Prostate Cancer Therapy

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

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 21618

Special Issue Editor

Department and Outpatient Clinic for Urology and Pediatric Urology, University Medical Center of Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
Interests: prostate cancer; penile cancer; robot-assisted surgery; translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Breakthrough scientific and clinical achievements in the area of prostate cancer therapy have recently revolutionized routine practice and fostered individualized medicine. In localized disease, treatment decision making is becoming increasingly sophisticated and tailored, while focal therapy as well as active surveillance have advanced to a clinical constant in addition to evergreens radical prostatectomy and radiation therapy. In metastasized hormone-sensitive prostate cancer, upfront combination of androgen deprivation therapy with either docetaxel or novel secondary hormonal therapy has yielded a remarkable improvement of patient outcomes. In castration-resistant disease, PARP inhibitors have expanded the therapeutic armamentarium, and those most beneficial drug sequences according to current knowledge have been established. Great scientific and clinical efforts are ongoing in all areas of disease management, warranting cutting-edge findings in the nearest future.

We are pleased to invite you to contribute to this Special issue on “Prostate Cancer Therapy”. This Special Issue aims to summarize the current state of knowledge and present novel findings related to various treatment aspects of prostate cancer in all disease stages. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not be limited to) the following: prostatectomy, radiotherapy, focal therapy, active surveillance, (oligo)metastatic disease, chemotherapy, hormonal therapy, targeted therapy, and metastasis-directed treatment.

I look forward to receiving your contributions.

Prof. Dr. Igor Tsaur
Guest Editor

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Keywords

  • prostate cancer
  • prostatectomy
  • radiotherapy
  • focal therapy
  • active surveillance
  • oligometastatic disease
  • chemotherapy
  • hormonal therapy
  • targeted therapy
  • metastasis-directed treatment

Published Papers (7 papers)

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Research

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13 pages, 2838 KiB  
Article
Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre
by Wolfgang Thaiss, Friedemann Zengerling, Julia Friedrich, Veronika Hechler, Michael Grunert, Christian Bolenz, Thomas Wiegel, Ambros J. Beer and Vikas Prasad
Cancers 2023, 15(12), 3216; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15123216 - 16 Jun 2023
Viewed by 2305
Abstract
Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of [...] Read more.
Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of the CRPC patients do not benefit from Lu-PSMA treatment, and little is known about predictive factors for treatment success if Lu-PSMA is offered in an individualized approach based on clinical and laboratory features. In this monocentric retrospective study, 86 CRPC patients receiving Lu-PSMA treatment were evaluated. The focus of the study was to describe clinical factors at baseline and during early treatment that are related to overall survival (OS). In addition, PSMA PET/CT-, PSA-response, and safety and tolerability (CTCAE adverse event reporting) were assessed. Efficacy endpoints were calculated using stratified Kaplan–Meier methods and Cox regression models. Mean applied dose was 17.7 GBq (mean 5.3 ± 1.1 GBq per cycle) with an average of 3.6 (range 1–8) therapy cycles. Patients were followed up for a mean of 12.4 months (range 1–39). The median OS was 15 months (95% CI 12.8–17.2). The best overall response rate in patients assessed with PSMA PET/CT and PSA response was 27.9%, and 50.0% had at least stable disease. Nine patients had a ≥grade 3 adverse event with anemia being the most frequent adverse event. Positive predictors for prolonged OS from baseline parameters were pre-treatment hemoglobin level of ≥10 g/dL and a lower PSA values at treatment start, while the presence of visceral or liver metastases were not significantly associated with worse prognoses in this cohort. With careful patient selection, an individualized Lu-PSMA treatment approach is feasible and patients with dose-limiting factors or visceral metastases should be included in prospective trials. Full article
(This article belongs to the Special Issue Prostate Cancer Therapy)
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12 pages, 6020 KiB  
Article
High-Frequency Pulsed Electric Field Ablation in Beagle Model for Treatment of Prostate Cancer
by Seung Jeong, Song Hee Kim, Hongbae Kim, Jeon Min Kang, Yubeen Park, Dong-Sung Won, Ji Won Kim, Dae Sung Ryu, Chu Hui Zeng, Jong Hoon Chung, Bumjin Lim and Jung-Hoon Park
Cancers 2022, 14(20), 4987; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14204987 - 12 Oct 2022
Viewed by 1520
Abstract
Conventional irreversible electroporation (IRE) with low-frequency pulsed electric field (LF-PEF) is used to induce cell death; however, it has several disadvantages including a long procedure time and severe muscle contraction due to high-voltage electric field. This study investigates a novel IRE protocol with [...] Read more.
Conventional irreversible electroporation (IRE) with low-frequency pulsed electric field (LF-PEF) is used to induce cell death; however, it has several disadvantages including a long procedure time and severe muscle contraction due to high-voltage electric field. This study investigates a novel IRE protocol with high-frequency pulsed electric field (HF-PEF) of 500 Hz repetition to ablate the prostate tissue in beagles for treatment of prostate cancer. A finite element analysis was performed to validate optimal electrical field strength for the procedure. In total, 12 beagles received HF-PEF of 500 Hz and were sacrificed at 4 h, 4 days, and 28 days (3 each). The remaining three beagles underwent sham procedure. The outcomes of HF-PEF were assessed by histological responses. HF-PEF successfully decellularized the prostate tissues 4 h after the treatment. The prostate glands, duct, and urethra were well preserved after IRE with HF-PEF. The ablated prostatic tissues were gradually regenerated and appeared similar to the original tissues 28 d after IRE with HF-PEF. Moreover, electrocardiography and hematology demonstrated that IRE with HF-PEF did not seriously affect the cardiac tissue. HF-PEF was effective and safe in the beagle prostate and effectively induced the ablation and gradually recovered with cellular regeneration. Full article
(This article belongs to the Special Issue Prostate Cancer Therapy)
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16 pages, 3861 KiB  
Article
Amygdalin Exerts Antitumor Activity in Taxane-Resistant Prostate Cancer Cells
by Igor Tsaur, Anita Thomas, Michelle Monecke, Marion Zugelder, Jochen Rutz, Timothy Grein, Sebastian Maxeiner, Hui Xie, Felix K.-H. Chun, Florian Rothweiler, Jindrich Cinatl, Jr., Martin Michaelis, Axel Haferkamp and Roman A. Blaheta
Cancers 2022, 14(13), 3111; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14133111 - 24 Jun 2022
Cited by 8 | Viewed by 2194
Abstract
Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells [...] Read more.
Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable. An in vitro study was performed to investigate the influence of amygdalin (10 mg/mL) on the growth of a panel of therapy-naïve and docetaxel- or cabazitaxel-resistant PCa cell lines (PC3, DU145, and LNCaP cells). Tumor growth, proliferation, clonal growth, and cell cycle progression were investigated. The cell cycle regulating proteins (phospho)cdk1, (phospho)cdk2, cyclin A, cyclin B, p21, and p27 and the mammalian target of rapamycin (mTOR) pathway proteins (phospho)Akt, (phospho)Raptor, and (phospho)Rictor as well as integrin β1 and the cytoskeletal proteins vimentin, ezrin, talin, and cytokeratin 8/18 were assessed. Furthermore, chemotactic activity and adhesion to extracellular matrix components were analyzed. Amygdalin dose-dependently inhibited tumor growth and reduced tumor clones in all (parental and resistant) PCa cell lines, accompanied by a G0/G1 phase accumulation. Cell cycle regulating proteins were significantly altered by amygdalin. A moderate influence of amygdalin on tumor cell adhesion and chemotaxis was observed as well, paralleled by modifications of cytoskeletal proteins and the integrin β1 expression level. Amygdalin may, therefore, block tumor growth and disseminative characteristics of taxane-resistant PCa cells. Further studies are warranted to determine amygdalin’s value as an antitumor drug. Full article
(This article belongs to the Special Issue Prostate Cancer Therapy)
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19 pages, 3700 KiB  
Article
Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001
by Vilde Yuli Stenberg, Anna Julie Kjøl Tornes, Hogne Røed Nilsen, Mona-Elisabeth Revheim, Øyvind Sverre Bruland, Roy Hartvig Larsen and Asta Juzeniene
Cancers 2022, 14(11), 2784; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14112784 - 03 Jun 2022
Cited by 6 | Viewed by 2437
Abstract
This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand 212Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of 212Pb-NG001 were investigated [...] Read more.
This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand 212Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of 212Pb-NG001 were investigated in two human prostate cancer cell lines with different PSMA levels: C4-2 (PSMA+) and PC-3 PIP (PSMA+++). Despite 10-fold higher PSMA expression on PC-3 PIP cells, cytotoxicity and therapeutic efficacy of the radioligand was only 1.8-fold better than for the C4-2 model, possibly explained by lower cellular internalization and less blood-rich stroma in PC-3 PIP xenografts. Mice bearing subcutaneous PC-3 PIP xenografts were treated with 0.2, 0.4, and 0.8 MBq of 212Pb-NG001 that resulted in therapeutic indexes of 2.7, 3.0, and 3.5, respectively. A significant increase in treatment response was observed in mice that received repeated injections compared to the corresponding single dose (therapeutic indexes of 3.6 for 2 × 0.2 MBq and 4.4 for 2 × 0.4 MBq). The results indicate that 212Pb-NG001 can induce therapeutic effects at clinically transferrable doses, both in the C4-2 model that resembles solid tumors and micrometastases with natural PSMA expression and in the PC-3 PIP model that mimics poorly vascularized metastases. Full article
(This article belongs to the Special Issue Prostate Cancer Therapy)
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Review

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18 pages, 514 KiB  
Review
Treating Primary Node-Positive Prostate Cancer: A Scoping Review of Available Treatment Options
by Lotte G. Zuur, Hilda A. de Barros, Koen J. C. van der Mijn, André N. Vis, Andries M. Bergman, Floris J. Pos, Jeroen A. van Moorselaar, Henk G. van der Poel, Wouter V. Vogel and Pim J. van Leeuwen
Cancers 2023, 15(11), 2962; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15112962 - 29 May 2023
Viewed by 1983
Abstract
There is currently no consensus on the optimal treatment for patients with a primary diagnosis of clinically and pathologically node-positive (cN1M0 and pN1M0) hormone-sensitive prostate cancer (PCa). The treatment paradigm has shifted as research has shown that these patients could benefit from intensified [...] Read more.
There is currently no consensus on the optimal treatment for patients with a primary diagnosis of clinically and pathologically node-positive (cN1M0 and pN1M0) hormone-sensitive prostate cancer (PCa). The treatment paradigm has shifted as research has shown that these patients could benefit from intensified treatment and are potentially curable. This scoping review provides an overview of available treatments for men with primary-diagnosed cN1M0 and pN1M0 PCa. A search was conducted on Medline for studies published between 2002 and 2022 that reported on treatment and outcomes among patients with cN1M0 and pN1M0 PCa. In total, twenty-seven eligible articles were included in this analysis: six randomised controlled trials, one systematic review, and twenty retrospective/observational studies. For cN1M0 PCa patients, the best-established treatment option is a combination of androgen deprivation therapy (ADT) and external beam radiotherapy (EBRT) applied to both the prostate and lymph nodes. Based on most recent studies, treatment intensification can be beneficial, but more randomised studies are needed. For pN1M0 PCa patients, adjuvant or early salvage treatments based on risk stratification determined by factors such as Gleason score, tumour stage, number of positive lymph nodes, and surgical margins appear to be the best-established treatment options. These treatments include close monitoring and adjuvant treatment with ADT and/or EBRT. Full article
(This article belongs to the Special Issue Prostate Cancer Therapy)
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14 pages, 35981 KiB  
Review
Impact of Pelvic Anatomical Changes Caused by Radical Prostatectomy
by Yoshifumi Kadono, Takahiro Nohara, Shohei Kawaguchi, Hiroaki Iwamoto, Hiroshi Yaegashi, Kazuyoshi Shigehara, Kouji Izumi and Atsushi Mizokami
Cancers 2022, 14(13), 3050; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14133050 - 21 Jun 2022
Cited by 4 | Viewed by 5184
Abstract
During radical prostatectomy, the prostate is removed along with the seminal vesicles, and the urinary tract is reconstructed by dropping the bladder onto the pelvic floor and suturing the bladder and urethra together. This process causes damage to the pelvic floor and postoperative [...] Read more.
During radical prostatectomy, the prostate is removed along with the seminal vesicles, and the urinary tract is reconstructed by dropping the bladder onto the pelvic floor and suturing the bladder and urethra together. This process causes damage to the pelvic floor and postoperative complications due to the anatomical changes in the pelvic floor caused by the vesicourethral anastomosis. Urinary incontinence and erectile dysfunction are major complications that impair patients’ quality of life after radical prostatectomy. In addition, the shortening of the penis and the increased prevalence of inguinal hernia have been reported. Since these postoperative complications subsequently affect patients’ quality of life, their reduction is a matter of great interest, and procedural innovations such as nerve-sparing techniques, Retzius space preservation, and inguinal hernia prophylaxis have been developed. It is clear that nerve sparing is useful for preserving the erectile function, and nerve sparing, urethral length preservation, and Retzius sparing are useful for urinary continence. The evaluation of pre- and postoperative imaging to observe changes in pelvic anatomy is also beginning to clarify why these techniques are useful. Changes in pelvic anatomy after radical prostatectomy are inevitable and, therefore, postoperative complications cannot be completely eliminated; however, preserving as much of the tissue and structure around the prostate as possible, to the extent that prostate cancer control is not compromised, may help reduce the prevalence of postoperative complications. Full article
(This article belongs to the Special Issue Prostate Cancer Therapy)
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18 pages, 829 KiB  
Review
Patients with Positive Lymph Nodes after Radical Prostatectomy and Pelvic Lymphadenectomy—Do We Know the Proper Way of Management?
by Bartosz Małkiewicz, Miłosz Knura, Małgorzata Łątkowska, Maximilian Kobylański, Krystian Nagi, Dawid Janczak, Joanna Chorbińska, Wojciech Krajewski, Jakub Karwacki and Tomasz Szydełko
Cancers 2022, 14(9), 2326; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092326 - 08 May 2022
Cited by 3 | Viewed by 4830
Abstract
Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as [...] Read more.
Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish the potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be employed for patients with positive lymph nodes. Nowadays, therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However, the current guidelines are incoherent in terms of the most effective management approach. Future management strategies are expected to make use of novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate-specific membrane antigen. Nevertheless, this heterogeneous group of men remains a great therapeutic concern, and both the clarification of the guidelines and the optimal substratification of patients are required. Full article
(This article belongs to the Special Issue Prostate Cancer Therapy)
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