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Cancers
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Diagnosis of Prostate Cancer
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Diagnosis of Prostate Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 18847

Special Issue Editors

Dr. Simon P. Kim

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Guest Editor
University of Colorado Health Sciences Center, Denver, United States
Interests: nephron-preserving renal surgery, IVC tumor thrombus, robotic and open prostatectomy and cystectomy
Dr. Rodrigo R. Pessoa

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Guest Editor
University of Colorado Health Sciences Center, Denver, United States
Interests: minimally invasive urologic oncology; image-guided biopsy and ablation; robotic and open prostate; kidney; bladder and testicular cancer surgery

Special Issue Information

Dear Colleagues,

This Special Issue on "Diagnosis of Prostate Cancer" is edited by Dr. Simon P. Kim from the Division of Urology, University of Colorado Anschutz Medical Center, Aurora, CO, USA.

Dr. Simon Kim is a board-certified urologic oncologist at the University of Colorado—Denver Medical Campus. His clinical practice focuses on the surgical management of genitourinary malignancies. He specializes in the surgical treatment of bladder, kidney, prostate, testis, adrenal, and penile cancers. He performs robotic, laparoscopic, and open surgery for localized or locally advanced cancers. He previously served as a Director of Robotic Surgery and Director of Kidney and Bladder Cancer at his previous faculty appointment. He was recently appointed as the Associate Program Director for the Urology Residency at the University of Colorado. He is currently funded as a co-principal investigator through an R01 grant from the NCI to develop decision aids for men diagnosed with prostate cancer.

Prostate cancer remains one of the leading malignancies for new diagnoses and cancer-related mortality. Over the past decade, the diagnosis of prostate cancer has undergone marked changes with new imaging and biopsy techniques (targeted and transperineal) and the use of deep learning and genomic testing to better stratify risk prognostication and potentially individualize treatment decisions for men diagnosed with prostate cancer. These new diagnostic tests and imaging methods have already been shown to reduce the burden of prostate cancer by increasing active surveillance of low-risk prostate cancers and indicating the need for primary therapy in men who harbor clinically localized, aggressive prostate cancer. Understanding how to integrate these strategies is crucial to facilitating a greater quality of care for prostate cancer patients. In this summary, we have invited leaders in prostate cancer research to review each of the new diagnostic and management tests for prostate cancer.

Dr. Simon P. Kim
Dr. Rodrigo R. Pessoa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • Prostate cancer screening, diagnosis, and risk stratification
  • Optimizing prostate cancer diagnosis in the era of MRI-fusion biopsy and deep learning technology
  • MRI fusion biopsy
  • Comparative effectiveness of different prostate biopsy techniques
  • Molecular biomarkers in localized prostate cancer: what does the current evidence recommend
  • Advanced imaging for salvage therapy for recurrent prostate cancer

Published Papers (6 papers)

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Research

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10 pages, 1373 KiB  
Article
Evaluation of the Ginsburg Scheme: Where Is Significant Prostate Cancer Missed?
by August Sigle, Cordula A. Jilg, Timur H. Kuru, Nadine Binder, Jakob Michaelis, Markus Grabbert, Wolfgang Schultze-Seemann, Arkadiusz Miernik, Christian Gratzke, Matthias Benndorf and Rodrigo Suarez-Ibarrola
Cancers 2021, 13(10), 2502; https://doi.org/10.3390/cancers13102502 - 20 May 2021
Cited by 3 | Viewed by 2107
Abstract
Background: Systematic biopsy (SB) according to the Ginsburg scheme (GBS) is widely used to complement MRI-targeted biopsy (MR-TB) for optimizing the diagnosis of clinically significant prostate cancer (sPCa). Knowledge of the GBS’s blind sectors where sPCa is missed is crucial to improve biopsy [...] Read more.
Background: Systematic biopsy (SB) according to the Ginsburg scheme (GBS) is widely used to complement MRI-targeted biopsy (MR-TB) for optimizing the diagnosis of clinically significant prostate cancer (sPCa). Knowledge of the GBS’s blind sectors where sPCa is missed is crucial to improve biopsy strategies. Methods: We analyzed cancer detection rates in 1084 patients that underwent MR-TB and SB. Cancerous lesions that were missed or underestimated by GBS were re-localized onto a prostate map encompassing Ginsburg sectors and blind-sectors (anterior, central, basodorsal and basoventral). Logistic regression analysis (LRA) and prostatic configuration analysis were applied to identify predictors for missing sPCa with the GBS. Results: GBS missed sPCa in 39 patients (39/1084, 3.6%). In 27 cases (27/39, 69.2%), sPCa was missed within a blind sector, with 17/39 lesions localized in the anterior region (43.6%). Neither LRA nor prostatic configuration analysis identified predictors for missing sPCa with the GBS. Conclusions: This is the first study to analyze the distribution of sPCa missed by the GBS. GBS misses sPCa in few men only, with the majority localized in the anterior region. Adding blind sectors to GBS defined a new sector map of the prostate suited for reporting histopathological biopsy results. Full article
(This article belongs to the Special Issue Diagnosis of Prostate Cancer)
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11 pages, 1079 KiB  
Article
Predicting the Risk of Metastases by PSMA-PET/CT—Evaluation of 335 Men with Treatment-Naïve Prostate Carcinoma
by Stefan A. Koerber, Johannes Boesch, Clemens Kratochwil, Ingmar Schlampp, Jonas Ristau, Erik Winter, Stefanie Zschaebitz, Luisa Hofer, Klaus Herfarth, Klaus Kopka, Tim Holland-Letz, Dirk Jaeger, Markus Hohenfellner, Uwe Haberkorn, Juergen Debus and Frederik L. Giesel
Cancers 2021, 13(7), 1508; https://doi.org/10.3390/cancers13071508 - 25 Mar 2021
Cited by 8 | Viewed by 2981
Abstract
Men diagnosed with aggressive prostate cancer are at high risk of local relapse or systemic progression after definitive treatment. Treatment intensification is highly needed for that patient cohort; however, no relevant stratification tool has been implemented into the clinical work routine so far. [...] Read more.
Men diagnosed with aggressive prostate cancer are at high risk of local relapse or systemic progression after definitive treatment. Treatment intensification is highly needed for that patient cohort; however, no relevant stratification tool has been implemented into the clinical work routine so far. Therefore, the aim of the current study was to analyze the role of initial PSMA-PET/CT as a prediction tool for metastases. In total, 335 men with biopsy-proven prostate carcinoma and PSMA-PET/CT for primary staging were enrolled in the present, retrospective study. The number and site of metastases were analyzed and correlated with the maximum standardized uptake value (SUVmax) of the intraprostatic, malignant lesion. Receiver operating characteristic (ROC) curves were used to determine sensitivity and specificity and a model was created using multiple logistic regression. PSMA-PET/CT detected 171 metastases with PSMA-uptake in 82 patients. A statistically significant higher SUVmax was found for men with metastatic disease than for the cohort without distant metastases (median 16.1 vs. 11.2; p < 0.001). The area under the curve (AUC) in regard to predicting the presence of any metastases was 0.65. Choosing a cut-off value of 11.9 for SUVmax, a sensitivity and specificity (factor 1:1) of 76.0% and 58.4% was obtained. The current study confirms, that initial PSMA-PET/CT is able to detect a relatively high number of treatment-naïve men with metastatic prostate carcinoma. Intraprostatic SUVmax seems to be a promising parameter for the prediction of distant disease and could be used for treatment stratification—aspects which should be verified within prospective trials. Full article
(This article belongs to the Special Issue Diagnosis of Prostate Cancer)
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21 pages, 18440 KiB  
Article
Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment
by Marc Wiesehöfer, Elena Dilara Czyrnik, Martin Spahn, Saskia Ting, Henning Reis, Jaroslaw Thomas Dankert and Gunther Wennemuth
Cancers 2021, 13(3), 578; https://doi.org/10.3390/cancers13030578 - 02 Feb 2021
Cited by 6 | Viewed by 2356
Abstract
Patients with advanced prostate carcinoma are often treated with an androgen deprivation therapy but long-term treatment can result in a metastatic castration-resistant prostate cancer. This is a more aggressive, untreatable tumor recurrence often containing areas of neuroendocrine differentiated prostate cancer cells. Using an [...] Read more.
Patients with advanced prostate carcinoma are often treated with an androgen deprivation therapy but long-term treatment can result in a metastatic castration-resistant prostate cancer. This is a more aggressive, untreatable tumor recurrence often containing areas of neuroendocrine differentiated prostate cancer cells. Using an in vitro model of NE-like cancer cells, it could previously be shown that neuroendocrine differentiation of LNCaP cells leads to a strong deregulation of mRNA and miRNA expression. We observe elevated RNA and protein levels of AKT Serine/Threonine Kinase 3 (AKT3) in neuroendocrine-like LNCaP cells. We used prostate resections from patients with neuroendocrine prostate cancer to validate these results and detect a co-localization of neuroendocrine marker genes with AKT3. Analysis of downstream target genes FOXO3A and GSK3 strengthens the assumption AKT3 may play a role in neuroendocrine differentiation. Overexpression of AKT3 shows an increased survival rate of LNCaP cells after apoptosis induction, which in turn reflects the significance in vivo or for treatment. Furthermore, miR-17, −20b and −106b, which are decreased in neuroendocrine-like LNCaP cells, negatively regulate AKT3 biosynthesis. Our findings demonstrate AKT3 as a potential therapeutic target and diagnostic tool in advanced neuroendocrine prostate cancer and a new mRNA–miRNA interaction with a potential role in neuroendocrine differentiation of prostate cancer. Full article
(This article belongs to the Special Issue Diagnosis of Prostate Cancer)
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14 pages, 234 KiB  
Article
Diagnostic Performance of PET Imaging Using Different Radiopharmaceuticals in Prostate Cancer According to Published Meta-Analyses
by Salvatore Annunziata, Daniele Antonio Pizzuto and Giorgio Treglia
Cancers 2020, 12(8), 2153; https://doi.org/10.3390/cancers12082153 - 04 Aug 2020
Cited by 27 | Viewed by 2831
Abstract
A significant number of meta-analyses reporting data on the diagnostic performance of positron emission tomography (PET) in prostate cancer (PCa) is currently available in the literature. In particular, different PET radiopharmaceuticals were used for this purpose. The aim of this review is to [...] Read more.
A significant number of meta-analyses reporting data on the diagnostic performance of positron emission tomography (PET) in prostate cancer (PCa) is currently available in the literature. In particular, different PET radiopharmaceuticals were used for this purpose. The aim of this review is to summarize information retrieved by published meta-analyses on this topic. The first step included a systematic search of the literature (last search date: June 2020), screening two databases (PubMed/MEDLINE and Cochrane Library). This combination of key words was used: (A) “PET” OR “positron emission tomography” AND (B) “prostate” OR “prostatic” AND (C) meta-analysis. Only meta-analyses on Positron Emission Tomography/Computed Tomography (PET/CT) or Positron Emission Tomography/Magnetic Resonance (PET/MR) in PCa were selected. We have summarized the diagnostic performance of PET imaging in PCa, taking into account 39 meta-analyses published in the literature. Evidence-based data showed the good diagnostic performance of PET/CT with several radiopharmaceuticals, including prostate-specific membrane antigen (PSMA)-targeted agents, radiolabeled choline, fluciclovine, and fluoride in restaging and staging settings. Less evidence-based data were available for PET/MR with different radiotracers. More prospective multicentric studies and cost-effectiveness analyses are warranted. Full article
(This article belongs to the Special Issue Diagnosis of Prostate Cancer)

Review

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24 pages, 1917 KiB  
Review
More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
by Anniina Hyväkkä, Verneri Virtanen, Jukka Kemppainen, Tove J. Grönroos, Heikki Minn and Maria Sundvall
Cancers 2021, 13(9), 2244; https://doi.org/10.3390/cancers13092244 - 07 May 2021
Cited by 12 | Viewed by 5387
Abstract
Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen [...] Read more.
Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer. Full article
(This article belongs to the Special Issue Diagnosis of Prostate Cancer)
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17 pages, 725 KiB  
Review
Comparative Effectiveness of Techniques in Targeted Prostate Biopsy
by Dordaneh Sugano, Masatomo Kaneko, Wesley Yip, Amir H. Lebastchi, Giovanni E. Cacciamani and Andre Luis Abreu
Cancers 2021, 13(6), 1449; https://doi.org/10.3390/cancers13061449 - 22 Mar 2021
Cited by 10 | Viewed by 2203
Abstract
In this review, we evaluated literature regarding different modalities for multiparametric magnetic resonance imaging (mpMRI) and mpMRI-targeted biopsy (TB) for the detection of prostate cancer (PCa). We identified studies evaluating systematic biopsy (SB) and TB in the same patient, thereby allowing each patient [...] Read more.
In this review, we evaluated literature regarding different modalities for multiparametric magnetic resonance imaging (mpMRI) and mpMRI-targeted biopsy (TB) for the detection of prostate cancer (PCa). We identified studies evaluating systematic biopsy (SB) and TB in the same patient, thereby allowing each patient to serve as their own control. Although the evidence supports the accuracy of TB, there is still a proportion of clinically significant PCa (csPCa) that is detected only in SB, indicating the importance of maintaining SB in the diagnostic pathway, albeit with additional cost and morbidity. There is a growing subset of data which supports the role of TB alone, which may allow for increased efficiency and decreased complications. We also compared the literature on transrectal (TR) vs. transperineal (TP) TB. Although further high-level evidence is necessary, current evidence supports similar csPCa detection rate for both approaches. We also evaluated various TB techniques such as cognitive fusion biopsy (COG-TB) and in-bore biopsy (IB-TB). COG-TB has comparable detection rates to software fusion, but is operator-dependent and may have reduced accuracy for smaller lesions. IB-TB may allow for greater precision as lesions are directly targeted; however, this is costly and time-consuming, and does not account for MRI-invisible lesions. Full article
(This article belongs to the Special Issue Diagnosis of Prostate Cancer)
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