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11 pages, 1182 KiB

Open AccessArticle

Detection of Urothelial Bladder Cancer Based on Urine and Tissue Telomerase Activity Measured by Novel RT-TRAP-2PCR Method

by Alexander Glukhov, Natalya Potoldykova, Mark Taratkin, Sergey Gordeev, Konstantin Polyakovsky, Ekaterina Laukhtina, Marco Moschini, Mohammad Abufaraj, Shahrokh F. Shariat, Marina Sekacheva, Dmitry Enikeev and Petr Glybochko

J. Clin. Med. 2021, 10(5), 1055; https://doi.org/10.3390/jcm10051055 - 4 Mar 2021

Cited by 1 | Viewed by 2282

Abstract

Purpose: To assess the diagnostic performance of urine telomerase activity (TA) in detecting bladder cancer (BCa) using the modified Telomeric Repeat Amplification Protocol (TRAP) and the Real Time Telomeric Repeat Amplification Protocol with double Polymerase Chain Reaction (RT-TRAP-2PCR). Methods: In this case-control study, [...] Read more.

Purpose: To assess the diagnostic performance of urine telomerase activity (TA) in detecting bladder cancer (BCa) using the modified Telomeric Repeat Amplification Protocol (TRAP) and the Real Time Telomeric Repeat Amplification Protocol with double Polymerase Chain Reaction (RT-TRAP-2PCR). Methods: In this case-control study, matching urine (in the pre- and post-surgical period) and tissue samples from 68 patients with BCa were assessed for TA. As a control, 45 urine samples were examined from non-BCa patients. TA levels were measured using TRAP and RT-TRAP-2 PCR methods. Results: Preoperative urinary TA was elevated in 64 (94.1%) of the 68 BCa patients. Urine TA was undetectable in 44 control patients, while TA was detected in one patient with histologically verified cystitis. Sensitivity for BCa detection of 94.1% and specificity of 97.8% were observed for urinary TA, while tissue TA had 100% sensitivity and 97.8% specificity. Both urine and tissue TA levels were not significantly higher in patients with muscle-invasive disease compared to those with non-muscle invasive BCa (p > 0.05). Urine and tissue TA levels were not associated with higher tumor grade, stage, and number of tumors (p > 0.05). However, the association was found between higher urinary and tissue TA levels with tumor size ≥ 3 cm (p = 0.02 and p = 0.01, respectively). During the first postoperative year, 17 BCa patients experienced disease recurrence, and urinary TA was present in 14 (82.4%) of these patients. The sensitivity and specificity of urinary TA levels for BCa recurrence in patients with non-muscle invasive bladder cancer (NMIBC) during follow-up were 82% and 94.4%, respectively. Conclusions: This pilot study demonstrates a high diagnostic performance of urinary and tissue TA levels measured by a new RT-TRAP-2PCR method for detecting and monitoring BCa. Additionally, the association was found between higher urinary and tissue TA levels with tumor size ≥ 3 cm; however, higher TA levels failed for significant correlation with advanced tumor stage and grade. Our study could serve as a benchmark for the evaluation of novel biomarkers using the RT-TRAP-2PCR method. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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11 pages, 769 KiB

Open AccessArticle

Head-to-Head Comparison of Two Nomograms Predicting Probability of Lymph Node Invasion in Prostate Cancer and the Therapeutic Impact of Higher Nomogram Threshold

by Zilvinas Venclovas, Tim Muilwijk, Aivaras J. Matjosaitis, Mindaugas Jievaltas, Steven Joniau and Daimantas Milonas

J. Clin. Med. 2021, 10(5), 999; https://doi.org/10.3390/jcm10050999 - 2 Mar 2021

Cited by 11 | Viewed by 2593

Abstract

Introduction: The aim of the study was to compare the performance of the 2012 Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms as a predictor for pelvic lymph node invasion (LNI) in men who underwent radical prostatectomy (RP) with pelvic lymph [...] Read more.

Introduction: The aim of the study was to compare the performance of the 2012 Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms as a predictor for pelvic lymph node invasion (LNI) in men who underwent radical prostatectomy (RP) with pelvic lymph node dissection (PLND), to examine their performance and to analyse the therapeutic impact of using 7% nomogram cut-off. Materials and Methods: The study cohort consisted of 807 men with clinically localised prostate cancer (PCa) who underwent open RP with PLND between 2001 and 2019. The area under the curve (AUC) of the receiver operator characteristic analysis was used to quantify the accuracy of the 2012 Briganti and MSKCC nomograms to predict LNI. Calibration plots were used to visualise over or underestimation by the models and a decision curve analysis (DCA) was performed to evaluate the net benefit associated with the used nomograms. Results: A total of 97 of 807 patients had LNI (12%). The AUC of 2012 Briganti and MSKCC nomogram was 80.6 and 79.2, respectively. For the Briganti nomogram using the cut-off value of 7% would lead to reduce PLND in 47% (379/807), while missing 3.96% (15/379) cases with LNI. For the MSKCC nomogram using the cut-off value of 7% a PLND would be omitted in 44.5% (359/807), while missing 3.62% (13/359) of cases with LNI. Conclusions: Both analysed nomograms demonstrated high accuracy for prediction of LNI. Using a 7% nomogram cut-off would allow the avoidance up to 47% of PLNDs, while missing less than 4% of patients with LNI. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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14 pages, 1497 KiB

Open AccessArticle

Alcohol Intake and Alcohol–SNP Interactions Associated with Prostate Cancer Aggressiveness

by Hui-Yi Lin, Xinnan Wang, Tung-Sung Tseng, Yu-Hsiang Kao, Zhide Fang, Patricia E. Molina, Chia-Ho Cheng, Anders E. Berglund, Rosalind A. Eeles, Kenneth R. Muir, Nora Pashayan, Christopher A. Haiman, Hermann Brenner, Jong Y. Park and The PRACTICAL Consortium

J. Clin. Med. 2021, 10(3), 553; https://doi.org/10.3390/jcm10030553 - 2 Feb 2021

Cited by 5 | Viewed by 4189

Abstract

Excessive alcohol intake is a well-known modifiable risk factor for many cancers. It is still unclear whether genetic variants or single nucleotide polymorphisms (SNPs) can modify alcohol intake’s impact on prostate cancer (PCa) aggressiveness. The objective is to test the alcohol–SNP interactions of [...] Read more.

Excessive alcohol intake is a well-known modifiable risk factor for many cancers. It is still unclear whether genetic variants or single nucleotide polymorphisms (SNPs) can modify alcohol intake’s impact on prostate cancer (PCa) aggressiveness. The objective is to test the alcohol–SNP interactions of the 7501 SNPs in the four pathways (angiogenesis, mitochondria, miRNA, and androgen metabolism-related pathways) associated with PCa aggressiveness. We evaluated the impacts of three excessive alcohol intake behaviors in 3306 PCa patients with European ancestry from the PCa Consortium. We tested the alcohol–SNP interactions using logistic models with the discovery-validation study design. All three excessive alcohol intake behaviors were not significantly associated with PCa aggressiveness. However, the interactions of excessive alcohol intake and three SNPs (rs13107662 [CAMK2D, p = 6.2 × 10⁻⁶], rs9907521 [PRKCA,p = 7.1 × 10⁻⁵], and rs11925452 [ROBO1, p = 8.2 × 10⁻⁴]) were significantly associated with PCa aggressiveness. These alcohol–SNP interactions revealed contrasting effects of excessive alcohol intake on PCa aggressiveness according to the genotypes in the identified SNPs. We identified PCa patients with the rs13107662 (CAMK2D) AA genotype, the rs11925452 (ROBO1) AA genotype, and the rs9907521 (PRKCA) AG genotype were more vulnerable to excessive alcohol intake for developing aggressive PCa. Our findings support that the impact of excessive alcohol intake on PCa aggressiveness was varied by the selected genetic profiles. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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12 pages, 1580 KiB

Open AccessArticle

Should We Reconsider the Necessity of a Refinement of Prostate Cancer Risk Classification and Radiotherapy Treatment Strategy? Experiences from a Retrospective Analysis of Data from a Single Institution

by Viktória Temesfői, Róbert Herczeg, Zoltán Lőcsei, Klára Sebestyén, Zsolt Sebestyén, László Mangel and Miklós Damásdi

J. Clin. Med. 2021, 10(1), 110; https://doi.org/10.3390/jcm10010110 - 30 Dec 2020

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Abstract

Background: Radiation therapy has undergone significant technical development in the past decade. However, the complex therapy of intermediate-risk patients with organ-confined prostate carcinoma still poses many questions. Our retrospective study investigated the impact of selected components of the treatment process including radiotherapy, hormone [...] Read more.

Background: Radiation therapy has undergone significant technical development in the past decade. However, the complex therapy of intermediate-risk patients with organ-confined prostate carcinoma still poses many questions. Our retrospective study investigated the impact of selected components of the treatment process including radiotherapy, hormone deprivation, risk classification, and patients’ response to therapy. Methods: The impact of delivered dose, planning accuracy, duration of hormone deprivation, risk classification, and the time to reach prostate-specific antigen (PSA) nadir state were analyzed among ninety-nine individuals afflicted with organ-confined disease. Progression was defined as a radiological or biochemical relapse within five years from radiotherapy treatment. Results: We found that 58.3% of the progressive population consisted of intermediate-risk patients. The progression rate in the intermediate group was higher (21.9%) than in the high-risk population (12.1%). Dividing the intermediate group, according to the International Society of Urological Pathology (ISUP) recommendations, resulted in the non-favorable subgroup having the highest rate of progression (33.3%) and depicting the lowest percentage of progression-free survival (66.7%). Conclusion: Extended pelvic irradiation on the regional lymph nodes may be necessary for the ISUP Grade 3 subgroup, similarly to the high-risk treatment. Therapy optimization regarding the intermediate-risk population based on the ISUP subgrouping suggestions is highly recommended in the treatment of organ-confined prostate cancer. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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13 pages, 995 KiB

Open AccessArticle

Prognostic Significance of Primary Tumor Location in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Retrospective, Multi-Center Cohort Study in Taiwan

by Lian-Ching Yu, Chao-Hsiang Chang, Chi-Ping Huang, Chao-Yuan Huang, Jian-Hua Hong, Ta-Yao Tai, Han-Yu Weng, Chi-Wen Lo, Chung-You Tsai, Yu-Khun Lee, Yao-Chou Tsai, Thomas Y. Hsueh, Yung-Tai Chen, I-Hsuan Chen, Bing-Juin Chiang, Jen-Shu Tseng, Chia-Chang Wu, Wei-Yu Lin, Tsu-Ming Chien, Zai-Lin Sheu, Ching-Chia Li, Hung-Lung Ke, Wei-Ming Li, Hsiang-Ying Lee, Wen-Jeng Wu and Hsin-Chih Yeh Show full author list Hide full author list

J. Clin. Med. 2020, 9(12), 3866; https://doi.org/10.3390/jcm9123866 - 27 Nov 2020

Cited by 14 | Viewed by 3018

Abstract

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions [...] Read more.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121–1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169–2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095–1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141–1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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9 pages, 1052 KiB

Open AccessArticle

Prostate Cancer Screening with PSA: Ten Years’ Experience of Population Based Early Prostate Cancer Detection Programme in Lithuania

by Ausvydas Patasius, Agne Krilaviciute and Giedre Smailyte

J. Clin. Med. 2020, 9(12), 3826; https://doi.org/10.3390/jcm9123826 - 26 Nov 2020

Cited by 16 | Viewed by 3033

Abstract

The aim of this study is to report key performance estimates from the ten years of a population-based prostate cancer screening programme in Lithuania. Retrospective analysis of screening activities recorded in 2006–2015 among men aged 50–74 years was performed. We estimated screening coverage, [...] Read more.

The aim of this study is to report key performance estimates from the ten years of a population-based prostate cancer screening programme in Lithuania. Retrospective analysis of screening activities recorded in 2006–2015 among men aged 50–74 years was performed. We estimated screening coverage, cancer detection rate, compliance to biopsy, and positive predictive values in each screening round inside and outside the target population. In the first 10 years of screening, 16,061 prostate cancer cases were registered within the screening programme, 10,202 were observed among screened men but reported outside the screening programme, and 1455 prostate cancers were observed in a screening-naïve population. Screening cover reached up to 45.5% of the target population in the recent rounds. The proportion of prostate specific antigen (PSA) test-positive men decreased from 16.9% in 2006 to 10.7% in 2014–2015. Up to 40.0% of PSA test-positive men received a biopsy, of whom 42.0% were positive for prostate cancer. The cancer detection rate was 10.4−15.0% among PSA test-positives and 1.4–1.9% among screened individuals. Screening participants were more likely to be diagnosed with organ-confined disease as compared to non-participants. Despite the unorganized screening practices being employed and low coverage per screening round, 70% of the target population were screened at least once in the first 10 years of screening. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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12 pages, 1609 KiB

Open AccessArticle

Restaging Transurethral Resection of Bladder Tumours after BCG Immunotherapy Induction in Patients with T1 Non-Muscle-Invasive Bladder Cancer Might not Be Associated with Oncologic Benefit

by Wojciech Krajewski, Marco Moschini, Łukasz Nowak, Sławomir Poletajew, Andrzej Tukiendorf, Luca Afferi, Jeremy Teoh, Tim Muilwijk, Steven Joniau, Alessandro Tafuri, Alessandro Antonelli, Alessandra Gozzo, Andrea Mari, Ettore Di Trapani, Kees Hendricksen, Mario Alvarez-Maestro, Andrea Rodriguez Serrano, Giuseppe Simone, Stefania Zamboni, Claudio Simeone, Maria Cristina Marconi, Riccardo Mastroianni, Guillaume Ploussard, Paweł Rajwa, Ekaterina Laukhtina, Aleksandra Zdrojowy-Wełna, Anna Kołodziej, Andrzej Paradysz, Karl Tully, Joanna Krajewska, Radosław Piszczek, Evanguelos Xylinas and Romuald Zdrojowy Show full author list Hide full author list

J. Clin. Med. 2020, 9(10), 3306; https://doi.org/10.3390/jcm9103306 - 15 Oct 2020

Cited by 7 | Viewed by 3270

Abstract

Background and Purpose: The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2–6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no [...] Read more.

Background and Purpose: The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2–6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no studies comparing post-BCG reTURB with the classic pre-BCG approach. The aim of this study was to assess whether the performance of reTURB after BCG induction in T1HG bladder cancer is related to potential oncological benefits. Materials and Methods: Data from 645 patients with primary T1HG bladder cancer treated between 2001 and 2019 in 12 tertiary care centres were retrospectively reviewed. The study included patients who underwent reTURB before BCG induction (Pre-BCG group: 397 patients; 61.6%) and those who had reTURB performed after BCG induction (Post-BCG group: 248 patients, 38.4%). The decision to perform reTURB before or after BCG induction was according to the surgeon’s discretion, as well as a consideration of local proceedings and protocols. Due to variation in patients’ characteristics, both propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. Results: The five-year recurrence-free survival (RFS) was 64.7% and 69.1% for the Pre- and Post-BCG groups, respectively, and progression-free survival (PFS) was 82.7% and 83.3% for the Pre- and Post-BCG groups, respectively (both: p > 0.05). Similarly, neither RFS nor PFS differed significantly for a five-year period or in the whole time of observation after the PSM and IPW matching methods were used. Conclusions: Our results suggest that there might be no difference in recurrence-free survival and progression-free survival rates, regardless of whether patients have reTURB performed before or after BCG induction. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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10 pages, 233 KiB

Open AccessArticle

Epstein-Barr Virus and Human Adenovirus Viremia in Renal Tumors Is Associated with Histological Features of Malignancy

by Piotr Kryst, Sławomir Poletajew, Aleksandra Wyczałkowska-Tomasik, Stefan Gonczar, Maciej Wysocki, Renata Kapuścińska, Wojciech Krajewski, Wojciech Zgliczyński and Leszek Pączek

J. Clin. Med. 2020, 9(10), 3195; https://doi.org/10.3390/jcm9103195 - 2 Oct 2020

Cited by 7 | Viewed by 3005

Abstract

Background: There is growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic/latent viral infections with the clinical course of renal cell [...] Read more.

Background: There is growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic/latent viral infections with the clinical course of renal cell carcinoma (RCC). Methods: In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, Düren, Germany) from tumor tissue and using the EZ1 Virus Mini Kit v2.0 from plasma. The number of viral copies of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) in the tissue and plasma was assessed with real-time PCR. Results: Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p < 0.05), more commonly presented with chronic renal disease (OR 2.4, p < 0.05), diabetes (OR 4.2, p < 0.05) and overweight (OR 2.0, p < 0.05). Regarding oncological data, infected patients were found to have a higher rate of high-grade cancers (OR 5.0, p < 0.05) and a higher rate of papillary RCCs (OR 8.3, p < 0.05). Status of viral infections had no influence on the clinical cancer stage, surgical procedure or survival. Conclusions: EBV and ADV infections are common in renal cancer patients and increase the risk of high-grade RCC presence. While there is no significant impact on short term survival, further studies are needed to assess the relevance of these findings in a long run. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

11 pages, 856 KiB

Open AccessArticle

Organ-Sparing Surgery in Testicular Tumor: Is This the Right Approach for Lesions ≤ 20 mm?

by Nina Staudacher, Gennadi Tulchiner, Katie Bates, Michael Ladurner, Mona Kafka, Friedrich Aigner, Renate Pichler and Wolfgang Horninger

J. Clin. Med. 2020, 9(9), 2911; https://doi.org/10.3390/jcm9092911 - 9 Sep 2020

Cited by 12 | Viewed by 3113

Abstract

Background: This study was conducted in order to analyze factors predicting malignancy in patients undergoing organ-sparing surgery (OSS) for small testicular lesions. Methods: Patients with small (≤20 mm) marker-negative clinical stage I testicular tumors were managed by OSS with tumor enucleation and frozen [...] Read more.

Background: This study was conducted in order to analyze factors predicting malignancy in patients undergoing organ-sparing surgery (OSS) for small testicular lesions. Methods: Patients with small (≤20 mm) marker-negative clinical stage I testicular tumors were managed by OSS with tumor enucleation and frozen section examination (FSE) for the past 15 years at our institution. Benign and malignant cases were compared, focusing on preoperative and postoperative lesion sizes. Results: Eighty-nine patients were enrolled in this retrospective study. Ten (11.2%) of them were treated for synchronous bilateral tumors. Sixty-seven (67.7%) of ninety-nine lesions were benign, confirming a high concordance rate (98%) between FSE and final histology. Patients with benign tumors were significantly older than patients with malignant tumors (p = 0.026), and benign tumors were detected more frequently during urologic work-up of hormone disorders (p = 0.001). Preoperative tumor size was a strong predictor of malignancy (area under the curve (AUC) = 0.726; p < 0.001). According to the Youden index, the best cutoff to predict tumor dignity was 13.5 mm, resulting in a sensitivity and specificity of 53% and 85%, respectively. No cases of local recurrence or distant metastasis were confirmed after a median follow-up of 42 months. Conclusion: Our findings are consistent with previous reports, supporting an OSS approach in small testicular tumors whenever possible. Most tumors ≤ 20 mm were benign, and in the case of malignancy, OSS with FSE and consecutive orchiectomy is oncologically safe due to the high concordance rate of FSE and final histology, thus preventing a two-stage procedure. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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8 pages, 374 KiB

Open AccessArticle

Chronoradiation Therapy for Prostate Cancer: Morning Proton Beam Therapy Ameliorates Worsening Lower Urinary Tract Symptoms

by Hiromitsu Negoro, Takashi Iizumi, Yutaro Mori, Yoshitaka Matsumoto, Ichiro Chihara, Akio Hoshi, Hideyuki Sakurai, Hiroyuki Nishiyama and Hitoshi Ishikawa

J. Clin. Med. 2020, 9(7), 2263; https://doi.org/10.3390/jcm9072263 - 16 Jul 2020

Cited by 10 | Viewed by 2288

Abstract

Background and Purpose: Worsening lower urinary tract symptoms (LUTS) are a frequent adverse event following proton beam therapy (PBT) for localized prostate cancer. We investigated the differences in worsening LUTS among patients who received PBT at different times of day. Participants and Methods: [...] Read more.

Background and Purpose: Worsening lower urinary tract symptoms (LUTS) are a frequent adverse event following proton beam therapy (PBT) for localized prostate cancer. We investigated the differences in worsening LUTS among patients who received PBT at different times of day. Participants and Methods: Among 173 patients who underwent PBT for prostate cancer, 168 patients (median age 68.5 years) completed international prostate symptom score (IPSS) questionnaires and were included. Changes in the IPSS from baseline to the end of PBT were assessed by multiple linear regression analysis for age, National Comprehensive Cancer Network risk classification, androgen deprivation therapy, fractional PBT dose, clinical target volume, severity of IPSS, diabetes, LUTS medication use before PBT, anti-coagulant therapy and radiation time of day (morning (08:30–10:30), around noon (10:31–14:30), and late afternoon (14:31–16:30)). Results: IPSS total score and IPSS-Quality of Life (QoL) score (12 patients were excluded due to missing IPSS-QoL score) increased from eight to 14.9 (p < 0.0001) and from two to four (p < 0.0001), respectively. Time of day (morning) was the only determinant for worsening LUTS (β = −0.24, p < 0.01), voiding subscore (β = −0.22, p < 0.05) and IPSS-QoL (β = −0.27, p < 0.005), and was a determinant in item four (urgency) (β = −0.28, p < 0.005) with age (β = 0.19, p < 0.05). Conclusions: Morning PBT for localized prostate cancer significantly ameliorated worsening LUTS and improved QoL compared with treatment around noon or late afternoon. Chronoradiation therapy for localized prostate cancer may be effective and further research to elucidate the underlying mechanism is warranted. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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11 pages, 992 KiB

Open AccessArticle

Survival Benefits Based on the Number of Lymph Nodes Removed during Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis

by Min Soo Choo, Sangjun Yoo, Hyeong Dong Yuk, Chang Wook Jeong, Min Chul Cho, Cheol Kwak, Hyeon Jeong, Hyeon Hoe Kim and Ja Hyeon Ku

J. Clin. Med. 2020, 9(6), 1933; https://doi.org/10.3390/jcm9061933 - 21 Jun 2020

Cited by 6 | Viewed by 2313

Abstract

The role of lymph node dissection (LND) is still controversial for upper tract urothelial carcinoma (UTUC), and there are no guidelines regarding its use. This study was conducted to find a higher level of evidence for the survival benefits based on the number [...] Read more.

The role of lymph node dissection (LND) is still controversial for upper tract urothelial carcinoma (UTUC), and there are no guidelines regarding its use. This study was conducted to find a higher level of evidence for the survival benefits based on the number of LNs removed during radical nephroureterectomy (RNUx) through a systematic review and meta-analysis. We included studies comparing patients who underwent LND during RNUx for UTUC. We searched the major electronic databases (Pubmed, Embase^®, and Scopus^®) and conducted manual searches of the electronically available abstracts of the major international urology cancer meetings [American Society of Clinical Oncology (ASCO), American Urological Association (AUA), and Eropean Association of Urology (EAU)] prior to April 2019 using grouped terms of nephroureterectomy (nephroureterectom*) and lymph node excision (lymphadenectomy; lymph + node*; lymph* + metasta*) with variations in the terms. Study selection, data collection, and risk of bias assessment were performed by two independent authors (A and B). Six retrospective case-control studies included a total of 33,944 patients who underwent RNUx for UTUC, 5071 of whom underwent LND and were finally included in the meta-analysis. The pooled hazard ratio (HR) in these studies revealed that an increased number of LNs removed during RNUx was associated with improved cancer-specific survival (CSS) in patients with UTUC (HR = 0.95, 95% CI: 0.91–0.99; p = 0.07). In addition, increased numbers of LNs removed were associated with improved overall survival (OS) in pN0 patients. However, in pN+ patients, the number of LNs removed showed no survival benefit on CSS, overall survival (OS), or progression-free survival (PFS). Higher numbers of LNs removed during RNUx were associated with improved survival outcomes in patients with UTUC. This study confirmed that LND also has oncological benefits in UTUC patients. Although still a controversial topic, meticulous LND must be considered, and efforts should be made to eliminate as many LNs as possible when administering RNUx for UTUC, especially in patients without clear evidence of LN metastasis. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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12 pages, 695 KiB

Open AccessArticle

Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma

by Hsin-Chih Yeh, Ching-Chia Li, Sheng-Chen Wen, Nirmish Singla, Solomon L. Woldu, Haley Robyak, Chun-Nung Huang, Hung-Lung Ke, Wei-Ming Li, Hsiang-Ying Lee, Chia-Yang Li, Bi-Wen Yeh, Sheau-Fang Yang, Hung-Pin Tu, Shahrokh F. Shariat, Arthur I. Sagalowsky, Jay D. Raman, Yair Lotan, Jer-Tsong Hsieh, Vitaly Margulis and Wen-Jeng Wu Show full author list Hide full author list

J. Clin. Med. 2020, 9(4), 1218; https://doi.org/10.3390/jcm9041218 - 23 Apr 2020

Cited by 3 | Viewed by 2968

Abstract

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., [...] Read more.

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115–2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457–3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299–2.545, p = 0.0005). Kaplan–Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients’ region of presentation suggests its general applicability across different ethnicities. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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Review

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14 pages, 289 KiB

Open AccessReview

Nomograms in Urologic Oncology: Lights and Shadows

by Alessandro Morlacco, Daniele Modonutti, Giovanni Motterle, Francesca Martino, Fabrizio Dal Moro and Giacomo Novara

J. Clin. Med. 2021, 10(5), 980; https://doi.org/10.3390/jcm10050980 - 2 Mar 2021

Cited by 15 | Viewed by 2454

Abstract

Decision-making in urologic oncology involves integrating multiple clinical data to provide an answer to the needs of a single patient. Although the practice of medicine has always been an “art” involving experience, clinical data, scientific evidence and judgment, the creation of specialties and [...] Read more.

Decision-making in urologic oncology involves integrating multiple clinical data to provide an answer to the needs of a single patient. Although the practice of medicine has always been an “art” involving experience, clinical data, scientific evidence and judgment, the creation of specialties and subspecialties has multiplied the challenges faced every day by physicians. In the last decades, with the field of urologic oncology becoming more and more complex, there has been a rise in tools capable of compounding several pieces of information and supporting clinical judgment and experience when approaching a difficult decision. The vast majority of these tools provide a risk of a certain event based on various information integrated in a mathematical model. Specifically, most decision-making tools in the field of urologic focus on the preoperative or postoperative phase and provide a prognostic or predictive risk assessment based on the available clinical and pathological data. More recently, imaging and genomic features started to be incorporated in these models in order to improve their accuracy. Genomic classifiers, look-up tables, regression trees, risk-stratification tools and nomograms are all examples of this effort. Nomograms are by far the most frequently used in clinical practice, but are also among the most controversial of these tools. This critical, narrative review will focus on the use, diffusion and limitations of nomograms in the field of urologic oncology. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

11 pages, 2515 KiB

Open AccessReview

Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis

by Wojciech Krajewski, Łukasz Nowak, Marco Moschini, Sławomir Poletajew, Joanna Chorbińska, Andrea Necchi, Francesco Montorsi, Alberto Briganti, Rafael Sanchez-Salas, Shahrokh F Shariat, Juan Palou, Marek Babjuk, Jeremy YC Teoh, Francesco Soria, Benjamin Pradere, Paola Irene Ornaghi, Aleksandra Pawlak, Janusz Dembowski and Romuald Zdrojowy

J. Clin. Med. 2021, 10(4), 651; https://doi.org/10.3390/jcm10040651 - 8 Feb 2021

Cited by 10 | Viewed by 2973

Abstract

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found [...] Read more.

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3–T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3–T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. Materials and Methods: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). Results: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32–0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58–1.35; p = 0.58). Conclusions: The administration of AC in patients with MIBC and pT3–T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients. Full article

(This article belongs to the Special Issue Prevalence, Diagnosis and New Treatment Outcomes for Urologic Malignancies)

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