One-year clinical outcomes of MR-guided stereotactic body radiation therapy with rectal spacer for patients with localized prostate cancer.

BACKGROUND AND PURPOSE: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes. MATERIALS AND METHODS: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases. RESULTS: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains. CONCLUSIONS: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation.

Regulated Formation of lncRNA-DNA Hybrids Enables Faster Transcriptional Induction and Environmental Adaptation.

Long non-coding (lnc)RNAs, once thought to merely represent noise from imprecise transcription initiation, have now emerged as major regulatory entities in all eukaryotes. In contrast to the rapidly expanding identification of individual lncRNAs, mechanistic characterization has lagged behind. Here we provide evidence that the GAL lncRNAs in the budding yeast S. cerevisiae promote transcriptional induction in trans by formation of lncRNA-DNA hybrids or R-loops. The evolutionarily conserved RNA helicase Dbp2 regulates formation of these R-loops as genomic deletion or nuclear depletion results in accumulation of these structures across the GAL cluster gene promoters and coding regions. Enhanced transcriptional induction is manifested by lncRNA-dependent displacement of the Cyc8 co-repressor and subsequent gene looping, suggesting that these lncRNAs promote induction by altering chromatin architecture. Moreover, the GAL lncRNAs confer a competitive fitness advantage to yeast cells because expression of these non-coding molecules correlates with faster adaptation in response to an environmental switch.

Hybridization-mediated off-target effects of splice-switching antisense oligonucleotides.

Splice-switching antisense oligonucleotides (ASOs), which bind specific RNA-target sequences and modulate pre-mRNA splicing by sterically blocking the binding of splicing factors to the pre-mRNA, are a promising therapeutic modality to treat a range of genetic diseases. ASOs are typically 15-25 nt long and considered to be highly specific towards their intended target sequence, typically elements that control exon definition and/or splice-site recognition. However, whether or not splice-modulating ASOs also induce hybridization-dependent mis-splicing of unintended targets has not been systematically studied. Here, we tested the in vitro effects of splice-modulating ASOs on 108 potential off-targets predicted on the basis of sequence complementarity, and identified 17 mis-splicing events for one of the ASOs tested. Based on analysis of data from two overlapping ASO sequences, we conclude that off-target effects are difficult to predict, and the choice of ASO chemistry influences the extent of off-target activity. The off-target events caused by the uniformly modified ASOs tested in this study were significantly reduced with mixed-chemistry ASOs of the same sequence. Furthermore, using shorter ASOs, combining two ASOs, and delivering ASOs by free uptake also reduced off-target activity. Finally, ASOs with strategically placed mismatches can be used to reduce unwanted off-target splicing events.

A human-specific switch of alternatively spliced AFMID isoforms contributes to TP53 mutations and tumor recurrence in hepatocellular carcinoma.

Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients' survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A The switch of AFMID isoforms is human-specific and not detectable in other species, including primates. Finally, we show that overexpression of the full-length AFMID isoform leads to a higher NAD+ level, lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative analysis uncovered a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.

Consensus statements on the management of clinically localized prostate cancer from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

OBJECTIVE: To formulate consensus statements to facilitate physician management strategies for patients with clinically localized prostate cancer (PCa) in Hong Kong by jointly convening a panel of 12 experts from the two local professional organizations representing PCa specialists, who had previously established consensus statements on the management of metastatic PCa for the locality. METHODS: Through a series of meetings, the panellists discussed their clinical experience and the published evidence regarding various areas of the management of localized PCa, then drafted consensus statements. At the final meeting, each drafted statement was voted on by every panellist based on its practicability of recommendation in the locality. RESULTS: A total of 76 consensus statements were ultimately accepted and established by panel voting. CONCLUSION: Derived from the recent evidence and major overseas guidelines, along with local clinical experience and practicability, the consensus statements were aimed to serve as a practical reference for physicians in Hong Kong for the management of localized PCa.

Consensus statements on the management of metastatic prostate cancer from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

To establish a set of consensus statements to facilitate physician management strategies for patients with metastatic prostate cancer (mPCa) in Hong Kong. A local expert consensus was organized jointly by the two main professional organizations representing prostate cancer specialists in Hong Kong. A total of 12 experts were included in the consensus panel. Six of the most crucial and relevant areas of debate regarding the management of mPCa were identified. With the use of a modified Delphi method, several panel meetings were held for the members to discuss their clinical experience and the published literature relevant to the areas of debate. At the final meeting, each drafted statement was voted on by every member based on its practicability of recommendation in the locality. After the panel voting, a total of 45 consensus statements regarding the management of mPCa were ultimately accepted and established. The consensus statements were primarily derived from the latest clinical evidence and major overseas guidelines, with the consideration of local clinical experience and practicability. These are considered applicable recommendations for Hong Kong physicians for the management of mPCa patients.

Use of the International Prostate Symptom Score (IPSS) in Chinese male patients with benign prostatic hyperplasia.

PURPOSE: To test the psychometric properties of the International Prostate Symptom Score (Hong Kong Chinese version 2) (IPSS) in Chinese male patients with benign prostatic hyperplasia (BPH) under secondary care. METHODS: A prospective longitudinal study was done by interviewing subjects at baseline, at 2 week after baseline for assessing test-retest reliability and at 26 week after baseline for assessing responsiveness. All subjects were interviewed to complete a structured questionnaire including IPSS, Short Form-12 Health Survey version 2 (SF-12v2) and Depression Anxiety Stress Scale (DASS). RESULTS: The IPSS HRQOL score had weak correlations with SF-12v2 summary and DASS domain scores. For reliability analysis, Cronbach's alpha coefficient was 0.90 for the seven symptom-related items. The intraclass correlation coefficients of the IPSS total symptom score and HRQOL score were 0.90 and 0.86, respectively. For sensitivity, statistically significant differences were detected between the subjects with BPH and those without for IPSS total symptom score (effect size = 0.68) but not the IPSS HRQOL score. The areas under ROC curves for the IPSS total symptom and HRQOL scores were 0.67 and 0.60, respectively. CONCLUSIONS: The IPSS was valid, reliable instrument in Chinese patients with BPH. The IPSS total symptom score, but not the HRQOL score, is sensitive in differentiating subgroups.

Long noncoding RNAs promote transcriptional poising of inducible genes.

Long noncoding RNAs (lncRNAs) are a class of molecules that impinge on the expression of protein-coding genes. Previous studies have suggested that the GAL cluster-associated lncRNAs of Saccharomyces cerevisiae repress expression of the protein-coding GAL genes. Herein, we demonstrate a previously unrecognized role for the GAL lncRNAs in activating gene expression. In yeast strains lacking the RNA helicase, DBP2, or the RNA decay enzyme, XRN1, we find that the GAL lncRNAs specifically accelerate gene expression from a prior repressive state. Furthermore, we provide evidence that the previously suggested repressive role is a result of specific mutant phenotypes, rather than a reflection of the normal, wild-type function of these noncoding RNAs. To shed light on the mechanism for lncRNA-dependent gene activation, we show that rapid induction of the protein-coding GAL genes is associated with faster recruitment of RNA polymerase II and reduced association of transcriptional repressors with GAL gene promoters. This suggests that the GAL lncRNAs enhance expression by derepressing the GAL genes. Consistently, the GAL lncRNAs enhance the kinetics of transcriptional induction, promoting faster expression of the protein-coding GAL genes upon the switch in carbon source. We suggest that the GAL lncRNAs poise inducible genes for rapid activation, enabling cells to more effectively trigger new transcriptional programs in response to cellular cues.

FlgM proteins from different bacteria exhibit different structural characteristics.

Intrinsically disordered proteins (IDPs) are a unique class of proteins that do not require a stable structure for function. The importance of IDPs in many biological processes has been established but there remain unanswered questions about their evolution and conservation of their disordered state within a protein family. Our group has been studying the structural similarities among orthologous FlgM proteins, a model class of IDPs. We have previously shown that the FlgM protein from the thermophile Aquifex aeolicus has more structure at A. aeolicus' physiological temperature (85°C) than is observed for the Salmonella typhimurium FlgM, suggesting that the disordered nature of FlgM varies among organisms and is not universally conserved. In this work, we extend these studies to the FlgM proteins from Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, and Bacillus subtilis. We demonstrate that the B. subtilis, E. coli, and S. typhimurium FlgMs exist in a premolten globule-like conformation, though the B. subtilis FlgM is in a more compacted conformation than the other two. The P. aeruginosa and P. mirabilis FlgM proteins exist in a currently unknown conformation that is not either coil-like or premolten globule-like. The P. aeruginosa FlgM appears to contain more weak intramolecular contacts given its more compacted state than the P. mirabilis FlgM. These results provide experimental evidence that members of the same protein family can exhibit different degrees of disorder, though understanding how different disordered states evolve in the same protein family will require more study.

Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. INTERVENTION: Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. RESULTS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS: In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211). PATIENT SUMMARY: Conventionally, non-muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non-muscle-invasive bladder cancer.

The DEAD-box RNA helicase Dbp2 connects RNA quality control with repression of aberrant transcription.

DEAD-box proteins are a class of RNA-dependent ATP hydrolysis enzymes that rearrange RNA and RNA-protein (ribonucleoprotein) complexes. In an effort to characterize the cellular function of individual DEAD-box proteins, our laboratory has uncovered a previously unrecognized link between the DEAD-box protein Dbp2 and the regulation of transcription in Saccharomyces cerevisiae. Here, we report that Dbp2 is a double-stranded RNA-specific ATPase that associates directly with chromatin and is required for transcriptional fidelity. In fact, loss of DBP2 results in multiple gene expression defects, including accumulation of noncoding transcripts, inefficient 3' end formation, and appearance of aberrant transcriptional initiation products. We also show that loss of DBP2 is synthetic lethal with deletion of the nuclear RNA decay factor, RRP6, pointing to a global role for Dbp2 in prevention of aberrant transcriptional products. Taken together, we present a model whereby Dbp2 functions to cotranscriptionally modulate RNA structure, a process that facilitates ribonucleoprotein assembly and clearance of transcripts from genomic loci. These studies suggest that Dbp2 is a missing link in RNA quality control that functions to maintain the fidelity of transcriptional processes.

Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies.

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.

ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth.

The M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in regulation of the Warburg effect, which is characterized by the preference for aerobic glycolysis over oxidative phosphorylation for energy metabolism. PKM2 is an alternative-splice isoform of the PKM gene and is a potential therapeutic target. Antisense oligonucleotides (ASO) that switch PKM splicing from the cancer-associated PKM2 to the PKM1 isoform have been shown to induce apoptosis in cultured glioblastoma cells when delivered by lipofection. Here, we explore the potential of ASO-based PKM splice switching as a targeted therapy for liver cancer. A more potent lead constrained-ethyl (cEt)/DNA ASO induced PKM splice switching and inhibited the growth of cultured hepatocellular carcinoma (HCC) cells. This PKM isoform switch increased pyruvate-kinase activity and altered glucose metabolism. In an orthotopic HCC xenograft mouse model, the lead ASO and a second ASO targeting a nonoverlapping site inhibited tumor growth. Finally, in a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis, without observable toxicity. These results lay the groundwork for a potential ASO-based splicing therapy for HCC. SIGNIFICANCE: Antisense oligonucleotides are used to induce a change in PKM isoform usage in hepatocellular carcinoma, reversing the Warburg effect and inhibiting tumorigenesis.

The diagnostic value of rapid urine test platform UF-5000 for suspected urinary tract infection at the emergency department.

Background and objective: Urine culture is time consuming, which may take days to get the results and impede further timely treatment. Our objective is to evaluate whether the fast urinalysis and bacterial discrimination system called Sysmex UF-5000 may predict urinary tract infections (UTIs) (within minutes) compared with the clinical routine test in suspected UTI patients. In addition, we aimed to explore the accuracy of microbiologic information by UF-5000. Materials and Methods: Consecutive patients who were admitted from the emergency department at Queen Mary Hospital (a tertiary hospital in Hong Kong) from June 2019 to February 2020 were enrolled in the present study. The dipstick test, manual microscopic test with culture, and Sysmex UF-5000 test were performed in the urine samples at admission. Results: A total of 383 patients were finally included in the present study. UF-5000 urinalysis (area under the receiver operator characteristic curve, AUC=0.821, confidence interval, 95%CI: 0.767-0.874) outperformed the dipstick test (AUC=0.602, 95%CI: 0.550-0.654, P=1.32×10-10) for predicting UTIs in patients without prior antibiotic treatment. A significant net benefit from UF-5000 was observed compared with the dipstick test (NRI=39.9%, 95%CI: 19.4-60.4, P=1.36 × 10-4). The urine leukocyte tested by UF-5000 had similar performance (AUC) for predicting UTI compared with the manual microscopic test (P=0.27). In patients without a prior use of antibiotics, the concordance rates between UF-5000 and culture for predicting Gram-positive or -negative bacteriuria and a negative culture were 44.7% and 96.2%, respectively. Conclusions: UF-5000 urinalysis had a significantly better predictive value than the dipstick urine test for predicting UTIs.

Aquifex aeolicus FlgM protein exhibits a temperature-dependent disordered nature.

Studies on the nature and function of intrinsically disordered proteins (IDP) over the past 10 years have demonstrated the importance of IDPs in normal cellular function. Although many proteins predicted to be IDPs have been experimentally characterized on an individual basis, the conservation of disorder between homologous proteins from different organisms has not been fully studied. We now demonstrate that the FlgM protein from the thermophile Aquifex aeolicus exhibits a more ordered conformation at 20 degrees C than the previously characterized FlgM protein from Salmonella typhimurium. FlgM is an inhibitor of the RNA transcription factor sigma28, which is involved in regulation of the late-stage genes involved in flagella synthesis. Previous work has shown that the S. typhimurium FlgM protein is an intrinsically disordered protein, though the C-terminus becomes ordered when bound to sigma28 or under crowded solution conditions. In this work, we demonstrate that at 20 degrees C the A. aeolicus FlgM protein exhibits alpha-helical character in circular dichroism (CD) experiments, though the percentage of alpha-helical content decreases with increased temperature, consistent with the FlgM assuming a less folded conformation. We also show that the A. aeolicus FlgM exhibits cooperativity in chemical denaturation experiments, consistent with a globular nature. Furthermore, we use the fluorescent probe FlAsH to show that the H2 helix is ordered, even in the unbound state and that the H1 and H2 helices appear to be associated with each other in the absence of the sigma28 protein. Finally, we demonstrate that the H2 helix assumes an extended conformation at 85 degrees C. Based on our results, we propose that at 20 degrees C the A. aeolicus FlgM assumes a four-helix bundle-like conformation that becomes a more extended conformation at the A. aeolicus' physiological temperature of 85 degrees C.

Prostate cancer management in the era of COVID-19: Recommendations from the Hong Kong Urological Association and Hong Kong Society of Uro-oncology.

AIM: In response to the fast-developing coronavirus disease 2019 (COVID-19) pandemic, special arrangement and coordination are urgently required in the interdisciplinary care of patients across different medical specialties. This article provides recommendations on the management of different stages of localized or metastatic prostate cancer (PC) amid this pandemic. METHODS: The Hong Kong Urological Association and Hong Kong Society of Uro-oncology formed a joint discussion panel, which consisted of six urologists and six clinical oncologists with extensive experience in the public and private sectors. Following an evidence-based approach, the latest relevant publications were searched and reviewed, before proceeding to a structured discussion of relevant clinical issues. RESULTS: The joint panel provided recommendations for PC management during the pandemic, in terms of general considerations, diagnostic procedures, different disease stages, treatment modules, patient support, and interdisciplinary collaboration. The overall goal was to minimize the risk of infection while avoiding unnecessary delays and compromises in management outcomes. Practical issues during the pandemic were addressed such as the use of invasive diagnostic procedures, robotic-assisted laparoscopic prostatectomy, hypofractionated radiotherapy, and prolonged androgen deprivation therapy. The recommendations were explicated in the context of Hong Kong, a highly populated international city, in relation to the latest international guidelines and evidence. CONCLUSION: A range of recommendations on the management of PC patients during the COVID-19 pandemic was developed. Urologists, oncologists, and physicians treating PC patients may refer to them as practical guidance.

Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer-2019 Updates.

BACKGROUND: To update the Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer, the same panelists as in the previous consensus panel held a series of meetings to discuss updated clinical evidence and experiences. METHODS: The previous consensus statements were retained, deleted, or revised, and new statements were added. At the final meeting, all statements were reviewed and amended as appropriate, followed by panel voting. RESULTS: There were significant changes and additions to the previous consensus statements, primarily driven by the advances in androgen receptor signaling inhibitors, treatment sequencing in metastatic castration-resistant prostate cancer, and increasing recognition of oligometastatic prostate cancer since the introduction of prostate-specific membrane antigen positron emission tomography. In this update, a total of 59 consensus statements were accepted and established. CONCLUSIONS: The consensus panel updated consensus statements on the management of advanced prostate cancer, aiming to allow physicians in the region to keep abreast of the recent evidence on optimal clinical practices.

Iliac artery dissection - A rare complication of renal transplantation: A case report and literature review.

External iliac artery dissection is a rare and under-reported vascular complication after renal transplantation. The etiology is yet to be fully understood. The presentation, investigation and management of this condition are highly variable. Here we report a 52-year-old man successfully treated by endovascular stenting with nitinol stents for an external iliac artery dissection proximal to the anastomosis.

Risk factors in the prediction of long-term patency of Resonance metallic ureteric stent in malignant ureteric obstruction.

Objectives: Cancer is the second leading cause of death globally in 2018 with an estimated 9.6 million deaths. The costs of managing malignant ureteric obstruction (MUO) is a significant burden to any healthcare system. However, the management of MUO has long been a challenge for urologists. The standard options of percutaneous nephrostomy or polymer double J stents are fraught with problems. We report a large patient series with long-term follow-up in the use of Resonance metallic ureteric stents to relieve MUO, and identification of risk factors associated with stent failure. Patients and methods: All patients with MUO who were arranged to have Resonance metallic ureteric stent insertion at two university hospitals were included in this cohort study, starting from June 2011 to July 2016. Data were retrieved retrospectively. The primary outcome was the total duration of stent patency before stent failure due to malignant disease progression. Stent failure was defined as ureteric obstruction identified on imaging (functional radioisotope scan or antegrade pyelogram), acute renal failure resolved by subsequent percutaneous nephrostomy, or any other cause requiring stent removal prematurely. Secondary outcomes were identification of factors associated with stent failure, grade III or above complication, and development of a risk-adopted model to predict metallic ureteric stent patency rates in MUO patients. Median duration of functioning metallic ureteric stent was determined with Kaplan-Meier survival curve. Results: A total of 124 renal units in 95 patients with MUO were eligible for the study, with a median follow-up period of 22.9 months. About 106 (85.5%) renal units had successful metallic stent insertion, of whom 41 (33.1%) renal units ultimately progressed to ureteric obstruction despite the metallic stents, and required subsequent insertion of nephrostomies. Median duration of functioning metallic ureteric stents was 25 months. Female gender (HR 3.0, 95% CI: 1.3-7.2, P = .014) and suspicious bladder lesion (HR 2.9, 95% CI: 1.4-6.2, P = .005) were independent risk factors for stent failure, respectively. Stratifying patients into low (0 risk factor), intermediate (1 risk factor), and high (2 risk factors) risk groups, we found that this could predict the duration of stent patency in MUO with the metallic stents. (Low risk: 30.3 months vs intermediate group: 17.8 months vs high risk: 4.9 months, P < .001). Conclusion: Resonance metallic ureteral stents are able provide a median of 25 months of ureteric drainage in patients with MUO. Determining whether a patient has one or both risks factors (female gender and bladder lesion) will allow one to estimate the duration of metallic stent patency, which in turn may aid in determining cost-effectiveness in individual patients.