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Advances in the Diagnosis and Treatment for Prostate Cancer

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 13510

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Special Issue Editor

Dr. Ashley E. Ross

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Guest Editor

Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Interests: biomarkers; genetics; genomics; novel therapeutics; focal therapy; next-generation imaging; targeted therapies; precision medicine; immunotherapy; clinical trials

Special Issue Information

Dear Colleagues,

As you are aware, the previous several years have seen multiple advances in the diagnosis and treatment of prostate cancer. Biomarkers assessed in the urine or serum, with greater accuracy than PSA, have been developed for use prior to diagnosis. Imaging, particularly MRI and functional imaging via PET, are emerging and playing larger roles across the spectrum of disease. Likewise, our understanding of and the impact of molecular biomarkers as well as patient and tumor genetics has increased, in some cases with associated therapies. With improved visualization and characterization of disease, therapeutic opportunities have increased as well. We have increased our understanding of how systemic treatments should be intensified and sequenced. Finally, a multitude of promising agents are currently in clinical trials.

In light of these new advancements, the Journal of Clinical Medicine (Impact Factor 5.583) is developing a Special Issue on advancements in the diagnosis and treatment of prostate cancer. We are prioritizing high-quality original studies, but also welcome well-designed meta-analyses and well reviews. We look forward to your contribution.

Dr. Ashley E. Ross
Guest Editor

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Keywords

biomarkers
genetics
novel therapeutics
targeted therapies
focal therapy
next-generation imaging
immunotherapy

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Published Papers (5 papers)

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Research

9 pages, 518 KiB

Open AccessArticle

Same Day Discharge versus Inpatient Surgery for Robot-Assisted Radical Prostatectomy: A Comparative Study

by Razvan George Rahota, Ambroise Salin, Jean Romain Gautier, Christophe Almeras, Guillaume Loison, Christophe Tollon, Jean Baptiste Beauval and Guillaume Ploussard

J. Clin. Med. 2021, 10(4), 661; https://doi.org/10.3390/jcm10040661 - 9 Feb 2021

Cited by 16 | Viewed by 2193

Abstract

(1) Background: no study has compared outcomes of same day discharge (SDD) versus inpatient robot-assisted radical prostatectomy (RARP) in homogenous cohorts. Our aim was to compare perioperative outcomes and urinary continence recovery between SDD and inpatient RARP in contemporary, comparable patients. (2) Methods: we included consecutive patients undergoing RARP between 2018 and 2020 (n = 376). Only patients eligible for SDD (no oral anticoagulant, distance home-hospital <150 km) and having >6-month follow-up were included (n = 180). All patients underwent RARP with or without lymph node dissection. Comparisons were performed between SDD (n = 42) and inpatient RARP (n = 138). Primary outcomes were 90-day complication and readmission rates and continence rates at 1 and 6 months. (3) Results: median patient age was 66.7 years. Median duration of surgery and blood loss was 134 min and 200 mL, respectively. Lymph node dissection and nerve-sparing procedures were performed in 76.7% and 82.2% of cases, respectively. Median follow-up was 19.5 months. No difference was seen regarding patient features, peri-operative outcomes, and pathology parameters between both groups. The proportion of SDD RARP was stable over time (23.5%). The 90-day unplanned visits, readmission and complication rates were 9.5%, 7.1%, and 19.0% in SDD patients versus 14.5% (p = 0.407), 10.1% (p = 0.560), 28.3% (p = 0.234) for inpatient RARP, respectively. Trends favoring SDD were not statistically significant. Continence rates at 1-(p = 0.589) and 6-months (p = 0.674) were comparable between SDD and inpatient RARP. The main limitation was the lack of randomization. (4) Conclusions: this multi-surgeon comparative study confirms the safety of routine SDD RARP in terms of perioperative and functional outcomes. Trends favoring SDD in terms of complications, emergency visits and readmission have to be confirmed. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment for Prostate Cancer)

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13 pages, 1456 KiB

Open AccessArticle

MRI Characteristics Accurately Predict Biochemical Recurrence after Radical Prostatectomy

by Cécile Manceau, Jean-Baptiste Beauval, Marine Lesourd, Christophe Almeras, Richard Aziza, Jean-Romain Gautier, Guillaume Loison, Ambroise Salin, Christophe Tollon, Michel Soulié, Bernard Malavaud, Mathieu Roumiguié and Guillaume Ploussard

J. Clin. Med. 2020, 9(12), 3841; https://doi.org/10.3390/jcm9123841 - 26 Nov 2020

Cited by 20 | Viewed by 2147

Abstract

Background: After radical prostatectomy (RP), biochemical recurrence (BCR) is associated with an increased risk of developing distant metastasis and prostate cancer specific and overall mortality. Methods: The two-centre study included 521 consecutive patients undergoing RP for positive pre-biopsy magnetic resonance imaging (MRI) and pathologically proven prostate cancer (PCa), after which a combination scheme of fusion-targeted biopsy (TB) and systematic biopsy was performed. We assessed correlations between MRI characteristics, International Society of Urological Pathology (ISUP) grade group in TB, and outcomes after RP. We developed an imaging-based risk classification for improving BCR prediction. Results: Higher Prostate Imaging and Reporting and Data System (PI-RADS) score (p = 0.013), higher ISUP grade group in TB, and extracapsular extension (ECE) on the MRI were significantly associated with more advanced disease (pTstage), higher ISUP grade group (p = 0.001), regional lymph nodes metastasis in RP specimens (p < 0.001), and an increased risk of recurrence after surgery. A positive margin status was significantly associated with ECE-MRI (p < 0.001). Our imaging-based classification included ECE on MRI, ISUP grade group on TB, and PI-RADS accurately predicted BCR (AUC = 0.714, p < 0.001). This classification had more improved area under the curve (AUC) than the standard d’Amico classification in our population. Validation was performed in a two-centre cohort. Conclusions: In this cohort, PI-RADS score, MRI stage, and ISUP grade group in MRI-TB were significantly predictive for disease features and recurrence after RP. Imaging-based risk classification integrating these three factors competed with d’Amico classification for predicting BCR. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment for Prostate Cancer)

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13 pages, 2214 KiB

Open AccessArticle

Tumor Immune Microenvironment Clusters in Localized Prostate Adenocarcinoma: Prognostic Impact of Macrophage Enriched/Plasma Cell Non-Enriched Subtypes

by Neil K. Jairath, Mark W. Farha, Sudharsan Srinivasan, Ruple Jairath, Michael D. Green, Robert T. Dess, William C. Jackson, Adam B. Weiner, Edward M. Schaeffer, Shuang G. Zhao, Felix Y. Feng, Issam El Naqa and Daniel E. Spratt

J. Clin. Med. 2020, 9(6), 1973; https://doi.org/10.3390/jcm9061973 - 24 Jun 2020

Cited by 13 | Viewed by 2648

Abstract

Background: Prostate cancer (PCa) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of prostate adenocarcinomas (n = 492) was utilized. The immune microenvironment was characterized using the CIBERSORTX tool to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Analyses of progression-free survival (PFS), distant metastases, and overall survival (OS) were performed using Kaplan–Meier estimates and Cox regression multivariable analyses. Results: Four immune clusters were identified, largely defined by plasma cell, CD4⁺ Memory Resting T Cells (CD4 MR), and M0 and M2 macrophage content (CD4 MR^HighPlasma Cell^HighM0^LowM2^Mid, CD4 MR^LowPlasma Cell^HighM0^LowM2^Low, CD4 MR^HighPlasma Cell^LowM0^HighM2^Low, and CD4 MR^HighPlasma Cell^LowM0^LowM2^High). The two macrophage-enriched/plasma cell non-enriched clusters (3 and 4) demonstrated worse PFS (HR 2.24, 95% CI 1.46–3.45, p = 0.0002) than the clusters 1 and 2. No metastatic events occurred in the plasma cell enriched, non-macrophage-enriched clusters. Comparing clusters 3 vs. 4, in patients treated by surgery alone, cluster 3 had zero progression events (p < 0.0001). However, cluster 3 patients had worse outcomes after post-operative radiotherapy (p = 0.018). Conclusion: Distinct tumor immune clusters with a macrophage-enriched, plasma cell non-enriched phenotype and reduced plasma cell enrichment independently characterize an aggressive phenotype in localized prostate cancer that may differentially respond to treatment. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment for Prostate Cancer)

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12 pages, 784 KiB

Open AccessArticle

Immune Modulation in Prostate Cancer Patients Treated with Androgen Receptor (AR)-Targeted Therapy

by Vincenza Conteduca, Orazio Caffo, Emanuela Scarpi, Pierangela Sepe, Luca Galli, Lucia Fratino, Francesca Maines, Vincenzo Emanuele Chiuri, Matteo Santoni, Elisa Zanardi, Francesco Massari, Ilaria Toma, Cristian Lolli, Giuseppe Schepisi, Andrea Sbrana, Stefania Kinspergher, Maria Concetta Cursano, Chiara Casadei, Caterina Modonesi, Daniele Santini, Giuseppe Procopio and Ugo De Giorgi Show full author list Hide full author list

J. Clin. Med. 2020, 9(6), 1950; https://doi.org/10.3390/jcm9061950 - 22 Jun 2020

Cited by 3 | Viewed by 2766

Abstract

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63–75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status (p = 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03–2.27, p = 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05–2.60, p = 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment for Prostate Cancer)

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18 pages, 3268 KiB

Open AccessArticle

Unleashing the Diagnostic, Prognostic and Therapeutic Potential of the Neuronostatin/GPR107 System in Prostate Cancer

by Prudencio Sáez-Martínez, Juan M. Jiménez-Vacas, Antonio J. León-González, Vicente Herrero-Aguayo, Antonio J. Montero Hidalgo, Enrique Gómez-Gómez, Rafael Sánchez-Sánchez, María J. Requena-Tapia, Justo P. Castaño, Manuel D. Gahete and Raúl M. Luque

J. Clin. Med. 2020, 9(6), 1703; https://doi.org/10.3390/jcm9061703 - 2 Jun 2020

Cited by 8 | Viewed by 2870

Abstract

Certain components of the somatostatin-system play relevant roles in Prostate Cancer (PCa), whose most aggressive phenotype (Castration-Resistant-PCa (CRPC)) remains lethal nowadays. However, neuronostatin and the G protein-coupled receptor 107 (GPR107), two novel members of the somatostatin-system, have not been explored yet in PCa. Consequently, we investigated the pathophysiological role of NST/GPR107-system in PCa. GPR107 expression was analyzed in well-characterized PCa patient′s cohorts, and functional/mechanistic assays were performed in response to GPR107-silencing and NST-treatment in PCa cells (androgen-dependent (AD: LNCaP) and androgen-independent (AI: 22Rv1/PC-3), which are cell models of hormone-sensitive and CRPC, respectively), and normal prostate cells (RWPE-1 cell-line). GPR107 was overexpressed in PCa and associated with key clinical parameters (e.g., advance stage of PCa, presence of vascular invasion and metastasis). Furthermore, GPR107-silencing inhibited proliferation/migration rates in AI-PCa-cells and altered key genes and oncogenic signaling-pathways involved in PCa aggressiveness (i.e., KI67/CDKN2D/MMP9/PRPF40A, SST₅TMD4/AR-v7/In1-ghrelin/EZH2 splicing-variants and AKT-signaling). Interestingly, NST treatment inhibited proliferation/migration only in AI-PCa cells and evoked an identical molecular response than GPR107-silencing. Finally, NST decreased GPR107 expression exclusively in AI-PCa-cells, suggesting that part of the specific antitumor effects of NST could be mediated through a GPR107-downregulation. Altogether, NST/GPR107-system could represent a valuable diagnostic and prognostic tool and a promising novel therapeutic target for PCa and CRPC. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment for Prostate Cancer)

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