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PET/CT in Prostate Cancer
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PET/CT in Prostate Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Survivorship and Quality of Life".

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 31879

Special Issue Editors

Dr. Stefano Fanti

E-Mail Website
Guest Editor
Department of Nuclear Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Interests: PET imaging; PET/CT; molecular imaging; radiopharmaceuticals; prostate cancer; PSMA
Special Issues, Collections and Topics in MDPI journals
Dr. Laura Evangelista

E-Mail Website
Guest Editor
Department of Nuclear Medicine, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
Interests: PET/CT; molecular imaging; radiopharmaceuticals; prostate cancer; PET/MRI
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate cancer represents the most common tumor disease in males worldwide. Biomarkers of disease and conventional imaging modalities, such as computed tomography and bone scintigraphy, often fail in the early identification of lymph node and distant organ metastases both in staging and in restaging settings. Magnetic resonance imaging can be useful for the detection of primary tumor and local recurrence, but it still not considered the gold standard.    

The Special Issue entitled “PET/CT in prostate cancer” will be focused on the role of PET/CT or PET/MRI in the management of patients with prostate cancer. The current available radiopharmaceutical agents and also the recent development in the manipulation of the images for the radiomic purposes have deeply affect the therapeutic and diagnostic management of patients affected by prostate cancer. Indeed, molecular imaging with PET can support the clinical experts in all phase of disease, from the initial diagnosis to the evaluation of patients with an advanced cancer. Moreover, the recent introduction of receptor-targeted radiopharmaceutical agents represents an important step for guiding personalized treatment approaches.

Prof. Stefano Fanti
Dr. Laura Evangelista
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • PET/CT
  • PSMA
  • radiopharmaceuticals
  • prostate cancer
  • radiomic

Published Papers (15 papers)

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Editorial

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3 pages, 177 KiB  
Editorial
PET/CT in Prostate Cancer
by Laura Evangelista and Stefano Fanti
Cancers 2023, 15(15), 3751; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15153751 - 25 Jul 2023
Viewed by 799
Abstract
Over the last decade, PET/CT has played a crucial role in managing patients with prostate cancer (PCa), significantly impacting various aspects of the disease [...] Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)

Research

Jump to: Editorial, Review, Other

12 pages, 1211 KiB  
Article
An Apparent Diffusion Coefficient-Based Machine Learning Model Can Improve Prostate Cancer Detection in the Grey Area of the Prostate Imaging Reporting and Data System Category 3: A Single-Centre Experience
by Caterina Gaudiano, Margherita Mottola, Lorenzo Bianchi, Beniamino Corcioni, Lorenzo Braccischi, Makoto Taninokuchi Tomassoni, Arrigo Cattabriga, Maria Adriana Cocozza, Francesca Giunchi, Riccardo Schiavina, Stefano Fanti, Michelangelo Fiorentino, Eugenio Brunocilla, Cristina Mosconi and Alessandro Bevilacqua
Cancers 2023, 15(13), 3438; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15133438 - 30 Jun 2023
Cited by 2 | Viewed by 1053
Abstract
The Prostate Imaging and Reporting Data System (PI-RADS) has a key role in the management of prostate cancer (PCa). However, the clinical interpretation of PI-RADS 3 score lesions may be challenging and misleading, thus postponing PCa diagnosis to biopsy outcome. Multiparametric magnetic resonance [...] Read more.
The Prostate Imaging and Reporting Data System (PI-RADS) has a key role in the management of prostate cancer (PCa). However, the clinical interpretation of PI-RADS 3 score lesions may be challenging and misleading, thus postponing PCa diagnosis to biopsy outcome. Multiparametric magnetic resonance imaging (mpMRI) radiomic analysis may represent a stand-alone noninvasive tool for PCa diagnosis. Hence, this study aims at developing a mpMRI-based radiomic PCa diagnostic model in a cohort of PI-RADS 3 lesions. We enrolled 133 patients with 155 PI-RADS 3 lesions, 84 of which had PCa confirmation by fusion biopsy. Local radiomic features were generated from apparent diffusion coefficient maps, and the four most informative were selected using LASSO, the Wilcoxon rank-sum test (p < 0.001), and support vector machines (SVMs). The selected features where augmented and used to train an SVM classifier, externally validated on a holdout subset. Linear and second-order polynomial kernels were exploited, and their predictive performance compared through receiver operating characteristics (ROC)-related metrics. On the test set, the highest performance, equally for both kernels, was specificity = 76%, sensitivity = 78%, positive predictive value = 80%, and negative predictive value = 74%. Our findings substantially improve radiologist interpretation of PI-RADS 3 lesions and let us advance towards an image-driven PCa diagnosis. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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9 pages, 249 KiB  
Article
A Retrospective Multicenter Analysis of the Incidence of Bone-Only Disease at PSMA PET/CT in Castration Resistant Prostate Cancer Patients
by Francesca Serani, Wolfgang P. Fendler, Paolo Castellucci, Christoph Berliner, Francesco Barbato, Ken Herrmann, Andrea Farolfi and Stefano Fanti
Cancers 2023, 15(8), 2208; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15082208 - 08 Apr 2023
Cited by 2 | Viewed by 1578
Abstract
PSMA PET/CT has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC), which can be applied in a metastasis-directed therapy approach. PSMA PET/CT (PET) also has a role in the selection of patients for metastasis-directed therapy or radioligand therapy and therapy [...] Read more.
PSMA PET/CT has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC), which can be applied in a metastasis-directed therapy approach. PSMA PET/CT (PET) also has a role in the selection of patients for metastasis-directed therapy or radioligand therapy and therapy assessment in CRPC patients. The purpose of this multicenter retrospective study was to determine the incidence of bone-only metastasis in CRPC patients who underwent PSMA PET/CT for restaging, as well as identifying potential predictors of bone-only PET positivity. The study analyzed data from 179 patients from two centers in Essen and Bologna. Results showed that 20.1% of the patients had PSMA uptake only in the bone, with the most frequent lesions located in the vertebrae, ribs, and hip bone. Half half of the patients showed oligo disease in bone and may benefit from a bone-metastasis-directed therapy. Initial positive nodal status and solitary ADT were shown to be negative predictors of osseous metastasis. The role of PSMA PET/TC in this patient population needs to be further explored in terms of its role in the evaluation and adoption of bone-specific therapies. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
13 pages, 2316 KiB  
Article
Histology and PSMA Expression on Immunohistochemistry in High-Risk Prostate Cancer Patients: Comparison with 68Ga-PSMA PET/CT Features in Primary Staging
by Luigia Vetrone, Riccardo Mei, Lorenzo Bianchi, Francesca Giunchi, Andrea Farolfi, Paolo Castellucci, Matteo Droghetti, Massimiliano Presutti, Alessio Degiovanni, Riccardo Schiavina, Eugenio Brunocilla, Antonietta D’Errico and Stefano Fanti
Cancers 2023, 15(6), 1716; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15061716 - 10 Mar 2023
Cited by 7 | Viewed by 1903
Abstract
PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression [...] Read more.
PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression in a cohort of biopsy-proven high-risk PCa candidates for surgery. Clinical information (age, iPSA-value, and grading group) and PSMA-PET/CT parameters (SUVmax, PSMA tumor volume [PSMA-TV], and total lesion [PSMA-TL]) were compared with pT (including histologic pattern, Gleason grade, and lymphovascular invasion [LVI]) and PSMA-IHC features, including visual quantification (VS) with a four-tiered score (0 = negative, 1+ = weak, 2+ = moderate, 3+ = strong), growth pattern (infiltrative vs expansive), and visual pattern (cytoplasmic vs membranous). In total, 44 patients were enrolled, with a median age of 67 (IQR 57-77); the median iPSA was 9.4 ng/dL (IQR 12.5-6.0). One patient (3%) was grading group (GG) 3, 27/44 (61%) were GG4, and 16/44 (36%) were GG5. PSMA-PET/CT detection rate for the presence of primary prostate cancer was 100%. Fused/poorly formed Gleason grade 4 features were predominant (22/44–50%); a cribriform pattern was present in 18/44 (41%) and acinar in 4/44 (9%). We found that lower PSMA-TVs were mostly related to acinar, while higher PSMA-TVs correlated with a higher probability to have a cribriform pattern (p-value 0.04). LVI was present in 21/44(48%) patients. We found that higher PSMA-TV and PSMA-TL are predictive of LVI p-value 0.002 and p-value 0.01, respectively. There was no correlation between PET-parameters and perineural invasion (PNI), probably because this was present in almost all the patients. Moreover, patients with high PSMA-TL values displayed the highest PSMA-IHC expression (VS3+) with a membranous pattern. In conclusion, PSMA-TV and PSMA-TL are predictors of a cribriform pattern and LVI. These conditions are mostly related to higher aggressiveness and worse outcomes. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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12 pages, 881 KiB  
Article
Oligometastatic Prostate Cancer Treated with Metastasis-Directed Therapy Guided by Positron Emission Tomography: Does the Tracer Matter?
by Francesco Lanfranchi, Liliana Belgioia, Michela Marcenaro, Elisa Zanardi, Giorgia Timon, Mattia Riondato, Veronica Giasotto, Jeries Paolo Zawaideh, Laura Tomasello, Guglielmo Mantica, Nataniele Piol, Marco Borghesi, Paolo Traverso, Camilla Satragno, Daniele Panarello, Claudio Scaffidi, Andrea Romagnoli, Sara Elena Rebuzzi, Angela Coco, Bruno Spina, Silvia Morbelli, Gianmario Sambuceti, Carlo Terrone, Salvina Barra, Giuseppe Fornarini and Matteo Baucknehtadd Show full author list remove Hide full author list
Cancers 2023, 15(1), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15010323 - 03 Jan 2023
Cited by 2 | Viewed by 3094
Abstract
The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa [...] Read more.
The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13–38.00 vs. 40.93 months, 95% CI: 40.93–40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the “tip of the iceberg”, by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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12 pages, 1644 KiB  
Article
PSMA PET for the Evaluation of Liver Metastases in Castration-Resistant Prostate Cancer Patients: A Multicenter Retrospective Study
by Susanna Mattoni, Andrea Farolfi, Fabio Formaggio, Gabriel Bruno, Paola Caroli, Juliano Julio Cerci, Matthias Eiber, Wolfgang Peter Fendler, Rita Golfieri, Ken Herrmann, Federica Matteucci, Cristina Mosconi, Giulia Paolani, Miriam Santoro, Lidia Strigari, Cristina Nanni, Paolo Castellucci and Stefano Fanti
Cancers 2022, 14(22), 5680; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225680 - 18 Nov 2022
Cited by 2 | Viewed by 1630
Abstract
Background: To evaluate the diagnostic performance of PSMA-PET compared to conventional imaging/liver biopsy in the detection of liver metastases in CRPC patients. Moreover, we evaluated a PSMA-PET/CT-based radiomic model able to identify liver metastases. Methods: Multicenter retrospective study enrolling patients with the following [...] Read more.
Background: To evaluate the diagnostic performance of PSMA-PET compared to conventional imaging/liver biopsy in the detection of liver metastases in CRPC patients. Moreover, we evaluated a PSMA-PET/CT-based radiomic model able to identify liver metastases. Methods: Multicenter retrospective study enrolling patients with the following inclusion criteria: (a) proven CRPC patients, (b) PSMA-PET and conventional imaging/liver biopsy performed in a 6 months timeframe, (c) no therapy changes between PSMA-PET and conventional imaging/liver biopsy. PSMA-PET sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for liver metastases were calculated. After the extraction of radiomic features, a prediction model for liver metastases identification was developed. Results: Sixty CRPC patients were enrolled. Within 6 months before or after PSMA-PET, conventional imaging and liver biopsy identified 24/60 (40%) patients with liver metastases. PSMA-PET sensitivity, specificity, PPV, NPV, and accuracy for liver metastases were 0.58, 0.92, 0.82, 0.77, and 0.78, respectively. Either number of liver metastases and the maximum lesion diameter were significantly associated with the presence of a positive PSMA-PET (p < 0.05). On multivariate regression analysis, the radiomic feature-based model combining sphericity, and the moment of inverse difference (Idm), had an AUC of 0.807 (95% CI:0.686-0.920). Conclusion: For liver metastases assessment, [68Ga]Ga-PSMA-11-PET demonstrated moderate sensitivity while high specificity, PPV, and inter-reader agreement compared to conventional imaging/liver biopsy in CRPC patients. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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12 pages, 1377 KiB  
Article
Radiomics Analysis on [68Ga]Ga-PSMA-11 PET and MRI-ADC for the Prediction of Prostate Cancer ISUP Grades: Preliminary Results of the BIOPSTAGE Trial
by Giacomo Feliciani, Monica Celli, Fabio Ferroni, Enrico Menghi, Irene Azzali, Paola Caroli, Federica Matteucci, Domenico Barone, Giovanni Paganelli and Anna Sarnelli
Cancers 2022, 14(8), 1888; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14081888 - 08 Apr 2022
Cited by 12 | Viewed by 2045
Abstract
Prostate cancer (PCa) risk categorization based on clinical/PSA testing results in a substantial number of men being overdiagnosed with indolent, early-stage PCa. Clinically non-significant PCa is characterized as the presence of ISUP grade one, where PCa is found in no more than two [...] Read more.
Prostate cancer (PCa) risk categorization based on clinical/PSA testing results in a substantial number of men being overdiagnosed with indolent, early-stage PCa. Clinically non-significant PCa is characterized as the presence of ISUP grade one, where PCa is found in no more than two prostate biopsy cores.MRI-ADC and [68Ga]Ga-PSMA-11 PET have been proposed as tools to predict ISUP grade one patients and consequently reduce overdiagnosis. In this study, Radiomics analysis is applied to MRI-ADC and [68Ga]Ga-PSMA-11 PET maps to quantify tumor characteristics and predict histology-proven ISUP grades. ICC was applied with a threshold of 0.6 to assess the features’ stability with variations in contouring. Logistic regression predictive models based on imaging features were trained on 31 lesions to differentiate ISUP grade one patients from ISUP two+ patients. The best model based on [68Ga]Ga-PSMA-11 PET returned a prediction efficiency of 95% in the training phase and 100% in the test phase whereas the best model based on MRI-ADC had an efficiency of 100% in both phases. Employing both imaging modalities, prediction efficiency was 100% in the training phase and 93% in the test phase. Although our patient cohort was small, it was possible to assess that both imaging modalities add information to the prediction models and show promising results for further investigations. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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11 pages, 1001 KiB  
Article
Prognostic Value of the BIO-Ra Score in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223 after the European Medicines Agency Restricted Use: Secondary Investigations of the Multicentric BIO-Ra Study
by Matteo Bauckneht, Sara Elena Rebuzzi, Marta Ponzano, Roberto Borea, Alessio Signori, Viviana Frantellizzi, Elisa Lodi Rizzini, Manlio Mascia, Valentina Lavelli, Alberto Miceli, Maria Silvia De Feo, Antonio Rosario Pisani, Susanna Nuvoli, Vincenzo Tripoli, Alessio Giuseppe Morganti, Paolo Mammucci, Salvatore Caponnetto, Guglielmo Mantica, Angelo Domenico Di Nicola, Carlo Villano, Luca Cindolo, Silvia Morbelli, Gianmario Sambuceti, Stefano Fanti, Renato Patrizio Costa, Angela Spanu, Giuseppe Rubini, Fabio Monari, Giuseppe De Vincentis and Giuseppe Fornariniadd Show full author list remove Hide full author list
Cancers 2022, 14(7), 1744; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071744 - 29 Mar 2022
Cited by 7 | Viewed by 1839
Abstract
The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in [...] Read more.
The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p < 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p < 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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18 pages, 3433 KiB  
Article
[18F]Fluciclovine PET/CT Improves the Clinical Management of Early Recurrence Prostate Cancer Patients
by Anna Giulia Nappi, Cristina Ferrari, Paolo Mammucci, Dino Rubini, Valentina Lavelli, Angela Sardaro, Antonio Rosario Pisani and Giuseppe Rubini
Cancers 2022, 14(6), 1461; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061461 - 12 Mar 2022
Cited by 4 | Viewed by 1885
Abstract
We investigated the [18F]Fluciclovine PET/CT reliability in the early detection of recurrent prostate cancer (PCa) and its impact on therapeutic decision making. We retrospectively analyzed 58 [18F]Fluciclovine PET/CT scans performed to identify early PCa recurrence. Detection rate (DR) and [...] Read more.
We investigated the [18F]Fluciclovine PET/CT reliability in the early detection of recurrent prostate cancer (PCa) and its impact on therapeutic decision making. We retrospectively analyzed 58 [18F]Fluciclovine PET/CT scans performed to identify early PCa recurrence. Detection rate (DR) and semiquantitative analysis were evaluated in relation to biochemical and clinical–histological features. Clinical follow-up data were collected and considered as gold standard to evaluate sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV). The impact of [18F]Fluciclovine PET/CT on clinical management was also assessed. Overall DR resulted as 66%, while DR was 53%, 28%, and 7% in prostate/bed, lymph nodes, and bone, respectively. DR significantly increased with higher PSA values (p = 0.009) and 0.45 ng/mL was identified as the optimal cut-off value. Moreover, SUVmax and SUVmean resulted significant parameters in interpreting malignant from benign findings. [18F]Fluciclovine PET/CT reached a sensitivity, specificity, PPV, NPV, and accuracy of 87.10%, 80.00%, 87.10%, 80.00%, and 84.31%, respectively. Therapeutic strategy was changed in 51% of patients. Our results support [18F]Fluciclovine PET/CT as a reliable tool for early restaging of PCa patients, especially for local recurrence detection, leading to a significant impact on clinical management. Semiquantitative analysis could improve specificity in interpreting malignant from benign lesions. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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10 pages, 1245 KiB  
Article
Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [177Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome
by Philipp E. Hartrampf, Constantin Lapa, Sebastian E. Serfling, Andreas K. Buck, Anna Katharina Seitz, Philipp T. Meyer, Juri Ruf and Kerstin Michalski
Cancers 2021, 13(17), 4270; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13174270 - 25 Aug 2021
Cited by 7 | Viewed by 2156
Abstract
Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined [...] Read more.
Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [18F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA−) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA− lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA− lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA− lesion were compared to patients without any FDG+/PSMA− lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA− metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA− lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA− findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA− lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA− lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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11 pages, 1629 KiB  
Article
Value of Combined PET Imaging with [18F]FDG and [68Ga]Ga-PSMA-11 in mCRPC Patients with Worsening Disease during [177Lu]Lu-PSMA-617 RLT
by Fadi Khreish, Kalle Ribbat, Mark Bartholomä, Stephan Maus, Tobias Stemler, Ina Hierlmeier, Johannes Linxweiler, Mathias Schreckenberger, Samer Ezziddin and Florian Rosar
Cancers 2021, 13(16), 4134; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164134 - 17 Aug 2021
Cited by 14 | Viewed by 2272
Abstract
Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC), some patients show worsening disease during PSMA-RLT. We investigated the value of combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging in this setting. [...] Read more.
Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC), some patients show worsening disease during PSMA-RLT. We investigated the value of combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging in this setting. In n = 29 mCRPC patients with worsening disease after a median of four cycles of [177Lu]Lu-PSMA-617 RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging was performed to detect [18F]FDG-avid lesions with low or no PSMA expression (mismatch lesions). To evaluate prognostic implication of mismatch, survival analyses regarding presence, location, and [18F]FDG PET-derived parameters such as SUVmax, metabolic tumor volume (MTVm), and total lesion glycolysis (TLGm) of mismatch findings were performed. Seventeen patients (59%) showed at least one mismatch metastasis. From the time point of combined PET imaging, the median overall survival (OS) of patients with mismatch findings was significantly (p = 0.008) shorter than those without (3.3 vs. 6.1 mo). Patients with a high MTVm revealed a significantly (p = 0.034) shorter OS of 2.6 mo than patients with low MTVm (5.3 mo). Furthermore, patients with hepatic mismatch showed a significantly (p = 0.049) shorter OS than those without (2.9 vs. 5.3 mo). Difference in OS regarding SUVmax and TLGm was not significant. In mCRPC patients with worsening disease during PSMA-RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging is essential to identify mismatch findings, as these are associated with poor outcomes requiring a change in therapy management. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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Review

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19 pages, 620 KiB  
Review
Management of Patients with Recurrent and Metachronous Oligometastatic Prostate Cancer in the Era of PSMA PET
by Ali Sabbagh, Osama Mohamad, Katie E. Lichter and Thomas A. Hope
Cancers 2022, 14(24), 6194; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246194 - 15 Dec 2022
Cited by 6 | Viewed by 1783
Abstract
Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans have higher sensitivity and specificity for detecting lymph nodes or metastatic disease relative to conventional imaging in prostate cancer staging. Since its FDA approval and incorporation into treatment guidelines, the use of PSMA PET [...] Read more.
Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans have higher sensitivity and specificity for detecting lymph nodes or metastatic disease relative to conventional imaging in prostate cancer staging. Since its FDA approval and incorporation into treatment guidelines, the use of PSMA PET has increased in patients undergoing initial staging, those with recurrence after initial definitive treatment, and patients with metastatic disease. Although the early detection of metastatic lesions is changing disease management, it is unclear whether this impact on management translates into clinical benefit. This review will summarize evidence pertaining to the change in patient management due to PSMA PET use and will discuss the implications of PSMA PET on treatment decisions in prostate cancer, particularly in the settings of biochemical recurrence and metachronous oligometastatic disease. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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16 pages, 1670 KiB  
Review
The Role of [68Ga]PSMA PET/CT for Clinical Suspicion of Prostate Cancer in Patients with or without Previous Negative Biopsy: A Systematic Review
by Matteo Caracciolo, Angelo Castello, Luca Urso, Francesca Borgia, Naima Ortolan, Licia Uccelli, Corrado Cittanti, Massimo Castellani, Mirco Bartolomei, Massimo Lazzeri and Egesta Lopci
Cancers 2022, 14(20), 5036; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14205036 - 14 Oct 2022
Cited by 10 | Viewed by 2169
Abstract
The purpose of the study is to systematically evaluate the evidence regarding the role of [68Ga]PSMA PET/CT for clinical suspicions of prostate cancer in patients with or without previous negative biopsy. We performed a critical review of PubMed and Web of [...] Read more.
The purpose of the study is to systematically evaluate the evidence regarding the role of [68Ga]PSMA PET/CT for clinical suspicions of prostate cancer in patients with or without previous negative biopsy. We performed a critical review of PubMed and Web of Science according to the PRISMA statement. Eighteen publications were selected for inclusion in this analysis. QUADAS-2 evaluation was adopted for quality analyses. [68Ga]PSMA-11 was the radiotracer of choice in 15 studies, while [68Ga]PSMA-617 was used in another 3. In 8 articles, there was a direct comparison with mpMRI. The total number of patients included was 1379, ranging from 15 to 291, with a median age of 64 years (range: 42–90). The median baseline PSA value was 12.9 ng/mL, ranging from 0.85 to 4156 ng/mL. Some studies evaluated the PSMA uptake comparing the SUVmax of suspicious lesions with the SUVmax of the normal biodistribution to find out optimal cut-off points. In addition, some studies suggested a significant association between PSA levels, PSA density, and [68Ga]PSMA PET/CT finding. [68Ga]PSMA PET/CT seems to be more accurate in identifying primary prostate cancer with PSA values between 4 and 20 ng/mL than mpMRI. Moreover, in some trials, the combination of PSMA PET/CT and MRI improved the NPV in the detection of clinically significant prostate cancer (csPCa) than MRI alone. Our findings are limited by the small numbers of studies and patient heterogeneity. [68Ga]PSMA PET/CT is a promising technique in patients with clinical suspicion of PCa and precedent negative biopsy or contraindications to MRI. Furthermore, its use combined with MRI improves sensitivity for csPCa detection and can avoid unnecessary biopsies. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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23 pages, 1280 KiB  
Systematic Review
PSMA and Choline PET for the Assessment of Response to Therapy and Survival Outcomes in Prostate Cancer Patients: A Systematic Review from the Literature
by Pierpaolo Alongi, Riccardo Laudicella, Helena Lanzafame, Andrea Farolfi, Paola Mapelli, Maria Picchio, Irene A. Burger, Andrei Iagaru, Fabio Minutoli and Laura Evangelista
Cancers 2022, 14(7), 1770; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071770 - 31 Mar 2022
Cited by 20 | Viewed by 3345
Abstract
The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and [...] Read more.
The aims of this systematic review were to (1) assess the utility of PSMA-PET and choline-PET in the assessment of response to systemic and local therapy, and to (2) determine the value of both tracers for the prediction of response to therapy and survival outcomes in prostate cancer. We performed a systematic literature search in PubMed/Scopus/Google Scholar/Cochrane/EMBASE databases (between January 2010 and October 2021) accordingly. The quality of the included studies was evaluated following the “Quality Assessment of Prognostic Accuracy Studies” tool (QUAPAS-2). We selected 40 articles: 23 articles discussed the use of PET imaging with [68Ga]PSMA-11 (16 articles/1123 patients) or [11C]/[18F]Choline (7 articles/356 patients) for the prediction of response to radiotherapy (RT) and survival outcomes. Seven articles (three with [68Ga]PSMA-11, three with [11C]Choline, one with [18F]Choline) assessed the role of PET imaging in the evaluation of response to docetaxel (as neoadjuvant therapy in one study, as first-line therapy in five studies, and as a palliative regimen in one study). Seven papers with radiolabeled [18F]Choline PET/CT (n = 121 patients) and three with [68Ga]PSMA-11 PET (n = 87 patients) were selected before and after enzalutamide/abiraterone acetate. Finally, [18F]Choline and [68Ga]PSMA-11 PET/CT as gatekeepers for the treatment of metastatic prostate cancer with Radium-223 were assessed in three papers. In conclusion, in patients undergoing RT, radiolabeled choline and [68Ga]PSMA-11 have an important prognostic role. In the case of systemic therapies, the role of such new-generation imaging techniques is still controversial without sufficient data, thus requiring additional in this scenario. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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12 pages, 830 KiB  
Systematic Review
Additional Value of PET Radiomic Features for the Initial Staging of Prostate Cancer: A Systematic Review from the Literature
by Priscilla Guglielmo, Francesca Marturano, Andrea Bettinelli, Michele Gregianin, Marta Paiusco and Laura Evangelista
Cancers 2021, 13(23), 6026; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13236026 - 30 Nov 2021
Cited by 17 | Viewed by 2645
Abstract
We performed a systematic review of the literature to provide an overview of the application of PET radiomics for the prediction of the initial staging of prostate cancer (PCa), and to discuss the additional value of radiomic features over clinical data. The most [...] Read more.
We performed a systematic review of the literature to provide an overview of the application of PET radiomics for the prediction of the initial staging of prostate cancer (PCa), and to discuss the additional value of radiomic features over clinical data. The most relevant databases and web sources were interrogated by using the query “prostate AND radiomic* AND PET”. English-language original articles published before July 2021 were considered. A total of 28 studies were screened for eligibility and 6 of them met the inclusion criteria and were, therefore, included for further analysis. All studies were based on human patients. The average number of patients included in the studies was 72 (range 52–101), and the average number of high-order features calculated per study was 167 (range 50–480). The radiotracers used were [68Ga]Ga-PSMA-11 (in four out of six studies), [18F]DCFPyL (one out of six studies), and [11C]Choline (one out of six studies). Considering the imaging modality, three out of six studies used a PET/CT scanner and the other half a PET/MRI tomograph. Heterogeneous results were reported regarding radiomic methods (e.g., segmentation modality) and considered features. The studies reported several predictive markers including first-, second-, and high-order features, such as “kurtosis”, “grey-level uniformity”, and “HLL wavelet mean”, respectively, as well as PET-based metabolic parameters. The strengths and weaknesses of PET radiomics in this setting of disease will be largely discussed and a critical analysis of the available data will be reported. In our review, radiomic analysis proved to add useful information for lesion detection and the prediction of tumor grading of prostatic lesions, even when they were missed at visual qualitative assessment due to their small size; furthermore, PET radiomics could play a synergistic role with the mpMRI radiomic features in lesion evaluation. The most common limitations of the studies were the small sample size, retrospective design, lack of validation on external datasets, and unavailability of univocal cut-off values for the selected radiomic features. Full article
(This article belongs to the Special Issue PET/CT in Prostate Cancer)
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