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Advances and Challenges in the Diagnosis and Treatment of Urological...
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Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 48459

Special Issue Editors

Dr. Bartosz Małkiewicz

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Guest Editor
University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland
Interests: uro-oncology; lymph node metastasis-growth and immune evasion; minimally invasive surgery; radio-guided surgery; prostate cancer; bladder cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jakub Dobruch

E-Mail Website
Guest Editor
Department of Urology, Centre of Postgraduate Medical Education, Independent Public Hospital of Professor W. Orlowski, 00-416 Warsaw, Poland
Interests: urologic oncology; molecular diagnostics; endoscopic surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The incidence of urological tumors has increased significantly over the past 40 years, and prostate cancer is the second most common malignancy among men. Even if in most cases the initial treatment is curative, a certain number of patients experience a poor course of disease with local or distant recurrence, and require further treatment, which significantly worsens their quality of life.

Over the past two decades, great efforts have been made to improve diagnosis and treatment outcomes. Molecular biomarkers have been investigated and introduced into clinical practice, and new pathological and clinical classifications have been proposed to account for tumor behavior and risk of disease recurrence. At the same time, new surgical and pharmacological approaches have been developed to improve treatment outcomes.

Nevertheless, many issues remain a matter of debate regarding accurate diagnosis, targeted therapy and multidisciplinary management.

This Special Issue of Cancers will cover all aspects of urological cancers, including original research into advanced imaging, molecular characterization, current and experimental treatment options, and quality of life. Expert opinions, systematic reviews and meta-analyses are also welcome.

Dr. Bartosz Małkiewicz
Prof. Dr. Jakub Dobruch
Guest Editors

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
  • bladder cancer
  • upper urinary tract tumors
  • kidney cancer
  • testicular tumors
  • molecular markers
  • lymph node metastasis
  • diagnosis
  • radical treatment
  • systemic treatment

Published Papers (24 papers)

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16 pages, 24395 KiB  
Article
DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis
by Tomoki Yamamoto, Min Gi, Satoshi Yamashita, Shugo Suzuki, Masaki Fujioka, Arpamas Vachiraarunwong, Runjie Guo, Guiyu Qiu, Anna Kakehashi, Minoru Kato, Junji Uchida and Hideki Wanibuchi
Cancers 2023, 15(21), 5274; https://doi.org/10.3390/cancers15215274 - 03 Nov 2023
Viewed by 841
Abstract
Arsenic is a known human urinary bladder carcinogen. While arsenic is known to cause aberrant DNA methylation, the mechanism of arsenic-triggered bladder carcinogenesis is not fully understood. The goal of this study was to identify aberrant DNA methylation in rat bladder urothelial carcinoma [...] Read more.
Arsenic is a known human urinary bladder carcinogen. While arsenic is known to cause aberrant DNA methylation, the mechanism of arsenic-triggered bladder carcinogenesis is not fully understood. The goal of this study was to identify aberrant DNA methylation in rat bladder urothelial carcinoma (UC) induced by dimethylarsinic acid (DMAV), a major organic metabolite of arsenic. We performed genome-wide DNA methylation and microarray gene expression analyses of DMAV-induced rat UCs and the urothelium of rats treated for 4 weeks with DMAV. We identified 40 genes that were both hypermethylated and downregulated in DMAV-induced rat UCs. Notably, four genes (CPXM1, OPCML, TBX20, and KCND3) also showed reduced expression in the bladder urothelium after 4 weeks of exposure to DMAV. We also found that CPXM1 is aberrantly methylated and downregulated in human bladder cancers and human bladder cancer cells. Genes with aberrant DNA methylation and downregulated expression in DMAV-exposed bladder urothelium and in DMAV-induced UCs in rats, suggest that these alterations occurred in the early stages of arsenic-induced bladder carcinogenesis. Further study to evaluate the functions of these genes will advance our understanding of the role of aberrant DNA methylation in arsenic bladder carcinogenesis, and will also facilitate the identification of new therapeutic targets for arsenic-related bladder cancers. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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17 pages, 3172 KiB  
Article
Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance
by Paweł Kiełb, Maciej Kaczorowski, Kamil Kowalczyk, Aleksandra Piotrowska, Łukasz Nowak, Wojciech Krajewski, Joanna Chorbińska, Krzysztof Dudek, Piotr Dzięgiel, Agnieszka Hałoń, Tomasz Szydełko and Bartosz Małkiewicz
Cancers 2023, 15(18), 4578; https://doi.org/10.3390/cancers15184578 - 15 Sep 2023
Cited by 1 | Viewed by 625
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with [...] Read more.
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with lymphadenectomy and lymph node metastasis (LN+). We assessed the expression levels of IL-17A and IL-17RA in cancer cells in prostate and, for the first time, also in LN+. Prostate IL-17A expression positively correlated with BMI (p = 0.028). In LN+, the expression of IL-17A was positively correlated with the percentage of affected lymph nodes (p = 0.006) and EAU risk groups (p = 0.001). Additionally, in the group with high IL-17A expression in LN+, the extracapsular extension (ECE) of the prostate was significantly more frequent (p = 0.033). Also, significant correlations with the level of IL-17RA expression was found—expression was higher in prostate than in LN+ (p = 0.009); in LN+, expression positively correlated with the EAU risk group (p = 0.045), and in the group of high expression in LN+ ECE of lymph nodes was detected significantly more often (p = 0.009). Our findings support the potential role of IL-17A and IL-17RA as PCa markers; however, further studies are needed to determine their roles and potential clinical applications. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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7 pages, 909 KiB  
Communication
Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma
by Takashi Kawahara, Akihito Hasizume, Koichi Uemura, Katsuya Yamaguchi, Hiroki Ito, Teppei Takeshima, Hisashi Hasumi, Jun-ichi Teranishi, Kimito Ousaka, Kazuhide Makiyama and Hiroji Uemura
Cancers 2023, 15(17), 4227; https://doi.org/10.3390/cancers15174227 - 23 Aug 2023
Cited by 2 | Viewed by 1595
Abstract
Background: Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. [...] Read more.
Background: Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. However, more data, especially from larger real-world studies, are needed to further assess its effectiveness in Japanese patients. Methods: A total of 6007 urothelial cancer patients inducted with pembrolizumab as a second-line treatment were analyzed. Among them, 563 patients received enfortumab vedotin after pembrolizumab, while 443 patients received docetaxel or paclitaxel after pembrolizumab, and all were included in the study for efficacy as a life prolonging agent. Results: The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). In multivariate analysis, enfortumab vedotin induction was the independent risk factor for overall survival (p = 0.013, HR: 0.70). There were no significant differences in cancer-specific survival. Conclusions: Enfortumab vedotin prolonged the overall survival for Japanese advanced or metastatic urothelial carcinoma patients compared to paclitaxel or docetaxel after pembrolizumab treatment. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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13 pages, 1190 KiB  
Article
Enhancing Triage Efficiency and Accuracy in Emergency Rooms for Patients with Metastatic Prostate Cancer: A Retrospective Analysis of Artificial Intelligence-Assisted Triage Using ChatGPT 4.0
by Georges Gebrael, Kamal Kant Sahu, Beverly Chigarira, Nishita Tripathi, Vinay Mathew Thomas, Nicolas Sayegh, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami and Haoran Li
Cancers 2023, 15(14), 3717; https://doi.org/10.3390/cancers15143717 - 22 Jul 2023
Cited by 12 | Viewed by 2933
Abstract
Background: Accurate and efficient triage is crucial for prioritizing care and managing resources in emergency rooms. This study investigates the effectiveness of ChatGPT, an advanced artificial intelligence system, in assisting health providers with decision-making for patients presenting with metastatic prostate cancer, focusing on [...] Read more.
Background: Accurate and efficient triage is crucial for prioritizing care and managing resources in emergency rooms. This study investigates the effectiveness of ChatGPT, an advanced artificial intelligence system, in assisting health providers with decision-making for patients presenting with metastatic prostate cancer, focusing on the potential to improve both patient outcomes and resource allocation. Methods: Clinical data from patients with metastatic prostate cancer who presented to the emergency room between 1 May 2022 and 30 April 2023 were retrospectively collected. The primary outcome was the sensitivity and specificity of ChatGPT in determining whether a patient required admission or discharge. The secondary outcomes included the agreement between ChatGPT and emergency medicine physicians, the comprehensiveness of diagnoses, the accuracy of treatment plans proposed by both parties, and the length of medical decision making. Results: Of the 147 patients screened, 56 met the inclusion criteria. ChatGPT had a sensitivity of 95.7% in determining admission and a specificity of 18.2% in discharging patients. In 87.5% of cases, ChatGPT made the same primary diagnoses as physicians, with more accurate terminology use (42.9% vs. 21.4%, p = 0.02) and more comprehensive diagnostic lists (median number of diagnoses: 3 vs. 2, p < 0.001). Emergency Severity Index scores calculated by ChatGPT were not associated with admission (p = 0.12), hospital stay length (p = 0.91) or ICU admission (p = 0.54). Despite shorter mean word count (169 ± 66 vs. 272 ± 105, p < 0.001), ChatGPT was more likely to give additional treatment recommendations than physicians (94.3% vs. 73.5%, p < 0.001). Conclusions: Our hypothesis-generating data demonstrated that ChatGPT is associated with a high sensitivity in determining the admission of patients with metastatic prostate cancer in the emergency room. It also provides accurate and comprehensive diagnoses. These findings suggest that ChatGPT has the potential to assist health providers in improving patient triage in emergency settings, and may enhance both efficiency and quality of care provided by the physicians. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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13 pages, 1649 KiB  
Article
Critical Appraisal of Leibovich 2018 and GRANT Models for Prediction of Cancer-Specific Survival in Non-Metastatic Chromophobe Renal Cell Carcinoma
by Mattia Luca Piccinelli, Simone Morra, Stefano Tappero, Cristina Cano Garcia, Francesco Barletta, Reha-Baris Incesu, Lukas Scheipner, Andrea Baudo, Zhe Tian, Stefano Luzzago, Francesco Alessandro Mistretta, Matteo Ferro, Fred Saad, Shahrokh F. Shariat, Luca Carmignani, Sascha Ahyai, Derya Tilki, Alberto Briganti, Felix K. H. Chun, Carlo Terrone, Nicola Longo, Ottavio de Cobelli, Gennaro Musi and Pierre I. Karakiewiczadd Show full author list remove Hide full author list
Cancers 2023, 15(7), 2155; https://doi.org/10.3390/cancers15072155 - 05 Apr 2023
Cited by 2 | Viewed by 1409
Abstract
Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories [...] Read more.
Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories were applied to predict 5- and 10-year cancer-specific survival (CSS). Subsequently, a novel multivariable nomogram was developed. Accuracy, calibration and decision curve analyses (DCA) tested the Cox regression-based nomogram as well as the Leibovich 2018 and GRANT risk categories in the external validation cohort. The accuracy of the Leibovich 2018 and GRANT models was 0.65 and 0.64 at ten years, respectively. The novel prognostic nomogram had an accuracy of 0.78 at ten years. All models exhibited good calibration. In DCA, Leibovich 2018 outperformed the novel nomogram within selected ranges of threshold probabilities at ten years. Conversely, the novel nomogram outperformed Leibovich 2018 for other values of threshold probabilities. In summary, Leibovich 2018 and GRANT risk categories exhibited borderline low accuracy in predicting CSS in North American non-metastatic chRCC patients. Conversely, the novel nomogram exhibited higher accuracy. However, in DCA, all examined models exhibited limitations within specific threshold probability intervals. In consequence, all three examined models provide individual predictions that might be suboptimal and be affected by limitations determined by the natural history of chRCC, where few deaths occur within ten years from surgery. Further investigations regarding established and novel predictors of CSS and relying on large sample sizes with longer follow-up are needed to better stratify CSS in chRCC. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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20 pages, 1714 KiB  
Article
MiR-21 Is Induced by Hypoxia and Down-Regulates RHOB in Prostate Cancer
by Charlotte Zoe Angel, Mei Yu Cynthia Stafford, Christopher J. McNally, Heather Nesbitt and Declan J. McKenna
Cancers 2023, 15(4), 1291; https://doi.org/10.3390/cancers15041291 - 17 Feb 2023
Cited by 4 | Viewed by 1723
Abstract
Tumour hypoxia is a well-established contributor to prostate cancer progression and is also known to alter the expression of several microRNAs. The over-expression of microRNA-21 (miR-21) has been consistently linked with many cancers, but its role in the hypoxic prostate tumour environment has [...] Read more.
Tumour hypoxia is a well-established contributor to prostate cancer progression and is also known to alter the expression of several microRNAs. The over-expression of microRNA-21 (miR-21) has been consistently linked with many cancers, but its role in the hypoxic prostate tumour environment has not been well studied. In this paper, the link between hypoxia and miR-21 in prostate cancer is investigated. A bioinformatic analysis of The Cancer Genome Atlas (TCGA) prostate biopsy datasets shows the up-regulation of miR-21 is significantly associated with prostate cancer and clinical markers of disease progression. This up-regulation of miR-21 expression was shown to be caused by hypoxia in the LNCaP prostate cancer cell line in vitro and in an in vivo prostate tumour xenograft model. A functional enrichment analysis also revealed a significant association of miR-21 and its target genes with processes related to cellular hypoxia. The over-expression of miR-21 increased the migration and colony-forming ability of RWPE-1 normal prostate cells. In vitro and in silico analyses demonstrated that miR-21 down-regulates the tumour suppressor gene Ras Homolog Family Member B (RHOB) in prostate cancer. Further a TCGA analysis illustrated that miR-21 can distinguish between different patient outcomes following therapy. This study presents evidence that hypoxia is a key contributor to the over-expression of miR-21 in prostate tumours, which can subsequently promote prostate cancer progression by suppressing RHOB expression. We propose that miR-21 has good potential as a clinically useful diagnostic and prognostic biomarker of hypoxia and prostate cancer. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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11 pages, 1045 KiB  
Article
Differentiation of Urothelial Carcinoma and Normal Bladder Tissues by Means of Fiber-Based ATR IR Spectroscopy
by Rimantė Bandzevičiūtė, Gediminas Platkevičius, Justinas Čeponkus, Arūnas Želvys, Albertas Čekauskas and Valdas Šablinskas
Cancers 2023, 15(2), 499; https://doi.org/10.3390/cancers15020499 - 13 Jan 2023
Cited by 1 | Viewed by 1347
Abstract
Surgical treatment is widely applied curative approach for bladder cancer. White light cystoscopy (WLC) is currently used for intraoperative diagnostics of malignant lesions but has relatively high false-negative rate. Here we represent an application of label free fiber-based attenuated total reflection infrared spectroscopy [...] Read more.
Surgical treatment is widely applied curative approach for bladder cancer. White light cystoscopy (WLC) is currently used for intraoperative diagnostics of malignant lesions but has relatively high false-negative rate. Here we represent an application of label free fiber-based attenuated total reflection infrared spectroscopy (ATR IR) for freshly resected human bladder tissue examination for 54 patients. Defined molecular spectral markers allow to identify normal and urothelial carcinoma tissues. While methods of statistical analysis (Hierarchical cluster analysis (HCA) and Principal component analysis (PCA)) used for spectral data treatment allow to discriminate tissue types with 91% sensitivity and 96–98% specificity. In the present study the described method was applied for tissue examination under ex vivo conditions. However, after method validation the equipment could be translated from laboratory studies to in situ or even in vivo studies in operating room. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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10 pages, 268 KiB  
Article
Prostate Cancer in Renal Transplant Recipients: Results from a Large Contemporary Cohort
by Giancarlo Marra, Francesco Soria, Federica Peretti, Marco Oderda, Charles Dariane, Marc-Olivier Timsit, Julien Branchereau, Oussama Hedli, Benoit Mesnard, Derya Tilki, Jonathon Olsburgh, Meghana Kulkarni, Veeru Kasivisvanathan, Cedric Lebacle, Oscar Rodriguez-Faba, Alberto Breda, Timo Soeterik, Giorgio Gandaglia, Paola Todeschini, Luigi Biancone, Paolo Gontero and on behalf of the Collaborators add Show full author list remove Hide full author list
Cancers 2023, 15(1), 189; https://doi.org/10.3390/cancers15010189 - 28 Dec 2022
Cited by 1 | Viewed by 1429
Abstract
Objectives: The aim of this study was to assess the natural history of prostate cancer (PCa) in renal transplant recipients (RTRs) and to clarify the controversy over whether RTRs have a higher risk of PCa and poorer outcomes than non-RTRs, due to factors [...] Read more.
Objectives: The aim of this study was to assess the natural history of prostate cancer (PCa) in renal transplant recipients (RTRs) and to clarify the controversy over whether RTRs have a higher risk of PCa and poorer outcomes than non-RTRs, due to factors such as immunosuppression. Patients and Methods: We performed a retrospective multicenter study of RTRs diagnosed with cM0 PCa between 2001 and 2019. Primary outcomes were overall (OS) and cancer-specific survival (CSS). Secondary outcomes included biochemical recurrence and/or progression after active surveillance (AS) and evaluation of variables possibly influencing PCa aggressiveness and outcomes. Management modalities included surgery, radiation, cryotherapy, HIFU, AS, and watchful waiting. Results: We included 166 men from nine institutions. Median age and eGFR at diagnosis were 67 (IQR 60–73) and 45.9 mL/min (IQR 31.5–63.4). ASA score was >2 in 58.4% of cases. Median time from transplant to PCa diagnosis was 117 months (IQR 48–191.5), and median PSA at diagnosis was 6.5 ng/mL (IQR 5.02–10). The biopsy Gleason score was ≥8 in 12.8%; 11.6% and 6.1% patients had suspicion of ≥cT3 > cT2 and cN+ disease. The most frequent management method was radical prostatectomy (65.6%), followed by radiation therapy (16.9%) and AS (10.2%). At a median follow-up of 60.5 months (IQR 31–106) 22.9% of men (n = 38) died, with only n = 4 (2.4%) deaths due to PCa. Local and systemic progression rates were 4.2% and 3.0%. On univariable analysis, no major influence of immunosuppression type was noted, with the exception of a protective effect of antiproliferative agents (HR 0.39, 95% CI 0.16–0.97, p = 0.04) associated with a decreased risk of biochemical recurrence (BCR) or progression after AS. Conclusion: PCa diagnosed in RTRs is mainly of low to intermediate risk and organ-confined at diagnosis, with good cancer control and low PCa death at intermediate follow-up. RTRs have a non-negligible risk of death from causes other than PCa. Aggressive upfront management of the majority of RTRs with PCa may, therefore, be avoided. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
10 pages, 601 KiB  
Article
Sex Remains Negative Prognostic Factor in Contemporary Cohort of High-Risk Non-Muscle-Invasive Bladder Cancer
by Konrad Bilski, Mieszko Kozikowski, Michał A. Skrzypczyk, Aleksandra Dobruch, Kees Hendricksen, David D’Andrea, Anna Katarzyna Czech and Jakub Dobruch
Cancers 2022, 14(24), 6110; https://doi.org/10.3390/cancers14246110 - 12 Dec 2022
Cited by 2 | Viewed by 1449
Abstract
Sex-specific differences in outcomes of patients diagnosed with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have been reported with controversial findings. This study aims to investigate sex-specific diversities in the treatment and oncologic outcomes of primary HR-NMIBC in a multicenter setting. A multicenter retrospective analysis [...] Read more.
Sex-specific differences in outcomes of patients diagnosed with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have been reported with controversial findings. This study aims to investigate sex-specific diversities in the treatment and oncologic outcomes of primary HR-NMIBC in a multicenter setting. A multicenter retrospective analysis of 519 patients (388 men and 131 women) treated with transurethral resection (TUR) for primary HR-NMIBC was performed. Univariable and multivariable Cox regression models were used to investigate the association of clinico-pathologic features and generate hazard ratios (HRs). Second-look TUR (reTUR) was performed in 406 (78%) patients. A total of 218 (42%) of patients were subjected to an induction course of intravesical BCG (Bacillus Calmette–Guérin) plus maintenance therapy. The median follow-up was 44 months. Among the entire cohort, 238 (46%) and 86 patients (17%) had recurred and progressed to muscle-invasive disease (MIBC), respectively. Female sex was associated with increased risk of disease recurrence in the entire cohort: HR = 1.94, 95% CI = 1.48–2.55, p < 0.001 and HR = 1.91, 95% CI = 1.39–2.60, p < 0.001 in univariate and multivariate analysis, respectively. In patients subjected to reTUR and treated additionally with BCG, female sex was associated with increased risk of disease recurrence in univariate analysis (HR 1.81, 95% CI 1.07–3.06, p = 0.03), but not in multivariate analysis (HR 1.99, 95% CI 0.98–4.02, p = 0.06). There was no difference between sexes with regard to disease progression. HR-NMIBC diagnosed in females is associated with higher risk of disease recurrence when compared to males. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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8 pages, 616 KiB  
Article
Differences in Cancer-Specific Mortality after Trimodal Therapy for T2N0M0 Bladder Cancer according to Histological Subtype
by Francesco Barletta, Stefano Tappero, Andrea Panunzio, Reha-Baris Incesu, Cristina Cano Garcia, Mattia Luca Piccinelli, Zhe Tian, Giorgio Gandaglia, Marco Moschini, Carlo Terrone, Alessandro Antonelli, Derya Tilki, Felix K. H. Chun, Ottavio de Cobelli, Fred Saad, Shahrokh F. Shariat, Francesco Montorsi, Alberto Briganti and Pierre I. Karakiewicz
Cancers 2022, 14(23), 5766; https://doi.org/10.3390/cancers14235766 - 23 Nov 2022
Cited by 4 | Viewed by 1564
Abstract
We aimed at assessing the impact of non-urothelial variant histology (VH), relative to urothelial carcinoma of the urinary bladder (UCUB), on cancer-specific mortality (CSM) in T2N0M0 bladder cancer patients treated with trimodal therapy (TMT). TMT patients treated for T2N0M0 bladder cancer were identified [...] Read more.
We aimed at assessing the impact of non-urothelial variant histology (VH), relative to urothelial carcinoma of the urinary bladder (UCUB), on cancer-specific mortality (CSM) in T2N0M0 bladder cancer patients treated with trimodal therapy (TMT). TMT patients treated for T2N0M0 bladder cancer were identified within the Surveillance, Epidemiology, and End Results database (2000−2018). Patients who underwent TMT received trans-urethral resection of the bladder tumor, chemotherapy, and radiotherapy. CSM-FS rates were tested using Kaplan–Meier plots and multivariable Cox-regression (MCR) models according to histological subtype: UCUB vs. neuroendocrine carcinoma vs. squamous cell carcinoma vs. adenocarcinoma. A total of 3846 T2N0MO bladder cancer patients treated with TMT were identified. Of these, 3627 (94.3%) harbored UCUB, while 105 (2.7%), 85 (2.2%), and 29 (0.8%) harbored neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma, respectively. In Kaplan–Meier analyses, 3-yr CSM-FS rates were 57% for UCUB, 51% for neuroendocrine carcinoma, 35% for squamous cell carcinoma, and 60% for adenocarcinoma (p-value < 0.0001). In MCR models, only squamous cell carcinoma exhibited higher CSM than UCUB (HR 1.98, 95%CI 1.5–2.61, p-value < 0.001). Despite the small number of observations, squamous cell carcinoma distinguished itself from UCUB based on worse survival in T2N0M0 patients after TMT. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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15 pages, 2141 KiB  
Article
Radiotherapy-Related Gene Signature in Prostate Cancer
by Paraskevi Kogionou, Sotirios P. Fortis, Maria Goulielmaki, Nicolas Aubert, Panagiota Batsaki, Sotirios Ouzounis, Dionisis Cavouras, Gilles Marodon, Savvas Stokidis, Angelos D. Gritzapis and Constantin N. Baxevanis
Cancers 2022, 14(20), 5032; https://doi.org/10.3390/cancers14205032 - 14 Oct 2022
Cited by 3 | Viewed by 1718 | Correction
Abstract
Radiotherapy for localized prostate cancer has increased the cure and survival rates of patients. Besides its local tumoricidal effects, ionizing radiation has been linked to mechanisms leading to systemic immune activation, a phenomenon called the abscopal effect. In this study, we performed gene [...] Read more.
Radiotherapy for localized prostate cancer has increased the cure and survival rates of patients. Besides its local tumoricidal effects, ionizing radiation has been linked to mechanisms leading to systemic immune activation, a phenomenon called the abscopal effect. In this study, we performed gene expression analysis on peripheral blood from prostate cancer patients obtained post- radiotherapy and showed that 6 genes, including CCR7, FCGR2B, BTLA, CD6, CD3D, and CD3E, were down-regulated by a range of 1.5–2.5-fold as compared to pre-radiotherapy samples. The expression of the signature consisting of these six genes was also significantly lower post- vs. pre-radiotherapy. These genes are involved in various tumor-promoting immune pathways and their down-regulation post-radiotherapy could be considered beneficial for patients. This is supported by the fact that low mRNA expression levels for the 6-gene signature in the prostate tumor tissue was linked to better survival. Importantly, we report that this 6-gene signature strongly correlated with a favorable prognosis regardless of poor standard clinicopathological parameters (i.e., Gleason score ≥ 8 and T3 (including T3a and T3b). Our pioneering data open the possibility that the 6-gene signature identified herein may have a predictive value, but this requires further long-term studies. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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13 pages, 1679 KiB  
Article
Diagnostic Value of Radio-Guided Sentinel Node Detection in Patients with Prostate Cancer Undergoing Radical Prostatectomy with Modified-Extended Lymphadenectomy
by Bartosz Małkiewicz, Błażej Bugla, Maciej Czarnecki, Jakub Karwacki, Paulina Długosz, Adam Gurwin, Paweł Kiełb, Artur Lemiński, Wojciech Krajewski, Diana Jędrzejuk, Marek Bolanowski, Agnieszka Hałoń and Tomasz Szydełko
Cancers 2022, 14(20), 5012; https://doi.org/10.3390/cancers14205012 - 13 Oct 2022
Cited by 3 | Viewed by 1742
Abstract
Background. In many malignancies, sentinel lymph node dissection (SLND) is being used as a nodal staging tool. We prospectively evaluated the diagnostic value of radio-guided sentinel lymph node (SLN) detection in patients with prostate cancer (PCa). This study aimed to investigate the reliability [...] Read more.
Background. In many malignancies, sentinel lymph node dissection (SLND) is being used as a nodal staging tool. We prospectively evaluated the diagnostic value of radio-guided sentinel lymph node (SLN) detection in patients with prostate cancer (PCa). This study aimed to investigate the reliability of the radio-guided SLN detection technique for perioperative localization of LNs metastases as well as to map lymphatic drainage patterns of the prostate. Methods. Forty-three patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging underwent radical prostatectomy with modified-extended pelvic lymph node dissection (mePLND). A day before the planned surgery, a Tc-99m nanocolloid was injected into the prostate under the control of transrectal ultrasonography (TRUS). Preoperative single-photon emission computed tomography (SPECT-CT) imaging and intraoperative gamma-probe were used to identify SLNs. All positive lesions were excised, followed by mePLND. The excised lymph nodes (LNs) were then submitted for histopathological examination, which was used as a reference for the calculation of diagnostic parameters of the SLN technique for SPECT-CT and the intraoperative gamma-probe. Results. In total, 119 SLNs were detected preoperatively (SPECT-CT) and 118 intraoperatively (gamma-probe). The study revealed that both SLN detection techniques showed a sensitivity of 90% and a specificity of 6.06%. The negative predictive value (NPV) was 66.67%. SLN technique would have correctly staged nine of 10 patients, which is the same result as in the case of limited LND. However, it allowed the removal of all metastatic nodes only in four of them. SLND would have comprised 69.7% of preoperatively detected LNs, and removed 13 out of 19 positive LNs (68.42%), respectively. Conclusions. Radio-guided SLND has a low diagnostic rate and is a poor staging tool. ePLND remains the gold standard in nodal metastases assessment in PCa. Our study indicates that lymphatic drainage of the prostate and actual metastasis routes may vary significantly. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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11 pages, 1497 KiB  
Article
Optimized Adaptive Radiotherapy with Individualized Plan Library for Muscle-Invasive Bladder Cancer Using Internal Target Volume Generation
by Yoon Young Jo, Ji Woon Yea, Jaehyeon Park, Se An Oh and Jae Won Park
Cancers 2022, 14(19), 4674; https://doi.org/10.3390/cancers14194674 - 26 Sep 2022
Cited by 3 | Viewed by 1324
Abstract
The bladder is subject to filling variation, which poses a challenge to radiotherapy (RT) delivery. We aimed to assess feasibility and clinical outcomes in patients with bladder cancer treated with adaptive RT (ART) using individualized plan libraries. We retrospectively analyzed 19 patients who [...] Read more.
The bladder is subject to filling variation, which poses a challenge to radiotherapy (RT) delivery. We aimed to assess feasibility and clinical outcomes in patients with bladder cancer treated with adaptive RT (ART) using individualized plan libraries. We retrospectively analyzed 19 patients who underwent RT for muscle-invasive bladder cancer (MIBC) in 2015–2021. Four planning computed tomography (CT) scans were acquired at 15-min intervals, and a library of three intensity-modulated RT plans were generated using internal target volumes (ITVs). A post-treatment cone-beam CT (CBCT) scan was acquired daily to assess intra-fraction filling and coverage. All patients completed the treatment, with 408 post-treatment CBCT scans. The bladder was out of the planning target volume (PTV) range in 12 scans. The volumes of the evaluated PTV plans were significantly smaller than those of conventional PTV. The 1-year and 2-year overall survival rates were 88.2% and 63.7%, respectively. Of eight cases that experienced recurrence, only two developed MIBC. There were no grade 3 or higher RT-related adverse events. ART using plan libraries and ITVs demonstrated good survival outcomes with a high local control rate. Irradiated normal tissue volume and treatment margins may be reduced through this approach, potentially resulting in lower toxicity rates. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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11 pages, 964 KiB  
Article
Online Crowdfunding for Urologic Cancer Care
by Pawel Rajwa, Philip Hopen, Jakub Wojnarowicz, Julia Kaletka, Iga Paszkiewicz, Olga Lach-Wojnarowicz, Hadi Mostafaei, Wojciech Krajewski, David D’Andrea, Bartosz Małkiewicz, Andrzej Paradysz, Guillaume Ploussard, Marco Moschini, Benjamin N. Breyer, Benjamin Pradere, Shahrokh F. Shariat and Michael S. Leapman
Cancers 2022, 14(17), 4104; https://doi.org/10.3390/cancers14174104 - 25 Aug 2022
Cited by 1 | Viewed by 1553
Abstract
Background: we aimed to characterize the financial needs expressed through online crowdfunding for urologic cancers. Methods: the data used in this study came from the online crowdfunding platform GoFundMe.com. Using an automated software method, we extracted data for campaigns related to urologic cancers. [...] Read more.
Background: we aimed to characterize the financial needs expressed through online crowdfunding for urologic cancers. Methods: the data used in this study came from the online crowdfunding platform GoFundMe.com. Using an automated software method, we extracted data for campaigns related to urologic cancers. Subsequently, four independent investigators reviewed all extracted data on prostate, bladder, kidney and testicular cancer. We analyzed campaigns’ basic characteristics, goals, fundraising, type of treatment and factors associated with successful campaigns. Results: in total, we identified 2126 individual campaigns, which were related to direct treatment costs (34%), living expenses (17%) or both (48%). Median fundraising amounts were greatest for testicular cancer. Campaigns for both complementary and alternative medicine (CAM) (median $11,000) or CAM alone (median $8527) achieved higher fundraising totals compared with those for conventional treatments alone (median $5362) (p < 0.01). The number of social media shares was independently associated with campaign success and highest quartile of fundraising. Conclusions: using an automated web-based approach, we identified and characterized online crowdfunding for urologic cancer care. These findings indicated a diverse range of patient needs related to urologic care and factors related to campaigns’ success. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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14 pages, 2799 KiB  
Article
Molecular Profiles of Advanced Urological Cancers in the PERMED-01 Precision Medicine Clinical Trial
by Emilien Billon, Gwenaelle Gravis, Arnaud Guille, Nadine Carbuccia, Jose Adelaide, Séverine Garnier, Pascal Finetti, Emilie Denicolaï, Patrick Sfumato, Serge Brunelle, Jeanne Thomassin-Piana, Géraldine Pignot, Jochen Walz, Christian Chabannon, Jihane Pakradouni, Renaud Sabatier, Cécile Vicier, Cornel Popovici, Emilie Mamessier, Anthony Gonçalves, Daniel Birnbaum, Max Chaffanet and François Bertucciadd Show full author list remove Hide full author list
Cancers 2022, 14(9), 2275; https://doi.org/10.3390/cancers14092275 - 03 May 2022
Viewed by 2414
Abstract
Introduction. The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine. Methods: the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients [...] Read more.
Introduction. The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine. Methods: the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients with tumor actionable genetic alterations (AGA), feasibility, description of molecular alterations, treatment, and clinical outcome. We present here those results in the 64 patients enrolled with AUC. DNA extracted from a new tumor biopsy was profiled in real-time (targeted NGS, whole-genome array-comparative genomic hybridization), and the results were discussed during a weekly molecular tumor board meeting. Results: a complete molecular profile was obtained in 49 patients (77%). Thirty-eight (59%) had at least one AGA. Twelve (19%) received a matched therapy on progression, of which 42% had a PFS2/PFS1 ratio ≥ 1.3 versus 5% in the “non-matched therapy group” (n = 25). The objective response and disease control rates were higher in the “matched therapy group” (33% and 58%, respectively) than in the “non-matched therapy group” (13% and 22%), as was the 6-month OS (75% vs. 42%). Conclusion: the profiling of a newly biopsied tumor sample identified AGA in 59% of patients with AUC, led to “matched therapy” in 19%, and provided clinical benefit in 8%. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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15 pages, 2160 KiB  
Article
Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer
by Anita Thomas, Kimberly Sue Slade, Roman A. Blaheta, Sascha D. Markowitsch, Philipp Stenzel, Katrin E. Tagscherer, Wilfried Roth, Mario Schindeldecker, Martin Michaelis, Florian Rothweiler, Jaroslav Cinatl, Robert Dotzauer, Olesya Vakhrusheva, Maarten Albersen, Axel Haferkamp, Eva Juengel, Jindrich Cinatl, Jr. and Igor Tsaur
Cancers 2022, 14(7), 1683; https://doi.org/10.3390/cancers14071683 - 25 Mar 2022
Cited by 2 | Viewed by 2157
Abstract
Whereas the lack of biomarkers in penile cancer (PeCa) impedes the development of efficacious treatment protocols, preliminary evidence suggests that c-MET and associated signaling elements may be dysregulated in this disorder. In the following study, we investigated whether c-MET and associated key molecular [...] Read more.
Whereas the lack of biomarkers in penile cancer (PeCa) impedes the development of efficacious treatment protocols, preliminary evidence suggests that c-MET and associated signaling elements may be dysregulated in this disorder. In the following study, we investigated whether c-MET and associated key molecular elements may have prognostic and therapeutic utility in PeCa. Formalin-fixed, paraffin-embedded tumor tissue from therapy-naïve patients with invasive PeCa was used for tissue microarray (TMA) analysis. Immunohistochemical staining was performed to determine the expression of the proteins c-MET, PPARg, β-catenin, snail, survivin, and n-MYC. In total, 94 PeCa patients with available tumor tissue were included. The median age was 64.9 years. High-grade tumors were present in 23.4%, and high-risk HPV was detected in 25.5%. The median follow-up was 32.5 months. High expression of snail was associated with HPV-positive tumors. Expression of β-catenin was inversely associated with grading. In both univariate COX regression analysis and the log-rank test, an increased expression of PPARg and c-MET was predictive of inferior disease-specific survival (DSS). Moreover, in multivariate analysis, a higher expression of c-MET was independently associated with worse DSS. Blocking c-MET with cabozantinib and tivantinib induced a significant decrease in viability in the primary PeCa cell line UKF-PeC3 isolated from the tumor tissue as well as in cisplatin- and osimertinib-resistant sublines. Strikingly, a higher sensitivity to tivantinib could be detected in the latter, pointing to the promising option of utilizing this agent in the second-line treatment setting. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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10 pages, 954 KiB  
Article
The Prognostic Value of PI-RADS Score in CyberKnife Ultra-Hypofractionated Radiotherapy for Localized Prostate Cancer
by Marcin Miszczyk, Justyna Rembak-Szynkiewicz, Łukasz Magrowski, Konrad Stawiski, Agnieszka Namysł-Kaletka, Aleksandra Napieralska, Małgorzata Kraszkiewicz, Grzegorz Woźniak, Małgorzata Stąpór-Fudzińska, Grzegorz Głowacki, Benjamin Pradere, Ekaterina Laukhtina, Paweł Rajwa and Wojciech Majewski
Cancers 2022, 14(7), 1613; https://doi.org/10.3390/cancers14071613 - 23 Mar 2022
Cited by 4 | Viewed by 2391
Abstract
Prostate Imaging-Reporting and Data System (PI-RADS) has been widely implemented as a diagnostic tool for significant prostate cancer (PCa); less is known about its prognostic value, especially in the setting of primary radiotherapy. We aimed to analyze the association between PI-RADS v. 2.1 [...] Read more.
Prostate Imaging-Reporting and Data System (PI-RADS) has been widely implemented as a diagnostic tool for significant prostate cancer (PCa); less is known about its prognostic value, especially in the setting of primary radiotherapy. We aimed to analyze the association between PI-RADS v. 2.1 classification and risk of metastases, based on a group of 152 patients treated with ultra-hypofractionated stereotactic CyberKnife radiotherapy for localized low or intermediate risk-group prostate cancer. We found that all distant failures (n = 5) occurred in patients diagnosed with a PI-RADS score of 5, and axial measurements of the target lesion were associated with the risk of developing metastases (p < 0.001). The best risk stratification model (based on a combination of greatest dimension, the product of multiplication of PI-RADS target lesion axial measurements, and age) achieved a c-index of 0.903 (bootstrap-validated bias-corrected 95% CI: 0.848–0.901). This creates a hypothesis that PI-RADS 5 and the size of the target lesion are important prognostic factors in early-stage PCa patients and should be considered as an adverse prognostic measure for patients undergoing early treatment such as radiation or focal therapy. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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Review

Jump to: Research, Other

21 pages, 4028 KiB  
Review
Innovation in Radionuclide Therapy for the Treatment of Prostate Cancers: Radiochemical Perspective and Recent Therapeutic Practices
by Emmanuel Deshayes, Cyril Fersing, Constance Thibault, Mathieu Roumiguie, Philippe Pourquier and Nadine Houédé
Cancers 2023, 15(12), 3133; https://doi.org/10.3390/cancers15123133 - 10 Jun 2023
Cited by 3 | Viewed by 2219
Abstract
Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists [...] Read more.
Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists or taxane-based chemotherapies are added in the case of tumor relapse. Nevertheless, patients become invariably resistant to castration with a median survival that rarely exceeds 3 years. This fostered the search for alternative strategies, independent of the androgen receptor signaling pathway. In this line, radionuclide therapies may represent an interesting option as they could target either the microenvironment of sclerotic bone metastases with the use of radiopharmaceuticals containing samarium-153, strontium-89 or radium-223 or tumor cells expressing the prostate-specific membrane antigen (PSMA), a protein found at the surface of prostate cancer cells. This review gives highlights the chemical properties of radioligands targeting prostate cancer cells and recapitulates the clinical trials evaluating the efficacy of radionuclide therapies, alone or in combination with other approved treatments, in patients with castration-resistant prostate tumors. It discusses some of the encouraging results obtained, especially the benefit on overall survival that was reported with [177Lu]-PSMA-617. It also addresses the specific requirements for the use of this particular class of drugs, both in terms of medical staff coordination and adapted infrastructures for efficient radioprotection. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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26 pages, 1600 KiB  
Review
Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+)
by Bartosz Małkiewicz, Adam Gurwin, Jakub Karwacki, Krystian Nagi, Klaudia Knecht-Gurwin, Krzysztof Hober, Magdalena Łyko, Kamil Kowalczyk, Wojciech Krajewski, Anna Kołodziej and Tomasz Szydełko
Cancers 2022, 14(21), 5286; https://doi.org/10.3390/cancers14215286 - 27 Oct 2022
Viewed by 2703
Abstract
The purpose of this review is to present the current knowledge about the diagnostic and treatment options for bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). This review shows compaction of CT and MRI performance in preoperative prediction of lymph node [...] Read more.
The purpose of this review is to present the current knowledge about the diagnostic and treatment options for bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). This review shows compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines; recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. The curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach, with a combination of neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND). The role of adjuvant chemotherapy (AC) remains uncertain; however, emerging evidence indicates comparable outcomes to NAC. Therefore, in cN+ patients who have not received NAC, AC should be implemented. The response to ChT is a crucial prognostic factor for cN+ patients. Recent studies demonstrated the growing importance of immunotherapy, especially in ChT-ineligible patients. Moreover, immunotherapy can be suitable as adjuvant therapy in selected cases. In cN+ patients, the extended template of PLND should be utilized, with the total resected node count being less important than the template. This review is intended to draw special attention to cN+ BCa patients, as the oncological outcomes are significantly worse for this group. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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13 pages, 3734 KiB  
Review
STEAP1–4 (Six-Transmembrane Epithelial Antigen of the Prostate 1–4) and Their Clinical Implications for Prostate Cancer
by Michael Xu, Latese Evans, Candice L. Bizzaro, Fabio Quaglia, Cecilia E. Verrillo, Li Li, Julia Stieglmaier, Matthew J. Schiewer, Lucia R. Languino and William K. Kelly
Cancers 2022, 14(16), 4034; https://doi.org/10.3390/cancers14164034 - 20 Aug 2022
Cited by 18 | Viewed by 4071
Abstract
Six-Transmembrane Epithelial Antigen of the Prostate 1–4 (STEAP1–4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are [...] Read more.
Six-Transmembrane Epithelial Antigen of the Prostate 1–4 (STEAP1–4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1–4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1–4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1–4 to provide context for past and current efforts to translate STEAP1–4 into the clinic. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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16 pages, 785 KiB  
Review
Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review
by Yash B. Shah, Amy L. Shaver, Jacob Beiriger, Sagar Mehta, Nikita Nikita, William Kevin Kelly, Stephen J. Freedland and Grace Lu-Yao
Cancers 2022, 14(15), 3773; https://doi.org/10.3390/cancers14153773 - 03 Aug 2022
Cited by 3 | Viewed by 3383
Abstract
Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and [...] Read more.
Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and facilitate informed treatment decision making. A registered protocol utilizing PRISMA scoping review methodology was utilized to identify real-world studies. Of 433 non-duplicated publications, 23 were selected by three independent reviewers. ENZ offered a faster and more frequent biochemical response (30–50% vs. 70–75%), slowed progression (HR 0.66; 95% CI 0.50–0.88), and improved overall survival versus AA. ENZ was associated with more fatigue and neurological adverse effects. Conversely, AA increased risk of cardiovascular- (HR 1.82; 95% CI 1.09–3.05) and heart failure-related (HR 2.88; 95% CI 1.09–7.63) hospitalizations. Ultimately, AA was associated with increased length of hospital stay, emergency department visits, and hospitalizations (HR 1.26; 95% CI 1.04–1.53). Accordingly, total costs were higher for AA, although pharmacy costs alone were higher for ENZ. Existing data suggest that AA and ENZ have important differences in outcomes including toxicities, response, disease progression, and survival. Additionally, adherence, healthcare utilization, and costs differ. Further investigation is warranted to inform treatment decisions which optimize patient outcomes. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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24 pages, 2684 KiB  
Review
Alternatives for MRI in Prostate Cancer Diagnostics—Review of Current Ultrasound-Based Techniques
by Adam Gurwin, Kamil Kowalczyk, Klaudia Knecht-Gurwin, Paweł Stelmach, Łukasz Nowak, Wojciech Krajewski, Tomasz Szydełko and Bartosz Małkiewicz
Cancers 2022, 14(8), 1859; https://doi.org/10.3390/cancers14081859 - 07 Apr 2022
Cited by 7 | Viewed by 3050
Abstract
The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) started to be [...] Read more.
The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) started to be recommended for every patient suspected of PCa before performing a biopsy. It enabled targeted sampling of the suspicious prostate regions, improving the accuracy of the traditional systematic biopsy. However, mpMRI is associated with high costs, relatively low availability, long and separate procedure, or exposure to the contrast agent. The novel ultrasound modalities, such as shear wave elastography (SWE), contrast-enhanced ultrasound (CEUS), or high frequency micro-ultrasound (MicroUS), may be capable of maintaining the performance of mpMRI without its limitations. Moreover, the real-time lesion visualization during biopsy would significantly simplify the diagnostic process. Another value of these new techniques is the ability to enhance the performance of mpMRI by creating the image fusion of multiple modalities. Such models might be further analyzed by artificial intelligence to mark the regions of interest for investigators and help to decide about the biopsy indications. The dynamic development and promising results of new ultrasound-based techniques should encourage researchers to thoroughly study their utilization in prostate imaging. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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Other

Jump to: Research, Review

1 pages, 180 KiB  
Correction
Correction: Kogionou et al. Radiotherapy-Related Gene Signature in Prostate Cancer. Cancers 2022, 14, 5032
by Paraskevi Kogionou, Sotirios P. Fortis, Maria Goulielmaki, Nicolas Aubert, Panagiota Batsaki, Sotirios Ouzounis, Dionisis Cavouras, Gilles Marodon, Savvas Stokidis, Angelos D. Gritzapis and Constantin N. Baxevanis
Cancers 2023, 15(14), 3616; https://doi.org/10.3390/cancers15143616 - 14 Jul 2023
Cited by 1 | Viewed by 643
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
14 pages, 406 KiB  
Systematic Review
Non-Invasive Biomarkers in the Diagnosis of Upper Urinary Tract Urothelial Carcinoma—A Systematic Review
by Łukasz Białek, Konrad Bilski, Jakub Dobruch, Wojciech Krajewski, Tomasz Szydełko, Piotr Kryst and Sławomir Poletajew
Cancers 2022, 14(6), 1520; https://doi.org/10.3390/cancers14061520 - 16 Mar 2022
Cited by 11 | Viewed by 2222
Abstract
Beyond laboratory, imaging and endoscopic procedures, new diagnostic tools are increasingly being sought for the diagnosis of upper urinary tract urothelial carcinoma (UTUC), especially those that are non-invasive. In this systematic review, we aimed to determine the effectiveness of non-invasive tests in the [...] Read more.
Beyond laboratory, imaging and endoscopic procedures, new diagnostic tools are increasingly being sought for the diagnosis of upper urinary tract urothelial carcinoma (UTUC), especially those that are non-invasive. In this systematic review, we aimed to determine the effectiveness of non-invasive tests in the diagnosis of UTUC. PubMed and Embase electronic databases were searched to identify studies assessing effectiveness of non-invasive tests in the primary diagnosis of UTUC. The study protocol was registered with PROSPERO (CRD42020216480). Among 10,084 screened publications, 25 were eligible and included in the analysis. Most of them were conducted on small samples of patients and the control groups were heterogenous. The test used in the largest number of studies was voided urinary cytology, which has poor sensitivity (11–71.1%) with favorable specificity (54–100%). Fluorescence in situ hybridization in diagnostic cytology showed higher sensitivity (35–85.7%) with equally good specificity (80–100%). There were also studies on the use of tests known to diagnose bladder cancer such as NMP22, uCYT or BTA test. Other urine or blood tests have been the subject of only isolated studies, with varying results. To conclude, currently there is a lack of high-quality data that could confirm good effectiveness of non-invasive tests used in the diagnosis of UTUC. Full article
(This article belongs to the Special Issue Advances and Challenges in the Diagnosis and Treatment of Urological Malignancies)
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