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Cancers
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Aggressive Prostate Cancer
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Aggressive Prostate Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 6311

Special Issue Editor

Dr. Indu Kohaar

E-Mail Website
Guest Editor
1. Henry Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, MD 20817, USA
2. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD 20814, USA
Interests: biomarkers; genetics and genomics of prostate cancer; health disparity

Special Issue Information

Dear Colleagues,

Prostate cancer is the most prevalent non-skin cancer in men and is the leading cause of cancer-related death. Prostate cancer is asymptomatic in the early-stage disease with a large subset of the indolent cancer type and comprises diverse clinico-pathologic and progression features including biochemical recurrence and metastasis at advanced stages of the disease. Therefore, it is important to develop a personalized approach for early detection, disease stratification (non-aggressive vs. aggressive), and the prediction of treatment response for prostate cancer, with the ultimate goal of helping patients.

The Special Issue “Aggressive Prostate Cancer” falls under the current scope of the journal Cancers, covering the basic, translational and clinical studies relating to biomarkers of aggressive prostate cancer. 

This Special Issue aims to Biomarkers for prostate cancer include markers with the ability to detect aggressive disease early, to inform disease prognosis, the therapeutic response, and staging, to help select patients for different treatment options, with the ultimate goal of benefitting patients.

In this Special Issue, original research articles and reviews are welcome. We look forward to receiving your contributions. 

Dr. Indu Kohaar
Guest Editor

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
  • aggressive prostate cancer
  • biomarkers
  • diagnosis
  • prognosis

Published Papers (4 papers)

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Research

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12 pages, 597 KiB  
Article
A Diagnostic Accuracy Study of Targeted and Systematic Biopsies to Detect Clinically Significant Prostate Cancer, including a Model for the Partial Omission of Systematic Biopsies
by Juan Morote, Natàlia Picola, Jesús Muñoz-Rodriguez, Nahuel Paesano, Xavier Ruiz-Plazas, Marta V. Muñoz-Rivero, Anna Celma, Gemma García-de Manuel, Ignacio Aisian, Pol Servian and José M. Abascal
Cancers 2023, 15(18), 4543; https://doi.org/10.3390/cancers15184543 - 13 Sep 2023
Cited by 2 | Viewed by 757
Abstract
The primary objective of this study was to analyse the current accuracy of targeted and systematic prostate biopsies in detecting csPCa. A secondary objective was to determine whether there are factors predicting the finding of csPCa in targeted biopsies and, if so, to [...] Read more.
The primary objective of this study was to analyse the current accuracy of targeted and systematic prostate biopsies in detecting csPCa. A secondary objective was to determine whether there are factors predicting the finding of csPCa in targeted biopsies and, if so, to explore the utility of a predictive model for csPCa detection only in targeted biopsies. We analysed 2122 men with suspected PCa, serum PSA > 3 ng/mL, and/or a suspicious digital rectal examination (DRE), who underwent targeted and systematic biopsies between 2021 and 2022. CsPCa (grade group 2 or higher) was detected in 1026 men (48.4%). Discrepancies in csPCa detection in targeted and systematic biopsies were observed in 49.6%, with 13.9% of csPCa cases being detected only in systematic biopsies and 35.7% only in targeted biopsies. A predictive model for csPCa detection only in targeted biopsies was developed from the independent predictors age (years), prostate volume (mL), PI-RADS score (3 to 5), mpMRI Tesla (1.5 vs. 3.0), TRUS-MRI fusion image technique (cognitive vs. software), and prostate biopsy route (transrectal vs. transperineal). The csPCa discrimination ability of targeted biopsies showed an AUC of 0.741 (95% CI 0.721–0.762). The avoidance rate of systematic prostate biopsies went from 0.5% without missing csPCa to 18.3% missing 4.6% of csPCa cases. We conclude that the csPCa diagnostic accuracy of targeted biopsies is higher than that of systematic biopsies. However, a significant rate of csPCa remains detected only in systematic biopsies. A predictive model for the partial omission of systematic biopsies was developed. Full article
(This article belongs to the Special Issue Aggressive Prostate Cancer)
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14 pages, 2613 KiB  
Article
High-Risk Pedigree Study Identifies LRBA (rs62346982) as a Likely Predisposition Variant for Prostate Cancer
by Lisa A. Cannon-Albright, Jeff Stevens, Julio C. Facelli, Craig C. Teerlink, Kristina Allen-Brady and Neeraj Agarwal
Cancers 2023, 15(7), 2085; https://doi.org/10.3390/cancers15072085 - 31 Mar 2023
Cited by 1 | Viewed by 1352
Abstract
There is evidence for contribution of inherited factors to prostate cancer, and more specifically to lethal prostate cancer, but few responsible genes/variants have been identified. We examined genetic sequence data for 51 affected cousin pairs who each died from prostate cancer and who [...] Read more.
There is evidence for contribution of inherited factors to prostate cancer, and more specifically to lethal prostate cancer, but few responsible genes/variants have been identified. We examined genetic sequence data for 51 affected cousin pairs who each died from prostate cancer and who were members of high-risk prostate cancer pedigrees in order to identify rare variants shared by the cousins as candidate predisposition variants. Candidate variants were tested for association with prostate cancer risk in UK Biobank data. Candidate variants were also assayed in 1195 additional sampled Utah prostate cancer cases. We used 3D protein structure prediction methods to analyze structural changes and provide insights into mechanisms of pathogenicity. Almost 4000 rare (<0.005) variants were identified as shared in the 51 affected cousin pairs. One candidate variant was also significantly associated with prostate cancer risk among the 840 variants with data in UK Biobank, in the gene LRBA (p = 3.2 × 10−5; OR = 2.09). The rare risk variant in LRBA was observed to segregate in five pedigrees. The overall predicted structures of the mutant protein do not show any significant overall changes upon mutation, but the mutated structure loses a helical structure for the two residues after the mutation. This unique analysis of closely related individuals with lethal prostate cancer, who were members of high-risk prostate cancer pedigrees, has identified a strong set of candidate predisposition variants which should be pursued in independent studies. Validation data for a subset of the candidates identified are presented, with strong evidence for a rare variant in LRBA. Full article
(This article belongs to the Special Issue Aggressive Prostate Cancer)
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14 pages, 3071 KiB  
Article
Urinary PSA and Serum PSA for Aggressive Prostate Cancer Detection
by Naseruddin Höti, Tung-Shing Lih, Mingming Dong, Zhen Zhang, Leslie Mangold, Alan W. Partin, Lori J. Sokoll, Qing Kay Li and Hui Zhang
Cancers 2023, 15(3), 960; https://doi.org/10.3390/cancers15030960 - 2 Feb 2023
Cited by 2 | Viewed by 2018
Abstract
Serum PSA, together with digital rectal examination and imaging of the prostate gland, have remained the gold standard in urological practices for the management of and intervention for prostate cancer. Based on these adopted practices, the limitations of serum PSA in identifying aggressive [...] Read more.
Serum PSA, together with digital rectal examination and imaging of the prostate gland, have remained the gold standard in urological practices for the management of and intervention for prostate cancer. Based on these adopted practices, the limitations of serum PSA in identifying aggressive prostate cancer has led us to evaluate whether urinary PSA levels might have any clinical utility in prostate cancer diagnosis. Utilizing the Access Hybritech PSA assay, we evaluated a total of n = 437 urine specimens from post-DRE prostate cancer patients. In our initial cohort, PSA tests from a total of one hundred and forty-six (n = 146) urine specimens were obtained from patients with aggressive (Gleason Score ≥ 8, n = 76) and non-aggressive (Gleason Score = 6, n = 70) prostate cancer. A second cohort, with a larger set of n = 291 urine samples from patients with aggressive (GS ≥ 7, n = 168) and non-aggressive (GS = 6, n = 123) prostate cancer, was also utilized in our study. Our data demonstrated that patients with aggressive disease had lower levels of urinary PSA compared to the non-aggressive patients, while the serum PSA levels were higher in patients with aggressive prostate disease. The discordance between serum and urine PSA levels was further validated by immuno-histochemistry (IHC) assay in biopsied tumors and in metastatic lesions (n = 62). Our data demonstrated that aggressive prostate cancer was negatively correlated with the PSA in prostate cancer tissues, and, unlike serum PSA, urinary PSA might serve a better surrogate for capitulating tissue milieus to detect aggressive prostate cancer. We further explored the utility of urine PSA as a cancer biomarker, either alone and in combination with serum PSA, and their ratio (serum to urine PSA) to predict disease status. Comparing the AUCs for the urine and serum PSA alone, we found that urinary PSA had a higher predictive power (AUC= 0.732) in detecting aggressive disease. Furthermore, combining the ratios between serum to urine PSA with urine and serum assay enhanced the performance (AUC = 0.811) in predicting aggressive prostate disease. These studies support the role of urinary PSA in combination with serum for detecting aggressive prostate cancer. Full article
(This article belongs to the Special Issue Aggressive Prostate Cancer)
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Review

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17 pages, 1345 KiB  
Review
The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer
by Haidar Al Saffar, David C. Chen, Carlos Delgado, Jacob Ingvar, Michael S. Hofman, Nathan Lawrentschuk, Marlon Perera, Declan G. Murphy and Renu Eapen
Cancers 2024, 16(5), 939; https://doi.org/10.3390/cancers16050939 - 26 Feb 2024
Cited by 2 | Viewed by 1606
Abstract
The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, [...] Read more.
The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, and its potential as a prognostic indicator for biochemical recurrence and overall survival. Additionally, we focused on the variability of PSMA’s expression and its impact on personalised treatment, particularly the use of [177Lu] Lu-PSMA-617 radioligand therapy. This review emphasises the essential role of PSMA PET/CT in enhancing treatment approaches, improving patient outcomes, and reducing unnecessary interventions, positioning it as a key element in personalised PCa management. Full article
(This article belongs to the Special Issue Aggressive Prostate Cancer)
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