Detection Of Metastatic Prostate Cancer Research Articles

A Systematic Review on Artificial Intelligence Evaluating Metastatic Prostatic Cancer and Lymph Nodes on PSMA PET Scans

Early detection of metastatic prostate cancer (mPCa) is crucial. Whilst the prostate-specific membrane antigen (PSMA) PET scan has high diagnostic accuracy, it suffers from inter-reader variability, and the time-consuming reporting process. This systematic review was registered on PROSPERO (ID CRD42023456044) and aims to evaluate AI’s ability to enhance reporting, diagnostics, and predictive capabilities for mPCa on PSMA PET scans. Inclusion criteria covered studies using AI to evaluate mPCa on PSMA PET, excluding non-PSMA tracers. A search was conducted on Medline, Embase, and Scopus from inception to July 2023. After screening 249 studies, 11 remained eligible for inclusion. Due to the heterogeneity of studies, meta-analysis was precluded. The prediction model risk of bias assessment tool (PROBAST) indicated a low overall risk of bias in ten studies, though only one incorporated clinical parameters (such as age, and Gleason score). AI demonstrated a high accuracy (98%) in identifying lymph node involvement and metastatic disease, albeit with sensitivity variation (62–97%). Advantages included distinguishing bone lesions, estimating tumour burden, predicting treatment response, and automating tasks accurately. In conclusion, AI showcases promising capabilities in enhancing the diagnostic potential of PSMA PET scans for mPCa, addressing current limitations in efficiency and variability.

Traditional and novel imaging modalities for advanced prostate cancer: A critical review.

Accurate detection of metastatic prostate cancer in the setting of preoperative staging as well as posttreatment recurrence is crucial to provide patients with appropriate and timely treatment of their disease. This has traditionally been accomplished with a combination of computed tomography, magnetic resonance imaging, and bone scan. Recently, more novel imaging techniques have been developed to help improve the detection of advanced and metastatic prostate cancer. This review discusses the efficacy of the traditional imaging modalities as well as the novel imaging techniques in detecting metastatic prostate cancer. Articles discussed were gathered through a formal PubMed search.

OR Practice–Data Analytics for Optimal Detection of Metastatic Prostate Cancer

We used data-analytics approaches to develop, calibrate, and validate predictive models, to help urologists in a large statewide collaborative make prostate cancer staging decisions on the basis of individual patient risk factors. The models were validated using statistical methods based on bootstrapping and evaluation on out-of-sample data. These models were used to design guidelines that optimally weigh the benefits and harms of radiological imaging for the detection of metastatic prostate cancer. The Michigan Urological Surgery Improvement Collaborative, a statewide medical collaborative, implemented these guidelines, which were predicted to reduce unnecessary imaging by more than 40% and limit the percentage of patients with missed metastatic disease to be less than 1%. The effects of the guidelines were measured after implementation to confirm their impact on reducing unnecessary imaging across the state of Michigan.

ZHER2 Affibody as a Good Candidate for Detection of Metastatic Prostate Cancer.

The article abstract is not available.

Comparison of the diagnostic utility of 99mTc-PSMA scintigraphy versus 68Ga-PSMA-11 PET/CT in the detection of metastatic prostate cancer and dosimetry analysis: a gamma-camera-based alternate prostate-specific membrane antigen imaging modality.

The present study was performed for head-to-head comparison between 68Ga-prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) and 99mTc-PSMA whole-body and regional single-photon emission computed tomography (SPECT)/CT for the detection of prostate cancer metastases. Ten patients with metastatic prostate cancer underwent 99mTc-PSMA whole-body scan after intravenous injection of 230-330 MBq 99mTc-PSMA. Anterior and posterior whole-body images were acquired at 10 min, 2, 4 and/or 5/6 h post-injection. Additional SPECT/CT images were acquired for the involved sites, where planar images did not clearly identify the metastatic sites. All patients also underwent whole-body 68Ga-PSMA PET/CT and the results between the two techniques were compared for the detection of the metastatic lesions. Dosimetry analysis of the 99mTc-PSMA studies was performed using the MIRD-OLINDA approach. 68Ga-PSMA PET/CT detected lesions in all 10 patients, whereas 99mTc-PSMA imaging detected lesions in 9/10 patients. 68Ga-PSMA PET/CT imaging identified a total of 112 PSMA avid metastatic lesions compared to 57 (51%) lesions on 99mTc-PSMA imaging. Eighteen out of 57 lesions were detected only on delayed 99mTc-PSMA imaging at 4 h and/or 6 h. The regional 99mTc-PSMA SPECT detected 51/83 (61.0%) lesions seen on 68Ga-PSMA PET/CT. The dosimetry results demonstrated that 99mTc-PSMA provided organs' radiation absorbed/effective doses comparable with 99mTc-PSMA imaging. Whole-body 99mTc-PSMA combined with regional SPECT/CT could be a potential alternative to 68Ga-PSMA PET for the detection of the advanced stage metastatic prostate cancer and for response evaluation to PSMA-based targeted therapies.

Use of prostate-specific membrane antigen positron-emission tomography/CT in response assessment following upfront chemohormonal therapy in metastatic prostate cancer.

Prostate-specific membrane antigen (PSMA) PET/CT imaging is increasingly being utilised in clinical practice, demonstrating greater sensitivity in the detection of metastatic prostate cancer (mPC) compared to conventional imaging [1]. Prior studies have primarily focussed on its use following biochemical recurrence to detect oligometastatic disease potentially amenable to salvage therapies [2-4]. However, the role of PSMA PET/CT in assessing treatment response remains unclear. Standardised criteria for metabolic response have not been established, particularly to account for whole body tumour burden and the effects of systemic therapies on PSMA expression.

Novel treatment options in the management of metastatic castration-naïve prostate cancer; which treatment modality to choose?

Androgen-deprivation therapy (ADT) has been the mainstay of treatment of metastatic prostate cancer since the first report of its hormonal dependence in the 1940s. Since 2015, the addition of docetaxel and the addition of abiraterone to ADT have conferred substantial overall survival benefit in men with metastatic castration-naïve prostate cancer (mCNPC). The shift of these treatment options for metastatic prostate cancer from the castration-resistant setting to the castration-naïve setting has led to new challenges in the management of this disease. It remains to be determined which patients may benefit most from either early concomitant docetaxel or from abiraterone with ADT, since biomarkers for early therapy response and risk stratification are currently lacking. Therefore, the ability to personalize medicine is hampered. Furthermore, the earlier detection of metastatic prostate cancer by using new imaging modalities makes the application of clinical trial results in daily practice increasingly challenging. Recently, both local radiotherapy to the primary tumor combined with ADT and abiraterone combined with ADT showed a survival benefit in low-volume disease patients. The latest data also demonstrated a survival benefit with the addition of apalutamide or enzalutamide to ADT. The extent of metastatic disease may become one of the most important factors to determine treatment choice. In this review article, we summarize trial data to provide guidance for treatment selection in metastatic castration-naïve prostate cancer.

68Ga-PSMA-11 PET-Based Prostate Cancer Lymph Node Atlas Reveals Patterns of Potential Geographic Miss in Consensus Pelvic Nodal Contours

Gallium-68 prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) enables highly sensitive and specific detection of metastatic prostate cancer. We aimed to characterize patterns of prostate cancer lymph node metastasis through development of a PSMA PET-based lymph node atlas. We then compared our results to the RTOG consensus prostate cancer pelvic nodal atlas to reveal areas of potential geographic miss during radiation therapy. From December 2015 to October 2018, 378 patients were enrolled in a prospective study evaluating the use of 68Ga-PSMA-11 PET in the staging of prostate cancer. We identified 84 previously untreated prostate cancer patients in the study cohort who underwent staging 68Ga-PSMA PET demonstrating pelvic lymph node metastasis. DICOM images were exported to the commercially available deformable registration algorithm, and PET avid lymph nodes were manually contoured. Each node was categorized by laterality, location and volume. Finally, rigid and deformable image fusion was performed, and the location of involved pelvic lymph nodes was compared to the RTOG consensus prostate cancer pelvic nodal contours. We identified 242 68Ga-PSMA-11 PET avid lymph nodes with an average volume of 2.3mL (range 0.9-55.96mL). Among all patients, external iliac and internal iliac nodal basins were most often involved with avid nodes found in 60.7% and 34.5% of patients respectively. Pelvic (32.1%), common iliac (25.0%), perirectal (13.1%), and presacral (10.7%) nodal basins were also commonly involved followed by low frequency involvement of obturator, inguinal, anterior bladder, and retropubic regions (1.2% each). In total, 57 of 242 (24%) PSMA PET avid lymph nodes were located outside of RTOG consensus prostate cancer pelvic nodal contours; missed nodes were found in 37 of the 84 (44%) patients. The most common sites of geographic miss were in the proximal common iliac, distal anterior external iliac, low presacral and perirectal regions. We used 68Ga-PSMA-11 PET imaging to generate a prostate cancer lymph node atlas in previously untreated prostate cancer patients, revealing that more than 1 in 5 involved lymph nodes may be prone to geographic miss by current consensus pelvic nodal contours. These findings suggest that 68Ga-PSMA-11 PET may be used to supplement conventional target delineation. Further research may refine clinical scenarios in which extended lymph node delineation is warranted.

Single Lesion on Prostate-specific Membrane Antigen-ligand Positron Emission Tomography and Low Prostate-specific Antigen Are Prognostic Factors for a Favorable Biochemical Response to Prostate-specific Membrane Antigen-targeted Radioguided Surgery in Recurrent Prostate Cancer

BackgroundProstate-specific membrane antigen (PSMA)-ligand positron emission tomography (PET) allows detection of metastatic prostate cancer (PC) lesions at low prostate-specific antigen (PSA) values. To facilitate their intraoperative detection during salvage surgery, we recently introduced PSMA-targeted radioguided surgery (RGS). ObjectiveTo describe the outcome of a large cohort of patients treated with PSMA-targeted RGS and to establish prognostic factors. Design, setting, and participantsA total of 121 consecutive patients with recurrent PC as defined by PSMA-ligand PET (median PSA: 1.13ng/ml) underwent PSMA-targeted RGS. Outcome measurements and statistical analysisThe frequency of a complete biochemical response (cBR; PSA <0.2ng/ml) without additional treatment and the duration of biochemical recurrence-free survival (bRFS, time from PSMA-targeted RGS with PSA <0.2ng/ml without further treatment) were evaluated and correlated with preoperatively available clinical variables. Results and limitationsIn almost all patients (120/121, 99%) metastatic tissue could be removed. A cBR was achieved in 77 patients (66%). The chance of cBR was highest in patients with both low preoperative PSA and a single lesion (38/45: 84%). Median bRFS was 6.4mo in the whole patient cohort and 19.8mo for patients with cBR. Significantly longer median bRFS was observed in patients with a low preoperative PSA value (p=0.004, hazard ratio 1.48, 95% confidence interval 1.13–1.93) and with a single lesion in preoperative PSMA-ligand PET (14.0 vs 2.5mo, p=0.002). ConclusionsPSMA-targeted RGS leads to a remarkable interval of bRFS in a subset of patients. The frequency of cBR and the duration of bRFS were highest in patients with a low preoperative PSA value and a single lesion on PSMA-ligand PET. Patient summaryProstate-specific membrane antigen radioguided surgery delays disease progression in selected patients with recurrent prostate cancer after radical prostatectomy. Patients with a single lesion of recurrence and a low prostate-specific antigen value had the best outcome.

Novel Imaging in Detection of Metastatic Prostate Cancer.

This review aims to highlight the limitations of current standard-of-care prostate cancer (PCa) imaging and discuss novel clinical imaging in advanced disease. PCa staging through imaging is important for proper selections in clinical treatment. Traditional imaging techniques for metastatic disease (i.e., computed tomography [CT], magnetic resonance imaging [MRI], and radionuclide bone scan) have suboptimal performance in early recurrent or metastatic disease. Novel positron emission tomography agents including radiolabeled prostate specific membrane antigen (PSMA), choline, and anti-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) have demonstrated improved sensitivity and specificity in initial staging and early biochemical recurrence (BCR). Conventional imaging modalities for PCa incompletely characterize disease burden. The development of new PET tracers in combination with CT and MRI offers superior anatomic localization and biologic correlation of tumor sites, which enhance providers' abilities to make appropriate decisions regarding treatment.

Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

Outcomes of Prostate-specific Antigen-based Prostate Cancer Screening Among Men Using Nonsteroidal Anti-inflammatory Drugs

BackgroundThe Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC), the largest component of the European Randomized Study of Screening for Prostate Cancer (ERSPC), showed a smaller, nonsignificant reduction in prostate cancer–specific mortality by systematic prostate-specific antigen (PSA)-based screening compared with the overall ERSPC results. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation and also PSA elevations due to intraprostatic inflammation. ObjectiveTo explore whether NSAID usage modifies the effects of PSA-based screening on prostate cancer incidence and mortality. Design, setting, and participantsA cohort of 78 165 men from the FinRSPC were linked to a comprehensive national prescription database to obtain information on NSAID reimbursements prior to screening. Outcome measurements and statistical analysisProstate cancer risk and mortality were compared between the FinRSPC screening arm and the control arm among NSAID users and nonusers using an age-adjusted Cox regression model. Results and limitationsScreening increased the detection of Gleason 6 (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.47–1.72 and HR 1.39, 95% CI 1.26–1.54) and localized prostate tumors (HR 1.25, 95% CI 1.18–1.32 and HR 1.11, 95% CI 1.03–1.20) more among baseline NSAID nonusers than among users, respectively (p for interaction <0.04 for both). This difference was observed in all three screening rounds. Detection of metastatic prostate cancer was similar in both NSAID users and nonusers. Screening decreased prostate cancer mortality among men using NSAIDs at FinRSPC randomization (HR 0.66, 95% CI 0.49–0.90) but not among nonusers (HR 0.95, 95% CI 0.81–1.12); p for interaction=0.04. ConclusionsScreening detected fewer well-differentiated localized tumors among NSAID users than among nonusers. This suggests that PSA screening may cause less overdiagnosis within this subgroup, whereas mortality benefit may be greater among NSAID users. Patient summaryProstate cancer screening causes less overdiagnosis of well-differentiated localized prostate tumors among men who use nonsteroidal anti-inflammatory drugs.

Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a (111)In-radiolabelled monoclonal antibody, 11B6.

BackgroundProstate cancer is a leading cause of death in the male population of the western world. Human kallikrein-related peptidase 2 (hK2) is abundantly expressed in malignant prostatic tissue, and its gene, KLK2, is regulated by the androgen receptor. 11B6 is a murine IgG1 monoclonal antibody directed against free human hK2. In this study, we performed a preclinical evaluation of 111In-labelled 11B6 in mouse xenografts to investigate its potential in the clinical staging and assessment of metastatic prostate cancer.Methods11B6 was radiolabelled with 111In through CHX-A″-DTPA chelation. In vivo biodistribution and uptake of 111In-DTPA-11B6 were measured until 168 h post-injection in NMRI nude mice bearing subcutaneous LNCaP xenografts. The binding specificity to hK2 was evaluated by both in vivo competitive binding assays with excess non-labelled 11B6 and hK2-negative DU145 xenografts. SPECT/CT imaging of subcutaneous and intra-tibial LNCaP xenografts was used to visualize the tumours.ResultsTumour uptake of 111In-DTPA-11B6 in LNCaP xenografts was 19% ± 0.78%IA/g at 48 h, giving a tumour-to-blood ratio of 1.6, which increases to 2.4 at 1 week post-injection. Accumulation was low in other organs except for the salivary glands, which is probably the result of cross-reactivity with mouse kallikreins. Significantly lower tumour accumulation was observed in competitive assays and DU145 xenografts. SPECT/CT imaging could clearly visualize the subcutaneous and intra-tibial LNCaP xenografts.ConclusionsOur study demonstrates the potential of 111In-DTPA-11B6 for the detection of metastatic prostate cancer and monitoring anti-androgen therapy, as it exhibits an increased uptake and accumulation in viable tumour when compared to normal tissue. A humanised version of the 11B6 monoclonal antibody is currently under evaluation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0051-5) contains supplementary material, which is available to authorized users.

Total submission of pelvic lymphadenectomy tissues removed during radical prostatectomy for prostate cancer increases lymph node yield and detection of micrometastases

The detection of lymph node metastases has prognostic and therapeutic implications for patients undergoing radical prostatectomy for prostate cancer. Macroscopic identification of pelvic lymph nodes in surgical lymphadenectomy specimens can be difficult, with a potential for incomplete submission of lymph nodes for microscopic examination. This study was undertaken to determine whether complete sampling of lymphadenectomy specimens would improve the detection of metastatic disease in patients undergoing radical prostatectomy. We examined 109 pelvic lymphadenectomies accompanying radical prostatectomy specimens to assess the benefit of complete submission of the lymph node packets to detect extra lymph nodes and metastatic disease. We found that blocking the residual tissue, after all palpable lymph nodes had been identified, increased the mean number of lymph nodes from 3.8 to 10.8, with an average of 0.84 macroscopically undetectable nodes being recovered per block submitted. Metastatic prostate cancer was identified in eight cases, one of which had cancer in an impalpable lymph node only. Submission of all pelvic lymphadenectomy tissue for histological examination improves the yield of lymph nodes and the detection of metastatic prostate cancer.

Chemoaffinity capture of pre‐targeted prostate cancer cells with magnetic beads

Prostate circulating tumor cells (PCTCs) in circulation are shed from either a primary tumor or metastases, which are directly responsible for most prostate cancer deaths. Quantifying exfoliated PCTCs may serve as an indicator for the clinical management of prostate cancer, isolating and removing of PCTCs could potentially reduce prostate cancer metastasis, and culturing and characterizing captured PCTCs could facilitate the development of personalized treatment options. Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer being strongly expressed on prostate tumor cells associated with high-grade primary, androgen independent, and metastatic tumors. Suspensions of PSMA+ (LNCaP) cells were pre-targeted with the irreversible PSMA inhibitor biotin-PEG(12)-CTT-54 to serve as a bait to capture PSMA+ cells using streptavidin-coated magnetic beads. Decreasing numbers of LNCaP cells were spiked into blood to determine the cell captured efficiency, recovery and viability. High selectivity, recovery, and viability were achieved for the capture of PSMA+ cells in both model experiments with mixtures of LNCaP cells and WBCs as well as blood samples spiked with LNCaP cells. As low as 10 cells were captured from 1 ml of blood with nearly 90% viability. More importantly, captured cells could be subsequently propagated in vitro. This methodology for the detection, isolation, and culture of PCTCs from peripheral blood can serve as an effective tool for the detection of metastatic prostate cancer, treatment monitoring, and the development of personalized therapy based on the responsiveness of PCTCs to chemotherapeutic strategies.

Quality of life in prostate cancer patients.

Quality of life in prostate cancer patients.

Pharmacokinetics and dosimetry of [111In] F(ab')2 fragments against prostatic acid phosphatase after intraprostatic injection for immunoscintigraphy in prostate cancer.

The purpose of this study was to investigate the pharmacokinetics and dosimetry of using [111In]-labelled F(ab')2 fragments against prostate acid phosphatase (FC-3001, Orion Corporation Farmos, Finland) for the detection of metastatic prostate cancer. Five patients in all were subjected to intraprostatic injection of 1 mg FC-3001 labelled with 85-100 MBq [111In]. In four of the patients the biodistribution was studied by sequential whole-body counting, gamma-camera scintigraphy of the abdomen in antero-posterior and postero-anterior projections. Blood and urine samples were collected sequentially up to 72 h after injection. Initially, significant amounts of antibody fragments were released from the site of injection. After the first 4 h, 22.0% of injected antibody (2.2-41.3% ID) remained in the prostate and was slowly released with a final half-life of 80.4 h (49.9-141.8 h). Labelled antibody appeared in the blood shortly after injection and was cleared from the blood with a final half-life of 27.7-300.9 h. The liver, the bone marrow and, in two patients, the kidneys accumulated antibody fragments in significant amounts during the period of investigation. An apparent relationship between the initial whole-body clearance and renal uptake is described. The effective dose averaged 0.37 mSv/MBq (range 0.24-0.52 mSv/MBq). The highest equivalent doses were received by the kidneys (0.46-2.81 mGy/MBq) the liver (0.44-1.59 mGy/MBq) and the bone marrow (0.37-0.57 mGy/MBq). Only in two of the patients with known metastases were pathological foci seen. The disappointing imaging results were probably caused by the biphasic release of antibody from the prostate, and indicates that intraprostatic injection of this antibody has no advantage for imaging, as well as being unpleasant for the patient. The biodistribution of the antibody following release from the prostate is similar to but more variable than the biodistribution seen in patients after intravenous injection of labelled antibodies.

Cytochemistry of the Acid Phosphatases

Cytochemistry of acid phosphatases has recently enjoyed an increase in clinical application. Better known among these methods is the tartrate-resistant acid phosphatase stain for the hairy cells of hairy-cell leukemia. The demonstration of prostatic acid phosphatase in tumor cells outside the prostate may further aid in the detection of metastatic prostate cancer. Aside from these methods for cytologic and histologic materials, it is now possible to cytochemically demonstrate acid phosphatase activity in subcellular organelles, extracts of whole tissue and cellular preparations, and in biological fluids and secretions. The methods for optimal staining of acid phosphatase activity in these various materials are necessarily different in one or more respects. The methods for cytochemical demonstration of acid phosphatase are reviewed in the context of the applications for which they may be used. Emphasis is placed on those methods for cytologic and histologic preparations. Applications where cytochemistry is frequently used in combination with biochemical, electrophoretic and immunologic techniques are also reviewed.

Cytochemistry of the Acid Phosphatases

Cytochemistry of acid phosphatases has recently enjoyed an increase in clinical application. Better known among these methods is the tartrate-resistant acid phosphatase stain for the hairy cells of hairy-cell leukemia. The demonstration of prostatic acid phosphatase in tumor cells outside the prostate may further aid in the detection of metastatic prostate cancer. Aside from these methods for cytologic and histologic materials, it is now possible to cytochemically demonstrate acid phosphatase activity in subcellular organelles, extracts of whole tissue and cellular preparations, and in biological fluids and secretions. The methods for optimal staining of acid phosphatase activity in these various materials are necessarily different in one or more respects. The methods for cytochemical demonstration of acid phosphatase are reviewed in the context of the applications for which they may be used. Emphasis is placed on those methods for cytologic and histologic preparations. Applications where cytochemistry is frequently used in combination with biochemical, electrophoretic and immunologic techniques are also reviewed.