Urological Cancer

A topical collection in Cancers (ISSN 2072-6694). This collection belongs to the section "Cancer Therapy".

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Editors

Topical Collection Information

Dear Colleagues,

Cancer of the urological sphere is a disease continuously growing in numbers in the statistics of tumor malignancies in Western countries. Although this fact is mainly due to the contemporary increase in the life expectancy of the people in these geographic areas, many other factors do also contribute to this growth. Urological cancer is a complex and varied disease of different organs and mainly affects the male population. In fact, kidney, prostate, and bladder cancer are regularly included in the top-ten list of the most frequent neoplasms in males in most statistics. The female population, however, has also increasingly found itself affected by renal and bladder cancer in the last decade. Considering these facts altogether, urological cancer is a problem of major concern in developed societies. This Topical Collection of Cancers intends to shed some light on the complexity of this field, and will consider all useful and appropriate contributions that scientists and clinicians may provide in order to improve urological cancer knowledge for patients’ benefit. The following paragraphs display only a partial view of this complexity.

Renal cancer is probably the best example of inter- and intra-tumor heterogeneity in oncology, and remains a hot topic for clinicians and researchers worldwide. A precise histological and molecular characterization of the papillary group of renal cancer and a better profiling of immunotherapy in clear cell renal cell carcinomas are two of the most challenging areas today.

Prostate cancer is also a polyhedral disease. The correct definition of the so-called clinically insignificant disease; the dilemma of choosing not only between active clinical surveillance versus the focal therapy, but also between radical surgery versus radical radiotherapy; the management of the oligometastatic patient; and the richness of the genomic and epigenomic events underlying this disease will attract the attention of many urologists, pathologists, and basic researchers.

Cancer of the urinary tract also needs a more precise definition, as well as the investigation of several key points. The precise identification of the molecular routes involved; the diagnostic pathological criteria in the grey zones; the dilemma of T1G3 management; and the possible treatment options between superficial, nonmuscle-invasive, and muscle-invasive diseases will be particularly welcomed in this Collection.

Germ cell tumors of the testes still remain a puzzling problem in terms of conceptual tumorigenesis, with several grey zones having an impact in clinics. Basic researchers will find the perfect ground to venture deep into the borderland between anaplastic seminoma and embryonal carcinoma, as well as other poorly understood issues.

Dr. José I. López
Dr. Claudia Manini
Collection Editors

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Published Papers (8 papers)

2024

Jump to: 2023

12 pages, 278 KiB  
Review
Novel Approaches with HIF-2α Targeted Therapies in Metastatic Renal Cell Carcinoma
by Charles B. Nguyen, Eugene Oh, Piroz Bahar, Ulka N. Vaishampayan, Tobias Else and Ajjai S. Alva
Cancers 2024, 16(3), 601; https://doi.org/10.3390/cancers16030601 - 31 Jan 2024
Cited by 2 | Viewed by 987
Abstract
Germline inactivation of the Von Hippel-Lindau (VHL) tumor suppressor is the defining hallmark in hereditary VHL disease and VHL-associated renal cell carcinoma (RCC). However, somatic VHL mutations are also observed in patients with sporadic RCC. Loss of function VHL mutations result [...] Read more.
Germline inactivation of the Von Hippel-Lindau (VHL) tumor suppressor is the defining hallmark in hereditary VHL disease and VHL-associated renal cell carcinoma (RCC). However, somatic VHL mutations are also observed in patients with sporadic RCC. Loss of function VHL mutations result in constitutive activation of hypoxia-inducible factor-2 alpha (HIF-2α), which leads to increased expression of HIF target genes that promote angiogenesis and tumor growth. As of 2023, belzutifan is currently the only approved HIF-2α inhibitor for both VHL-associated and sporadic metastatic RCC (mRCC). However, there is potential for resistance with HIF-2α inhibitors which warrants novel HIF-2α-targeting strategies. In this review, we discuss the potential resistance mechanisms with belzutifan and current clinical trials evaluating novel combinations of belzutifan with other targeted therapies and immune checkpoint inhibitors which may enhance the efficacy of HIF-2α targeting. Lastly, we also discuss newer generation HIF-2α inhibitors that are currently under early investigation and outline future directions and challenges with HIF-2α inhibitors for mRCC. Full article

2023

Jump to: 2024

10 pages, 629 KiB  
Article
Early Evolution in Cancer: A Mathematical Support for Pathological and Genomic Evidence in Clear Cell Renal Cell Carcinoma
by Annick Laruelle, Claudia Manini, José I. López and André Rocha
Cancers 2023, 15(24), 5897; https://doi.org/10.3390/cancers15245897 - 18 Dec 2023
Viewed by 663
Abstract
Clear cell renal cell carcinoma (CCRCC) is an aggressive form of cancer and a paradigmatic example of intratumor heterogeneity (ITH). The hawk-dove game is a mathematical tool designed to analyze competition in biological systems. Using this game, the study reported here analyzes the [...] Read more.
Clear cell renal cell carcinoma (CCRCC) is an aggressive form of cancer and a paradigmatic example of intratumor heterogeneity (ITH). The hawk-dove game is a mathematical tool designed to analyze competition in biological systems. Using this game, the study reported here analyzes the early phase of CCRCC development, comparing clonal fitness in homogeneous (linear evolutionary) and highly heterogeneous (branching evolutionary) models. Fitness in the analysis is a measure of tumor aggressiveness. The results show that the fittest clone in a heterogeneous environment is fitter than the clone in a homogeneous context in the early phases of tumor evolution. Early and late periods of tumor evolution in CCRCC are also compared. The study shows the convergence of mathematical, histological, and genomics studies with respect to clonal aggressiveness in different periods of the natural history of CCRCC. Such convergence highlights the importance of multidisciplinary approaches for obtaining a better understanding of the intricacies of cancer. Full article
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13 pages, 703 KiB  
Article
Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab
by Yasunori Akashi, Yutaka Yamamoto, Mamoru Hashimoto, Shogo Adomi, Kazutoshi Fujita, Keisuke Kiba, Takafumi Minami, Kazuhiro Yoshimura, Akihide Hirayama and Hirotsugu Uemura
Cancers 2023, 15(24), 5780; https://doi.org/10.3390/cancers15245780 - 09 Dec 2023
Viewed by 835
Abstract
Introduction: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for [...] Read more.
Introduction: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. Methods: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). Results: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. Conclusions: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response. Full article
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9 pages, 1895 KiB  
Article
Increasing Patient Safety and Treatment Quality by Using Intraoperative MRI for Organ-Preserving Tumor Resection and High-Dose Rate Brachytherapy in Children with Bladder/Prostate and Perianal Rhabdomyosarcoma
by Andreas Schmidt, Constantin Roder, Franziska Eckert, David Baumann, Maximilian Niyazi, Frank Fideler, Ulrike Ernemann, Marcos Tatagiba, Jürgen Schäfer, Cristian Urla, Simon Scherer, Jörg Fuchs, Frank Paulsen and Benjamin Bender
Cancers 2023, 15(13), 3505; https://doi.org/10.3390/cancers15133505 - 05 Jul 2023
Viewed by 1052
Abstract
In children with bladder/prostate (BP) and perianal rhabdomyosarcoma (RMS), we use a hybrid treatment concept for those suitable, combining organ-preserving tumor resection and high-dose rate brachytherapy (HDR-BT). This treatment concept has been shown to improve outcomes. However, it is associated with specific challenges [...] Read more.
In children with bladder/prostate (BP) and perianal rhabdomyosarcoma (RMS), we use a hybrid treatment concept for those suitable, combining organ-preserving tumor resection and high-dose rate brachytherapy (HDR-BT). This treatment concept has been shown to improve outcomes. However, it is associated with specific challenges for the clinicians. The exact position of the tubes for BT is a prerequisite for precise radiotherapy. It can finally be determined only with an MRI or CT scan. We evaluated the use of an intraoperative MRI (iMRI) to control the position of the BT tubes and for radiotherapy planning in all patients with BP and perianal RMS who received the above-mentioned combination therapy in our department since January 2021. iMRI was used in 12 children. All tubes were clearly localized. No adverse events occurred. In all 12 children, radiotherapy could be started on time. In a historical cohort without iMRI, this was not possible in 3 out of 20 children. The use of iMRI in children with BP and perianal RMS improved patient safety and treatment quality. This technology has proven to be successful for the patient population we have defined and has become a standard procedure in our institution. Full article
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13 pages, 937 KiB  
Article
Utility of Patient-Reported Symptom and Functional Outcomes to Indicate Recovery after First 90 Days of Radical Cystectomy: A Longitudinal Study
by Xin Shelley Wang, Kelly K. Bree, Neema Navai, Mona Kamal, Shu-En Shen, Elizabeth Letona, Charles S. Cleeland, Qiuling Shi and Vijaya Gottumukkala
Cancers 2023, 15(11), 3051; https://doi.org/10.3390/cancers15113051 - 04 Jun 2023
Viewed by 1145
Abstract
This is a longitudinal prospective study that tracked multiple symptom burden and functioning status for bladder cancer (BLC) patients for 3 months post-radical cystectomy at The University of Texas MD Anderson Cancer Center, using a validated disease-specific patient-reported outcome measure (PROM) tool, the [...] Read more.
This is a longitudinal prospective study that tracked multiple symptom burden and functioning status for bladder cancer (BLC) patients for 3 months post-radical cystectomy at The University of Texas MD Anderson Cancer Center, using a validated disease-specific patient-reported outcome measure (PROM) tool, the MD Anderson Symptom Inventory (the MDASI-PeriOp-BLC). The feasibility of collecting an objective measure for physical functioning, using “Timed Up & Go test” (TUGT) and PRO scores at baseline, discharge and end of study, was tested. Patients (n = 52) received care under an ERAS pathway. The more severe scores of fatigue, sleep disturbance, distress, drowsiness, frequent urination and urinary urgency at baseline predicted poor functional recovery postoperatively (OR = 1.661, 1.039–2.655, p = 0.034); other more severe symptoms at discharge (pain, fatigue, sleep disturbance, lack of appetite, drowsiness, bloating/abdominal tightness) predicted poor functional recovery (OR = 1.697, 1.114–2.584, p = 0.014) postoperatively. Compliance rates at preoperative, discharge and end of study were 100%, 79% and 77%, while TUGT completion rates were 88%, 54% and 13%, respectively. This prospective study found that more severe symptom burden at baseline and discharge is associated with poor functional recovery post-radical cystectomy for BLC. The collection of PROs is more feasible than using performance measures (TUGT) of function following radical cystectomy. Full article
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9 pages, 603 KiB  
Article
Subsequent Upper Urinary Tract Carcinoma Related to Worse Survival in Patients Treated with BCG
by Kazuyuki Numakura, Makito Miyake, Mizuki Kobayashi, Yumina Muto, Yuya Sekine, Nobutaka Nishimura, Kota Iida, Masanori Shiga, Shuichi Morizane, Takahiro Yoneyama, Yoshiaki Matsumura, Takashige Abe, Takeshi Yamada, Kazumasa Matsumoto, Junichi Inokuchi, Naotaka Nishiyama, Rikiya Taoka, Takashi Kobayashi, Takahiro Kojima, Hiroshi Kitamura, Hiroyuki Nishiyama, Kiyohide Fujimoto and Tomonori Habuchiadd Show full author list remove Hide full author list
Cancers 2023, 15(7), 2002; https://doi.org/10.3390/cancers15072002 - 28 Mar 2023
Cited by 1 | Viewed by 1317
Abstract
Upper urinary tract urothelial carcinoma (UTUC) after intravesical bacillus Calmette-Guerin (BCG) therapy is rare, and its incidence, clinical impact, and risk factors are not fully understood. To elucidate the clinical implications of UTUC after intravesical BCG therapy, this retrospective cohort study used data [...] Read more.
Upper urinary tract urothelial carcinoma (UTUC) after intravesical bacillus Calmette-Guerin (BCG) therapy is rare, and its incidence, clinical impact, and risk factors are not fully understood. To elucidate the clinical implications of UTUC after intravesical BCG therapy, this retrospective cohort study used data collected between January 2000 and December 2019. A total of 3226 patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and treated with intravesical BCG therapy were enrolled (JUOG-UC 1901). UTUC impact was evaluated by comparing intravesical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) rates. The predictors of UTUC after BCG treatment were assessed. Of these patients, 2873 with a medical history that checked UTUC were analyzed. UTUC was detected in 175 patients (6.1%) during the follow-up period. Patients with UTUC had worse survival rates than those without UTUC. Multivariate analyses revealed that tumor multiplicity (odds ratio [OR], 1.681; 95% confidence interval [CI], 1.005–2.812; p = 0.048), Connaught strain (OR, 2.211; 95% CI, 1.380–3.543; p = 0.001), and intravesical recurrence (OR, 5.097; 95% CI, 3.225–8.056; p < 0.001) were associated with UTUC after BCG therapy. In conclusion, patients with subsequent UTUC had worse RFS, CSS, and OS than those without UTUC. Multiple bladder tumors, treatment for Connaught strain, and intravesical recurrence after BCG therapy may be predictive factors for subsequent UTUC diagnosis. Full article
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23 pages, 370 KiB  
Review
Bispecific T-Cell Engagers Therapies in Solid Tumors: Focusing on Prostate Cancer
by Diana C. Simão, Kevin K. Zarrabi, José L. Mendes, Ricardo Luz, Jorge A. Garcia, William K. Kelly and Pedro C. Barata
Cancers 2023, 15(5), 1412; https://doi.org/10.3390/cancers15051412 - 23 Feb 2023
Cited by 6 | Viewed by 4743
Abstract
Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering [...] Read more.
Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors’ immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research. Full article
18 pages, 2023 KiB  
Article
Gene-Transcript Expression in Urine Supernatant and Urine Cell-Sediment Are Different but Equally Useful for Detecting Prostate Cancer
by Marcelino Yazbek Hanna, Mark Winterbone, Shea P. O’Connell, Mireia Olivan, Rachel Hurst, Rob Mills, Colin S. Cooper, Daniel S. Brewer and Jeremy Clark
Cancers 2023, 15(3), 789; https://doi.org/10.3390/cancers15030789 - 27 Jan 2023
Cited by 2 | Viewed by 2371
Abstract
There is considerable interest in urine as a non-invasive liquid biopsy to detect prostate cancer (PCa). PCa-specific transcripts such as the TMPRSS2:ERG fusion gene can be found in both urine extracellular vesicles (EVs) and urine cell-sediment (Cell) but the relative usefulness of these [...] Read more.
There is considerable interest in urine as a non-invasive liquid biopsy to detect prostate cancer (PCa). PCa-specific transcripts such as the TMPRSS2:ERG fusion gene can be found in both urine extracellular vesicles (EVs) and urine cell-sediment (Cell) but the relative usefulness of these and other genes in each fraction in PCa detection has not been fully elucidated. Urine samples from 76 men (PCa n = 40, non-cancer n = 36) were analysed by NanoString for 154 PCa-associated genes-probes, 11 tissue-specific, and six housekeeping. Comparison to qRT-PCR data for four genes (PCA3, OR51E2, FOLH1, and RPLP2) was strong (r = 0.51–0.95, Spearman p < 0.00001). Comparing EV to Cells, differential gene expression analysis found 57 gene-probes significantly more highly expressed in 100 ng of amplified cDNA products from the EV fraction, and 26 in Cells (p < 0.05; edgeR). Expression levels of prostate-specific genes (KLK2, KLK3) measured were ~20× higher in EVs, while PTPRC (white-blood Cells) was ~1000× higher in Cells. Boruta analysis identified 11 gene-probes as useful in detecting PCa: two were useful in both fractions (PCA3, HOXC6), five in EVs alone (GJB1, RPS10, TMPRSS2:ERG, ERG_Exons_4-5, HPN) and four from Cell (ERG_Exons_6-7, OR51E2, SPINK1, IMPDH2), suggesting that it is beneficial to fractionate whole urine prior to analysis. The five housekeeping genes were not significantly differentially expressed between PCa and non-cancer samples. Expression signatures from Cell, EV and combined data did not show evidence for one fraction providing superior information over the other. Full article
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