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Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multicenter, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL- 5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876–1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment timepoints. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I–III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70–90), indicating good overall health on average during ADT initiation. Conclusions: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.

Purpose: We reviewed the clinical experience of using the ureteral tumor stent (Bard®, angiomed UROSOFT) in the National Taiwan University Hospital. We focused on the efficacy and durability of the ureteral tumor stent. Materials and Methods: We collected the patient data from April 2013 to 2014. A total of 94 patients with 157 ureteral units which received ureteral tumor stent in the National Taiwan University Hospital were enrolled. We analyzed the effectiveness according to the hydronephrosis grading. The durability was counted if it did not match any of the failure criteria including the following: 1. Hydronephrosis upgrade, 2. Serum creatinine elevated over 150% of baseline, 3. Ipsilateral percutaneous nephrostomy insertion or failure to remove it after antegrade insertion, and 4. Replacement due to clinically significant symptoms. Results: In general, 65% hydronephrosis downgrade, 25% remained stationary without severe hydronephrosis, while only 10% deteriorated or remain severe hydronephrosis. The median durability was 6.8 months. The bacteriuria and size of the ureteral tumor stent were the significant factors about the durability in single variant analysis. Conclusion: The ureteral tumor stent would improve the obstructive uropathy and persist functional for an average period over half a year.

Background/purpose: Several strategies have been reported for improving the integrity of transurethral resection of bladder tumor (TURBT). However, no standard has been established. Stratified TURBT (SR) is one of protocols for TURBT, wherein exophytic tumors are first resected and retrieved, and tumor bases are then resected. In this study, we aimed to evaluate the outcomes of SR in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: From January 2012 to December 2017, patients newly diagnosed as having NMIBC with a follow-up period of more than 2 years were enrolled and categorized into SR and conventional TURBT (CR) groups. Propensity score matching at a 2:1 ratio was performed. Outcomes were the detrusor muscle sampling rate, recurrence-free survival (RFS), and progression-free survival (PFS). Results: In total, 205 patients were included in our study. The detrusor muscle sampling rate was higher in the SR group (P = 0.043). After propensity score matching, 162 patients were selected for outcome analysis, with 108 and 54 patients undergoing SR and CR, respectively. Compared with the CR group, the SR group showed a lower recurrence rate (P = 0.015) and better RFS in univariate (P = 0.010) and multivariate (P = 0.006) Cox proportional hazards regression. Progression rate and PFS were not significantly different between the two groups. Conclusion: SR results in a higher detrusor muscle sampling rate and better disease outcomes. Our findings suggest that SR is a promising strategy for TURBT in patients with NMIBC.

Abstract Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan–Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p

Purpose: Deficiencies in methionine sulfoxide reductase (MSR) enzymes, which function as a defense system against oxidative stress, have been linked to age-related diseases, including cancer and neurodegenerative diseases. This study aimed to assess the association between genetic variants in MSR genes and susceptibility to renal cell carcinoma (RCC). Materials and methods: We systematically evaluated the effects of 89 common MSR gene polymorphisms on the risk of developing RCC in a cohort of 630 patients and controls. Furthermore, publicly available gene expression datasets were used to analyze gene expression and patient prognosis. Results: After adjusting for covariates and multiple testing corrections, MSRA rs56198596 and rs11782000 showed significant associations with the risk of RCC. Analysis of expression quantitative trait loci indicated that the risk alleles of these 2 variants tended to correlate with reduced MSRA expression. Pooled analyses of 19 kidney cancer gene expression datasets revealed that RCC exhibited lower MSRA expression than did normal tissues (P < 0.001) and that higher MSRA expression was associated with improved patient prognosis (P < 0.001). Conclusion: These findings suggest that MSRA gene variants may affect the risk of RCC, highlighting the potential protective role of MSRA and its contribution to a favorable RCC prognosis. [ABSTRACT FROM AUTHOR]

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis:

BackgroundThe advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data.Design, Setting, and ParticipantsPatients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information.InterventionThose patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not.Outcome Measurements and Statistical AnalysisPropensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival.Results and LimitationsFor the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285–0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208–0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155–0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number.ConclusionsAdjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

PurposeThis study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU).MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan–Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (−) groups.ResultsA total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.ConclusionsWe found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

RESUMO Objetivo: Relatar os modelos atualmente disponíveis de predição para o desenvolvimento de lesão renal aguda em unidades de terapia para adultos heterogêneas. Métodos: Foi realizada revisão sistemática dos modelos de predição de lesão renal aguda em unidades de terapia intensiva para pacientes adultos. Fizemos busca na base PubMed® quanto a publicações que relatassem desenvolvimento de um novo modelo de predição, validação de um modelo estabelecido, ou impacto de um modelo de predição existente para diagnóstico precoce de lesão renal aguda em unidades de terapia intensiva. Resultados: Triamos 583 artigos potencialmente relevantes. Dentre os 32 artigos que restaram após a primeira seleção, apenas 5 cumpriram os critérios para inclusão. As adaptações não padronizadas feitas para definir o valor inicial de creatinina sérica, quando o valor desse exame antes da admissão estava faltando, levaram a definições heterogêneas do resultado. Preditores comumente incluídos foram sepse, idade e nível de creatinina sérica. Os modelos finais incluíram entre 5 e 19 fatores de risco. As áreas sob a curva Característica de Operação do Receptor para predição do desenvolvimento de lesão renal aguda nas coortes de validação interna variaram entre 0,78 e 0,88. Apenas dois estudos tiveram validação externa. Conclusão: Os modelos de predição clínica de lesão renal aguda podem ajudar na aplicação em tempo apropriado de intervenções preventivas para os pacientes adequados. Contudo, poucos modelos foram externamente validados para as populações da unidade de terapia intensiva. Além disto, definições heterogêneas para lesão renal aguda e critérios de avaliação, e a falta de análise do impacto comprometem uma comparação abrangente dos modelos existentes. São necessárias novas pesquisas para validar os modelos estabelecidos e analisar seu impacto clínico, antes que estes possam ser aplicados na prática clínica.

BackgroundTaiwan is one of the endemic regions where upper tract urothelial carcinoma (UTUC) accounts for approximately a third of all urothelial tumors. Owing to its high prevalence, extensive experience has been accumulated in minimally invasive radical nephroureterectomy (RNU). Although a variety of predictive factors have been explored in numerous studies, most of them were on a single-center or limited institutional basis and data from a domestic cohort are lacking.ObjectiveThis study aims to identify significant predicting factors of oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS), following RNU for UTUC in Taiwan.MethodsA multicenter registry database, Taiwan UTUC Collaboration Group, was utilized to analyze oncological outcomes of 3,333 patients undergoing RNU from 1988 to 2021 among various hospitals in Taiwan. Clinicopathological parameters were recorded according to the principles established by consensus meetings. The Kaplan-Meier estimator was utilized to estimate the survival rates, and the curves were compared using the stratified log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model to explore potential predicting factors.ResultsWith a median follow-up of 41.8 months in 1,808 patients with complete information, the 5-year IVRFS, DFS, CSS, and OS probabilities were 66%, 72%, 81%, and 70%, respectively. In total, 482 patients experienced intravesical recurrence, 307 died of UTUC, and 583 died of any cause. Gender predominance was female (57%). A total of 1,531 patients (84.7%) had high-grade tumors; preoperative hydronephrosis presented in 1,094 patients (60.5%). Synchronous bladder UC was identified in 292 patients (16.2%). Minimally invasive procedures accounted for 78.8% of all surgeries, including 768 hand-assisted laparoscopic (42.5%) and 494 laparoscopic (27.3%) approaches. Synchronous bladder UC was the dominant adverse predicting factor for all survival outcomes. Other independent predicting factors for OS, CSS, and DFS included age ≧70, presence of preoperative hydronephrosis, positive surgical margin, LVI, pathological T and N staging, and laparoscopic RNU.ConclusionSynchronous UC of the urinary bladder is an independent adverse prognostic factor for survival in UTUC. The presence of preoperative hydronephrosis was also corroborated as a disadvantageous prognostic factor. Our multivariate analysis suggested that laparoscopic RNU might provide better oncological control.

BackgroundProstate-specific antigen (PSA) is considered neither sensitive nor specific for prostate cancer (PCa). We aimed to compare total PSA (tPSA), percentage of free PSA (%fPSA), the PSA density (PSAD), Prostate Health Index (PHI), and the PHI density (PHID) to see which one could best predict clinically significant prostate cancer (csPCa): a potentially lethal disease.MethodsA total of 412 men with PSA of 2–20 ng/mL were prospectively included. Serum biomarkers for PCa was collected before transrectal ultrasound guided prostate biopsy. PHI was calculated by the formula: (p2PSA/fPSA) x √tPSA. PHID was calculated as PHI divided by prostate volume measured by transrectal ultrasound.ResultsOf the 412 men, 134 (32.5%) and 94(22.8%) were diagnosed with PCa and csPCa, respectively. We used the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA) to compare the performance of PSA related parameters, PHI and PHID in diagnosing csPCa. AUC for tPSA, %fPSA, %p2PSA, PSAD, PHI and PHID were 0.56、0.63、0.76、0.74、0.77 and 0.82 respectively for csPCa detection. In the univariate analysis, the prostate volume, tPSA, %fPSA, %p2PSA, PHI, PSAD, and PHID were all significantly associated with csPCa, and PHID was the most important predictor (OR 1.41, 95% CI 1.15–1.72). Besides, The AUC of PHID was significantly larger than PHI in csPCa diagnosis (p=0.004). At 90% sensitivity, PHID had the highest specificity (54.1%) for csPCa and could reduce the most unnecessary biopsies (43.7%) and miss the fewest csPCa (8.5%) when PHID ≥ 0.67. In addition to AUC, DCA re-confirmed the clinical benefit of PHID over all PSA-related parameters and PHI in csPCa diagnosis. The PHID cut-off value was positively correlated with the csPCa ratio in the PHID risk table, which is useful for evaluating csPCa risk in a clinical setting.ConclusionThe PHID is an excellent predictor of csPCa. The PHID risk table may be used in standard clinical practice to pre-select men at the highest risk of harboring csPCa.

PurposeThis study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.ResultsAmong the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p

Ferroptosis is a type of iron-dependent cell death pertaining to an excess of lipid peroxidation. It has been suggested that sorafenib—an anti-angiogenic medication for hepatocellular carcinoma (HCC)—induces ferroptosis, but the underlying mechanism for this remains largely unknown. We employed siRNA-mediated gene silencing to investigate the role of Src homology region 2 domain-containing phosphatase-1 (SHP-1), following sorafenib treatment, in cystine/glutamate-antiporter-system-Xc−-regulated cystine uptake. Co-immunoprecipitation was also performed to examine the interactions between MCL1, beclin 1 (BECN1), and solute carrier family 7 member 11 (SLC7A11), which functions as the catalytic subunit of system Xc−. The results of this study showed that sorafenib enhanced the activity of SHP-1, dephosphorylated STAT3, downregulated the expression of MCL1 and, consequently, reduced the association between MCL1 and BECN1. In contrast, increased binding between BECN1 and SLC7A11 was observed following sorafenib treatment. The elevated interaction between BECN1 and SLC7A11 inhibited the activity of system Xc−, whereas BECN1 silencing restored cystine intake and protected cells from ferroptosis. Notably, ectopic expression of MCL1 uncoupled BECN1 from SLC7A11 and rescued cell viability by attenuating lipid peroxidation. The results revealed that ferroptosis could be induced in HCC via SHP-1/STAT3-mediated downregulation of MCL1 and subsequent inhibition of SLC7A11 by increased BECN1 binding.

Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multicenter, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876–1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment timepoints. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I–III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70–90), indicating good overall health on average during ADT initiation. Conclusions: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making. [ABSTRACT FROM AUTHOR]

Purpose: According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods: This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results: A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6-84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion: SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to demonstrate the feasibility and safety of the Senhance robotic system in urologic surgeries. Materials and methods: Patients were included prospectively from July 2018 to December 2020. The exclusion criteria included severe cardiopulmonary diseases and previous extensive abdominal surgeries. Institutional approval and informed consent were obtained. We used the Clavien-Dindo classification system to evaluate the complications that occurred within 30 days after surgery. Common technical and mechanical events encountered were also recorded. Results: A total of 173 patients were recruited. The median age was 65 (58-74) years, and the median body mass index was 24.7 (16.5-35.6) kg/m². Seventeen (9.8%) patients had previously undergone abdominal surgeries. Eighty-three (48%) cases had total extraperitoneal hernioplasty and 32 (18.5%) cases radical prostatectomy, which were the largest 2 surgeries in our study. Sixty-one (35.3%) patients received surgeries due to malignancy. The median docking time was 5 (1-35) minutes. There were 28 (16.2%) cases with grade I complications and 9 (5.2%) cases with grade II complications. Only one case of a grade IIIb complication occurred during radical prostatectomy. No grade IV complications or mortalities were noted. Robotic arm collisions and forces exceeding the limit were the most commonly encountered problems intraoperatively. Conclusion: In our initial experiences, the Senhance robotic system was feasible in oncologic and nononcologic urologic surgeries and had acceptable outcomes. The haptic feedback system is unique and requires a learning period. This system may serve as an alternative tool for robotic urologic surgeries. [ABSTRACT FROM AUTHOR]

Abstract The aberrant expression of cell adhesion molecules is a hallmark of epithelial‐to‐mesenchymal transition, resulting in the transformation of cancer cells to a more aggressive phenotype. This study investigated the association between genetic variants in cell adhesion pathways and the prognosis of patients with prostate cancer following radical prostatectomy (RP). A total of 18 haplotype‐tagging single‐nucleotide polymorphisms (SNPs) in eight cancer‐related adhesion molecules were genotyped in 458 prostate cancer patients, followed by the replication of the top SNPs in an additional set of 185 patients. Log‐rank test and multivariate Cox regression analysis adjusted for covariates were used to evaluate associations with the risk of biochemical recurrence (BCR) after RP. In the discovery set, four SNPs in CDH2 were marginally associated with BCR. Among these, CDH2 rs643555C > T was found to be associated with BCR in the replication set. Patients with rs643555TT genotype had a significantly shorter BCR‐free survival compared with those with CC/CT genotypes in the combined analysis (adjusted hazard ratio 1.78, 95% confidence interval 1.19‐2.67, P = 0.005). Additional analyses revealed that rs643555T was associated with higher expression of CDH2, and upregulated CDH2 was correlated with tumor aggressiveness and shortened BCR‐free survival. In conclusion, rs643555C > T affects CDH2 expression, and thus influences BCR in localized prostate cancer patients treated with RP. CDH2 rs643555 may be a promising biomarker to identify patients at high risk of poor prostate cancer prognosis.

DNA damage repair is frequently dysregulated in advanced prostate cancer and has been linked to cancer susceptibility and survival outcomes. The aim of this study is to assess the influence of genetic variants in DNA damage repair pathways on the prognosis of prostate cancer. Specifically, 167 single nucleotide polymorphisms (SNPs) in 18 DNA damage repair pathway genes were assessed for association with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in a cohort of 630 patients with advanced prostate cancer receiving androgen deprivation therapy. Univariate analysis identified four SNPs associated with CSS, four with OS, and two with PFS. However, only MSH2 rs1400633 C > G showed a significant association upon multivariate analysis and multiple testing adjustments (hazard ratio = 0.75, 95% confidence interval = 0.63–0.90, p = 0.002). Furthermore, rs1400633 risk allele C increased MSH2 expression in the prostate and other tissues, which correlated with more aggressive prostate cancer characteristics. A meta-analysis of 31 gene expression datasets revealed significantly higher MSH2 expression in prostate cancer than in normal tissues (p < 0.001), and this high expression was associated with a poor prognosis of prostate cancer (p = 0.002). In summary, we identified MSH2 rs1400633 as an independent prognostic biomarker for prostate cancer survival, and the association of MSH2 with cancer progression lends relevance to our findings.

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

Background: The addition of androgen-deprivation therapy (ADT) or pelvic radiation to prostate bed salvage radiotherapy (SRT) has been debated for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy. This study aimed to assess the outcomes and propose prediction models for exclusive prostate bed SRT. Methods: This is a prospective observational cohort study with patients who underwent SRT with a pre-SRT PSA < 1.5 ng/mL after radical prostatectomy. Patients were treated with 70-Gy SRT to the prostate bed exclusively. Kaplan–Meier survival analyses and Cox regression analyses were applied for depicting and predicting BCR-free survival, ADT-free survival, and metastasis-free survival (MFS). Regression-based coefficients were used to develop nomograms. Results: A total of 105 patients were included and 91 patients were eligible. The median follow-up period was 39 months. The 5-year BCR-free survival, ADT-free survival, and MFS were 37%, 50%, and 66%, respectively. Multivariable analysis showed that a pre-SRT PSA < 0.45 ng/mL was the only independent factor associated with longer BCR-free survival (p = 0.034), while a PSA-DT > 8 months had better ADT-free survival (p = 0.008). Patients with a PSA-DT > 8 months showed a 100% MFS and a 43% 5-year absolute benefit in MFS than a PSA-DT ≤ 8 months. All patients with a pre-SRT PSA < 0.45 ng/mL and PSA-DT > 8 months were free from subsequent ADT and any metastasis. Conclusions: In patients with a PSA < 0.45 ng/mL and PSA-DT > 8 months for post-prostatectomy BCR, prostate bed SRT provided excellent outcomes without the need for concomitant ADT or pelvic radiotherapy.

The optimal adjuvant treatment for stage IB endometrial cancer remains undefined. We investigated the benefit of modern adjuvant radiotherapy for women with stage IB endometrial cancer. We retrospectively reviewed patients with surgically staged, pure stage IB endometrioid adenocarcinoma (2010 to 2018). Adjuvant modern radiotherapy consists of external-beam radiotherapy (EBRT) by intensity, volumetric-modulated arc radiotherapy, or image-guided vaginal brachytherapy (VBT). The study included 180 stage IB patients. Patients with grade 3 diseases had frequent aggressive histology patterns (lymphovascular space invasion (LVSI); low uterine segment involvement) and experienced significantly shorter recurrence-free survival (RFS) and overall survival (OS) than patients with grade 1/2 diseases. Adjuvant modern radiotherapy decreased the incidence of acute/chronic grade ≥2 gastrointestinal toxicity. In IB grade 1/2 patients, EBRT significantly lengthened survival (RFS/OS); patients with age >60 years, myometrial invasion beyond the outer third, or LVSI benefited the most from EBRT. EBRT also significantly improved survival (RFS/OS) in IB grade 3 patients, where patients with bulky tumors or LVSI benefited the most from EBRT. Therefore, EBRT may be beneficial for all stage IB patients.

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.

Background/Aim: Oxidative stress plays an important role in various pathogenic processes, and disruption in the coordinated production of NADPH oxidase (NOX)-derived reactive oxygen species has been associated with carcinogenesis. However, little is known about whether genetic variants in NOX can contribute to the development of renal cell carcinoma (RCC). Patients and Methods: This study aimed to bridge this knowledge gap by analysing the association of 10 single-nucleotide polymorphisms in the phagocyte NOX genes, CYBA and CYBB, with RCC risk and tumour characteristics in 630 RCC patients and controls. Differential gene expression and patient prognosis analyses were performed using gene expression data obtained from public databases. Results: Multivariate analysis and multiple testing corrections revealed the A allele of rs7195830 in CYBA to be a significant risk allele for RCC, compared to the G allele [odds ratio (OR)=1.70, 95% confidence interval (CI)=1.27-2.26, p<0.001]. A pooled analysis of 17 renal cancer gene expression datasets revealed a higher CYBA expression in RCC than in normal tissues. Moreover, high CYBA expression was associated with advanced tumour characteristics and worse patient prognosis. Conclusion: CYBA might play an oncogenic role in RCC and serve as a predictive indicator of patient prognosis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate differences in healthcare service utilization between patients with and those without benign prostatic hyperplasia (BPH) using Taiwan′s National Health Insurance population-based database. A total of 7413 patients with BPH and 7413 age-matched patients without BPH were included. The outcome variable was 1-year utilization of healthcare services including the number of outpatient visits, inpatient days, and the costs of outpatient and inpatient treatments. In addition, we separated healthcare services into urology services and nonurology services for analysis. We found that as to the utilization of outpatient urological services, patients with BPH had more outpatient services (7.84 vs 0.52, P< 0.001), higher outpatient costs (US$372 vs US$34, P< 0.001), a longer length of inpatient stay (0.55 vs 0.11, P< 0.001), higher in-patients costs (US$149 vs US$32, P< 0.001), and higher total costs (US$521 vs US$67, P< 0.001) than the comparison group. As for nonurological services, patients with BPH also had more outpatient services (49.11 vs 24.79, P< 0.001), higher outpatient costs (US$1794 vs US$1014, P< 0.001), a longer length of in-patient stay (3.72 vs 2.04, P< 0.001), higher inpatient costs (US$874 vs US$486, P< 0.001), and higher total costs (US$2668 vs US$1500, P< 0.001) compared to comparison patients. We also found that the average total cost was about 2-fold greater for patients with BPH than comparison patients. We concluded that patients with BPH had higher healthcare utilization than comparison patients without BPH.