Imaging Of Recurrent Prostate Cancer Research Articles

Invited Commentary: Advanced Anatomic and Molecular Imaging in Recurrent Prostate Cancer.

Invited Commentary: Advanced Anatomic and Molecular Imaging in Recurrent Prostate Cancer.

Stereotactic Body Radiation Therapy Salvage for Lymph Node Recurrent Prostate Cancer in the Era of PSMA PET Imaging.

Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.

Molecular Imaging in Recurrent Prostate Cancer Presented as a Mixed Small Neuroendocrine Tumor/Acinar Adenocarcinoma.

Molecular imaging is an important tool for evaluating patients with prostate cancer, including those with hybrid histopathology. Although rare, mixed small neuroendocrine tumor/acinar adenocarcinoma exhibit aggressive behavior that necessitates optimal therapy. Molecular imaging has been implemented previously to assess radioligand therapy eligibility in such cases. Interestingly, the uptake of radiotracers targeting prostate-specific membrane antigen (PSMA) and somatostatin receptor may be reduced and can potentially lead to false negative readings in certain tumor types with hybrid features. Therefore, physicians should be aware of different kinds of disparities when assessing these tumor types with the aforementioned modalities.

With New Technology Comes Great Responsibility: Prostate-Specific Membrane Antigen Imaging in Recurrent Prostate Cancer.

With New Technology Comes Great Responsibility: Prostate-Specific Membrane Antigen Imaging in Recurrent Prostate Cancer.

Invited Commentary: Changing Landscape of Imaging in Recurrent Prostate Cancer.

Invited Commentary: Changing Landscape of Imaging in Recurrent Prostate Cancer.

Best Practices for 18F-Fluciclovine PET/CT Imaging of Recurrent Prostate Cancer: A Guide for Technologists.

18F-fluciclovine is a Food and Drug Administration-approved PET tracer indicated for patients suspected to have recurrent prostate cancer based on a prostate-specific antigen rise after prior therapy. 18F-fluciclovine PET/CT is performed significantly differently from 18F-FDG PET/CT and requires special attention to patient preparation, injection technique, and imaging time. This article aims to provide nuclear medicine technologists with the best-practice guidelines for the 18F-fluciclovine PET/CT protocol.

PET imaging of hepatocellular carcinoma with anti-1-amino-3-[18F]fluorocyclobutanecarboxylic acid in comparison with l-[S-methyl-11C]methionine

Purpose[11C]methionine ([11C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types. However, the short half-life of 11C decay limited further clinical development of [11C]Met. Synthetic amino acid analog anti-1-amino-3-[18F]fluoro-cyclobutyl-1-carboxylic acid ([18F]FCABC) was developed and FDA-approved for PET imaging of recurrent prostate cancer. This study investigated “repurposed” [18F]FACBC for PET imaging of primary liver cancer such as hepatocellular carcinoma (HCC) in comparison with [11C]Met.Methods[11C]Met was synthesized in the lab, and [18F]FACBC was purchased from a commercial outlet. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for PET imaging. Bioinformatics analysis was performed for the expression of amino acid transporters responsible for radiotracer uptake and validated by PCR. Dynamic PET scans of [11C]Met and [18F]FACBC were acquired within 1 week. Standardized uptake value (SUV) was calculated for regions of interest (ROIs) defined over HCC and a liver background region. H&E staining and immunohistochemical (IHC) staining were performed with harvested tissues post-imaging.ResultsHigher expression of ACST2 and LAT1 was found in HCC than in the surrounding liver tissues. PCR validated this differential expression. [11C]Met and [18F]FACBC displayed some differences in their uptake and retention in HCC. Both peaked in HCC with an SUV of 3.5 after 10 min post-injection. Met maintained a plateaued contrast uptake in HCC to that in the liver while [18F]FCABC declined in HCC and liver after peak uptake. The pathological assessment revealed the liver tumor as moderately differentiated similar to the human HCC and proliferative.ConclusionBoth [18F]FACBC and [11C]Met showed uptake in HCC through the use of a clinically relevant animal model of woodchuck HCC. The uptake and retention of [18F]FACBC and [11C]Met depend on their metabolism and also rely on the distribution of their principal amino acid transporters.

Review of 18F-Fluciclovine PET for Detection of Recurrent Prostate Cancer.

Fluorine 18 (18F) fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC]) is a radiolabeled amino acid analog that takes advantage of the amino acid transport upregulation in several types of cancer cells. FACBC is taken up to a greater extent in prostate cancer cells than in surrounding normal tissue, providing an opportunity for its use in cases of this common cancer. In 2016, the U.S. Food and Drug Administration found the accuracy of FACBC PET to be superior to that of other molecular imaging techniques and subsequently granted approval for its use in PET of recurrent prostate cancer. As FACBC is an 18F radiotracer, an on-site cyclotron is not required for its production. This feature enables the widespread clinical availability of this agent and, in turn, an opportunity for improved patient care. The clinical pharmacology and imaging features of FACBC are reviewed, and the role of this agent in the imaging of recurrent prostate cancer, within the context of research that supports its effectiveness, is discussed. The administration of and image acquisition facilitated by using FACBC, as compared with 18F fluorodeoxyglucose, which is more widely used, are described. In addition, the criteria for interpreting FACBC imaging findings are outlined, with emphasis on common causes of false-positive and false-negative findings. ©RSNA, 2019.

Prostate-specific membrane antigen positron emission tomography in the management of recurrent prostate cancer.

There is an unmet clinical need for early, accurate imaging of recurrent prostate cancer to improve patient outcomes. Staging, by conventional bone scintigraphy and CT have become outdated. 68Ga-PSMA PET/CT imaging in this setting has developed rapidly, with widespread International adoption in line with evidence-based guidelines in this group of patients. A PubMed search of English language articles was performed using following keywords: PSMA, PET/CT, biochemical recurrence, prostate cancer. The search revealed 85 articles, of which 75 were original; 70 of these involved use of the most widely available type of PSMA tracer (HBED). The review also relied on the clinical experience of reporting over 1000 PSMA PET/CT studies at a major tertiary referral centre for uro-oncology, with the majority of cases having been performed in the biochemical recurrence setting from 2015 to 2018. 68Ga-PSMA PET is a game changer and superior to choline PET and other established tracers which have been used in prostate cancer evaluation. Detection of recurrence at the prostate bed remains challenging due to bladder and urethral tracer accumulation. The main strength of PSMA PET/CT is its ability to identify small (<8 mm) pathological lymph nodes, upstaging nodal status in up to two-thirds of cases. Additionally, PSMA PET/CT, detects bone and bone marrow metastases missed by conventional bone and CT imaging. Thus, PSMA PET/CT has major impact on patient management, with studies reporting overall changes in 39-76% of cases. Controversy exists regarding patient access and NHS affordability of PSMA PET/CT imaging. Currently, no reimbursement is available under the NHS tariff system. The cost outlay for tertiary hospital linked PET centres ranges from £150-170 K. Large referral volumes, and technical advances in manufacturing process will make this tracer cost neutral and similar to the current funded, but less sensitive, choline PET. Current NICE guidelines for prostate cancer management do not include a recommendation on when PSMA PET/CT should be used and this is likely to remain the case in the next revision, due in 2019. Although PSMA PET/CT imaging results in significant management change, there is a need for high quality economic evaluation and cost analysis for this modality. Lack of this data will result in poor adoption of this technique and thus limit patient access. Furthermore, it is hoped that future tracers will become even more sensitive and identify disease at earlier thresholds. Well-designed clinical trials with consideration of the health economic benefit of using PSMA PET/CT will be essential to provide a basis for entry into guidelines such as NICE and to provide a rationale for reimbursement.

Bayesian penalised likelihood reconstruction (Q.Clear) of 18F-fluciclovine PET for imaging of recurrent prostate cancer: semi-quantitative and clinical evaluation.

Objective:18F-Fluciclovine (FACBC) is an amino acid PET radiotracer approved for recurrent prostate cancer imaging. We investigate the use of Bayesian penalised likelihood (BPL) reconstruction for 18F-fluciclovine PET.Methods:15 18F-fluciclovine scans were reconstructed using ordered subset expectation maximisation (OSEM), OSEM + point spread function (PSF) modelling and BPL using β-values 100–600. Lesion maximum standardised uptake value (SUVmax), organ SUVmean and standard deviation were measured.Deidentified reconstructions (OSEM, PSF, BPL using β200–600) from 10 cases were visually analysed by two readers who indicated their most and least preferred reconstructions, and scored overall image quality, noise level, background marrow image quality and lesion conspicuity.Results:Comparing BPL to OSEM, there were significant increments in lesion SUVmax and signal-to-background up to β400, with highest gain in β100 reconstructions (mean ΔSUVmax 3.9, p < 0.0001). Organ noise levels increased on PSF, β100 and β200 reconstructions. Across BPL reconstructions, there was incremental reduction in organ noise with increasing β, statistically significant beyond β300–500 (organ-dependent). Comparing with OSEM and PSF, lesion signal-to-noise was significantly increased in BPL reconstructions where β ≥ 300 and ≥ 200 respectively.On visual analysis, β 300 had the first and second highest scores for image quality, β500 and β600 equal highest scores for marrow image quality and least noise, PSF and β 200 had first and second highest scores for lesion conspicuity. For overall preference, one reader preferred β 300 in 9/10 cases and the other preferred β 200 in all cases.Conclusion:BPL reconstruction of 18F-fluciclovine PET images improves signal-to-noise ratio, affirmed by overall reader preferences. On balance, β300 is suggested for 18F-fluciclovine whole body PET image reconstruction using BPL.Advances in knowledge:The optimum β is different to that previously published for 18F-fluorodeoxyglucose, and has practical implications for a relatively new tracer in an environment with modern reconstruction technologies.

68Ga-PSMA PET/CT imaging in recurrent prostate cancer: Where are we now?

IntroductionProstate cancer (PCa) is a major health concern worldwide with up to 60% of patients experiencing biochemical relapse after radical treatment. Early diagnosis of PCa recurrence is of high importance for successful salvage therapy. The need for accurate imaging has prompted the introduction of prostate-specific membrane antigen (PSMA)-based radiotracers for positron emission tomography (PET).Material and methodsIn this review we summarized and discussed the results of the studies analyzing the utility of 68Ga-PSMA PET/CT in patients who experienced a biochemical relapse of prostate cancer.ResultsPSMA-based PET scans have been proved to provide a superior diagnostic performance over other modalities for localization of the site of early PCa recurrence. 68Ga-PSMA has been also shown to have a higher sensitivity and specificity than other established PET radiotracers such as radiocholines.ConclusionsThe early studies show promising results and support the use of 68Ga-PSMA for PCa restaging. However, the number of studies concerning the utility of 68Ga-PSMA PET in the context of secondary PCa staging is limited and there is still a considerable scope for further research in this field.

Multiparametric Magnetic Resonance Imaging of Recurrent Prostate Cancer.

There is growing consensus that multiparametric magnetic resonance imaging (mpMRI) is an effective modality in the detection of locally recurrent prostate cancer after prostatectomy and radiation therapy. The emergence of magnetic resonance (MR)-guided focal therapies, such as cryoablation, high-intensity focused ultrasound, and laser ablation, have made the use of mpMRI even more important, as the normal anatomy is inevitably altered and the detection of recurrence is made more difficult. The aim of this article is to review the utility of mpMRI in detecting recurrent prostate cancer in patients following radical prostatectomy, radiation therapy, and focal therapy and to discuss expected post-treatment mpMRI findings, the varied appearance of recurrent tumors, and their mimics.

Multiparametric Magnetic Resonance Imaging of Recurrent Prostate Cancer.

Multiparametric magnetic resonance (MR) imaging of the prostate combines both morphological and functional MR techniques by utilizing small field of view T1-weighted, T2-weighted, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and MR spectroscopy to accurately detect, localize, and stage primary and recurrent prostate cancer. Localizing the site of recurrence in patients with rising prostate-specific antigen following treatment affects decision making regarding treatment and can be accomplished with multiparametric prostate MR. Several different treatment options are available for prostate cancer including radical prostatectomy, external beam radiation therapy, brachytherapy, androgen deprivation therapy, or a number of focal therapy techniques. The findings of recurrent prostate cancer can be different depending on the treatment the patient has received, and the radiologist must be able to recognize the variety of imaging findings seen with this common disease. This review article will detail the findings of recurrent prostate cancer on multiparametric MR and describe common posttreatment changes which may create challenges to accurate interpretation.

Imaging for Prostate Cancer Recurrence

ContextCorrect identification of metastatic sites in recurrent prostate cancer (PCa) is of crucial importance because it leads to further treatment decisions. ObjectiveTo provide an overview on current imaging procedures and their performance in recurrent PCa. Evidence acquisitionMedline search via PubMed was performed with the keywords imaging, recurrent, and prostate cancer as well as more detailed searches including the keywords bone scan, bone scintigraphy, computed tomography, magnetic resonance imaging, positron emission tomography, PET, choline, FDG, prostate-specific membrane antigen, and PSMA, with emphasis on recent literature from 2010 to the present. Non-English published literature was excluded. Abstracts and full-text articles were reviewed and assessed for relevant content. Evidence synthesisIn diagnostic imaging and particularly with newer technologies like positron emission tomography (PET), a profound lack of prospectively designed studies in recurrent PCa has to be noted. In most studies histologic validation has only been performed in a subset of patient cohorts. Heterogeneity of included patient cohorts, lack of standardized assessment, as well as diverging end points, hamper systematic comparison of different image modalities. Thus evidence for currently used imaging in recurrent PCa is only presented descriptively. ConclusionsComputed tomography and magnetic resonance imaging (MRI) as well as bone scintigraphy still represent the standard imaging for recurrent PCa; however, particularly for detection of local recurrence, multiparametric MRI is a valuable imaging modality. PET using choline and particularly tracers against prostate-specific membrane antigen might improve visualization of metastatic lesions. These findings need to be validated in prospective trials. Patient summaryImaging of recurrent prostate cancer (PCa) is important to guide further treatment. Computed tomography, magnetic resonance imaging, and bone scintigraphy represent the current standard. Positron emission tomography, especially with cancer-specific tracers, might improve imaging of recurrent PCa in the future.

Prostate-specific antigen and prostate-specific antigen velocity as threshold indicators in 11C-acetate PET/CTAC scanning for prostate cancer recurrence.

PurposeThe aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer.MethodsFrom 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients’ characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan.ResultsIn total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning.ConclusionsThis retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer.

Radionuclide and hybrid imaging of recurrent prostate cancer

Prostate cancer is one of the most common cancers in men, leading to substantial morbidity and mortality. After definitive therapy with surgery or radiation, many patients have biochemical relapse of disease--ie, an increase in their prostate-specific antigen level--which often precedes clinically apparent disease by months or even years. Therefore, imaging of the site and extent of tumour recurrence (local, regional, distant, or a combination) is of great interest. Conventional morphological imaging methods showed limited accuracy for assessment of recurrent prostate cancer; however, in recent years, functional and molecular imaging have offered the possibility of imaging molecular or cellular processes of individual tumours, often with more accuracy than morphological imaging. Hybrid imaging modalities (PET-CT, and single-photon emission CT [SPECT]-CT) have been introduced that combine functional and morphological data and allow whole-body imaging. Here, we review the contribution of radionuclide imaging and hybrid imaging for assessment of recurrent prostate cancer (local vs regional vs distant disease). We discuss available data on PET-CT and SPECT-CT, and provide an overview of experimental tracers and their preclinical and clinical development. Finally, we present a perspective on the potential of future hybrid magnetic resonance-PET imaging.

PET/CT imaging of recurrent prostate cancer

PET/CT imaging of recurrent prostate cancer