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Cancers
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Prostate Cancer Metastasis
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Prostate Cancer Metastasis

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

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 18602

Special Issue Editor

Prof. Dr. Arnulf Stenzl

E-Mail Website
Guest Editor
Department of Urology, University Hospital Tuebingen, 72076 Tuebingen, Germany
Interests: urology; bladder cancer; prostate cancer

Special Issue Information

Dear Colleagues,

The aim of this issue is to share the latest developments in the detection of metastasis in advanced prostate cancer. This may be an early event after primary curative treatment, the early detection of hormone-sensitive metastatic disease—whether it is oligometastatic or extensively metastatic—or the various stages of castration-resistant prostate cancer. There may be exclusive treatment options for non-metastatic CRPC and CRPC after one or several previous lines of treatment. Recent developments also include biomarker-based treatment which predicts applicability and prognosis of certain treatments. Last but not least, the recent addition of novel hormone treatments, chemotherapy, PSMA ligands, and genetic-based treatment modalities has led to the question of optimal sequences. In this Special Issue, original research articles and reviews are welcome.

We look forward to receiving your contributions.

Prof. Dr. Arnulf Stenzl
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 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
  • metastasis
  • hormone-sensitive
  • castration-resistant prostate cancer
  • imaging
  • PSMA
  • ligand therapy
  • sequence
  • oligometastatic
  • biomarker

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Published Papers (7 papers)

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Research

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10 pages, 691 KiB  
Article
Oncological Outcomes of Patients with High-Volume mCRPC: Results from a Longitudinal Real-Life Multicenter Cohort
by Mariaconsiglia Ferriero, Francesco Prata, Umberto Anceschi, Serena Astore, Alfredo Maria Bove, Aldo Brassetti, Fabio Calabrò, Silvia Chiellino, Cosimo De Nunzio, Gaetano Facchini, Elisena Franzese, Michela Izzo, Riccardo Mastroianni, Leonardo Misuraca, Richard Naspro, Rocco Papalia, Annalisa Pappalardo, Giorgia Tema, Gabriele Tuderti, Beatrice Turchi, Andrea Tubaro and Giuseppe Simoneadd Show full author list remove Hide full author list
Cancers 2023, 15(19), 4809; https://doi.org/10.3390/cancers15194809 - 29 Sep 2023
Viewed by 1302
Abstract
Registrative trials recommended the use of upfront chemotherapy in high-volume metastatic prostate cancer. We reported survival outcomes of patients with high-volume mCRPC treated with ARTA in a chemo-naïve setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. [...] Read more.
Registrative trials recommended the use of upfront chemotherapy in high-volume metastatic prostate cancer. We reported survival outcomes of patients with high-volume mCRPC treated with ARTA in a chemo-naïve setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. We retrospectively collected data on mCRPC patients treated at six centers. The dataset was queried for high-volume disease (defined as more than 6 bone lesions or bulky nodes ≥ 5 cm). We compared the main clinical features of chemo-naïve versus chemo-treated patients. The Mann–Whitney U test and Chi-squared test were used to compare continuous and categorial variables, respectively. The Kaplan–Meier method was used to compare differences in terms of progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS) in an upfront ARTA or chemo-treated setting. Survival probabilities were computed at 12, 24, 48, and 60 months. Out of 216 patients, 88 cases with high-volume disease were selected. Sixty-nine patients (78.4%) received upfront ARTA, while 19 patients received chemotherapy as the first-line treatment option. Forty-eight patients received Abiraterone (AA), 21 patients received Enzalutamide (EZ) as the first-line treatment. The ARTA population was older (p = 0.007) and less likely to receive further lines of treatment (p = 0.001) than the chemo-treated cohort. The five-year PFS, CSS and OS were 60%, 73.3%, and 72.9%, respectively. Overall, 28 patients (31.8%) shifted after their first-line therapy to a second-line therapy: EZ was prescribed in 17 cases, AA in seven cases and radiometabolic therapy in four patients. Sixteen cases (18.2%) developed significant progression and were treated with chemotherapy. At Kaplan–Meyer analysis PFS, CSS and OS were comparable for upfront ARTA vs chemo-treated patients (log rank p = 0.10, p = 0.64 and p = 0.36, respectively). We reported comparable survival probabilities in a real-life series of high-volume mCRPC patients who either received upfront ARTA or chemotherapy. Patients primarily treated with chemotherapy were younger and more likely to receive further treatment lines than the upfront ARTA cohort. Our data support the use of novel antiandrogens as first line treatment regardless tumor burden, delaying the beginning of a more toxic chemotherapy in case of significant disease progression. Full article
(This article belongs to the Special Issue Prostate Cancer Metastasis)
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13 pages, 1695 KiB  
Article
Degenerative Changes in Aging Human Pelvic Lymph Nodes—A Reason to Rethink Staging and Therapy of Regional Malignancies?
by Daniel Gödde, Stephan Degener, Christine Walles, Rosalie Keller, Katharina Graf, Marco Tosch, Susanne Krege, Michael Musch, Hans Michael Kvasnicka, Maximilian Ackermann, Stephan Störkel and Friedrich-Carl von Rundstedt
Cancers 2023, 15(19), 4754; https://doi.org/10.3390/cancers15194754 - 27 Sep 2023
Cited by 2 | Viewed by 1617
Abstract
Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence [...] Read more.
Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence and extent. A total of 5173 pelvic lymph nodes of 390 patients aged 44 to 79 years (median 68 years, IQR 62–71 years) were histologically examined for degenerative structural changes. Lymph node size, lipomatous atrophy, capsular fibrosis, framework fibrosis, and calcifications were recorded semi-quantitatively and evaluated by age group. Significantly more lymph nodes <10 mm were found in older patients (p = 0.001). The incidence of framework fibrosis, capsular fibrosis, and calcifications increased significantly with increasing patient age (p < 0.001). In lipomatous atrophy, an increase in mild to moderate lipomatous atrophy was observed with increasing age (p < 0.001). In this, the largest study to date on this topic, age-related degenerative changes in pelvic lymph nodes were proven. Due to the consecutive decrease in hte filtration function of pelvic lymph nodes with increasing age, staging and therapy of metastatic pelvic urologic carcinomas should be reconsidered. Full article
(This article belongs to the Special Issue Prostate Cancer Metastasis)
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9 pages, 658 KiB  
Article
Advanced PSMA-PET/CT Imaging Parameters in Newly Diagnosed Prostate Cancer Patients for Predicting Metastatic Disease
by Yaniv Yechiel, Yaly Orr, Konstantin Gurevich, Ronit Gill and Zohar Keidar
Cancers 2023, 15(4), 1020; https://doi.org/10.3390/cancers15041020 - 6 Feb 2023
Cited by 2 | Viewed by 1765
Abstract
(1) Purpose: Recent studies indicate that advanced imaging parameters such as prostate PSMA tumor volume may have a value in predicting response to treatment of castration-resistant prostate cancer patients. In this study, we examine whether a relationship can be found between advanced imaging [...] Read more.
(1) Purpose: Recent studies indicate that advanced imaging parameters such as prostate PSMA tumor volume may have a value in predicting response to treatment of castration-resistant prostate cancer patients. In this study, we examine whether a relationship can be found between advanced imaging parameters such as prostate PSMA-TV and the presence of metastatic disease in newly diagnosed prostate cancer patients undergoing PSMA-PET/CT for staging purposes; (2) Methods: We retrospectively analyzed PET/CT studies of 91 patients with newly diagnosed prostate cancer. Prostate PSMA-TV was measured using the MIRADA-XD software. PET/CT results were recorded, as well as additional clinical parameters such as the Gleason score, etc.; (3) Results: Prostate PSMA-TV measurements were found to be able to significantly differentiate metastatic from the non-metastatic patient groups (13.7 vs. 5.5, p-value < 0.05). Overall, 54% percent of patients with levels of over 8.1 PSMA-TV had metastatic lesions found on their PSMA-PET/CT. A model based on this cutoff attained a sensitivity of 80%, a specificity of 68.3%, and a negative predictive value of 93.5% for identifying metastatic disease. Another bin model was found statistically capable of assessing the likelihood of the presence of metastatic disease with a p-value of 0.001; (4) Conclusions: Prostate PSMA-TV measurement has the potential to predict the presence of metastatic disease at staging and thus may impact further treatment decision and patient management. Full article
(This article belongs to the Special Issue Prostate Cancer Metastasis)
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13 pages, 2444 KiB  
Article
Epithelial and Stromal Characteristics of Primary Tumors Predict the Bone Metastatic Subtype of Prostate Cancer and Patient Survival after Androgen-Deprivation Therapy
by Pernilla Wikström, Sofia Halin Bergström, Andreas Josefsson, Julius Semenas, Annika Nordstrand, Elin Thysell, Sead Crnalic, Anders Widmark, Camilla Thellenberg Karlsson and Anders Bergh
Cancers 2022, 14(21), 5195; https://doi.org/10.3390/cancers14215195 - 23 Oct 2022
Cited by 6 | Viewed by 1948
Abstract
Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen [...] Read more.
Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells. Full article
(This article belongs to the Special Issue Prostate Cancer Metastasis)
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18 pages, 6033 KiB  
Article
Transcriptomic Profiling Analysis of Castration-Resistant Prostate Cancer Cell Lines Treated with Chronic Intermittent Hypoxia
by Chung Lyul Lee, Minji Lee, Ji Yong Lee, Sin-hyoung Hong, Seung Woo Yang, Ji-hyeon Min, Dong-eon Lee, Joonyoung Baek, Chanseul Kim, Jae Sung Lim, Ki Hak Song, Ju Hyun Shin and Gun-Hwa Kim
Cancers 2022, 14(16), 3959; https://doi.org/10.3390/cancers14163959 - 16 Aug 2022
Cited by 2 | Viewed by 2332
Abstract
Castration-resistant prostate cancer (CRPC) is still a major concern in men’s health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the [...] Read more.
Castration-resistant prostate cancer (CRPC) is still a major concern in men’s health, with 375,000 cancer deaths annually. Hypoxia, which is a marked characteristic of advanced solid tumors, has been suggested to induce prostate cancer towards CRPC, metastasis and treatment resistance. To evaluate the effect of hypoxia on prostate cancer, two and five cycles of hypoxia and reoxygenation were administered using 22Rv1 cell lines and denominated as 22Rv1-CI and 22Rv1-PCI, respectively. Cancer cell migration was promoted in 22Rv1-CI compared to controls, and the expression of COL13A1 was significantly up-regulated in 22Rv1-CI according to differentially expressed gene analysis of RNA sequencing among groups. Cancer cell migration was impeded in a wound healing assay after transfecting si-COL13A1. Moreover, the expression of COL13A1 was also higher in the cell line originating from bone metastatic prostate cancer compared to other cell lines. Using the open database GEO, we also confirmed that the expression of COL13A1 was higher in bone metastatic prostate cancer tissue than in localized prostate cancer tissue in patients. Therefore, COL13A1 may be closely related to the bony metastasis of prostate cancer, and our findings may provide valuable information on the pathophysiology of the metastatic niche induced by hypoxia in patients with CRPC. Full article
(This article belongs to the Special Issue Prostate Cancer Metastasis)
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Review

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18 pages, 1525 KiB  
Review
Molecular Targeted Therapies in Metastatic Prostate Cancer: Recent Advances and Future Challenges
by Carlo Sorrentino and Emma Di Carlo
Cancers 2023, 15(11), 2885; https://doi.org/10.3390/cancers15112885 - 23 May 2023
Cited by 12 | Viewed by 3261
Abstract
Prostate cancer is the most frequent malignant tumor in men, and, despite the great improvements in survival in patients with localized cancer, the prognosis for metastatic disease remains poor. Novel molecular targeted therapies, which block specific molecules or signaling pathways in tumor cells [...] Read more.
Prostate cancer is the most frequent malignant tumor in men, and, despite the great improvements in survival in patients with localized cancer, the prognosis for metastatic disease remains poor. Novel molecular targeted therapies, which block specific molecules or signaling pathways in tumor cells or in their microenvironment, have shown encouraging results in metastatic castration-resistant prostate cancer. Among these therapeutic approaches, prostate-specific membrane antigen-targeted radionuclide therapies and DNA repair inhibitors represent the most promising ones, with some therapeutic protocols already approved by the FDA, whereas therapies targeting tumor neovascularization and immune checkpoint inhibitors have not yet demonstrated clear clinical benefits. In this review, the most relevant studies and clinical trials on this topic are illustrated and discussed, together with future research directions and challenges. Full article
(This article belongs to the Special Issue Prostate Cancer Metastasis)
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24 pages, 1358 KiB  
Review
Bone Metastases and Health in Prostate Cancer: From Pathophysiology to Clinical Implications
by Cinzia Baldessari, Stefania Pipitone, Eleonora Molinaro, Krisida Cerma, Martina Fanelli, Cecilia Nasso, Marco Oltrecolli, Marta Pirola, Elisa D’Agostino, Giuseppe Pugliese, Sara Cerri, Maria Giuseppa Vitale, Bruno Madeo, Massimo Dominici and Roberto Sabbatini
Cancers 2023, 15(5), 1518; https://doi.org/10.3390/cancers15051518 - 28 Feb 2023
Cited by 12 | Viewed by 5494
Abstract
Clinically relevant bone metastases are a major cause of morbidity and mortality for prostate cancer patients. Distinct phenotypes are described: osteoblastic, the more common osteolytic and mixed. A molecular classification has been also proposed. Bone metastases start with the tropism of cancer cells [...] Read more.
Clinically relevant bone metastases are a major cause of morbidity and mortality for prostate cancer patients. Distinct phenotypes are described: osteoblastic, the more common osteolytic and mixed. A molecular classification has been also proposed. Bone metastases start with the tropism of cancer cells to the bone through different multi-step tumor–host interactions, as described by the “metastatic cascade” model. Understanding these mechanisms, although far from being fully elucidated, could offer several potential targets for prevention and therapy. Moreover, the prognosis of patients is markedly influenced by skeletal-related events. They can be correlated not only with bone metastases, but also with “bad” bone health. There is a close correlation between osteoporosis—a skeletal disorder with decreased bone mass and qualitative alterations—and prostate cancer, in particular when treated with androgen deprivation therapy, a milestone in its treatment. Systemic treatments for prostate cancer, especially with the newest options, have improved the survival and quality of life of patients with respect to skeletal-related events; however, all patients should be evaluated for “bone health” and osteoporotic risk, both in the presence and in the absence of bone metastases. Treatment with bone-targeted therapies should be evaluated even in the absence of bone metastases, as described in special guidelines and according to a multidisciplinary evaluation. Full article
(This article belongs to the Special Issue Prostate Cancer Metastasis)
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