasm Mimics Prostate Cancer on 18 F-DCFPyl PET/CT.

18 F-DCFPyl is a Food and Drug Administration-approved radiotracer that targets prostate-specific membrane antigen and is used in the detection of recurrent or metastatic prostate cancer. As its use has increased, a growing number of nonprostatic disease entities have been identified that express prostate-specific membrane antigen and can mimic prostate cancer. Thus, the interpreting physician must also consider other variables such as serum prostate-specific antigen levels and the distribution of uptake to avoid an inappropriate diagnosis of metastatic prostate cancer. We describe 18 F-DCFPyl uptake associated with a hepatic small vessel neoplasm, an association previously undescribed in the literature.

P020 - BCG installations may mimic prostate cancer on multiparametric magnetic resonance

P020 - BCG installations may mimic prostate cancer on multiparametric magnetic resonance

Abstract 3318: PSMA-targeted thorium-227 conjugate (PSMA-TTC) inhibits tumor growth and abnormal bone changes in the intratibial LNCaP xenograft model of bone-metastatic prostate cancer

Abstract Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein specifically overexpressed on the cell membrane of prostate cancer cells. PSMA-targeted thorium-227 conjugate (PSMA-TTC, BAY 2315497) consists of a human PSMA-targeting antibody covalently linked to a 3,2-HOPO (hydroxypyridinone) chelator moiety, radiolabeled with alpha-particle emitting thorium-227. Previous studies have demonstrated PSMA-TTC to be an attractive therapy option for patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we investigated the efficacy of PSMA-TTC in the LNCaP intratibial model mimicking prostate cancer metastasized to bone. LNCaP prostate cancer cells were inoculated into the right tibiae of male NOD.scid mice. The mice were randomized to treatment groups (n=12/group) based on serum prostate-specific antigen (PSA) and treated with a single dose of vehicle or PSMA-TTC (300 kBq/kg, 0.75 mg/kg, i.v.). Tumor growth was followed by biweekly serum PSA measurements for 42 days. Tumor-induced abnormal bone growth, PSMA-TTC uptake, bone microarchitecture, bone formation rate and tumor area in tumor-bearing tibiae were determined by radiography, gamma counter, microCT, and dynamic and static histomorphometry, respectively. A single injection of PSMA-TTC efficiently inhibited intratibial tumor growth (p<0.001) as evidenced by a 82.6% decrease from baseline PSA value in the treatment group at the end of the study, whereas the vehicle group increased by 380% from baseline. Furthermore, the tumor-bearing tibiae were heavier (138%) than the non-tumor-bearing tibiae in the vehicle group, whereas in the PSMA-TTC-treated mice no such difference was observed (103%). PSMA-TTC decreased tumor-induced abnormal bone area in the tumor-bearing tibiae (43.5% of the vehicle). PSMA-TTC uptake relative to tibia weight was higher in the tumor-bearing tibiae compared with the non-tumor-bearing tibiae, resulting in higher levels of thorium-227 and its daughter isotype radium-223 both 3 days and 3 weeks post injection. In this preclinical study, PSMA-TTC showed robust antitumor efficacy, for the first time, in a model mimicking prostate cancer metastasized to bone as evidenced by a decrease in serum PSA levels, tumor-induced abnormal bone changes, and tumor-bearing tibia weights in the PSMA-TTC-treated mice. PSMA-TTC binds to PSMA-expressing cancer cells, delivering a cytotoxic dose of alpha radiation. The decay product of thorium-227, radium-223 binds to bone matrix and this could also contribute to the antitumor efficacy in this bone-metastatic model. Taken together, our data indicate activity of PSMA-TTC in bone-metastatic CRPC. PSMA-TTC as a monotherapy as well as in combination with darolutamide is currently being investigated in patients with mCRPC in a phase 1 clinical trial (NCT03724747). Citation Format: Christoph Schatz, Mari I. Suominen, Matias Knuuttila, Sabine Zitzmann-Kolbe, Jukka Rissanen, Sanna-Maria Käkönen, Urs Hagemann, Arne Scholz. PSMA-targeted thorium-227 conjugate (PSMA-TTC) inhibits tumor growth and abnormal bone changes in the intratibial LNCaP xenograft model of bone-metastatic prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3318.

Label-free discrimination of tumorigenesis stages using in vitro prostate cancer bone metastasis model by Raman imaging

Metastatic prostate cancer colonizes the bone to pave the way for bone metastasis, leading to skeletal complications associated with poor prognosis and morbidity. This study demonstrates the feasibility of Raman imaging to differentiate between cancer cells at different stages of tumorigenesis using a nanoclay-based three-dimensional (3D) bone mimetic in vitro model that mimics prostate cancer bone metastasis. A comprehensive study comparing the classification of as received prostate cancer cells in a two-dimensional (2D) model and cancer cells in a 3D bone mimetic environment was performed over various time intervals using principal component analysis (PCA). Our results showed distinctive spectral differences in Raman imaging between prostate cancer cells and the cells cultured in 3D bone mimetic scaffolds, particularly at 1002, 1261, 1444, and 1654 cm−1, which primarily contain proteins and lipids signals. Raman maps capture sub-cellular responses with the progression of tumor cells into metastasis. Raman feature extraction via cluster analysis allows for the identification of specific cellular constituents in the images. For the first time, this work demonstrates a promising potential of Raman imaging, PCA, and cluster analysis to discriminate between cancer cells at different stages of metastatic tumorigenesis.

Abstract 1392: Synergistic antitumor efficacy of radium-223 in combination with enzalutamide in the intratibial LNCaP prostate cancer xenograft model

Abstract Radium-223 dichloride (Ra-223) is a targeted alpha therapy that binds to newly formed bone matrix in bone metastases and induces DNA double-strand breaks in cancer cells, osteoblasts and osteoclasts. It is used for treating men with castration-resistant prostate cancer (CRPC) and bone metastases. Enzalutamide is a second-generation androgen receptor inhibitor also used for treating the same patient population, and the combination of Ra-223 and enzalutamide is currently being investigated in clinical trials. We evaluated the antitumor efficacy of Ra-223 and enzalutamide in the LNCaP intratibial model mimicking prostate cancer metastasized to bone. LNCaP prostate cancer cells were inoculated into the right tibia of male NOD.scid mice. The mice were randomized (n=9/group) based on serum PSA and treated with vehicle, Ra-223 (330 kBq/kg, i.v., Q4W x 2), enzalutamide (30 mg/kg, p.o., QD) or with a combination treatment of Ra-223 and enzalutamide, for 28 days. Serum PSA levels were analyzed at the end of the study and compared to the pre-treatment levels. Serum bone formation and resorption biomarkers, PINP and CTX, respectively, were measured during the study. Tumor-induced abnormal bone area, Ra-223 uptake and bone formation were determined by X-ray, gamma counter and histomorphometry, respectively. The healthy tibiae were evaluated by microCT. Combination treatment showed synergistic antitumor efficacy as observed by lower PSA levels when compared to the vehicle, Ra-223 or enzalutamide monotherapies (p=0.04, p=0.008 and p=0.002, respectively). A statistical interaction between Ra-223 and enzalutamide treatments was found (p=0.003), confirming the synergistic effect. In combination treatment, the serum PSA change relative to pre-treatment levels was 18% of the vehicle. Accordingly, a decreasing trend (p=0.08) in tumor-induced abnormal bone changes was associated with the combination treatment in the tumor-bearing tibiae (46% of the vehicle), whereas no changes in total bone structure were observed in the healthy tibiae. The serum levels of PINP and CTX were lowest in mice treated with the combination treatment. Compared to Ra-223 monotherapy, concurrent administration of enzalutamide with Ra-223 did not affect either Ra-223 uptake or bone formation rate in tumor-bearing or healthy tibiae, respectively. Compared to Ra-223 and enzalutamide monotherapies, the combination treatment demonstrated synergistic antitumor efficacy by decreasing PSA levels in the LNCaP intratibial model. Despite of prominent effects on tumor growth, the combination treatment was not observed to compromise bone health in the healthy tibiae. In conclusion, these preclinical results support the ongoing phase 3 trials PEACE III (NCT02194842) & ESCALATE (NCT04237584) of this combination. Citation Format: Mari I. Suominen, Matias Knuuttila, Jukka Vääräniemi, Birgitta Sjöholm, Esa Alhoniemi, Dominik Mumberg, Sanna-Maria Käkönen, Arne Scholz. Synergistic antitumor efficacy of radium-223 in combination with enzalutamide in the intratibial LNCaP prostate cancer xenograft model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1392.

Synergistic antitumor efficacy of radium-223 and enzalutamide in the intratibial LNCaP prostate cancer xenograft model.

105 Background: Radium-223 dichloride (Ra-223) is a targeted alpha therapy that binds to newly formed bone matrix in bone metastases and induces DNA double-strand breaks in cancer cells, osteoblasts and osteoclasts. It is used for treating men with castration-resistant prostate cancer (CRPC) and bone metastases. Enzalutamide (enza) is a second-generation androgen receptor inhibitor also used for treating the same patient population, and the combination of Ra-223 and enza is currently being investigated in clinical trials. We evaluated the antitumor efficacy of Ra-223 and enza in the LNCaP intratibial model mimicking prostate cancer metastasized to bone. Previously, additive or synergistic antitumor effects were not observed when Ra-223 was combined with abiraterone and prednisone in the LNCaP model (Suominen et al., AACR 2020). Methods: LNCaP prostate cancer cells were inoculated into the right tibia of male NOD.scid mice. The mice were randomized (n = 9/group) based on serum PSA and treated with vehicle, Ra-223 (330 kBq/kg, i.v., Q4W x 2), enza (30 mg/kg, p.o., QD) or with a combination treatment of Ra-223 and enza, for 28 days. Serum PSA levels were analyzed at the end of the study and compared to the pre-treatment levels. Serum bone formation and resorption biomarkers, PINP and CTX, respectively, were measured during the study. Tumor-induced abnormal bone area and Ra-223 uptake were determined by X-ray and gamma counter, respectively. The healthy tibiae were evaluated by microCT. Results: Combination treatment showed synergistic antitumor efficacy as observed by lower PSA levels when compared to the vehicle, Ra-223 or enza monotherapies (p = 0.04, p = 0.008 and p = 0.002, respectively). A statistical interaction between Ra-223 and enza treatments was found (p = 0.003), confirming the synergistic effect. In combination treatment, the serum PSA change relative to pre-treatment levels was 18% of the vehicle. Accordingly, a decreasing trend (p = 0.08) in tumor-induced abnormal bone changes was associated with the combination treatment in the tumor-bearing tibiae (46% of the vehicle), whereas no changes in total bone structure/quality were observed in the healthy tibiae. Compared to monotherapies, the combination treatment had the most prominent lowering effect on the bone metabolism biomarkers PINP and CTX during the study. Concurrent administration of enza with Ra-223 did not affect Ra-223 uptake in tumor-bearing tibiae. Conclusions: Compared to Ra-223 and enza monotherapies, the combination treatment demonstrated synergistic antitumor efficacy by decreasing PSA levels in the LNCaP intratibial model. Despite of prominent effects on tumor growth, the combination treatment was not observed to compromise bone health in the healthy tibiae. In conclusion, these preclinical results support the ongoing phase 3 trials PEACE III (NCT02194842) & ESCALATE (NCT04237584) of this combination.

Case Report: Prostatitis tuberculosis mimicking prostate cancer

A 56-year-old male who presented with recurrent gross hematuria and moderate lower urinary tract symptoms. After taking the patient’s medical history and performing a physical exam, suspicion of prostate cancer arose with prostate enlargement during rectal examination without tenderness and palpable nodes. Ultrasound showed estimated prostate volume of 95 gr and prostate specific antigen of 5.5. Transurethral resection of the prostate was performed and prostate tissue was checked by a pathologist, with histopathological examination showing active tuberculosis lesions. An interferon gamma release assay test was performed, which showed a positive result. The patient was diagnosed with prostatitis tuberculosis and treated with standard nine-month regimen for extra-pulmonary tuberculosis. Prostate enlargement due to tuberculosis is rare and its presence may mimic prostate cancer presentation; however, due to its rarity, careful examination is needed in order to provide optimal management.

False Positive Multiparametric Magnetic Resonance Imaging Phenotypes in the Biopsy-naïve Prostate: Are They Distinct from Significant Cancer-associated Lesions? Lessons from PROMIS

BackgroundFalse positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer. ObjectiveTo compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM). Design, setting, and participantsPROMIS participants (n=235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3+4 of any length and/or maximum cancer core length ≥4mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4+3 of any length and/or maximum cancer core length ≥6mm of any grade). Outcome measurements and statistical analysisIndex and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics. Results and limitationsMost lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p< 0.001). In the former group, index lesions were larger (mean volume 0.68 vs 0.50 ml; p< 0.001, Wilcoxon test), more conspicuous (Likert 4–5: 79% vs 22%; p< 0.001), and diffusion restricted (mean apparent diffusion coefficient [ADC]: 0.73 vs 0.86; p< 0.001, Wilcoxon test). In men with Likert 3 index lesions, log2PSA density and index lesion ADC were significant predictors of definition 1/2 disease in a logistic regression model (mean cross-validated area under the receiver-operator characteristic curve: 0.77 [95% confidence interval: 0.67–0.87]). ConclusionsSignificant cancer-associated MRI lesions in biopsy-naïve men have clinical-radiological differences, with lesions seen in prostates without significant disease. MRI-calculated PSA density and ADC could predict significant cancer in those with indeterminate MRI phenotypes. Patient summaryMagnetic resonance imaging (MRI) lesions that mimic prostate cancer but are, in fact, benign prompt unnecessary biopsies in thousands of men with raised prostate-specific antigen. In this study we found that, on closer look, such false positive lesions have different features from cancerous ones. This means that doctors could potentially develop better tools to identify cancer on MRI and spare some patients from unnecessary biopsies.

A Low Cost Sensitive Transrectal Photoacoustic Probe With Single-Fiber Bright-Field Illumination for In Vivo Canine Prostate Imaging and Real-Time Biopsy Needle Guidance

In implementing prostate cancer screening using photoacoustic imaging (PAI), transrectal delivery of light and transrectal ultrasound (TRUS) transducer for signal detection is the most commonly used approach for PAI system design. In this approach, energy-efficient light delivery and good alignment of laser excitation and acoustic detection are very important for optimal imaging sensitivity. The previously published works adopted dark-field illumination for their probes. In this study, we proposed and achieved bright-field illumination, which enables more laser energy to be delivered to the region of interest for imaging, resulting in higher sensitivity of the probe. Further, by using a single optical fiber instead of fiber bundle, the efficiency of laser transmission was significantly enhanced. The adoption of single optical fiber also enhances the flexibility of the probe for operation and lower the cost. A custom designed photoacoustic imaging system was built in this study to verify the feasibility of the probe for clinical translational application. The spatial resolution and enhanced signal-to-noise ratio (SNR) of the proposed probe were validated using PAI of phantoms. We demonstrated the use of probe in diagnosing prostate cancer in vivo using a canine model mimicking prostate cancer. Our results showed that the proposed probe could achieve high sensitivity and a wide field-of-view (FOV) in imaging prostate cancer. We also performed minimally-invasive real-time guidance of needle biopsy in ex vivo prostate, showing the potential of the probe for early screening of prostate cancer and early preventive treatment of prostate tumor.

Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is an attractive target for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC). PSMA-targeted alpha therapy (TAT) has shown early signs of activity in patients with prostate cancer refractory to beta radiation. We describe a novel, antibody-based TAT, the PSMA-targeted thorium-227 conjugate PSMA-TTC (BAY 2315497) consisting of the alpha-particle emitter thorium-227 complexed by a 3,2-HOPO chelator covalently linked to a fully human PSMA-targeting antibody. PSMA-TTC was characterized for affinity, mode of action, and cytotoxic activity in vitro. Biodistribution, pharmacokinetics, and antitumor efficacy were investigated in vivo using cell line and patient-derived xenograft (PDX) models of prostate cancer. PSMA-TTC was selectively internalized into PSMA-positive cells and potently induced DNA damage, cell-cycle arrest, and apoptosis in vitro. Decrease in cell viability was observed dependent on the cellular PSMA expression levels. In vivo, PSMA-TTC showed strong antitumor efficacy with T/C values of 0.01 to 0.31 after a single injection at 300 to 500 kBq/kg in subcutaneous cell line and PDX models, including models resistant to standard-of-care drugs such as enzalutamide. Furthermore, inhibition of both cancer and cancer-induced abnormal bone growth was observed in a model mimicking prostate cancer metastasized to bone. Specific tumor uptake and efficacy were demonstrated using various PSMA-TTC doses and dosing schedules. Induction of DNA double-strand breaks was identified as a key mode of action for PSMA-TTC both in vitro and in vivo. The strong preclinical antitumor activity of PSMA-TTC supports its clinical evaluation, and a phase I trial is ongoing in mCRPC patients (NCT03724747).

Granulomatous Prostatitis Mimicking Prostate Cancer

Multiparametric magnetic resonance imaging plays an important role in the detection of clinically significant prostate cancer. However, there is some overlap between prostate cancer and granulomatous prostatitis. We describe the imaging features of granulomatous prostatitis, which frequently mimics prostate cancer, and differential diagnosis between these conditions according to Prostate Imaging-Reporting and Data System (PI-RADS) version.12

Prostate MR: pitfalls and benign lesions.

Multiparametric MRI (mpMRI) of the prostate has evolved to be an integral component for the diagnosis, risk stratification, staging, and targeting of prostate cancer. However, anatomic and histologic mimics of prostate cancer on mpMRI exist. Anatomic feature that mimic prostate cancer on mpMRI include anterior fibromuscular stroma, normal central zone, periprostatic venous plexus, and thickened surgical capsule (transition zone pseudocapsule). Benign conditions such as post-biopsy hemorrhage, prostatitis or inflammation, focal prostate atrophy, benign prostatic hyperplasia nodules, and prostatic calcifications can also mimic prostate cancer on mpMRI. Technical challenges and other pitfalls such as image distortion, motion artifacts, and endorectal coil placements can also limit the efficacy of mpMRI. Knowledge of prostate anatomy, location of the lesion and its imaging features on different sequences, and being familiar with the common pitfalls are critical for the radiologists who interpret mpMRI. Therefore, this article reviews the pitfalls (anatomic structures and technical challenges) and benign lesions or abnormalities that may mimic prostate cancer on mpMRI and how to interpret them.

Multidisciplinary approach to prostatitis.

Multidisciplinary approach to prostatitis.

Inflammation appears as high Prostate Imaging-Reporting and Data System scores on prostate magnetic resonance imaging (MRI) leading to false positive MRI fusion biopsy.

PurposeTo investigate if inflammation as a potential cause of false-positive lesions from recent UroNav magnetic resonance imaging (MRI) fusion prostate biopsy patients.Materials and MethodsWe retrospectively identified 43 men with 61 MRI lesions noted on prostate MRI before MRI ultrasound-guided fusion prostate biopsy. Men underwent MRI with 3T Siemens TIM Trio MRI system (Siemens AG, Germany), and lesions were identified and marked in DynaCAD system (Invivo Corporation, USA) with subsequent biopsy with MRI fusion with UroNav. We obtained targeted and standard 12-core needle biopsies. We retrospectively reviewed pathology reports for inflammation.ResultsWe noted a total of 43 (70.5%) false-positive lesions with 28 having no cancer on any cores, and 15 lesions with cancer noted on systematic biopsy but not in the target region. Of the men with cancer, 6 of the false positive lesions had inflammation in the location of the targeted region of interest (40.0%, 6/15). However, when we examine the 21/28 lesions with an identified lesion on MRI with no cancer in all cores, 54.5% had inflammation on prostate biopsy pathology (12/22, p=0.024). We noted the highest proportion of inflammation.ConclusionsInflammation can confound the interpretation of MRI by mimicking prostate cancer. We suggested focused efforts to differentiate inflammation and cancer on prostate MRI.