Editorial

6 pages, 230 KiB

Open AccessEditorial

Urological Cancer Panorama in the Second Year of the COVID-19 Pandemic

by Estibaliz López-Fernández, Javier C. Angulo, José I. López and Claudia Manini

Cancers 2022, 14(3), 493; https://doi.org/10.3390/cancers14030493 - 19 Jan 2022

Cited by 1 | Viewed by 1239

A total of 22 contributions conforms this Special Issue that covers a wide spectrum of contemporary issues in urological cancer, a group of neoplasms with high incidence, prevalence, and mortality rates, especially in the male population of Western countries [...] Full article

(This article belongs to the Special Issue Urological Cancer 2021)

Research

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10 pages, 3675 KiB

Open AccessArticle

Prognostic Effect of Preoperative Psoas Muscle Hounsfield Unit at Radical Cystectomy for Bladder Cancer

by Yusuke Sugino, Takeshi Sasaki, Manabu Kato, Satoru Masui, Kouhei Nishikawa, Takashi Okamoto, Shinya Kajiwara, Takuji Shibahara, Takehisa Onishi, Shiori Tanaka, Hideki Kanda, Hiroshi Matsuura and Takahiro Inoue

Cancers 2021, 13(22), 5629; https://doi.org/10.3390/cancers13225629 - 10 Nov 2021

Cited by 5 | Viewed by 2432

Abstract

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as [...] Read more.

Radical cystectomy (RC) is the standard treatment for patients with advanced bladder cancer. Since RC is a highly invasive procedure, the surgical indications in an aging society must be carefully judged. In recent years, the concept of “frailty” has been attracting attention as a term used to describe fragility due to aging. We focused on the psoas muscle Hounsfield unit (PMHU) and analyzed its appropriateness as a prognostic factor together with other clinical factors in patients after RC. We retrospectively analyzed the preoperative prognostic factors in 177 patients with bladder cancer who underwent RC between 2008 and 2020. Preoperative non-contrast computed tomography axial image at the third lumbar vertebral level was used to measure the mean Hounsfield unit (HU) and cross-sectional area (mm²) of the psoas muscle. Univariate analysis showed significant differences in age, sex, clinical T stage, and PMHU. In multivariate analysis using the Cox proportional hazards model, age (hazard ratio (HR) = 1.734), sex (HR = 2.116), cT stage (HR = 1.665), and PMHU (HR = 1.758) were significant predictors for overall survival. Furthermore, using these four predictors, it was possible to stratify the prognosis of patients after RC. Finally, PMHU was useful as a simple and significant preoperative factor that correlated with prognosis after RC. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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10 pages, 1412 KiB

Open AccessArticle

Serum Epiplakin Might Be a Potential Serodiagnostic Biomarker for Bladder Cancer

by Soichiro Shimura, Kazumasa Matsumoto, Yuriko Shimizu, Kohei Mochizuki, Yutaka Shiono, Shuhei Hirano, Dai Koguchi, Masaomi Ikeda, Yuichi Sato and Masatsugu Iwamura

Cancers 2021, 13(20), 5150; https://doi.org/10.3390/cancers13205150 - 14 Oct 2021

Cited by 4 | Viewed by 1545

Abstract

Tumor markers that can be detected at an early stage are needed. Here, we evaluated the epiplakin expression levels in sera from patients with bladder cancer (BC). Using a micro-dot blot array, we evaluated epiplakin expression levels in 60 patients with BC, 20 [...] Read more.

Tumor markers that can be detected at an early stage are needed. Here, we evaluated the epiplakin expression levels in sera from patients with bladder cancer (BC). Using a micro-dot blot array, we evaluated epiplakin expression levels in 60 patients with BC, 20 patients with stone disease, and 28 healthy volunteers. The area under the curve (AUC) and best cut-off point were calculated using receiver-operating characteristic (ROC) analysis. Serum epiplakin levels were significantly higher in patients with BC than in those with stone disease (p = 0.0013) and in healthy volunteers (p < 0.0001). The AUC-ROC level for BC was 0.78 (95% confidence interval (CI) = 0.69–0.87). Using a cut-off point of 873, epiplakin expression levels exhibited 68.3% sensitivity and 79.2% specificity for BC. However, the serum epiplakin levels did not significantly differ by sex, age, pathological stage and grade, or urine cytology. We performed immunohistochemical staining using the same antibody on another cohort of 127 patients who underwent radical cystectomy. Univariate and multivariate analysis results showed no significant differences between epiplakin expression, clinicopathological findings, and patient prognoses. Our results showed that serum epiplakin might be a potential serodiagnostic biomarker in patients with BC. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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17 pages, 3695 KiB

Open AccessArticle

Treatment Pattern and Outcomes with Systemic Therapy in Men with Metastatic Prostate Cancer in the Real-World Patients in the United States

by Umang Swami, Jennifer Anne Sinnott, Benjamin Haaland, Nicolas Sayegh, Taylor Ryan McFarland, Nishita Tripathi, Benjamin L. Maughan, Nityam Rathi, Deepika Sirohi, Roberto Nussenzveig, Manish Kohli, Sumanta K. Pal and Neeraj Agarwal

Cancers 2021, 13(19), 4951; https://doi.org/10.3390/cancers13194951 - 30 Sep 2021

Cited by 25 | Viewed by 4981

Abstract

Background: Both novel hormonal therapies and docetaxel are approved for treatment of metastatic prostate cancer (mPC; in castration sensitive or refractory settings). Present knowledge gaps include lack of real-world data on treatment patterns in patients with newly diagnosed mPC, and comparative effectiveness of [...] Read more.

Background: Both novel hormonal therapies and docetaxel are approved for treatment of metastatic prostate cancer (mPC; in castration sensitive or refractory settings). Present knowledge gaps include lack of real-world data on treatment patterns in patients with newly diagnosed mPC, and comparative effectiveness of novel hormonal therapies (NHT) versus docetaxel after treatment with a prior NHT. Methods: Herein we extracted patient-level data from a large real-world database of patients with mPC in United States. Utilization of NHT or docetaxel for mPC and comparative effectiveness of an alternate NHT versus docetaxel after one prior NHT was evaluated. Comparative effectiveness was examined via Cox proportional hazards model with propensity score matching weights. Each patient’s propensity for treatment was modeled via random forest based on 22 factors potentially driving treatment selection. Results: The majority of patients (54%) received only androgen deprivation therapy for mPC. In patients treated with an NHT, alternate NHT was the most common next therapy and was associated with improved median overall survival over docetaxel (abiraterone followed by docetaxel vs. enzalutamide (8.7 vs. 15.6 months; adjusted hazards ratio; aHR 1.32; p = 0.009; and enzalutamide followed by docetaxel vs. abiraterone (9.7 vs. 13.2 months aHR 1.40; p = 0.009). Limitations of the study include retrospective design. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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8 pages, 805 KiB

Open AccessCommunication

Multiparametric Magnetic Resonance Imaging-Ultrasound Fusion Transperineal Prostate Biopsy: Diagnostic Accuracy from a Single Center Retrospective Study

by Andrea Fulco, Francesco Chiaradia, Luigi Ascalone, Vincenzo Andracchio, Antonio Greco, Manlio Cappa, Marcello Scarcia, Giuseppe Mario Ludovico, Vincenzo Pagliarulo, Camillo Palmieri and Stefano Alba

Cancers 2021, 13(19), 4833; https://doi.org/10.3390/cancers13194833 - 28 Sep 2021

Cited by 4 | Viewed by 1866

Abstract

The management of prostate biopsy in men with clinical suspicion of prostate cancer has changed in the last few years, especially with the introduction of imaging techniques, to overcome the low efficacy of risk stratification based on PSA levels. Here, we aimed to [...] Read more.

The management of prostate biopsy in men with clinical suspicion of prostate cancer has changed in the last few years, especially with the introduction of imaging techniques, to overcome the low efficacy of risk stratification based on PSA levels. Here, we aimed to compare the diagnostic accuracy of multiparametric MRI with fusion ultrasound-guided prostate biopsy and standard biopsy, both performed through the transperineal route. To this end, we retrospectively analyzed 272 patients who underwent combined transperineal targeted and standard biopsy during the same session. The primary outcome was to compare the cancer detection rate between targeted and standard biopsy. The secondary outcome was to evaluate the added value of combined targeted and standard biopsy approach as compared to only targeted or standard biopsy. Results showed that a rate of 16.7% clinically significant tumors (International Society of Urological Pathology (ISUP) grade ≥ 2) would have been lost if only the standard biopsy had been used. The combined targeted and standard biopsy showed an added value of 10.3% and 9.9% in reducing the risk of prostate cancer missing after targeted or standard biopsy alone, respectively. The combined targeted and standard biopsy pathway is recommended to reduce the risk of missing clinically significant prostate cancer. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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25 pages, 6291 KiB

Open AccessArticle

Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma

by Mathilda Jing Chow, Yan Gu, Lizhi He, Xiaozeng Lin, Ying Dong, Wenjuan Mei, Anil Kapoor and Damu Tang

Cancers 2021, 13(17), 4483; https://doi.org/10.3390/cancers13174483 - 06 Sep 2021

Cited by 7 | Viewed by 2101

Abstract

Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC. The current understanding and management of pRCC remain poor. We report here OIP5 being a novel oncogenic factor and possessing robust prognostic values and therapeutic potential. OIP5 upregulation is observed [...] Read more.

Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC. The current understanding and management of pRCC remain poor. We report here OIP5 being a novel oncogenic factor and possessing robust prognostic values and therapeutic potential. OIP5 upregulation is observed in pRCC. The upregulation is associated with pRCC adverse features (T1P < T2P < CIMP, Stage1 + 2 < Stage 3 < Stage 4, and N0 < N1) and effectively stratifies the fatality risk. OIP5 promotes ACHN pRCC cell proliferation and xenograft formation; the latter is correlated with network alterations related to immune regulation, metabolism, and hypoxia. A set of differentially expressed genes (DEFs) was derived from ACHN OIP5 xenografts and primary pRCCs (n = 282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (p < 2

\times

10⁻¹⁶) and relapse (p < 2

\times

10⁻¹⁶) possibilities. High-risk tumors stratified by Overlap66 risk score possess an immune suppressive environment, evident by elevations in Treg cells and PD1 in CD8 T cells. Upregulation of PLK1 occurs in both xenografts and primary pRCC tumors with OIP5 elevations. PLK1 displays a synthetic lethality relationship with OIP5. PLK1 inhibitor BI2356 inhibits the growth of xenografts formed by ACHN OIP5 cells. Collectively, the OIP5 network can be explored for personalized therapies in management of pRCC patients. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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19 pages, 3994 KiB

Open AccessArticle

Targeting S1PR1 May Result in Enhanced Migration of Cancer Cells in Bladder Carcinoma

by Chin-Li Chen, En Meng, Sheng-Tang Wu, Hsing-Fan Lai, Yi-Shan Lu, Ming-Hsin Yang, Chih-Wei Tsao, Chien-Chang Kao and Yi-Lin Chiu

Cancers 2021, 13(17), 4474; https://doi.org/10.3390/cancers13174474 - 05 Sep 2021

Cited by 4 | Viewed by 2666

Abstract

Clinical bladder tumor histological analysis shows that high expression of S1PR1 is associated with poor patient prognosis. However, there are no studies that describe the underlying mechanism. To investigate the relative distribution and actual function of S1PR1 in bladder tumors, we analyzed multiple [...] Read more.

Clinical bladder tumor histological analysis shows that high expression of S1PR1 is associated with poor patient prognosis. However, there are no studies that describe the underlying mechanism. To investigate the relative distribution and actual function of S1PR1 in bladder tumors, we analyzed multiple clinical databases in combination with tumor purity and immune cell infiltration simulations, as well as databases of well-defined histological phenotypes of bladder cancer, and single-cell sequencing of adjacent normal tissues and bladder tumors, and further compared them with bladder cancer cell lines. The results showed that S1PR1 expression was generally higher in normal tissues than in bladder cancer tissues, and its distribution was mainly in endothelial cells or immune cells. The association between high S1PR1 expression and poor prognosis may be due to tumor invasion of adjacent normal tissues, where highly expressed S1PR1 may affect prognostic interpretation. The effect of S1PR1 itself on cancer cells was associated with cell adhesion, and in bladder cancer cells, S1PR1 expression was negatively correlated with cell motility. Moreover, the use of FTY-720 will cause an increased metastatic ability of bladder cancer cells. In conclusion, we suggest that the use of S1PR1-specific inhibition as a synergistic treatment requires more observation and consideration. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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8 pages, 1306 KiB

Open AccessArticle

Intraoperative Digital Analysis of Ablation Margins (DAAM) by Fluorescent Confocal Microscopy to Improve Partial Prostate Gland Cryoablation Outcomes

by Oscar Selvaggio, Ugo Giovanni Falagario, Salvatore Mariano Bruno, Marco Recchia, Maria Chiara Sighinolfi, Francesca Sanguedolce, Paola Milillo, Luca Macarini, Ardeshir R. Rastinehad, Rafael Sanchez-Salas, Eric Barret, Franco Lugnani, Bernardo Rocco, Luigi Cormio and Giuseppe Carrieri

Cancers 2021, 13(17), 4382; https://doi.org/10.3390/cancers13174382 - 30 Aug 2021

Cited by 8 | Viewed by 1753

Abstract

Partial gland cryoablation (PGC) aims at destroying prostate cancer (PCa) foci while sparing the unaffected prostate tissue and the functionally relevant structures around the prostate. Magnetic Resonance Imaging (MRI) has boosted PGC, but available evidence suggests that ablation margins may be positive due [...] Read more.

Partial gland cryoablation (PGC) aims at destroying prostate cancer (PCa) foci while sparing the unaffected prostate tissue and the functionally relevant structures around the prostate. Magnetic Resonance Imaging (MRI) has boosted PGC, but available evidence suggests that ablation margins may be positive due to MRI-invisible lesions. This study aimed at determining the potential role of intraoperative digital analysis of ablation margins (DAAM) by fluoresce confocal microscopy (FCM) of biopsy cores taken during prostate PGC. Ten patients with low to intermediate risk PCa scheduled for PGC were enrolled. After cryo-needles placement, 76 biopsy cores were taken from the ablation margins and stained by the urologist for FCM analysis. Digital images were sent for “real-time” pathology review. DAAM, always completed within the frame of PGC treatment (median time 25 min), pointed out PCa in 1/10 cores taken from 1 patient, thus prompting placement of another cryo-needle to treat this area. Standard HE evaluation confirmed 75 cores to be cancer-free while displayed a GG 4 PCa in 7% of the core positive at FCM. Our data point out that IDAAM is feasible and reliable, thus representing a potentially useful tool to reduce the risk of missing areas of PCa during PGC. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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8 pages, 1020 KiB

Open AccessCommunication

Stereotactic Body Radiotherapy for Frail Patients with Primary Renal Cell Carcinoma: Preliminary Results after 4 Years of Experience

by Laure Grelier, Michael Baboudjian, Bastien Gondran-Tellier, Anne-Laure Couderc, Robin McManus, Jean-Laurent Deville, Ana Carballeira, Raphaelle Delonca, Veronique Delaporte, Laetitia Padovani, Romain Boissier, Eric Lechevallier and Xavier Muracciole

Cancers 2021, 13(13), 3129; https://doi.org/10.3390/cancers13133129 - 23 Jun 2021

Cited by 11 | Viewed by 1862

Abstract

Introduction: The aim of this study was to report the oncological outcomes and toxicity of stereotactic body radiotherapy (SBRT) to treat primary renal cell carcinoma (RCC) in frail patients unfit for surgery or standard alternative ablative therapies. Methods: We retrospectively enrolled 23 patients [...] Read more.

Introduction: The aim of this study was to report the oncological outcomes and toxicity of stereotactic body radiotherapy (SBRT) to treat primary renal cell carcinoma (RCC) in frail patients unfit for surgery or standard alternative ablative therapies. Methods: We retrospectively enrolled 23 patients who had SBRT for primary, biopsy-proven RCC at our tertiary center between October 2016 and March 2020. Treatment-related toxicities were defined using CTCAE, version 4.0. The primary outcome was local control which was defined using the Response Evaluation Criteria in Solid Tumors. Results: The median age, Charlson score and tumor size were 81 (IQR 79–85) years, 7 (IQR 5–8) and 40 (IQR 28–48) mm, respectively. The most used dose fractionation schedule was 35 Gy (78.3%) in five or seven fractions. The median duration of follow-up for all living patients was 22 (IQR 10–39) months. Local recurrence-free survival, event-free survival, cancer-specific survival and overall survival were 96 (22/23), 74 (18/23), 96 (22/23) and 83% (19/23), respectively. There were no grade 3–4 side effects. No patients required dialysis during the study period. No treatment-related deaths or late complications were reported. Conclusion: SBRT appears to be a promising alternative to surgery or ablative therapy to treat primary RCC in frail patients. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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13 pages, 1770 KiB

Open AccessArticle

Intravesical Bacillus Calmette–Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies

by Makito Miyake, Nobutaka Nishimura, Kota Iida, Tomomi Fujii, Ryoma Nishikawa, Shogo Teraoka, Atsushi Takenaka, Hiroshi Kikuchi, Takashige Abe, Nobuo Shinohara, Eijiro Okajima, Takuto Shimizu, Shunta Hori, Norihiko Tsuchiya, Takuya Owari, Yasukiyo Murakami, Rikiya Taoka, Takashi Kobayashi, Takahiro Kojima, Naotaka Nishiyama, Hiroshi Kitamura, Hiroyuki Nishiyama and Kiyohide Fujimoto Show full author list Hide full author list

Cancers 2021, 13(11), 2615; https://doi.org/10.3390/cancers13112615 - 26 May 2021

Cited by 5 | Viewed by 2310

Abstract

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette–Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), [...] Read more.

The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette–Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000–2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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12 pages, 1378 KiB

Open AccessArticle

Response and Toxicity to the Second Course of 3 Cycles of ¹⁷⁷Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

by Sazan Rasul, Tim Wollenweber, Lucia Zisser, Elisabeth Kretschmer-Chott, Bernhard Grubmüller, Gero Kramer, Shahrokh F. Shariat, Harald Eidherr, Markus Mitterhauser, Chrysoula Vraka, Werner Langsteger, Marcus Hacker and Alexander R. Haug

Cancers 2021, 13(10), 2489; https://doi.org/10.3390/cancers13102489 - 20 May 2021

Cited by 6 | Viewed by 2593

Abstract

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [¹⁷⁷Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were [...] Read more.

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [¹⁷⁷Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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12 pages, 32020 KiB

Open AccessArticle

Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters

by Zin W. Myint, Ramon C. Sun, Patrick J. Hensley, Andrew C. James, Peng Wang, Stephen E. Strup, Robert J. McDonald, Donglin Yan, William H. St. Clair and Derek B. Allison

Cancers 2021, 13(9), 2157; https://doi.org/10.3390/cancers13092157 - 29 Apr 2021

Cited by 11 | Viewed by 3102

Abstract

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression [...] Read more.

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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16 pages, 2502 KiB

Open AccessArticle

Integration of Urinary EN2 Protein & Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy

by Shea P. Connell, Robert Mills, Hardev Pandha, Richard Morgan, Colin S. Cooper, Jeremy Clark, Daniel S. Brewer and The Movember GAP1 Urine Biomarker Consortium

Cancers 2021, 13(9), 2102; https://doi.org/10.3390/cancers13092102 - 27 Apr 2021

Cited by 6 | Viewed by 6062

Abstract

The objective is to develop a multivariable risk model for the non-invasive detection of prostate cancer prior to biopsy by integrating information from clinically available parameters, Engrailed-2 (EN2) whole-urine protein levels and data from urinary cell-free RNA. Post-digital-rectal examination urine samples collected as [...] Read more.

The objective is to develop a multivariable risk model for the non-invasive detection of prostate cancer prior to biopsy by integrating information from clinically available parameters, Engrailed-2 (EN2) whole-urine protein levels and data from urinary cell-free RNA. Post-digital-rectal examination urine samples collected as part of the Movember Global Action Plan 1 study which has been analysed for both cell-free-RNA and EN2 protein levels were chosen to be integrated with clinical parameters (n = 207). A previously described robust feature selection framework incorporating bootstrap resampling and permutation was applied to the data to generate an optimal feature set for use in Random Forest models for prediction. The fully integrated model was named ExoGrail, and the out-of-bag predictions were used to evaluate the diagnostic potential of the risk model. ExoGrail risk (range 0–1) was able to determine the outcome of an initial trans-rectal ultrasound guided (TRUS) biopsy more accurately than clinical standards of care, predicting the presence of any cancer with an area under the receiver operator curve (AUC) = 0.89 (95% confidence interval(CI): 0.85–0.94), and discriminating more aggressive Gleason ≥ 3 + 4 disease returning an AUC = 0.84 (95% CI: 0.78–0.89). The likelihood of more aggressive disease being detected significantly increased as ExoGrail risk score increased (Odds Ratio (OR) = 2.21 per 0.1 ExoGrail increase, 95% CI: 1.91–2.59). Decision curve analysis of the net benefit of ExoGrail showed the potential to reduce the numbers of unnecessary biopsies by 35% when compared to current standards of care. Integration of information from multiple, non-invasive biomarker sources has the potential to greatly improve how patients with a clinical suspicion of prostate cancer are risk-assessed prior to an invasive biopsy. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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17 pages, 7504 KiB

Open AccessArticle

Morphological and Molecular Characterization of Proliferative Inflammatory Atrophy in Canine Prostatic Samples

by Giovana de Godoy Fernandes, Bruna Pedrina, Patrícia de Faria Lainetti, Priscila Emiko Kobayashi, Verônica Mollica Govoni, Chiara Palmieri, Veridiana Maria Brianezi Dignani de Moura, Renée Laufer-Amorim and Carlos Eduardo Fonseca-Alves

Cancers 2021, 13(8), 1887; https://doi.org/10.3390/cancers13081887 - 14 Apr 2021

Cited by 7 | Viewed by 2780

Abstract

Proliferative inflammatory atrophy (PIA) is an atrophic lesion of the prostate gland that occurs in men and dogs and is associated with a chronic inflammatory infiltrate. In this study, we retrospectively reviewed canine prostatic samples from intact dogs, identifying 50 normal prostates, 140 [...] Read more.

Proliferative inflammatory atrophy (PIA) is an atrophic lesion of the prostate gland that occurs in men and dogs and is associated with a chronic inflammatory infiltrate. In this study, we retrospectively reviewed canine prostatic samples from intact dogs, identifying 50 normal prostates, 140 cases of prostatic hyperplasia, 171 cases of PIA, 84 with prostate cancer (PC), 14 with prostatic intraepithelial neoplasia (PIN) and 10 with bacterial prostatitis. PIA samples were then selected and classified according to the human classification. The presence of PIA lesions surrounding neoplastic areas was then evaluated to establish a morphological transition from normal to preneoplastic and neoplastic tissue. In addition, the expression of PTEN, P53, MDM2 and nuclear androgen receptor (AR) were analyzed in 20 normal samples and 20 PIA lesions by immunohistochemistry and qPCR. All PIA lesions showed variable degrees of mononuclear cell infiltration around the glands and simple atrophy was the most common histopathological feature. PIA was identified between normal glands and PC in 51 (61%) out of the 84 PC samples. PIA lesions were diffusely positive for molecular weight cytokeratin (HMWC). Decreased PTEN and AR gene and protein expression was found in PIA compared to normal samples. Overall, our results strongly suggest that PIA is a frequent lesion associated with PC. Additionally, this finding corroborates the hypothesis that in dogs, as is the case in humans, PIA is a pre neoplastic lesion that has the potential to progress into PC, indicating an alternative mechanism of prostate cancer development in dogs. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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13 pages, 2639 KiB

Open AccessArticle

Prognostic Impact of AHNAK2 Expression in Patients Treated with Radical Cystectomy

by Dai Koguchi, Kazumasa Matsumoto, Yuriko Shimizu, Momoko Kobayashi, Shuhei Hirano, Masaomi Ikeda, Yuichi Sato and Masatsugu Iwamura

Cancers 2021, 13(8), 1748; https://doi.org/10.3390/cancers13081748 - 09 Apr 2021

Cited by 6 | Viewed by 1980

Abstract

Data regarding expression levels of AHNAK2 in bladder cancer (BCa) have been very scarce. We retrospectively reviewed clinical data including clinicopathological features in 120 patients who underwent radical cystectomy (RC) for BCa. The expression levels of AHNAK2 in the specimens obtained by RC [...] Read more.

Data regarding expression levels of AHNAK2 in bladder cancer (BCa) have been very scarce. We retrospectively reviewed clinical data including clinicopathological features in 120 patients who underwent radical cystectomy (RC) for BCa. The expression levels of AHNAK2 in the specimens obtained by RC were classified as low expression (LE) or high expression (HE) by immunohistochemical staining. Statistical analyses were performed to compare associations between the two AHNAK2 expression patterns and the prognoses in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS). A Kaplan–Meier analysis showed that patients with HE had a significantly worse RFS and CSS than those with LE (hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.02–2.98, p = 0.027 and HR: 1.91, 95% CI: 1.08–3.38, p = 0.023, respectively). In a multivariate analysis, independent risk factors for worse RFS and CSS were shown as HE (HR: 1.96, 95% CI: 1.08–3.53, p = 0.026 and HR: 2.22, 95% CI: 1.14–4.31, p = 0.019, respectively) and lymph node metastasis (HR: 2.04, 95% CI: 1.09–3.84, p = 0.026 and HR: 1.19, 95% CI: 1.25–4.97, p = 0.009, respectively). The present study showed that AHNAK2 acts as a novel prognostic biomarker in patients with RC for BCa. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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13 pages, 1531 KiB

Open AccessArticle

Renal Cell Carcinoma with or without Tumor Thrombus Invading the Liver, Pancreas and Duodenum

by Javier González, Jeffrey J. Gaynor and Gaetano Ciancio

Cancers 2021, 13(7), 1695; https://doi.org/10.3390/cancers13071695 - 03 Apr 2021

Cited by 2 | Viewed by 2320

Abstract

Background: The purpose of this study is to report the outcomes of a series of patients with locally advanced renal cell carcinoma (RCC) who underwent radical nephrectomy, tumor thrombectomy, and visceral resection. Patients and methods: 18 consecutive patients who underwent surgical treatment in [...] Read more.

Background: The purpose of this study is to report the outcomes of a series of patients with locally advanced renal cell carcinoma (RCC) who underwent radical nephrectomy, tumor thrombectomy, and visceral resection. Patients and methods: 18 consecutive patients who underwent surgical treatment in the period 2003-2019 were included. Neoplastic extension was found extending into the pancreas, duodenum, and liver in 9(50%), 2(11.1%), and 7(38.8%) patients, respectively. Seven patients (38.8%) presented also inferior vena cava tumor thrombus level I (n = 3), II (n = 2), or III (n = 2). The resection was tailored according to the degree of invasiveness. Demographics, clinical presentation, disease characteristics, surgical details, 30-day postoperative complications, and overall survival (OS) were analyzed. Results: Median age was 56 years (range: 40–76). Median tumor size was 14.5 cm (range, 8.8–22), and 10 cm (range: 4–15) for those cases with pancreatico-duodenal and liver involvement, respectively. Median estimated blood loss (EBL) was 475 mL (range: 100–4000) and resulted higher for those cases requiring thrombectomy (300 mL vs. 750 mL). Nine patients (50%) required transfusions with a median requirement of 4 units (range: 2–8). No perioperative deaths were registered in the first 30 days. Overall complication rate was 44.4%. Major complications were detected in 6/18 patients (33.3%). Overall median follow-up was 24 months (range: 0–108). Five-year OS (actuarial) rate was 89.9% and 75%, for 9/11 patients with pancreatico-duodenal involvement and 6/7 patients with liver invasion, respectively. Conclusion: Our series establishes the technical feasibility of this procedure with acceptable complication rates, no deaths, and potential for durable response. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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14 pages, 298 KiB

Open AccessArticle

Restaging the Biochemical Recurrence of Prostate Cancer with [⁶⁸Ga]Ga-PSMA-11 PET/CT: Diagnostic Performance and Impact on Patient Disease Management

by Aloÿse Fourquet, Lucien Lahmi, Timofei Rusu, Yazid Belkacemi, Gilles Créhange, Alexandre de la Taille, Georges Fournier, Olivier Cussenot and Mathieu Gauthé

Cancers 2021, 13(7), 1594; https://doi.org/10.3390/cancers13071594 - 30 Mar 2021

Cited by 12 | Viewed by 1892

Abstract

Background: Detection rates of [⁶⁸Ga]Ga-PSMA-11 PET/CT on the restaging of prostate cancer (PCa) patients presenting with biochemical recurrence (BCR) have been well documented, but its performance and impact on patient management have not been evaluated as extensively. Methods: Retrospective analysis of [...] Read more.

Background: Detection rates of [⁶⁸Ga]Ga-PSMA-11 PET/CT on the restaging of prostate cancer (PCa) patients presenting with biochemical recurrence (BCR) have been well documented, but its performance and impact on patient management have not been evaluated as extensively. Methods: Retrospective analysis of PCa patients presenting with BCR and referred for [⁶⁸Ga]Ga-PSMA-11 PET/CT. Pathological foci were classified according to six anatomical sites and evaluated with a three-point scale according to the uptake intensity. The impact of [⁶⁸Ga]Ga-PSMA-11 PET/CT was defined as any change in management that was triggered by [⁶⁸Ga]Ga-PSMA-11 PET/CT. The existence of a PCa lesion was established according to a composite standard of truth based on all clinical data available collected during the follow-up period. Results: We included 294 patients. The detection rate was 69%. Per-patient sensitivity and specificity were both 70%. Patient disease management was changed in 68% of patients, and [⁶⁸Ga]Ga-PSMA-11 PET/CT impacted this change in 86% of patients. The treatment carried out on patient was considered effective in 89% of patients when guided by [⁶⁸Ga]Ga-PSMA-11 PET/CT versus 61% of patients when not guided by [⁶⁸Ga]Ga-PSMA-11 PET/CT (p < 0.001). Conclusions: [⁶⁸Ga]Ga-PSMA-11 PET/CT demonstrated high performance in locating PCa recurrence sites and impacted therapeutic management in nearly two out of three patients. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

16 pages, 2385 KiB

Open AccessArticle

Clinical Features and Multiplatform Molecular Analysis Assist in Understanding Patient Response to Anti-PD-1/PD-L1 in Renal Cell Carcinoma

by Eileen Shiuan, Anupama Reddy, Stephanie O. Dudzinski, Aaron R. Lim, Ayaka Sugiura, Rachel Hongo, Kirsten Young, Xian-De Liu, Christof C. Smith, Jamye O’Neal, Kimberly B. Dahlman, Renee McAlister, Beiru Chen, Kristen Ruma, Nathan Roscoe, Jehovana Bender, Joolz Ward, Ju Young Kim, Christine Vaupel, Jennifer Bordeaux, Shridar Ganesan, Tina M. Mayer, Gregory M. Riedlinger, Benjamin G. Vincent, Nancy B. Davis, Scott M. Haake, Jeffrey C. Rathmell, Eric Jonasch, Brian I. Rini, W. Kimryn Rathmell and Kathryn E. Beckermann Show full author list Hide full author list

Cancers 2021, 13(6), 1475; https://doi.org/10.3390/cancers13061475 - 23 Mar 2021

Cited by 11 | Viewed by 4287

Abstract

Predicting response to ICI therapy among patients with renal cell carcinoma (RCC) has been uniquely challenging. We analyzed patient characteristics and clinical correlates from a retrospective single-site cohort of advanced RCC patients receiving anti-PD-1/PD-L1 monotherapy (N = 97), as well as molecular parameters [...] Read more.

Predicting response to ICI therapy among patients with renal cell carcinoma (RCC) has been uniquely challenging. We analyzed patient characteristics and clinical correlates from a retrospective single-site cohort of advanced RCC patients receiving anti-PD-1/PD-L1 monotherapy (N = 97), as well as molecular parameters in a subset of patients, including multiplexed immunofluorescence (mIF), whole exome sequencing (WES), T cell receptor (TCR) sequencing, and RNA sequencing (RNA-seq). Clinical factors such as the development of immune-related adverse events (odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.05–5.91) and immunological prognostic parameters, including a higher percentage of circulating lymphocytes (23.4% vs. 17.4%, p = 0.0015) and a lower percentage of circulating neutrophils (61.8% vs. 68.5%, p = 0.0045), correlated with response. Previously identified gene expression signatures representing pathways of angiogenesis, myeloid inflammation, T effector presence, and clear cell signatures also correlated with response. High PD-L1 expression (>10% cells) as well as low TCR diversity (≤644 clonotypes) were associated with improved progression-free survival (PFS). We corroborate previously published findings and provide preliminary evidence of T cell clonality impacting the outcome of RCC patients. To further biomarker development in RCC, future studies will benefit from integrated analysis of multiple molecular platforms and prospective validation. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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13 pages, 1318 KiB

Open AccessArticle

Prognostic Index for Predicting Prostate Cancer Survival in a Randomized Screening Trial: Development and Validation

by Subas Neupane, Jaakko Nevalainen, Jani Raitanen, Kirsi Talala, Paula Kujala, Kimmo Taari, Teuvo L. J. Tammela, Ewout W. Steyerberg and Anssi Auvinen

Cancers 2021, 13(3), 435; https://doi.org/10.3390/cancers13030435 - 24 Jan 2021

Cited by 3 | Viewed by 2379

Abstract

We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up [...] Read more.

We developed and validated a prognostic index to predict survival from prostate cancer (PCa) based on the Finnish randomized screening trial (FinRSPC). Men diagnosed with localized PCa (N = 7042) were included. European Association of Urology risk groups were defined. The follow-up was divided into three periods (0–3, 3–9 and 9–20 years) for development and two corresponding validation periods (3–6 and 9–15 years). A multivariable complementary log–log regression model was used to calculate the full prognostic index. Predicted cause-specific survival at 10 years from diagnosis was calculated for the control arm using a simplified risk score at diagnosis. The full prognostic index discriminates well men with PCa with different survival. The area under the curve (AUC) was 0.83 for both the 3–6 year and 9–15 year validation periods. In the simplified risk score, patients with a low risk score at diagnosis had the most favorable survival, while the outcome was poorest for the patients with high risk scores. The prognostic index was able to distinguish well between men with higher and lower survival, and the simplified risk score can be used as a basis for decision making. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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Review

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17 pages, 872 KiB

Open AccessReview

Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

by Sara Elena Rebuzzi, Giuseppe Luigi Banna, Veronica Murianni, Alessandra Damassi, Emilio Francesco Giunta, Filippo Fraggetta, Ugo De Giorgi, Richard Cathomas, Pasquale Rescigno, Matteo Brunelli and Giuseppe Fornarini

Cancers 2021, 13(21), 5517; https://doi.org/10.3390/cancers13215517 - 03 Nov 2021

Cited by 8 | Viewed by 1959

Abstract

In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only [...] Read more.

In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients’ characteristics. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

11 pages, 587 KiB

Open AccessReview

Global Trends of Latent Prostate Cancer in Autopsy Studies

by Takahiro Kimura, Shun Sato, Hiroyuki Takahashi and Shin Egawa

Cancers 2021, 13(2), 359; https://doi.org/10.3390/cancers13020359 - 19 Jan 2021

Cited by 22 | Viewed by 3095

Abstract

The incidence of prostate cancer (PC) has been increasing in Asian countries, where it was previously low. Although the adoption of a Westernized lifestyle is a possible explanation, the incidence is statistically biased due to the increase in prostate-specific antigen (PSA) screening and [...] Read more.

The incidence of prostate cancer (PC) has been increasing in Asian countries, where it was previously low. Although the adoption of a Westernized lifestyle is a possible explanation, the incidence is statistically biased due to the increase in prostate-specific antigen (PSA) screening and the accuracy of national cancer registration systems. Studies on latent PC provide less biased information. This review included studies evaluating latent PC in several countries after excluding studies using random or single-section evaluations and those that did not mention section thickness. The findings showed that latent PC prevalence has been stable since 1950 in Western countries, but has increased over time in Asian countries. Latent PC in Asian men has increased in both prevalence and number of high-grade cases. Racial differences between Caucasian and Asian men may explain the tumor location of latent PC. In conclusion, the recent increase in latent PC in Asian men is consistent with an increase in clinical PC. Evidence suggests that this increase is caused not only by the increase in PSA screening, but also by the adoption of a more Westernized lifestyle. Autopsy findings suggest the need to reconsider the definition of clinically insignificant PC. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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22 pages, 1862 KiB

Open AccessFeature PaperReview

Review of Experimental Studies to Improve Radiotherapy Response in Bladder Cancer: Comments and Perspectives

by Linda Silina, Fatlinda Maksut, Isabelle Bernard-Pierrot, François Radvanyi, Gilles Créhange, Frédérique Mégnin-Chanet and Pierre Verrelle

Cancers 2021, 13(1), 87; https://doi.org/10.3390/cancers13010087 - 30 Dec 2020

Cited by 10 | Viewed by 2927

Abstract

Bladder cancer is among the top ten most common cancer types in the world. Around 25% of all cases are muscle-invasive bladder cancer, for which the gold standard treatment in the absence of metastasis is the cystectomy. In recent years, trimodality treatment associating [...] Read more.

Bladder cancer is among the top ten most common cancer types in the world. Around 25% of all cases are muscle-invasive bladder cancer, for which the gold standard treatment in the absence of metastasis is the cystectomy. In recent years, trimodality treatment associating maximal transurethral resection and radiotherapy combined with concurrent chemotherapy is increasingly used as an organ-preserving alternative. However, the use of this treatment is still limited by the lack of biomarkers predicting tumour response and by a lack of targeted radiosensitising drugs that can improve the therapeutic index, especially by limiting side effects such as bladder fibrosis. In order to improve the bladder-preserving treatment, experimental studies addressing these main issues ought to be considered (both in vitro and in vivo studies). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we conducted a literature search in PubMed on experimental studies investigating how to improve bladder cancer radiotherapy with different radiosensitising agents using a comprehensive search string. We made comments on experimental model selection, experimental design and results, formulating the gaps of knowledge still existing: such as the lack of reliable predictive biomarkers of tumour response to chemoradiation according to the molecular tumour subtype and lack of efficient radiosensitising agents specifically targeting bladder tumour cells. We provided guidance to improve forthcoming studies, such as taking into account molecular characteristics of the preclinical models and highlighted the value of using patient-derived xenografts as well as syngeneic models. Finally, this review could be a useful tool to set up new radiation-based combined treatments with an improved therapeutic index that is needed for bladder preservation. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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Other

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6 pages, 367 KiB

Open AccessPerspective

Metastasis, an Example of Evolvability

by Annick Laruelle, Claudia Manini, Elena Iñarra and José I. López

Cancers 2021, 13(15), 3653; https://doi.org/10.3390/cancers13153653 - 21 Jul 2021

Cited by 8 | Viewed by 2082

Abstract

This overview focuses on two different perspectives to analyze the metastatic process taking clear cell renal cell carcinoma as a model, molecular and ecological. On the one hand, genomic analyses have demonstrated up to seven different constrained routes of tumor evolution and two [...] Read more.

This overview focuses on two different perspectives to analyze the metastatic process taking clear cell renal cell carcinoma as a model, molecular and ecological. On the one hand, genomic analyses have demonstrated up to seven different constrained routes of tumor evolution and two different metastatic patterns. On the other hand, game theory applied to cell encounters within a tumor provides a sociological perspective of the possible behaviors of individuals (cells) in a collectivity. This combined approach provides a more comprehensive understanding of the complex rules governing a neoplasm. Full article

(This article belongs to the Special Issue Urological Cancer 2021)

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