Cancers

Research

17 pages, 3932 KiB

Open AccessArticle

Serrate RNA Effector Molecule (SRRT) Is Associated with Prostate Cancer Progression and Is a Predictor of Poor Prognosis in Lethal Prostate Cancer

by Yaser Gamallat, Muhammad Choudhry, Qiaowang Li, Jon George Rokne, Reda Alhajj, Ramy Abdelsalam, Sunita Ghosh, Jaron Arbet, Paul C. Boutros and Tarek A. Bismar

Cancers 2023, 15(10), 2867; https://doi.org/10.3390/cancers15102867 - 22 May 2023

Viewed by 1951

Abstract

Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate [...] Read more.

Arsenite-resistance protein 2, also known as serrate RNA effector molecule (ARS2/SRRT), is known to be involved in cellular proliferation and tumorigenicity. However, its role in prostate cancer (PCa) has not yet been established. We investigated the potential role of SRRT in 496 prostate samples including benign, incidental, advanced, and castrate-resistant patients treated by androgen deprivation therapy (ADT). We also explored the association of SRRT with common genetic aberrations in lethal PCa using immunohistochemistry (IHC) and performed a detailed analysis of SRRT expression using The Cancer Genome Atlas (TCGA PRAD) by utilizing RNA-seq, clinical information (pathological T category and pathological Gleason score). Our findings indicated that high SRRT expression was significantly associated with poor overall survival (OS) and cause-specific survival (CSS). SRRT expression was also significantly associated with common genomic aberrations in lethal PCa such as PTEN loss, ERG gain, mutant TP53, or ATM. Furthermore, TCGA PRAD data revealed that high SRRT mRNA expression was significantly associated with higher Gleason scores, PSA levels, and T pathological categories. Gene set enrichment analysis (GSEA) of RNAseq data from the TCGA PRAD cohort indicated that SRRT may play a potential role in regulating the expression of genes involved in prostate cancer aggressiveness. Conclusion: The current data identify the SRRT’s potential role as a prognostic for lethal PCa, and further research is required to investigate its potential as a therapeutic target. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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15 pages, 3010 KiB

Open AccessArticle

Phase I Trial of [^99mTc]Tc-maSSS-PEG₂-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors

by Vladimir Chernov, Anastasiya Rybina, Roman Zelchan, Anna Medvedeva, Olga Bragina, Nadejda Lushnikova, Artem Doroshenko, Evgeniy Usynin, Liubov Tashireva, Sergey Vtorushin, Ayman Abouzayed, Sara S. Rinne, Jens Sörensen, Vladimir Tolmachev and Anna Orlova

Cancers 2023, 15(6), 1631; https://doi.org/10.3390/cancers15061631 - 7 Mar 2023

Cited by 15 | Viewed by 2474

Abstract

The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [...] Read more.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [^99mTc]Tc-maSSS-PEG₂-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 µg of [^99mTc]Tc-maSSS-PEG₂-RM26 (600–700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [^99mTc]Tc-maSSS-PEG₂-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 ± 0.0007 for male patients and 0.008 ± 0.003 mSv/MBq for female patients. The accumulation of [^99mTc]Tc-maSSS-PEG₂-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [^99mTc]Tc-maSSS-PEG₂-RM26 was safe and well tolerated. [^99mTc]Tc-maSSS-PEG₂-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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14 pages, 2024 KiB

Open AccessArticle

A Novel Methylation Marker NRN1 plus TERT and FGFR3 Mutation Using Urine Sediment Enables the Detection of Urothelial Bladder Carcinoma

by Junjie Zhang, Ran Xu, Qiang Lu, Zhenzhou Xu, Jianye Liu, Pei Li, Yaqun Zhang, Chuanchi Zhou, Lufeng Luo, Wei Tang, Zhenting Wang, Manman Cao, Jian Cao, Genming Xu and Long Wang

Cancers 2023, 15(3), 615; https://doi.org/10.3390/cancers15030615 - 19 Jan 2023

Cited by 32 | Viewed by 2266

Abstract

Background: Aberrant DNA methylation is an early event during tumorigenesis. In the present study, we aimed to construct a methylation diagnostic tool using urine sediment for the detection of urothelial bladder carcinoma, and improved the diagnostic performance of the model by incorporating single-nucleotide [...] Read more.

Background: Aberrant DNA methylation is an early event during tumorigenesis. In the present study, we aimed to construct a methylation diagnostic tool using urine sediment for the detection of urothelial bladder carcinoma, and improved the diagnostic performance of the model by incorporating single-nucleotide polymorphism (SNP) sites. Methods: A three-stage analysis was carried out to construct the model and evaluate the diagnostic performance. In stage I, two small cohorts from Xiangya hospital were recruited to validate and identify the detailed regions of collected methylation biomarkers. In stage II, proof-of-concept study cohorts from the Hunan multicenter were recruited to construct a diagnostic tool. In stage III, a blinded cohort comprising suspicious UBC patients was recruited from Beijing single center to further test the robustness of the model. Results: In stage I, single NRN1 exhibited the highest AUC compared with six other biomarkers and the Random Forest model. At the best cutoff value of 5.16, a single NRN1 biomarker gave a diagnosis with a sensitivity of 0.93 and a specificity of 0.97. In stage II, the Random Forest algorithm was applied to construct a diagnostic tool, consisting of NRN1, TERT C228T and FGFR3 p.S249C. The tool exhibited AUC values of 0.953, 0.946 and 0.951 in training, test and all cohorts. At the best cutoff value, the model resulted in a sensitivity of 0.871 and a specificity of 0.947. In stage III, the diagnostic tool achieved a good discrimination in the external validation cohort, with an overall AUC of 0.935, sensitivity of 0.864 and specificity of 0.895. Additionally, the model exhibited a superior sensitivity and comparable specificity compared with conventional cytology and FISH. Conclusions: The diagnostic tool exhibited a highly specific and robust performance. It may be used as a replaceable approach for the detection of UBC. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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10 pages, 421 KiB

Open AccessArticle

Ultrasound-Guided Percutaneous Thermal Ablation of Renal Cancers—In Search for the Ideal Tumour

by Milosz Jasinski, Marta Bielinska, Jerzy Siekiera, Krzysztof Kamecki and Maciej Salagierski

Cancers 2023, 15(2), 518; https://doi.org/10.3390/cancers15020518 - 14 Jan 2023

Cited by 6 | Viewed by 1891

Abstract

Over the recent years, the progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation [...] Read more.

Over the recent years, the progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the success of percutaneous radiofrequency ablation (RFA) in relation to kidney tumour diameter and location. Between August 2016 and September 2021, 253 patients with 259 renal tumours underwent US-guided RFA as a primary treatment in our institution. A total of 67 patients were excluded from this study. Abdominal computed tomography (CT) and tumour biopsy were performed before the procedure. Patients were followed with contrast-enhanced CT, the average follow-up time was 28 months. The studied group was composed of 186 patients with 191 renal tumours—only biopsy-confirmed renal cancers were included. During the follow-up, 46 cases of residual disease and 4 cases of local progression were found. There was a significant correlation between tumour size and the ablation success rate. The success rate was 73.5% and 87.6% for lesions ≤25 mm, 94.6% for lesions ≤25 mm and exophytic, 79.1% for lesions 26–30 mm and 84.4% for lesions 26–30 mm and exophytic, respectively. Four Clavien-Dindo grade ≥2 complications were observed. US-guided percutaneous RFA of T1a renal cancers is safe and well-tolerated. Its effectiveness depends on tumour size, with best results for exophytic lesions smaller than 3 cm. Most of the recurrent or residual tumours can be successfully re-treated with US-guided percutaneous RFA. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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15 pages, 2830 KiB

Open AccessArticle

Preclinical Characterisation of PSMA/GRPR-Targeting Heterodimer [⁶⁸Ga]Ga-BQ7812 for PET Diagnostic Imaging of Prostate Cancer: A Step towards Clinical Translation

by Fanny Lundmark, Ayman Abouzayed, Sara S. Rinne, Vasiliy Timofeev, Nadezhda Sipkina, Maria Naan, Anastasia Kirichenko, Maria Vasyutina, Daria Ryzhkova, Vladimir Tolmachev, Ulrika Rosenström and Anna Orlova

Cancers 2023, 15(2), 442; https://doi.org/10.3390/cancers15020442 - 10 Jan 2023

Cited by 6 | Viewed by 2569

Abstract

The development of radioligands targeting prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) has shown promising results for the imaging and therapy of prostate cancer. However, studies have shown that tumors and metastases can express such targets heterogeneously. To overcome this issue [...] Read more.

The development of radioligands targeting prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) has shown promising results for the imaging and therapy of prostate cancer. However, studies have shown that tumors and metastases can express such targets heterogeneously. To overcome this issue and to improve protein binding, radioligands with the ability to bind both PSMA and GRPR have been developed. Herein, we present the preclinical characterization of [⁶⁸Ga]Ga-BQ7812; a PSMA/GRPR-targeting radioligand for the diagnostic PET imaging of prostate cancer. This study aimed to evaluate [⁶⁸Ga]Ga-BQ7812 to promote the translation of such imaging probes into the clinic. [⁶⁸Ga]Ga-BQ7812 demonstrated rapid and specific binding to both targets in a PSMA/GRPR-expressing PC3-pip cell line. Results from the biodistribution study in PC3-pip xenografted mice showed specific binding to both targets, with the highest activity uptake at 1 h pi in tumor (PSMA+/GRPR+, 10.4 ± 1.0% IA/g), kidneys (PSMA+, 45 ± 16% IA/g), and pancreas (GRPR+, 5.6 ± 0.7% IA/g). At 3h pi, increased tumour-to-organ ratios could be seen due to higher retention in the tumor compared with other PSMA or GRPR-expressing organs. These results, together with low toxicity and an acceptable estimated dosimetry profile (total effective dose = 0.0083 mSv/MBq), support the clinical translation of [⁶⁸Ga]Ga-BQ7812 and represent a step towards its first clinical trial. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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12 pages, 1001 KiB

Open AccessArticle

Effect of Neoadjuvant Chemotherapy on Complications, in-Hospital Mortality, Length of Stay and Total Hospital Costs in Bladder Cancer Patients Undergoing Radical Cystectomy

by Benedikt Hoeh, Rocco Simone Flammia, Lukas Hohenhorst, Gabriele Sorce, Francesco Chierigo, Andrea Panunzio, Zhe Tian, Fred Saad, Michele Gallucci, Alberto Briganti, Carlo Terrone, Shahrokh F. Shariat, Markus Graefen, Derya Tilki, Alessandro Antonelli, Luis A. Kluth, Philipp Mandel, Felix K. H. Chun and Pierre I. Karakiewicz

Cancers 2022, 14(5), 1222; https://doi.org/10.3390/cancers14051222 - 26 Feb 2022

Cited by 9 | Viewed by 2449

Abstract

Background: To test for differences in complication rates, in-hospital mortality, length of stay (LOS) and total hospital costs (THCs) in patients treated with neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). Methods: Within the National (Nationwide) Inpatient Sample (NIS) database (2016–2019), we identified [...] Read more.

Background: To test for differences in complication rates, in-hospital mortality, length of stay (LOS) and total hospital costs (THCs) in patients treated with neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). Methods: Within the National (Nationwide) Inpatient Sample (NIS) database (2016–2019), we identified RC-treated, non-metastatic, lymph-node negative bladder cancer patients, stratified by NAC status. Trend analyses, multivariable logistic, multivariable Poisson and multivariable linear regression models were used. Results: We identified 4347 RC-treated bladder cancer patients. Of those, 805 (19%) received NAC prior to RC. Overall, complications rates did not differ (65 vs. 66%; p = 0.7). However, NAC patients harbored lower rates of surgical site (6 vs. 9%), cardiac (13 vs. 19%) and genitourinary (5.5 vs. 9.7%) complications. In-hospital mortality (<1.7 vs. 1.8%) and LOS (6 vs. 7 days) was lower in NAC patients (all p < 0.05). Moreover, NAC was an independent predictor of shorter LOS in multivariable Poisson regression models (Risk ratio: 0.86; p < 0.001) and an independent predictor for higher THCs in multivariable linear regression models (Odds ratio: 1474$; p = 0.02). Conclusion: NAC was not associated with higher complication rates and in-hospital mortality. Contrary, NAC was associated with shorter LOS, yet moderately higher THCs. The current analysis suggests no detriment from NAC in the context of RC. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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12 pages, 10415 KiB

Open AccessArticle

Pre- and Post-Resection Urine Metabolic Profiles of Bladder Cancer Patients: Results of Preliminary Studies on Time Series Metabolomics Analysis

by Julia Jacyna, Marta Kordalewska, Małgorzata Artymowicz, Marcin Markuszewski, Marcin Matuszewski and Michał J. Markuszewski

Cancers 2022, 14(5), 1210; https://doi.org/10.3390/cancers14051210 - 25 Feb 2022

Cited by 9 | Viewed by 2688

Abstract

The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic [...] Read more.

The incidence of bladder cancer (BCa) has remained high for many years. Nevertheless, its pathomechanism has not yet been fully understood and is still being studied. Therefore, multiplatform untargeted urinary metabolomics analysis has been performed in order to study differences in the metabolic profiles of urine samples collected at three time points: before transurethral resection of bladder tumor (TURBT), the day after the procedure and two weeks after TURBT. Collected samples were analyzed with the use of high-performance liquid chromatography hyphenated with time-of-flight mass spectrometry detection (HPLC-TOF/MS) and gas chromatography coupled with triple quadrupole mass spectrometry detection (GC-QqQ/MS, in a scan mode). Levels of metabolites selected in our previous study were assessed in order to confirm their potential to differentiate the healthy and diseased samples, regardless of the risk factors and individual characteristics. Hippuric acid, pentanedioic acid and uridine confirmed their potential for sample differentiation. Based on the results of statistical analysis for the paired samples (comparison of metabolic profiles of samples collected before TURBT and two weeks after), a set of metabolites belonging to nucleotide metabolism and methylation processes was also selected. Longitudinal studies proved to be useful for the evaluation of metabolic changes in bladder cancer. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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19 pages, 3351 KiB

Open AccessArticle

Integrative Transcriptome Profiling Reveals SKA3 as a Novel Prognostic Marker in Non-Muscle Invasive Bladder Cancer

by Chaelin You, Xuan-Mei Piao, Keunsoo Kang, Yong-June Kim and Kyuho Kang

Cancers 2021, 13(18), 4673; https://doi.org/10.3390/cancers13184673 - 17 Sep 2021

Cited by 11 | Viewed by 3495

Abstract

Approximately 80% of all new bladder cancer patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). However, approximately 15% of them progress to muscle-invasive bladder cancer (MIBC), for which prognosis is poor. The current study aimed to improve diagnostic accuracy associated with clinical [...] Read more.

Approximately 80% of all new bladder cancer patients are diagnosed with non-muscle invasive bladder cancer (NMIBC). However, approximately 15% of them progress to muscle-invasive bladder cancer (MIBC), for which prognosis is poor. The current study aimed to improve diagnostic accuracy associated with clinical outcomes in NMIBC patients. Nevertheless, it has been challenging to identify molecular biomarkers that accurately predict MIBC progression because this disease is complex and heterogeneous. Through integrative transcriptome profiling, we showed that high SKA3 expression is associated with poor clinical outcomes and MIBC progression. We performed RNA sequencing on human tumor tissues to identify candidate biomarkers in NMIBC. We then selected genes with prognostic significance by analyzing public datasets from multiple cohorts of bladder cancer patients. We found that SKA3 was associated with NMIBC pathophysiology and poor survival. We analyzed public single-cell RNA-sequencing (scRNA-seq) data for bladder cancer to dissect transcriptional tumor heterogeneity. SKA3 was expressed in an epithelial cell subpopulation expressing genes regulating the cell cycle. Knockdown experiments confirmed that SKA3 promotes bladder cancer cell proliferation by accelerating G2/M transition. Hence, SKA3 is a new prognostic marker for predicting NMIBC progression. Its inhibition could form part of a novel treatment lowering the probability of bladder cancer progression. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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Review

Jump to: Research, Other

17 pages, 646 KiB

Open AccessReview

Management of Advanced Prostate Cancer in the Precision Oncology Era

by Claire M. Gillette, Gabriel A. Yette, Scott D. Cramer and Laura S. Graham

Cancers 2023, 15(9), 2552; https://doi.org/10.3390/cancers15092552 - 29 Apr 2023

Cited by 6 | Viewed by 6249

Abstract

Prostate cancer (PC) is the second leading cause of cancer death in men in the United States. While diversified and improved treatment options for aggressive PC have improved patient outcomes, metastatic castration-resistant prostate cancer (mCRPC) remains incurable and an area of investigative therapeutic [...] Read more.

Prostate cancer (PC) is the second leading cause of cancer death in men in the United States. While diversified and improved treatment options for aggressive PC have improved patient outcomes, metastatic castration-resistant prostate cancer (mCRPC) remains incurable and an area of investigative therapeutic interest. This review will cover the seminal clinical data supporting the indication of new precision oncology-based therapeutics and explore their limitations, present utility, and potential in the treatment of PC. Systemic therapies for high-risk and advanced PC have experienced significant development over the past ten years. Biomarker-driven therapies have brought the field closer to the goal of being able to implement precision oncology therapy for every patient. The tumor agnostic approval of pembrolizumab (a PD-1 inhibitor) marked an important advancement in this direction. There are also several PARP inhibitors indicated for patients with DNA damage repair deficiencies. Additionally, theranostic agents for both imaging and treatment have further revolutionized the treatment landscape for PC and represent another advancement in precision medicine. Radiolabeled prostate-specific membrane antigen (PSMA) PET/CT is rapidly becoming a standard of care for diagnosis, and PSMA-targeted radioligand therapies have gained recent FDA approval for metastatic prostate cancer. These advances in precision-based oncology are detailed in this review. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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19 pages, 859 KiB

Open AccessReview

Advances in PARP Inhibitors for Prostate Cancer

by Steven Tisseverasinghe, Boris Bahoric, Maurice Anidjar, Stephan Probst and Tamim Niazi

Cancers 2023, 15(6), 1849; https://doi.org/10.3390/cancers15061849 - 20 Mar 2023

Cited by 13 | Viewed by 4308

Abstract

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought [...] Read more.

Poly-adenosine diphosphate-ribose polymerase plays an essential role in cell function by regulating apoptosis, genomic stability and DNA repair. PARPi is a promising drug class that has gained significant traction in the last decade with good outcomes in different cancers. Several trials have sought to test its effectiveness in metastatic castration resistant prostate cancer (mCRPC). We conducted a comprehensive literature review to evaluate the current role of PARPi in this setting. To this effect, we conducted queries in the PubMed, Embase and Cochrane databases. We reviewed and compared all major contemporary publications on the topic. In particular, recent phase II and III studies have also demonstrated the benefits of olaparib, rucaparib, niraparib, talazoparib in CRPC. Drug effectiveness has been assessed through radiological progression or overall response. Given the notion of synthetic lethality and potential synergy with other oncological therapies, several trials are looking to integrate PARPi in combined therapies. There remains ongoing controversy on the need for genetic screening prior to treatment initiation as well as the optimal patient population, which would benefit most from PARPi. PARPi is an important asset in the oncological arsenal for mCRPC. New combinations with PARPi may improve outcomes in earlier phases of prostate cancer. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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26 pages, 9737 KiB

Open AccessReview

Circulating Tumor Cells as Biomarkers for Renal Cell Carcinoma: Ready for Prime Time?

by Anabela Couto-Cunha, Carmen Jerónimo and Rui Henrique

Cancers 2023, 15(1), 287; https://doi.org/10.3390/cancers15010287 - 31 Dec 2022

Cited by 7 | Viewed by 2919

Abstract

Renal cell carcinoma (RCC) is among the 15 most common cancers worldwide, with rising incidence. In most cases, this is a silent disease until it reaches advance stages, demanding new effective biomarkers in all domains, from detection to post-therapy monitoring. Circulating tumor cells [...] Read more.

Renal cell carcinoma (RCC) is among the 15 most common cancers worldwide, with rising incidence. In most cases, this is a silent disease until it reaches advance stages, demanding new effective biomarkers in all domains, from detection to post-therapy monitoring. Circulating tumor cells (CTC) have the potential to provide minimally invasive information to guide assessment of the disease’s aggressiveness and therapeutic strategy, representing a special pool of neoplastic cells which bear metastatic potential. In some tumor models, CTCs’ enumeration has been associated with prognosis, but there is a largely unexplored potential for clinical applicability encompassing screening, diagnosis, early detection of metastases, prognosis, response to therapy and monitoring. Nonetheless, lack of standardization and high cost hinder the translation into clinical practice. Thus, new methods for collection and analysis (genomic, proteomic, transcriptomic, epigenomic and metabolomic) are needed to ascertain the role of CTC as a RCC biomarker. Herein, we provide a critical overview of the most recently published data on the role and clinical potential of CTCs in RCC, addressing their biology and the molecular characterization of this remarkable set of tumor cells. Furthermore, we highlight the existing and emerging techniques for CTC enrichment and detection, exploring clinical applications in RCC. Notwithstanding the notable progress in recent years, the use of CTCs in a routine clinical scenario of RCC patients requires further research and technological development, enabling multimodal analysis to take advantage of the wealth of information they provide. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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34 pages, 533 KiB

Open AccessReview

Stereotactic Radiation Therapy versus Brachytherapy: Relative Strengths of Two Highly Efficient Options for the Treatment of Localized Prostate Cancer

by Manon Kissel, Gilles Créhange and Pierre Graff

Cancers 2022, 14(9), 2226; https://doi.org/10.3390/cancers14092226 - 29 Apr 2022

Cited by 5 | Viewed by 3400

Abstract

Stereotactic body radiation therapy (SBRT) has become a valid option for the treatment of low- and intermediate-risk prostate cancer. In randomized trials, it was found not inferior to conventionally fractionated external beam radiation therapy (EBRT). It also compares favorably to brachytherapy (BT) even [...] Read more.

Stereotactic body radiation therapy (SBRT) has become a valid option for the treatment of low- and intermediate-risk prostate cancer. In randomized trials, it was found not inferior to conventionally fractionated external beam radiation therapy (EBRT). It also compares favorably to brachytherapy (BT) even if level 1 evidence is lacking. However, BT remains a strong competitor, especially for young patients, as series with 10–15 years of median follow-up have proven its efficacy over time. SBRT will thus have to confirm its effectiveness over the long-term as well. SBRT has the advantage over BT of less acute urinary toxicity and, more hypothetically, less sexual impairment. Data are limited regarding SBRT for high-risk disease while BT, as a boost after EBRT, has demonstrated superiority against EBRT alone in randomized trials. However, patients should be informed of significant urinary toxicity. SBRT is under investigation in strategies of treatment intensification such as combination of EBRT plus SBRT boost or focal dose escalation to the tumor site within the prostate. Our goal was to examine respective levels of evidence of SBRT and BT for the treatment of localized prostate cancer in terms of oncologic outcomes, toxicity and quality of life, and to discuss strategies of treatment intensification. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

15 pages, 627 KiB

Open AccessReview

New Directions and Challenges in Targeted Therapies of Advanced Bladder Cancer: The Role of FGFR Inhibitors

by Katarzyna Szklener, Paulina Chmiel, Adam Michalski and Sławomir Mańdziuk

Cancers 2022, 14(6), 1416; https://doi.org/10.3390/cancers14061416 - 10 Mar 2022

Cited by 12 | Viewed by 3758

Abstract

Bladder neoplasms, including the most common urothelial carcinoma, have been an escalating problem for years, especially in highly developed countries. Recent decades have brought us a steadily growing share of this cancer in terms of both morbidity and mortality statistics. Bladder neoplasms are [...] Read more.

Bladder neoplasms, including the most common urothelial carcinoma, have been an escalating problem for years, especially in highly developed countries. Recent decades have brought us a steadily growing share of this cancer in terms of both morbidity and mortality statistics. Bladder neoplasms are not only a therapeutic challenge but also an economical one due to the demanding, costly diagnostics and treatment. The treatment of urothelial cancer can be divided depending on the stage and advancement; thus, we can distinguish three main categories: non-muscle invasive bladder cancer, conventionally treated by surgical interventions; muscle invasive bladder cancer, conventionally treated with chemotherapeutics; and advanced bladder cancer with distant metastases, conventionally treated with the intensive chemotherapy in the MVAC scheme (methotrexate, vinblastine, doxorubicin, and cisplatin). Recent years have brought a breakthrough: immunotherapy and targeted therapy were discovered to be beneficial for patients disqualified from chemotherapy or patients who progressed despite treatment. This literature review summarizes the latest research into the use of targeted therapy in the treatment of advanced bladder cancer, its benefits, and its limitations. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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16 pages, 944 KiB

Open AccessReview

Antiangiogenic Therapy in Clear Cell Renal Carcinoma (CCRC): Pharmacological Basis and Clinical Results

by Alessandro Comandone, Federica Vana, Tiziana Comandone and Marcello Tucci

Cancers 2021, 13(23), 5896; https://doi.org/10.3390/cancers13235896 - 24 Nov 2021

Cited by 16 | Viewed by 2970

Abstract

Angiogenesis has a direct stimulatory effect on tumor growth, duplication, invasion and metastatic development. A significant portion of conventional renal cell carcinomas are angiogenesis-dependent tumors and the pathways supporting this process have been thoroughly investigated over the last 20 years. As a consequence, [...] Read more.

Angiogenesis has a direct stimulatory effect on tumor growth, duplication, invasion and metastatic development. A significant portion of conventional renal cell carcinomas are angiogenesis-dependent tumors and the pathways supporting this process have been thoroughly investigated over the last 20 years. As a consequence, many tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, pazopanib, axitinib, and cabozantinib), one monoclonal antibody (bevacizumab), and two mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus) have been investigated and approved for the treatment of advanced or metastatic clear cell renal carcinoma (metastatic CCRC) in first-line, as well as second-line, therapy, with impressive results in progression-free survival and in the objective response rate compared with previously available therapies or placebo. Recently, a new type of drug has been approved for metastatic CCRC: immunomodulatory checkpoint inhibitors (ICIs), alone or in combination with TKIs. However, many questions and areas to be explored still remain with regard to clear cell renal carcinoma (CCRC) treatment: research on predictive biomarkers, the best patient selection, how to overcome the mechanisms of resistance, and the best sequence of therapies in daily clinical practice. This review focuses on the pharmacological properties and anticancer activities of these drugs. The toxicity profile and clinical limitations of these therapies are also discussed. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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16 pages, 321 KiB

Open AccessReview

Characteristics and Treatment Challenges of Non-Clear Cell Renal Cell Carcinoma

by Pierangela Sepe, Arianna Ottini, Chiara Carlotta Pircher, Andrea Franza, Melanie Claps, Valentina Guadalupi, Elena Verzoni and Giuseppe Procopio

Cancers 2021, 13(15), 3807; https://doi.org/10.3390/cancers13153807 - 28 Jul 2021

Cited by 17 | Viewed by 3150

Abstract

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non [...] Read more.

Non-clear cell renal cell carcinomas (RCC) comprise several rare and poorly described diseases, often characterized by bad prognosis and with no standard treatments available. The gap in their clinical management is linked to the poor molecular characterization in handling the treatment of non clear-cell RCC with untailored therapies. Due to their rarity, non-clear RCC are in fact under-represented in prospective randomized trials. Thus, treatment choices are based on extrapolating results from clear cell RCC trials, retrospective data, or case reports. Over the last two decades, various options have been considered as the mainstay for the treatment of metastatic RCC (mRCC), including angiogenesis inhibitors, vascular endothelial growth factor receptor inhibitors, other tyrosine kinase inhibitors (TKIs), as well as MET inhibitors and mammalian targeting of rapamycin (mTOR) inhibitors. More recently, the therapeutic armamentarium has been enriched with immunotherapy, alone or in combination with targeted agents that have been shown to significantly improve outcomes of mRCC patients, if compared to TKI single-agent. It has been widely proven that non-clear cell RCC is a morphologically and clinically distinct entity from its clear cell counterpart but more knowledge about its biology is certainly needed. Histology-specific collaborative trials are in fact now emerging to investigate different treatments for non-clear cell RCC. This review summarizes pathogenetic mechanisms of non-clear cell RCC, the evolution of treatment paradigms over the last few decades, with a focus on immunotherapy-based trials, and future potential treatment options. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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18 pages, 907 KiB

Open AccessStudy Protocol

PSMA-PET/MRI-Based Focal Dose Escalation in Patients with Primary Prostate Cancer Treated with Stereotactic Body Radiation Therapy (HypoFocal-SBRT): Study Protocol of a Randomized, Multicentric Phase III Trial

by Constantinos Zamboglou, Simon K. B. Spohn, Sonja Adebahr, Maria Huber, Simon Kirste, Tanja Sprave, Christian Gratzke, Ronald C. Chen, Ernst Günther Carl, Wolfgang A. Weber, Michael Mix, Matthias Benndorf, Thomas Wiegel, Dimos Baltas, Carolin Jenkner and Anca L. Grosu

Cancers 2021, 13(22), 5795; https://doi.org/10.3390/cancers13225795 - 18 Nov 2021

Cited by 25 | Viewed by 4411

Abstract

Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time, and by (ii) enabling safe delivery of high RT doses. Several studies proposed a dose–response relationship [...] Read more.

Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a reduction of treatment time, and by (ii) enabling safe delivery of high RT doses. Several studies proposed a dose–response relationship for patients with primary PCa and especially in patients with high-risk features, as dose escalation leads to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography targeting prostate-specific-membrane antigen (PSMA-PET) evolved and enable an accurate depiction of the intraprostatic tumor mass for the first time. The HypoFocal-SBRT study combines ultra-hypofractionated RT/stereotactic body RT, with focal RT dose escalation on intraprostatic tumor sides by applying state of the art diagnostic imaging and most modern RT concepts. This novel strategy will be compared with moderate hypofractionated RT (MHRT), one option for the curative primary treatment of PCa, which has been proven by several prospective trials and is recommended and carried out worldwide. We suspect an increase in relapse-free survival (RFS), and we will assess quality of life in order to detect potential changes. Full article

(This article belongs to the Special Issue Diagnostic and Treatment for Three Urological Cancers: Bladder Cancer, Kidney Cancer and Prostate Cancer)

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