Actual Aspects of Prostate Cancer Treatment—An Interdisciplinary Approach (Volume II)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (22 September 2023) | Viewed by 10284

Special Issue Editors


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Guest Editor
Hannover Medical School, Department of Radiotherapy and Special Oncology, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany
Interests: high precision radiotherapy; radiobiology; prostate cancer; interdisciplinary oncology
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Guest Editor
Center for Radiotherapy and Radiooncology, Mozartstr. 30, D-26655 Westerstede, Germany
Interests: high precision radiotherapy; radiobiology; prostate cancer; interdisciplinary oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This collection is the second edition of the previous one "Actual Aspects of Prostate Cancer Treatment—an Interdisciplinary Approach"

(https://www.mdpi.com/journal/cancers/special_issues/Actual_Aspects_Prostate_Cancer_Treatment_Interdisciplinary_Approach).

Prostate cancer is one of the leading cancer diagnoses worldwide. By improving the different interdisciplinary therapeutic approaches, cure rates could be improved, especially for patients with localized disease.

For primary curative therapy, surgical and radiotherapeutic methods are used. Both methods have led to further advances in treatment over the past few decades, e.g., the establishment of robot-assisted surgery or the implementation of intensity-modulated techniques in radiotherapy.

Further actual scientific aspects concern the role of modern methods of imaging (e.g., PSMA-PET/CT), salvage therapy for recurrence after primary treatment, hypofractionation in radiotherapy, and the prediction of tumor responses. In this Special Issue of Cancers entitled “Actual Aspects of Prostate Cancer Treatment—An Interdisciplinary Approach”, we want to discuss at least some of these actual topics from an interdisciplinary point of view. Our scope includes current therapy concepts as well as innovative approaches.

Prof. Dr. Hans Christiansen
Prof. Dr. Robert Michael Hermann
Guest Editors

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Keywords

  • prostate cancer
  • surgery
  • radiotherapy
  • hypofractionation
  • interdisciplinarity
  • nuclear medicine
  • PSMA

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Published Papers (5 papers)

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17 pages, 3012 KiB  
Article
Regulation of EZH2 Expression by INPP4B in Normal Prostate and Primary Prostate Cancer
by Manqi Zhang, Yasemin Ceyhan, Shenglin Mei, Taghreed Hirz, David B. Sykes and Irina U. Agoulnik
Cancers 2023, 15(22), 5418; https://doi.org/10.3390/cancers15225418 - 15 Nov 2023
Cited by 1 | Viewed by 1483
Abstract
The phosphatases INPP4B and PTEN are tumor suppressors that are lost in nearly half of advanced metastatic cancers. The loss of PTEN in prostate epithelium initially leads to an upregulation of several tumor suppressors that slow the progression of prostate cancer in mouse [...] Read more.
The phosphatases INPP4B and PTEN are tumor suppressors that are lost in nearly half of advanced metastatic cancers. The loss of PTEN in prostate epithelium initially leads to an upregulation of several tumor suppressors that slow the progression of prostate cancer in mouse models. We tested whether the loss of INPP4B elicits a similar compensatory response in prostate tissue and whether this response is distinct from the one caused by the loss of PTEN. Knockdown of INPP4B but not PTEN in human prostate cancer cell lines caused a decrease in EZH2 expression. In Inpp4b−/− mouse prostate epithelium, EZH2 levels were decreased, as were methylation levels of histone H3. In contrast, Ezh2 levels were increased in the prostates of Pten−/− male mice. Contrary to PTEN, there was a positive correlation between INPP4B and EZH2 expression in normal human prostates and early-stage prostate tumors. Analysis of single-cell transcriptomic data demonstrated that a subset of EZH2-positive cells expresses INPP4B or PTEN, but rarely both, consistent with their opposing correlation with EZH2 expression. Unlike PTEN, INPP4B did not affect the levels of SMAD4 protein expression or Pml mRNA expression. Like PTEN, p53 protein expression and phosphorylation of Akt in Inpp4b−/− murine prostates were elevated. Taken together, the loss of INPP4B in the prostate leads to overlapping and distinct changes in tumor suppressor and oncogenic downstream signaling. Full article
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16 pages, 1864 KiB  
Article
Risk Biomarkers for Biochemical Recurrence after Radical Prostatectomy for Prostate Cancer Using Clinical and MRI-Derived Semantic Features
by Adalgisa Guerra, Filipe Caseiro Alves, Kris Maes, Rui Maio, Geert Villeirs and Helena Mouriño
Cancers 2023, 15(21), 5296; https://doi.org/10.3390/cancers15215296 - 5 Nov 2023
Cited by 1 | Viewed by 1742
Abstract
Objectives: This study aimed to assess the impact of the covariates derived from a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis was conducted from [...] Read more.
Objectives: This study aimed to assess the impact of the covariates derived from a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis was conducted from a single center between 2015 and 2022. Variables under consideration included prostate-specific antigen (PSA) levels, patient age, prostate volume, MRI semantic features, and Grade Group (GG). We also assessed the influence of pECE+ and positive surgical margins on BCRFS. To attain these goals, we used the Kaplan–Meier survival function and the multivariable Cox regression model. Additionally, we analyzed the MRI features on BCR (biochemical recurrence) in low/intermediate risk patients. Results: A total of 177 participants with a follow-up exceeding 6 months post-RARP were included. The 1-year, 2-year, and 4-year risks of BCR after radical prostatectomy were 5%, 13%, and 21%, respectively. The non-parametric approach for the survival analysis showed that adverse MRI features such as macroscopic ECE on MRI (mECE+), capsular disruption, high tumor capsular contact length (TCCL), GG ≥ 4, positive surgical margins (PSM), and pECE+ on pathology were risk factors for BCR. In low/intermediate-risk patients (pECE− and GG < 4), the presence of adverse MRI features has been shown to increase the risk of BCR. Conclusions: The study highlights the importance of incorporating predictive MRI features for detecting extracapsular extension pre-surgery in influencing early outcomes and clinical decision making; mECE+, TCCL, capsular disruption, and GG ≥ 4 based on pre-surgical biopsy were independent prognostic factors for early BCR. The presence of adverse features on MRI can assist in identifying low/intermediate-risk patients who will benefit from closer monitoring. Full article
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10 pages, 2759 KiB  
Article
Irisin Induces Apoptosis in Metastatic Prostate Cancer Cells and Inhibits Tumor Growth In Vivo
by Khalil H. Alshanqiti, Sumayyah F. Alomar, Nourah Alzoman and Aliyah Almomen
Cancers 2023, 15(15), 4000; https://doi.org/10.3390/cancers15154000 - 7 Aug 2023
Cited by 4 | Viewed by 2094
Abstract
Background: Prostate cancer is the second most common cancer in males worldwide, with αVβ5 in-tegrin, a coactivator receptor, being highly expressed in advanced prostate cancer. Irisin, a hormone secreted from skeletal muscles, can reduce cell viability and migration and potentially inhibit αVβ5. Objective: [...] Read more.
Background: Prostate cancer is the second most common cancer in males worldwide, with αVβ5 in-tegrin, a coactivator receptor, being highly expressed in advanced prostate cancer. Irisin, a hormone secreted from skeletal muscles, can reduce cell viability and migration and potentially inhibit αVβ5. Objective: This study investigates the potential impact of irisin on prostate cancer cells and its underlying mechanism. Methods: In vitro evaluation of the antiproliferative action of irisin on metastatic prostate cancer (PC-3) cells was tested through MTT assay, flow cytometry, and Western blot. An in vivo evaluation of the antiproliferative effect on prostate cancer xenograft was evaluated in nude mice. Results: In vitro evaluations showed that irisin reduced PC-3 cell viability to 70% and increased the Annexin-V/7AAD positive cell population. Irisin altered the expression of apoptotic proteins, αVβ5, and proteins involved in the P13k-Akt pathway. In vivo, irisin inhibited tumor growth and progression, positively affecting animal well-being. In conclusion, irisin has an apoptotic effect on PC-3, possibly through altering αVβ5 and the Bcl2/BAX and P13k-Akt signaling pathway, inhibiting tumor growth in vivo. Conclusion: Our findings can serve as a foundation for further evaluation of irisin’s role in prostate cancer. Full article
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11 pages, 434 KiB  
Article
Prophylactic A-Blockers for Radiotherapy-Induced Lower Urinary Tract Symptoms in Men with Prostate Cancer: A Phase III Randomized Trial
by Tamim Niazi, Edmond Kaldany, Steven Tisseverasinghe, Talía Malagón, Boris Bahoric, Victor McPherson, Alexis Rompre-Brodeur and Maurice Anidjar
Cancers 2023, 15(13), 3444; https://doi.org/10.3390/cancers15133444 - 30 Jun 2023
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Abstract
Purpose: The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTSs in prostate cancer patients receiving external beam radiotherapy (EBRT). Methods: A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic silodosin [...] Read more.
Purpose: The present phase III randomized trial assessed the efficacy of prophylactic versus therapeutic α-blockers at improving RI-LUTSs in prostate cancer patients receiving external beam radiotherapy (EBRT). Methods: A total of 148 prostate cancer patients were randomized 1:1 to receive either prophylactic silodosin on day one of EBRT or the occurrence of RI-LUTSs. LUTSs were quantified using the international prostate symptom score (IPSS) at regular intervals during the study. The primary endpoint was the change in the IPSS from baseline to the last day of radiotherapy (RT). Secondary endpoints included changes in IPSS from baseline to 4 weeks and 12 weeks after the start of RT. Results: Patient demographics, baseline IPSS, and prescribed radiation doses were balanced between arms. On the last day of RT, the mean IPSS was 14.8 (SD 7.6) in the experimental arm and 15.7 (SD 8.5) in the control arm (p = 0.40). There were no significant differences in IPSSs between the study arms in the intention-to-treat (ITT) analysis at baseline, the last day of RT, and 4 and 12 weeks post-RT. Conclusion: Prophylactic α-blockers were not effective at significantly reducing RI-LUTSs in prostate cancer patients treated with EBRT. Treating patients with α-blockers at the onset of RI-LUTSs will avoid unnecessary drug exposure and toxicity. Full article
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15 pages, 441 KiB  
Systematic Review
Neoadjuvant versus Concurrent Androgen Deprivation Therapy in Localized Prostate Cancer Treated with Radiotherapy: A Systematic Review of the Literature
by Rodrigo Cartes, Muneeb Uddin Karim, Steven Tisseverasinghe, Marwan Tolba, Boris Bahoric, Maurice Anidjar, Victor McPherson, Stephan Probst, Alexis Rompré-Brodeur and Tamim Niazi
Cancers 2023, 15(13), 3363; https://doi.org/10.3390/cancers15133363 - 27 Jun 2023
Cited by 4 | Viewed by 2861
Abstract
Background: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. Methods: We conducted a systematic review in [...] Read more.
Background: There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. Methods: We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. Findings: Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. Interpretation: The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa. Full article
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