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Cancers
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The Screening and Diagnostics of Prostate Cancer
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The Screening and Diagnostics 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 2023) | Viewed by 23394

Special Issue Editors

Prof. Dr. Chris H. Bangma

E-Mail Website
Guest Editor
Department of Urology, Erasmus MC, 3015 GD Rotterdam, The Netherlands
Interests: urologic oncology; prostate cancer; translational research
Prof. Dr. Axel Semjonow

E-Mail Website
Guest Editor
Department of Urology, Prostate Center, University Clinic Münster, 48149 Münster, Germany
Interests: prostate cancer surgery; radiotherapy; drug treatment

Special Issue Information

Dear Colleagues,

In this Special Issue dedicated to the screening and diagnostics of prostate cancer various controversies, several studies are presented which illustrate the ongoing improvement and discussion in the field worldwide. The technical progress in imaging with MRI, and PSMA-PET scanning, as well as the new serum and urinary assays, add a number of elements to the process of screening and diagnostic procedures. Multifactorial risk evaluation appears to be basic to make decisions by patients and their physicians. Profs Chris Bangma and Axel Semjonow highlight this dynamic evaluation of thoughts between specialists on early prostate cancer.

Prof. Dr. Chris H. Bangma
Prof. Dr. Axel Semjonow
Guest Editors

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Keywords

  • prostate cancer
  • screening
  • diagnosis
  • imaging
  • biomarkers

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Published Papers (9 papers)

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Research

Jump to: Review

8 pages, 248 KiB  
Communication
Surveillance Value of Apparent Diffusion Coefficient Maps: Multiparametric MRI in Active Surveillance of Prostate Cancer
by Aleksandar Georgiev, Lyubomir Chervenkov, Mladen Doykov, Katya Doykova, Petar Uchikov and Silvia Tsvetkova
Cancers 2023, 15(4), 1128; https://doi.org/10.3390/cancers15041128 - 10 Feb 2023
Cited by 3 | Viewed by 1545
Abstract
Background: This study aims to establish the value of apparent diffusion coefficient maps and other magnetic resonance sequences for active surveillance of prostate cancer. The study included 530 men with an average age of 66, who were under surveillance for prostate cancer. We [...] Read more.
Background: This study aims to establish the value of apparent diffusion coefficient maps and other magnetic resonance sequences for active surveillance of prostate cancer. The study included 530 men with an average age of 66, who were under surveillance for prostate cancer. We have used multiparametric magnetic resonance imaging with subsequent transperineal biopsy (TPB) to verify the imaging findings. Results: We have observed a level of agreement of 67.30% between the apparent diffusion coefficient (ADC) maps, other magnetic resonance sequences, and the biopsy results. The sensitivity of the apparent diffusion coefficient is 97.14%, and the specificity is 37.50%. According to our data, apparent diffusion coefficient is the most accurate sequence, followed by diffusion imaging in prostate cancer detection. Conclusions: Based on our findings we advocate that the apparent diffusion coefficient should be included as an essential part of magnetic resonance scanning protocols for prostate cancer in at least bi-parametric settings. The best option will be apparent diffusion coefficient combined with diffusion imaging and T2 sequences. Further large-scale prospective controlled studies are required to define the precise role of multiparametric and bi-parametric magnetic resonance in the active surveillance of prostate cancer. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
14 pages, 7194 KiB  
Article
Prospectively Accelerated T2-Weighted Imaging of the Prostate by Combining Compressed SENSE and Deep Learning in Patients with Histologically Proven Prostate Cancer
by Felix N. Harder, Kilian Weiss, Thomas Amiel, Johannes M. Peeters, Robert Tauber, Sebastian Ziegelmayer, Egon Burian, Marcus R. Makowski, Andreas P. Sauter, Jürgen E. Gschwend, Dimitrios C. Karampinos and Rickmer F. Braren
Cancers 2022, 14(23), 5741; https://doi.org/10.3390/cancers14235741 - 22 Nov 2022
Cited by 13 | Viewed by 2345
Abstract
Background: To assess the performance of prospectively accelerated and deep learning (DL) reconstructed T2-weighted (T2w) imaging in volunteers and patients with histologically proven prostate cancer (PCa). Methods: Prospectively undersampled T2w datasets were acquired with acceleration factors of 1.7 (reference), 3.4 and 4.8 in [...] Read more.
Background: To assess the performance of prospectively accelerated and deep learning (DL) reconstructed T2-weighted (T2w) imaging in volunteers and patients with histologically proven prostate cancer (PCa). Methods: Prospectively undersampled T2w datasets were acquired with acceleration factors of 1.7 (reference), 3.4 and 4.8 in 10 healthy volunteers and 23 patients with histologically proven PCa. Image reconstructions using compressed SENSE (C-SENSE) and a combination of C-SENSE and DL-based artificial intelligence (C-SENSE AI) were analyzed. Qualitative image comparison was performed using a 6-point Likert scale (overall image quality, noise, motion artifacts, lesion detection, diagnostic certainty); the T2 and PI-RADS scores were compared between the two reconstructions. Additionally, quantitative image parameters were assessed (apparent SNR, apparent CNR, lesion size, line profiles). Results: All C-SENSE AI-reconstructed images received a significantly higher qualitative rating compared to the C-SENSE standard images. Analysis of the quantitative parameters supported this finding, with significantly higher aSNR and aCNR. The line profiles demonstrated a significantly steeper signal change at the border of the prostatic lesion and the adjacent normal tissue in the C-SENSE AI-reconstructed images, whereas the T2 and PI-RADS scores as well as the lesion size did not differ. Conclusion: In this prospective study, we demonstrated the clinical feasibility of a novel C-SENSE AI reconstruction enabling a 58% acceleration in T2w imaging of the prostate while obtaining significantly better image quality. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
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14 pages, 2261 KiB  
Article
A Clinically Significant Prostate Cancer Predictive Model Using Digital Rectal Examination Prostate Volume Category to Stratify Initial Prostate Cancer Suspicion and Reduce Magnetic Resonance Imaging Demand
by Juan Morote, Ángel Borque-Fernando, Marina Triquell, Miriam Campistol, Anna Celma, Lucas Regis, José M. Abascal, Pol Servian, Jacques Planas, Olga Mendez, Luis M. Esteban and Enrique Trilla
Cancers 2022, 14(20), 5100; https://doi.org/10.3390/cancers14205100 - 18 Oct 2022
Cited by 12 | Viewed by 2149
Abstract
A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal [...] Read more.
A predictive model including age, PCa family history, biopsy status (initial vs repeat), DRE (normal vs abnormal), serum prostate-specific antigen (PSA), and DRE prostate volume ca-tegory was developed to stratify initial PCa suspicion in 1486 men with PSA > 3 ng/mL and/or abnormal DRE, in whom mpMRI followed; 2- to 4-core TRUS-guided biopsies where Prostate Imaging Report and Data System (PI-RADS) > 3 lesions and/or 12-core TRUS systematic biopsies were performed in one academic institution between 1 January 2016–31 December 2019. The csPCa detection rate, defined as International Society of Uro-Pathology grade group 2 or higher, was 36.9%. An external validation of designed BCN-RC 1 was carried out on 946 men from two other institutions in the same metropolitan area, using the same criteria of PCa suspicion and diagnostic approach, yielded a csPCa detection rate of 40.8%. The areas under the receiver operating characteristic curves of BCN-RC 1 were 0.823 (95% CI: 0.800–0.846) in the development cohort and 0.837 (95% CI: 0.811–0.863) in the validation cohort (p = 0.447). In both cohorts, BCN-RC 1 exhibited net benefit over performing mpMRI in all men from 8 and 12% risk thresholds, respectively. At 0.95 sensitivity of csPCa, the specificities of BCN-RC 1 were 0.24 (95% CI: 0.22–0.26) in the development cohort and 0.34 (95% CI: 0.31–0.37) in the validation cohort (p < 0.001). The percentages of avoided mpMRI scans were 17.2% in the development cohort and 22.3% in the validation cohort, missing between 1.8% and 2% of csPCa among men at risk of PCa. In summary, BCN-RC 1 can stratify initial PCa suspicion, reducing the demand of mpMRI, with an acceptable loss of csPCa. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
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11 pages, 1254 KiB  
Article
Clinical Utility of Prostate Health Index for Diagnosis of Prostate Cancer in Patients with PI-RADS 3 Lesions
by Chung-Un Lee, Sang-Min Lee, Jae-Hoon Chung, Minyong Kang, Hyun-Hwan Sung, Hwang-Gyun Jeon, Byong-Chang Jeong, Seong-Il Seo, Seong-Soo Jeon, Hyun-Moo Lee and Wan Song
Cancers 2022, 14(17), 4174; https://doi.org/10.3390/cancers14174174 - 29 Aug 2022
Cited by 7 | Viewed by 1839
Abstract
The risk of prostate cancer (PCa) in prostate imaging reporting and data system version 2 (PI-RADSv2) score-3 lesions is equivocal; it is regarded as an intermediate status of presented PCa. In this study, we evaluated the clinical utility of the prostate health index [...] Read more.
The risk of prostate cancer (PCa) in prostate imaging reporting and data system version 2 (PI-RADSv2) score-3 lesions is equivocal; it is regarded as an intermediate status of presented PCa. In this study, we evaluated the clinical utility of the prostate health index (PHI) for the diagnosis of PCa and clinically significant PCa (csPCa) in patients with PI-RADSv2 score-3 lesions. The study cohort included patients who underwent a transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy for PI-RADSv2 score-3 lesions between November 2018 and April 2021. Before prostate biopsy, the prostate-specific antigen (PSA) derivatives, such as total PSA (tPSA), [-2] proPSA (p2PSA) and free PSA (fPSA) were determined. The calculation equation of PHI is as follows: [(p2PSA/fPSA) × tPSA ½]. Using a receiver operating characteristic (ROC) curve analysis, the values of PSA derivatives measured by the area under the ROC curve (AUC) were compared. For this study, csPCa was defined as Gleason grade 2 or higher. Of the 392 patients with PI-RADSv2 score-3 lesions, PCa was confirmed in 121 (30.9%) patients, including 59 (15.1%) confirmed to have csPCa. Of all the PSA derivatives, PHI and PSA density (PSAD) showed better performance in predicting overall PCa and csPCa, compared with PSA (all p < 0.05). The AUC of the PHI for predicting overall PCa and csPCa were 0.807 (95% confidence interval (CI): 0.710–0.906, p = 0.001) and 0.819 (95% CI: 0.723–0.922, p < 0.001), respectively. By the threshold of 30, PHI was 91.7% sensitive and 46.1% specific for overall PCa, and was 100% sensitive for csPCa. Using 30 as a threshold for PHI, 34.4% of unnecessary biopsies could have been avoided, at the cost of 8.3% of overall PCa, but would include all csPCa. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
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9 pages, 283 KiB  
Article
Multiparametric MRI for Staging of Prostate Cancer: A Multicentric Analysis of Predictive Factors to Improve Identification of Extracapsular Extension before Radical Prostatectomy
by Marina Triquell, Lucas Regis, Mathias Winkler, Nicolás Valdés, Mercè Cuadras, Ana Celma, Jacques Planas, Juan Morote and Enrique Trilla
Cancers 2022, 14(16), 3966; https://doi.org/10.3390/cancers14163966 - 17 Aug 2022
Cited by 7 | Viewed by 1865
Abstract
The correct identification of extracapsular extension (ECE) of prostate cancer (PCa) on multiparametric magnetic resonance imaging (mpMRI) is crucial for surgeons in order to plan the nerve-sparing approach in radical prostatectomy. Nerve-sparing strategies allow for better outcomes in preserving erectile function and urinary [...] Read more.
The correct identification of extracapsular extension (ECE) of prostate cancer (PCa) on multiparametric magnetic resonance imaging (mpMRI) is crucial for surgeons in order to plan the nerve-sparing approach in radical prostatectomy. Nerve-sparing strategies allow for better outcomes in preserving erectile function and urinary continence, notwithstanding this can be penalized with worse oncologic results. The aim of this study was to assess the ability of preoperative mpMRI to predict ECE in the final prostatic specimen (PS) and identify other possible preoperative predictive factors of ECE as a secondary end-point. We investigated a database of two high-volume hospitals to identify men who underwent a prostate biopsy with a pre-biopsy mpMRI and a subsequent RP. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI in predicting ECE were calculated. A univariate analysis was performed to find the association between image staging and pathological staging. A multivariate logistic regression was performed to investigate other preoperative predictive factors. A total of 1147 patients were selected, and 203 out of the 1147 (17.7%) patients were classified as ECE according to the mpMRI. ECE was reported by pathologists in 279 out of the 1147 PS (24.3%). The PPV was 0.58, the NPV was 0.72, the sensitivity was 0.32, and the specificity was 0.88. The multivariate analysis found that PSA (OR 1.057, C.I. 95%, 1.016–1.100, p = 0.006), digital rectal examination (OR 0.567, C.I. 95%, 0.417–0.770, p = 0.0001), ratio of positive cores (OR 9.687, C.I. 95%, 3.744–25.006, p = 0.0001), and biopsy grade in prostate biopsy (OR 1.394, C.I. 95%, 1.025–1.612, p = 0.0001) were independent factors of ECE. The mpMRI has a great ability to exclude ECE, notwithstanding that low sensitivity is still an important limitation of the technique. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
13 pages, 760 KiB  
Article
Value of Targeted Biopsies and Combined PSMA PET/CT and mp-MRI Imaging in Locally Recurrent Prostate Cancer after Primary Radiotherapy
by Marnix Rasing, Marieke van Son, Marinus Moerland, Bart de Keizer, Frank Wessels, Trudy Jonges, Sandrine van de Pol, Wietse Eppinga, Juus Noteboom, Jan Lagendijk, Jochem van der Voort van Zijp and Max Peters
Cancers 2022, 14(3), 781; https://doi.org/10.3390/cancers14030781 - 3 Feb 2022
Cited by 11 | Viewed by 4728
Abstract
Radiorecurrent prostate cancer is conventionally confirmed using systematic and/or targeted biopsies. The availability of multiparametric (mp) MRI and prostate specific membrane antigen (PSMA) PET/CT has increased diagnostic accuracy. The objective was to determine the positive predictive value (PPV) of combined mp-MRI and PSMA [...] Read more.
Radiorecurrent prostate cancer is conventionally confirmed using systematic and/or targeted biopsies. The availability of multiparametric (mp) MRI and prostate specific membrane antigen (PSMA) PET/CT has increased diagnostic accuracy. The objective was to determine the positive predictive value (PPV) of combined mp-MRI and PSMA PET/CT and whether pathology verification with MR-targeted biopsies remains necessary for patients with radiorecurrent prostate cancer. Patients with locally recurrent prostate cancer who were referred for 19 Gy single-dose MRI-guided focal salvage high dose rate (HDR) brachytherapy between 2015 and 2018 were included in the current analysis. Patients were selected if they underwent pre-biopsy mp-MRI and PSMA PET/CT. Based on these images, lesions suspect for isolated tumor recurrence were transperineally biopsied using transrectal ultrasound fused with MRI. A total of 41 patients were identified from the database who underwent cognitive targeted (n = 7) or MRI/PSMA-transrectal ultrasound (TRUS) fused targeted (n = 34) biopsies. A total of 40 (97.6%) patients had positive biopsies for recurrent cancer. Five patients initially had negative biopsies (all MRI/PSMA-TRUS fusion targeted), four of whom recurrence was confirmed after a re-biopsy. One (2.4%) patient refused re-biopsy, leading to a positive predictive value (PPV) for combined imaging of 97.6%. Biopsies can therefore safely be withheld when the results of the combined mp-MRI and PSMA PET/CT are conclusive, avoiding an unnecessary invasive and burdensome procedure. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
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20 pages, 2339 KiB  
Article
Changing Threshold-Based Segmentation Has No Relevant Impact on Semi-Quantification in the Context of Structured Reporting for PSMA-PET/CT
by Patrick W. Mihatsch, Matthias Beissert, Martin G. Pomper, Thorsten A. Bley, Anna K. Seitz, Hubert Kübler, Andreas K. Buck, Steven P. Rowe, Sebastian E. Serfling, Philipp E. Hartrampf and Rudolf A. Werner
Cancers 2022, 14(2), 270; https://doi.org/10.3390/cancers14020270 - 6 Jan 2022
Cited by 10 | Viewed by 2152
Abstract
Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients [...] Read more.
Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with 18F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUVmax, SUVpeak, SUVmean) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50%). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUVmax and SUVpeak compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUVmax, p = 0.07; SUVpeak, p = 0.08). SUVmean (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in 18F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUVmean and TL-PSMA in contrast to PSMA-TV. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
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Review

Jump to: Research

18 pages, 1554 KiB  
Review
Volatilomics: An Emerging and Promising Avenue for the Detection of Potential Prostate Cancer Biomarkers
by Cristina V. Berenguer, Ferdinando Pereira, Jorge A. M. Pereira and José S. Câmara
Cancers 2022, 14(16), 3982; https://doi.org/10.3390/cancers14163982 - 17 Aug 2022
Cited by 18 | Viewed by 3316
Abstract
Despite the spectacular advances in molecular medicine, including genomics, proteomics, transcriptomics, lipidomics, and personalized medicine, supported by the discovery of the human genome, prostate cancer (PCa) remains the most frequent malignant tumor and a leading cause of oncological death in men. New methods [...] Read more.
Despite the spectacular advances in molecular medicine, including genomics, proteomics, transcriptomics, lipidomics, and personalized medicine, supported by the discovery of the human genome, prostate cancer (PCa) remains the most frequent malignant tumor and a leading cause of oncological death in men. New methods for prognostic, diagnostic, and therapy evaluation are mainly based on the combination of imaging techniques with other methodologies, such as gene or protein profiling, aimed at improving PCa management and surveillance. However, the lack of highly specific and sensitive biomarkers for its early detection is a major hurdle to this goal. Apart from classical biomarkers, the study of endogenous volatile organic metabolites (VOMs) biosynthesized by different metabolic pathways and found in several biofluids is emerging as an innovative, efficient, accessible, and non-invasive approach to establish the volatilomic biosignature of PCa patients, unravelling potential biomarkers. This review provides a brief overview of the challenges of PCa screening methods and emergent biomarkers. We also focus on the potential of volatilomics for the establishment of PCa biomarkers from non-invasive matrices. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
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17 pages, 502 KiB  
Review
Urinary microRNAs and Their Significance in Prostate Cancer Diagnosis: A 5-Year Update
by Jaroslav Juracek, Marie Madrzyk, Michal Stanik and Ondrej Slaby
Cancers 2022, 14(13), 3157; https://doi.org/10.3390/cancers14133157 - 28 Jun 2022
Cited by 10 | Viewed by 2402
Abstract
Current routine screening methods for the diagnosis of prostate cancer (PCa) have significantly increased early detection of the disease but often show unsatisfactory analytical parameters. A class of promising markers represents urinary microRNAs (miRNAs). In the last five years, there has been an [...] Read more.
Current routine screening methods for the diagnosis of prostate cancer (PCa) have significantly increased early detection of the disease but often show unsatisfactory analytical parameters. A class of promising markers represents urinary microRNAs (miRNAs). In the last five years, there has been an extensive increase in the number of studies on this topic. Thus, this review aims to update knowledge and point out technical aspects affecting urinary miRNA analysis. The review of relevant literature was carried out by searching the PubMed database for the keywords: microRNA, miRNA, urine, urinary, prostate cancer, and diagnosis. Papers discussed in this review were retrieved using PubMed, and the search strategy was as follows: (urine OR urinary) WITH (microRNA OR miRNA) AND prostate cancer. The search was limited to the last 5 years, January 2017 to December 2021. Based on the defined search strategy, 31 original publications corresponding to the research topic were identified, read and reviewed to present the latest findings and to assess possible translation of urinary miRNAs into clinical practice. Reviews or older publications were read and cited if they valuably extended the context and contributed to a better understanding. Urinary miRNAs are potentially valuable markers for the diagnosis of prostate cancer. Despite promising results, there is still a need for independent validation of exploratory data, which follows a strict widely accepted methodology taking into account the shortcomings and factors influencing the analysis. Full article
(This article belongs to the Special Issue The Screening and Diagnostics of Prostate Cancer)
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