Results in Journal European Urology Open Science: 2,544
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European Urology Open Science, Volume 29, pp 30-35; doi:10.1016/j.euros.2021.04.009
Serum prostate-specific antigen (PSA), used in prostate cancer screening, is nonspecific for cancer and is affected by age and prostate volume. More specific biomarkers could be more accurate for early detection of prostate cancer and reduce unnecessary prostate biopsies. To evaluate the association of age and prostate volume with urinary MyProstateScore (MPS) in a screened, longitudinal cohort without evidence of prostate cancer. The Olmsted County Study included men aged 40–79 yr who underwent biennial prostate cancer screening. PSA ≥4.0 ng/ml or abnormal rectal examination triggered prostate biopsy, and patients with cancer were excluded. The remaining men submitted urinary specimens for PCA3 and TMPRSS2:ERG testing. MPS was calculated using the validated, locked model for grade group ≥2 cancer that includes serum PSA, urinary PCA3, and urinary TMPRSS2:ERG. The associations of age and volume with biomarkers were assessed in multivariable regression models. The t statistic was used to quantify the strength of associations independent of the unit of measurement, and R2 values were used to estimate the proportion of biomarker variance explained by each factor. The study included 314 screened men without evidence of cancer. In multivariable models including age and volume, PCA3 score was significantly associated with age (t = 7.51; p < 0.001), while T2:ERG score was not associated with age or volume. MPS was significantly associated with both age (t = 7.45; p < 0.001) and volume (t = 3.56; p < 0.001), but accounting for age alone explained the variability observed (R2 = 0.29) in a similar way to the model including age and volume (R2 = 0.31). The variability of PCA3, T2:ERG, and MPS was less dependent on age and volume than the variability for PSA (R2 = 0.45). In a cohort of longitudinally screened men without evidence of cancer, we found that MPS demonstrated less variability with noncancer factors (age, prostate volume) than PSA did. These findings support the biology of these markers as more cancer-specific than PSA and highlight their promise in reducing the morbidity associated with PSA-based screening. In a group of men with no evidence of prostate cancer, we found that each of three urine-based markers of cancer—PCA3, T2:ERG, and the commercially available MyProstateScore test—showed less variability with noncancer factors (age and prostate volume) than serum PSA (prostate-specific antigen) did. These findings support their proposed use as noninvasive markers of prostate cancer that could improve the accuracy of early detection.
European Urology Open Science, Volume 29, pp 15-18; doi:10.1016/j.euros.2021.04.007
Life expectancy is increasing in many parts of the world. Using proportional hazard models for competing risks, we investigated whether this increase has changed outcomes after radical cystectomy in a sample of 1419 consecutive patients treated between 1993 and 2018. During the observation period, the mean age and the proportion of patients with American Society of Anesthesiologists physical status class 3 or 4 increased, whereas the proportion of patients with heart disease decreased. Competing mortality (causes other than bladder cancer) decreased in all subgroups (hazard ratios [HRs] per year ranged from 0.931 to 0.963) and after controlling for increasing age (HRs ranged from 1.018 to 1.081). In an optimal model resulting from an analysis including age (HR per year 1.048, 95% confidence interval [CI] 1.027–1.070; p < 0.0001), comorbidity, tumor-related variables, body mass index, (neoadjuvant and adjuvant) chemotherapy and smoking status, the HR per increment for year of surgery was 0.928 (95% CI 0.886–0.973; p = 0.0019). The effect of year of surgery was greater than the decrease in competing mortality that may be expected with increasing life expectancy (4 yr for females, 6 yr for males). In a review of data for 1993–2018, we found that death from other causes after removal of the bladder (radical cystectomy) for bladder cancer decreased over time. This decreasing trend might increase the age limit at which bladder cancer patients can benefit from radical cystectomy in the future.
Reply to Tommy Jiang, Sriram V. Eleswarapu, and Vadim Osadchiy’s Letter to the Editor re: Patrick Lewicki, Spyridon P. Basourakos, Bashir Al Hussein Al Awamlh, et al. Estimating the Impact of COVID-19 on Urology: Data from a Large Nationwide Cohort. Eur Urol Open Sci 2021;25:52–6. Impact of the COVID-19 Pandemic on Kidney Stones: Matching Online Discussions to Real World Data
European Urology Open Science, Volume 29, pp 47-48; doi:10.1016/j.euros.2021.05.005
European Urology Open Science, Volume 29, pp 49-49; doi:10.1016/j.euros.2021.03.012
European Urology Open Science, Volume 29, pp 77-81; doi:10.1016/j.euros.2021.05.007
As of April 13, 2021, 137 million cases of COVID-19 and 2.95 million deaths have been reported worldwide. On December 21, 2020, the Pfizer-BioNTech vaccine was approved for use in the European Union, with efficacy of 95% protection against COVID-19 infection. Several other vaccines are at different stages of assessment by the European Medicines Agency. In addition to the elderly, oncology patients are a vulnerable population in which COVID-19 infection may be more severe. However, owing to the design of the initial studies, evidence on the safety and efficacy of vaccination against SARS-CoV-2 in these patients is scarce and recommendations are based on the opinion of associations, stakeholders, and experts via extrapolation of information and experience for other vaccines, especially influenza vaccines. Despite the limited evidence, the consensus is that SARS-CoV-2 vaccines are safe and vaccination of oncology patients and their close relatives is recommended, although efficacy may be lower in patients with an impaired immune response and the need for additional booster doses is not yet clear. Recommendations include avoiding the use of vaccines based on viral vectors for patients with an impaired immune response, deferring vaccination for immunosuppressed patients or administering the vaccine before immunosuppression, and avoiding chemotherapy receipt between the two doses of a vaccine or on the same day that the vaccine is administered. These recommendations can be extrapolated to urology patients and although evidence is lacking, there should not be greater interference with SARS-CoV-2 vaccines from androgen deprivation therapy or intravesical bacillus Calmette-Guérin. However, large studies to provide strong evidence for uro-oncology patients are needed. We looked at the effects of COVID-19 vaccination for patients with urological cancers. The consensus is that the vaccines are safe, and vaccination of cancer patients and their close relatives is recommended.
European Urology Open Science, Volume 29; doi:10.1016/s2666-1683(21)00113-0
European Urology Open Science, Volume 29, pp 10-14; doi:10.1016/j.euros.2021.04.006
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal malignancy that usually follows an indolent course. The few existing reports of metastatic MTSCC show poor response to systemic therapy. Here we describe the unusual case of a 39-yr-old male with MTSCC presenting as a large renal mass with bulky retroperitoneal lymphadenopathy managed with complete resection of disease. He has remained free of recurrence for 1 yr postoperatively. On the basis of the experience reported here, aggressive surgical resection of MTSCC with isolated nodal metastases may be considered for similar patients in the future given the historically poor response rates to systemic therapy.
European Urology Open Science, Volume 29, pp 59-67; doi:10.1016/j.euros.2021.05.003
Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). However, the kinetics of serum androgens before and after ENZ treatment are unknown. To elucidate the kinetics of serum androgens and explore the possibility of identifying a useful marker for predicting the effects of ENZ. We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. Data were analyzed for 104 patients with CRPC treated with ENZ. We measured serum androgen levels using liquid chromatography-tandem mass spectrometry. Relationships with outcomes were assessed using multivariable Cox regression and log-rank analyses. The median age of the patients was 73 yr. Median serum testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. We performed multivariate analysis using Cox regression to predict prostate-specific antigen progression–free survival (PSA-PFS) and overall survival (OS). Hemoglobin level (≥12.5 vs <12.5 g/dl), docetaxel treatment history (no vs yes), and DHT level (≥5.9 vs <5.9 pg/ml) were significant predictors of PSA-PFS (p < 0.05). Eastern Cooperative Oncology Group performance status (0 vs. 1–2), hemoglobin level (≥12.5 vs <12.5 g/dl), presence of visceral metastasis (no vs yes), amount of bone metastasis (extent of disease 0–2 vs 3–4), and docetaxel treatment history (no vs yes) were significant predictors of OS (p < 0.05). Binomial logistic analysis of the predictors of any grade of anorexia, malaise, and fatigue showed that the presence of visceral metastasis and a low DHT level (<5.9 pg/ml) were significant. Our results suggest that serum androgen levels before ENZ treatment may be useful for predicting efficacy, prognosis, and the incidence of adverse events. We measured blood levels of testosterone and other male hormones before treatment with enzalutamide among men with prostate cancer resistant to castration. We found that the levels of these hormones may be useful for predicting the efficacy of enzalutamide treatment, prognosis, and the occurrence of adverse side effects.
European Urology Open Science, Volume 29, pp 89-92; doi:10.1016/j.euros.2021.05.008
The relationship between testosterone and premature mortality has caused recent controversy. While previous studies have demonstrated mixed results, this is partly because of variable patient populations, different testosterone thresholds, and the use of antiquated techniques to measure serum testosterone. Using the National Health and Nutrition Examination Survey we analyzed a cohort representative of men in the USA to explore the relationship between serum testosterone and premature mortality using contemporary guidelines and testosterone measurements. We found that men with low testosterone (<300 ng/dl) were at higher risk (odds ratio 2.07, 95% confidence interval 1.30–3.32; p < 0.01) of premature death compared to men with normal testosterone. Furthermore, men with low testosterone were also more likely to have treatable comorbid conditions that were independently predictive of premature mortality. Both testosterone and these comorbid conditions are also modulated by lifestyle modifications, rendering this an important therapeutic approach in men with either or both conditions. We explored the relationship between testosterone levels and premature death in a large US population. We found that low testosterone is associated with both premature death and related disease processes such as obesity, both of which can be initially treated with diet and exercise.
European Urology Open Science, Volume 29, pp 82-88; doi:10.1016/j.euros.2021.04.008
Late relapse (LR) of nonseminomatous germ cell tumour (NSGCT) is uncommon, with limited data published. LR is defined as relapse occurring after a disease-free interval of 2 yr. To review features of NSGCT LR in a UK tertiary centre. A total of 3064 patients were referred from January 2005 to December 2017. We identified patients who experienced LR after initial pathology demonstrated NSGCT and reviewed data for their original and LR presentation and management. Outcomes included time to LR measured from the date of diagnosis, and overall survival. This was assessed using Cox proportional Hazards modelling, with stratification or adjustment for potential confounders. We identified 101 patients with LR; the median time to LR was 96 mo. Forty-three patients (42.6%) experienced relapse after 10 yr. Univariable log-rank testing revealed that the median time to LR was significantly shorter for patients who had not received induction chemotherapy (iCTx; 54 mo, 95% confidence interval [CI] 48–108) than for those who did (112 mo, 95% CI 84–186; p = 0.04). Patients who had received iCTx were less likely to have elevated tumour markers (36% vs 46%) and more likely to undergo initial surgical resection at LR compared to CTx-naïve patients. Postpubertal teratoma (PPT), yolk sac, and dedifferentiated elements predominated for patients with iCTx exposure, whereas active GCT or fibrosis predominated in postchemotherapy resections for CTx-naïve patients at LR. Forty-one men underwent postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) as part of their initial treatment for metastatic disease. Of these, 20 experienced LR in the retroperitoneum, with 18 undergoing repeat RPLND as part of their LR management. Fifteen of the repeat RPLND histopathology specimens had a PPT component. There have been 23 deaths overall; survival was worse for patients presenting with symptoms (13/36, 33%) and those receiving CTx and no surgery (10/17, 59%) at LR. When LR of NSGCT occurs, it is frequently after an extended interval and is later among patients with prior iCTx, with PPT predominating. The high frequency of LR within the retroperitoneum following PC-RPLND reinforces the need for good-quality PC-RPLND. We reviewed data for patients who had a late relapse of testicular cancer. We found that patients who did not receive chemotherapy as the first treatment for their initial diagnosis had a shorter time to relapse. Our results highlight the importance of long-term follow-up for testicular cancer.
European Urology Open Science, Volume 29, pp 19-29; doi:10.1016/j.euros.2021.05.001
Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively. To explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis. We applied multiplex immunofluorescence and targeted transcriptomic analysis on 94 radical prostatectomy specimens in patients with (LN+) or without (LN–) pelvic nodal metastases. Both intraepithelial and stromal infiltrations of immune cells and differentially expressed genes (mRNA and protein levels) were correlated with the nodal status. The identified CD4 effector cell signature of nodal metastasis was validated in a comparable independent patient cohort of 184 informative cases. Patient outcome analysis and decision curve analysis were performed with the CD4 effector cell density–based signature. In the discovery cohort, both tumor epithelium and stroma from patients with nodal metastasis had significantly lower infiltration of multiple immune cell types, with stromal CD4 effector cells highlighted as the top candidate marker. Targeted gene expression analysis and confirmatory protein analysis revealed key alteration of extracellular matrix components in tumors with nodal metastasis. Of note, stromal CD4 immune cell density was a significant independent predictor of LN metastasis (odds ratio [OR] = 0.15, p = 0.004), and was further validated as a significant predictor of nodal metastasis in the validation cohort (OR = 0.26, p < 0.001). Decreased T-cell infiltrates in the primary tumor (particularly CD4 effector cells) are associated with a higher risk of LN metastasis. Future evaluation of CD4-based assays on prostate cancer diagnostic biopsy materials may improve selection of at-risk patients for the treatment of LN metastasis. In this report, we found that cancer showing evidence of cancer metastasis to the lymph nodes tends to have less immune cells present within the tumor. We conclude that the extent of immune cells present within a prostate tumor can help doctors determine the most appropriate treatment plan for individual patients.
European Urology Open Science, Volume 29, pp 50-58; doi:10.1016/j.euros.2021.05.002
Non–muscle-invasive bladder cancer (NMIBC) is over three times as common in men as it is in women; however, female patients do not respond as well to immunotherapeutic treatments and experience worse clinical outcomes than their male counterparts. Based on the established sexual dimorphism in mucosal immune responses, we hypothesized that the tumor immune microenvironment of bladder cancer differs between the sexes, and this may contribute to discrepancies in clinical outcomes. To determine biological sex-associated differences in the expression of immune regulatory genes and spatial organization of immune cells in tumors from NMIBC patients. Immune regulatory gene expression levels in tumors from male (n = 357) and female (n = 103) patients were measured using whole transcriptome profiles of tumors from the UROMOL cohort. Multiplexe immunofluorescence was performed to evaluate the density and spatial distribution of immune cells and immune checkpoints in tumors from an independent cohort of patients with NMIBC (n = 259 males and n = 73 females). Transcriptome sequencing data were analyzed using DESeq2 in R v4.0.1, followed by application of the Kruskal-Wallis test to determine gene expression differences between tumors from males and females. Immunofluorescence data analyses were conducted using R version 3.5.3. Survival analysis was performed using survminer packages. High-grade tumors from female patients exhibited significantly increased expression of B-cell recruitment (CXCL13) and function (CD40)-associated genes and the immune checkpoint genes CTLA4, PDCD1, LAG3, and ICOS. Tumors from female patients showed significantly higher infiltration of PD-L1+ cells and CD163+ M2-like macrophages than tumors from male patients. Increased abundance of CD163+ macrophages and CD79a+ B cells were associated with decreased recurrence-free survival. These novel findings highlight the necessity of considering sexual dimorphism in the design of future immunotherapy trials in NMIBC. In this study, we measured the abundance of various immune cell types between tumors from male and female patients with non–muscle-invasive bladder cancer. We demonstrate that tumors from female patients have a significantly higher abundance of immunosuppressive macrophages that express CD163. Higher abundance of tumor-associated CD163-expressing macrophages and B cells is associated with shorter recurrence-free survival in both male and female patients.
European Urology Open Science, Volume 29, pp 68-76; doi:10.1016/j.euros.2021.05.006
Radiotherapy to the prostate (RTp) prolongs survival for patients with low-volume, newly diagnosed metastatic prostate cancer (ndmPC). to evaluate whether cytoreductive radical prostatectomy (cRP) is equally beneficial as RTp in low-volume ndmPC. A multicenter prospective registry was established in 2014 to observe patients with ndmPC. Eligible patients were offered cRP or RTp. For this study we selected only patients with low-volume ndmPC (n = 109). Of these, 48, 26, and 35 patients underwent cRP, RTp, and no local therapy (NLT), respectively. Median follow-up was 32 mo (interquartile range 16–49). cRP was compared with RTp and NLT. Overall survival (OS), cancer-specific survival (CSS), and local event–free survival (LEFS) were calculated using the Kaplan-Meier method. Factors prognostic for OS were identified using univariate and multivariate Cox regression analysis. The 2-yr OS was 93%, 100%, and 69%, and 2-yr CSS was 93%, 100%, and 75% for cRP, RTp, and NLT, respectively. The cRP and RTp groups had better OS compared to NLT and there was no significant difference between cRP and RTp. The 2-yr LEFS was 92%, 77%, and 60% for cRP, RTp, and NLT, respectively. The cRP group had better LEFS compared to RTp and NLT, and there was no significant difference between RTp and NLT. Advanced tumor stage, Eastern Cooperative Oncology Group performance status ≥2, and NLT were negative prognostic factors for OS. The main limitation is selection of fitter patients with less advanced tumors for cRP and the small sample size. For selected patients with low-volume ndmPC, cRP is able to achieve similar OS and CSS to RTp. cRP is effective in preventing local events due to disease progression. Patients with a low volume of newly diagnosed prostate cancer that has spread beyond the prostate gland might benefit from removal of the prostate, which we found was as effective as radiotherapy to the prostate in prolonging survival. Removal of the prostate is effective in preventing urinary problems caused by cancer progression.
European Urology Open Science, Volume 29, pp 93-101; doi:10.1016/j.euros.2021.05.004
Ataxia Telangiectasia Mutated (ATM) serine/threonine protein kinase is a known tumor suppressor, involved in DNA damage repair. It has prognostic and predictive therapeutic implications and is associated with aggressive prostate cancer (PCa). To investigate the prognostic value of ATM protein expression in PCa patients and assessed the combined value of ATM, ERG, and PTEN status. This study consisted of 303 patients with incidental, locally advanced, and castrate-resistant PCa by transurethral resection of the prostate (TURP). TURP samples from 303 PCa patients were assessed by immunohistochemistry (IHC for ATM, ERG, and PTEN. Individual and combined marker status were correlated with International Society of Urological Pathology Gleason grade group, overall survival (OS), and PCa-specific mortality (PCSM). Decreased ATM expression (negative/weak intensity) occurred in 164/303 (54.1%) patients, and was associated with shorter OS and higher PCSM (p = 0.015 and p = 0.001, respectively). Negative/weak ATM expression was significantly associated with PCSM with a hazard ratio of 2.09 (95% confidence interval 1.34–3.27, p = 0.001). Assessment of Combined ATM/PTEN expression showed improved prognostic power to predict OS and PCSM, independent of Gleason grade groups. Decreased ATM protein expression is associated with poor outcomes in advanced PCa patients. Patients with combined low ATM/PTEN negative expression are at the highest risk for reduced OS and PCSM. Assessing the combined status of ATM/PTEN by IHC in PCa patients may aid in risk stratification relative to OS and PCSM. Moreover, since ATM plays an integral role in DNA damage response pathways, future studies will enhance our understanding of how outcomes of patients with altered ATM and PTEN expression can be improved further with poly-ADP ribose polymerase inhibitors (PARPi), combinations of PARPi and androgen receptor–targeted therapies, as well as platinum-based chemotherapies. Lower ATM intensity is associated with increased cancer-specific mortality in prostate cancer patients. Patients with lower ATM and PTEN negative expression showed decreased overall survival and increased cancer mortality compared with controls.
European Urology Open Science, Volume 29; doi:10.1016/s2666-1683(21)00112-9
European Urology Open Science, Volume 29; doi:10.1016/s2666-1683(21)00111-7
European Urology Open Science, Volume 29, pp 36-46; doi:10.1016/j.euros.2021.04.010
Despite strong evidence of heritability, few studies have attempted to unveil the genetic underpinnings of testosterone levels. To identify testosterone-associated loci in a large study and assess their biological and clinical implications. The participants were men from the UK Biobank. A two-stage genome-wide association study (GWAS) was first used to identify/validate loci for low testosterone (LowT, <8 nmol/l) in 80% of men (N = 148 902). The cumulative effect of independent LowT risk loci was then evaluated in the remaining 20% of men. Associations of single nucleotide polymorphisms (SNPs) with LowT were tested using an additive model. Analyses of the expression quantitative trait loci (eQTLs) were performed to assess the associations between significant SNPs and expression of nearby genes (within 1 Mbp). A genetic risk score (GRS) was used to assess the cumulative effect of multiple independent SNPs on LowT risk. The two-stage GWAS found SNPs in 141 loci of 41 cytobands that were significantly associated with LowT (p < 5 × 10–8), including 94 novel loci from 38 cytobands. An eQTL analysis of these 141 loci revealed significant associations with RNA expression of 155 genes, including previously implicated (SHBG and JMJD1C) and novel (LIN28B, LCMT2, and ZBTB4) genes. Among the 141 loci, 42 were independently associated with LowT after a multivariable analysis. The GRS based on these 42 loci was significantly associated with LowT risk in independent individuals (N = 37 225, ptrend = 3.16 × 10–162). The risk ratio for LowT between men in the top and those in the bottom GRS deciles was 4.98-fold. Results are limited in generalizability as only Caucasians were studied. Identification of the genetic variants associated with LowT may improve our understanding of its etiology and identify high-risk men for LowT screening. We identified 141 new genetic loci that can be incorporated into a genetic risk score that can potentially identify men with low testosterone.
European Urology Open Science, Volume 29, pp 1-9; doi:10.1016/j.euros.2021.03.011
Double J (DJ) ureteral stents are commonly inserted after ureteroscopy (URS) procedures for stone treatment. However, stent-related symptoms are still a major issue. To determine whether a commercially available pigtail suture stent (PSS) can reduce stent-related symptoms compared to a conventional DJ stent after uncomplicated URS. We designed a randomized, single-blind, parallel-group trial from January to November 2020. The inclusion criteria were stone-free URS without intraprocedural complications. Patients with distal ureteral stones were excluded. Insertion of a PSS or DJ stent after URS. The primary endpoint was the Urinary Symptom Index score on the Ureteral Stent Symptoms Questionnaire (USSQ) 2 wk after URS. Secondary endpoints were USSQ domain scores and responses to individual USSQ questions at 2 d and 2 wk after surgery. A total of 78 patients were randomized and treated according to protocol. The Urinary Symptom Index score (p = 0.004), overall Visual Analogue Scale (VAS) score (p = 0.022), and the percentage of patients complaining of pain (63.9% vs 86.1%, p = 0.029) were significantly in favor of PSS at both 2 d and 2 wk after URS. At 2 d, the VAS score among patients with pain (p = 0.025) and the General Health Index score (p = 0.036) were significantly better in the PSS group. No severe complications occurred in either group. Study limitations are the exclusion of patients with distal ureteral stones and the limited sample size. PSS significantly reduced stent-related symptoms after URS, in particular urinary symptoms and pain, compared to conventional DJ stents, and showed a good safety profile. Stents are hollow tubes placed in the passage between the kidney and the bladder (ureter). The standard stent has two coiled ends (double J stent) to keep it in place in both the kidney and the bladder. We tested a commercial stent with two strings at the bladder end (pigtail suture stent) after procedures to remove stones from the upper urinary tract and found that it caused less stent-related symptoms compared to a double J stent. This trial is registered at Clinicaltrials.gov as NCT03344120.
European Urology Open Science, Volume 28, pp 1-8; doi:10.1016/j.euros.2021.03.010
Morbidity after radical cystectomy (RC) is usually quantified in terms of rates of complications, mortality, reoperations, and readmissions, and length of stay (LOS). The overall burden following RC within the first 90 d following RC may be better described using days alive and out of hospital (DAOH), which is a validated, patient-centred proxy for both morbidity and mortality. To report short-term morbidity, LOS, and DAOH within 90 d after RC and risk factors associated with these parameters. The study included 729 patients undergoing RC for bladder cancer at a single academic centre from 2009 to 2019. Data were retrieved from national electronic medical charts. Multivariate analysis was used to investigate variables associated with a major complication, LOS >7 d, and DAOH 7 d and DAOH <80 d. RC was associated with significant short-term morbidity and DAOH was a good marker for cumulative morbidity after RC. We propose that DAOH should be a standard supplement for reporting surgical outcomes following RC for bladder cancer, which may facilitate better comparison of outcomes across treating institutions. We studied complications after surgical removal of the bladder for bladder cancer. We assessed a novel patient-centred tool that more accurately describes the total burden of complications after surgery than traditional models. We found that patients with a high body mass index and coexisting chronic diseases had a higher risk of a complicated surgical course.
European Urology Open Science, Volume 28, pp 26-35; doi:10.1016/j.euros.2021.04.001
Posterior urethral valves (PUVs) and ureteropelvic junction obstruction (UPJO) are congenital obstructive uropathies that may impair kidney development. To identify genetic variants associated with kidney injury in patients with obstructive uropathy. We included 487 patients born in 1981 or later who underwent pyeloplasty or valve resection before 18 yr of age in the discovery phase, 102 PUV patients in a first replication phase, and 102 in a second replication phase. Signs of kidney injury were defined as dialysis, nephrectomy, kidney transplantation, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, high blood pressure, antihypertensive medication use, proteinuria, and/or one kidney functioning at 600 000 single-nucleotide polymorphisms (SNPs) in the discovery sample comparing patients with and without signs of kidney injury within 5 yr after surgery. We performed stratified analyses for PUV and UPJO and Kaplan-Meier and Cox regression analyses in the discovery and two replication samples for the associated SNPs, and RNA and protein expression analyses for the associated gene in fetal tissues. Despite the small and nonhomogeneous sample, we observed suggestive associations for six SNPs in three loci, of which rs6874819 in the CDH12 gene was the most clear (p = 7.5 × 10–7). This SNP also seemed to be associated with time to kidney injury in the PUV discovery and replication samples. RNA expression analyses showed clear CDH12 expression in fetal kidneys, which was confirmed by protein immunolocalization. This study identified CDH12 as a candidate gene for kidney injury in PUV. We found that variants of the CDH12 gene increase the risk of kidney injury in patients with extra flaps of tissue in the urethra (posterior urethral valves). This is the first report on this gene in this context. Our study provides interesting new information about the pathways involved and important leads for further research for this condition.
European Urology Open Science, Volume 28; doi:10.1016/s2666-1683(21)00090-2
European Urology Open Science, Volume 28; doi:10.1016/s2666-1683(21)00088-4
European Urology Open Science, Volume 28, pp 52-61; doi:10.1016/j.euros.2021.04.005
Androgen deprivation therapy (ADT) for prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonists can be improved. To assess safety, the frequency and severity of hot flushes (HFs), bone health, and antitumor effects of high-dose estetrol (HDE4) when combined with ADT. A phase II, double-blind, randomized, placebo-controlled study was conducted in advanced prostate cancer patients requiring ADT (the PCombi study). Patients receiving LHRH agonist treatment were randomized 2:1 to 40 mg HDE4 (n = 41) or placebo (n = 21) cotreatment for 24 wk. Coprimary endpoints were frequency/severity of HFs and levels of total and free testosterone (T). Secondary endpoints included assessments of bone metabolism (osteocalcin and type I collagen telopeptide [CTX1]), prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH). Efficacy analysis was based on the selected per-protocol (PP) population. Of 62 patients included in the study, 57 were suitable for a PP analysis (37 HDE4; 20 placebo). No E4-related serious cardiovascular adverse events occurred at 24 wk. Weekly HFs were reported by 13.5% of patients with HDE4 and 60.0% with placebo (p < 0.001). Daily HFs occurred in 5.9% versus 55%. Bone turnover parameters decreased significantly with HDE4 (p < 0.0001). Total and free T decreased earlier (p < 0.05), and free T was suppressed further (p < 0.05). PSA suppression was more profound and earlier (p < 0.005). FSH levels were suppressed by 98% versus 57% (p < 0.0001). Estrogenic side effects were nipple sensitivity (34%) and gynecomastia (17%). HDE4 cotreatment of ADT patients with advanced prostate cancer was well tolerated, and no treatment-related cardiovascular adverse events were observed at 24 wk. HFs and bone turnover were substantially reduced. Suppression of free T, PSA, and FSH was more rapid and profound, suggesting enhanced disease control by HDE4 cotreatment. Larger and longer-lasting studies are needed to confirm the results of the study reported here. Cotreatment of androgen deprivation therapy with high-dose estetrol in advanced prostate cancer patients results in fewer occurrences of hot flushes, bone protection, and other antitumor benefits. Nipple sensitivity and gynecomastia may occur as side effects.
European Urology Open Science, Volume 28, pp 17-25; doi:10.1016/j.euros.2021.03.009
Although ureteroscopic surgery (URS) is beneficial for low-risk upper urinary tract carcinoma (UTUC), there is no standardized URS technique or navigation system for challenging cases. To present a URS technique for UTUC using thulium (Tm):YAG and holmium (Ho):YAG lasers under photodynamic diagnosis (PDD) guidance, named PDD-guided dual laser ablation (PDD-DLA) and compare its efficacy with that of conventional Ho:YAG laser ablation (HLA; historical control). The study included ten consecutive UTUC patients who underwent PDD-DLA between 2017 and 2019. The control group comprised 16 consecutive patients who underwent HLA between 2006 and 2016. After oral administration of 5-aminolevulinic acid (20 mg/kg), UTUC tumors were endoscopically resected via PDD-DLA. Clinical data were prospectively collected for our institutional UTUC data set. Disease progression, UTUC recurrence, and clinical outcomes were assessed. PDD-DLA was successfully performed in all patients. The median tumor size was 23.5 mm (interquartile range [IQR] 12.8–30.0) and there were four cases (40.0%) of high-grade tumor. The median operative time was 120 min (IQR 98.5–142.5). No Clavien-Dindo grade ≥3 complications were observed. There were no differences in most clinical characteristics between the PDD-DLA and HLA groups. The 2-yr progression-free survival rate was 100% in the PDD-DLA group and 58.7% in the HLA group (p = 0.0197), and the 2-yr recurrence-free survival rate was 57.1% and 41.3%, respectively (p = 0.072). The PDD-DLA group had a lower incidence rate of salvage RNU compared with the HLA group (0.0% vs 50%; p = 0.009). The small sample size might affect the reproducibility of these results. PDD-DLA seems to be an effective and feasible endoscopic technique for UTUC treatment with favorable oncological outcomes. We investigated a new laser technique for treating cancer of the upper urinary tract called photodynamic diagnosis–guided dual laser ablation. Our strategy was effective in removing tumors and stopping bleeding. Further studies in larger groups of patients are needed to confirm whether this technique improves cancer outcomes.
European Urology Open Science, Volume 28; doi:10.1016/s2666-1683(21)00089-6
European Urology Open Science, Volume 28, pp 9-16; doi:10.1016/j.euros.2021.03.008
Multiparametric magnetic resonance imaging (MRI) is increasingly used to diagnose prostate cancer (PCa). It is not yet established whether all men with negative MRI (Prostate Imaging-Reporting and Data System version 2 score 4 ng/ml, 4Kscore of >7%, PSA density ≥0.15 ng/ml/cm3, and/or suspicious digital rectal examination. The validation cohort included 182 men from another centre (University of Miami) with negative MRI who underwent systematic prostate biopsy with the same criteria. csPCa was defined as Gleason grade group ≥2 on biopsy. Multivariable logistic regression analysis was performed using coefficients of logit function for predicting PCa and csPCa. Nomogram validation was performed by calculating the area under receiver operating characteristic curves (AUC) and comparing nomogram-predicted probabilities with actual rates of PCa and csPCa. Of 200 men in the development cohort, 18% showed PCa and 8% showed csPCa on biopsy. Of 182 men in the validation cohort, 21% showed PCa and 6% showed csPCa on biopsy. PSA density, 4Kscore, and family history of PCa were significant predictors for PCa and csPCa. The AUC was 0.80 and 0.87 for prediction of PCa and csPCa, respectively. There was agreement between predicted and actual rates of PCa in the validation cohort. Using the prediction model at threshold of 40, 47% of benign biopsies and 15% of indolent PCa cases diagnosed could be avoided, while missing 10% of csPCa cases. The small sample size and number of events are limitations of the study. Our prediction model can reduce the number of prostate biopsies among men with negative MRI without compromising the detection of csPCa. We developed a tool for selection of men with negative MRI (magnetic resonance imaging) findings for prostate cancer who should undergo prostate biopsy. This risk prediction tool safely reduces the number of men who need to undergo the procedure.
European Urology Open Science, Volume 28, pp 36-42; doi:10.1016/j.euros.2021.04.003
The minimum volume standard is 100 robot-assisted radical prostatectomy (RARP) procedures per hospital in the Netherlands, so patients have to be referred to high-volume surgical centers for RARP. During preoperative work-up, prostate biopsies taken elsewhere are reassessed, with upgrading or downgrading of the initial Gleason grade group a possible consequence. To determine if prostate biopsy reassessment leads to adjustment of the surgical plan regarding a nerve-sparing approach and extended pelvic lymph node dissection (ePLND) during RARP. For 125 men who were referred to the Prosper prostate center at Canisius Wilhelmina Hospital (CWH) in the Netherlands between 2013 and 2016, results for the initial assessment of prostate biopsy by a local uropathologist were compared to results for biopsy reassessment by dedicated uropathologists at CWH. The pathologists reached agreement in 80% of the cases. In cases for which there was disagreement (n = 25), biopsy revision involved upgrading of the initial grade group in 68% and downgrading in 32%. Biopsy reassessment led to a change in surgical plan in ten cases (8%). As a result of upgrading, ePLND was performed in three patients (2%). ePLND was omitted in one patient (1%) because of downgrading. For three patients (2%) a non–nerve-sparing procedure was planned after upgrading of the initial grade group. For four patients (3%), a unilateral nerve-sparing procedure was performed after downgrading. This study shows that there is large interobserver agreement between uropathologists in the assessment of Gleason grade group in prostate biopsy specimens. Reassessment rarely leads to a change in surgical plan regarding the indication for a nerve-sparing approach and ePLND. Therefore, reassessment of prostate biopsy before radical prostatectomy can be omitted when the initial pathological assessment was performed by a dedicated uropathologist. Reassessment of the initial prostate biopsy specimen for patients referred to a specialist center for robot-assisted removal of the prostate rarely influences surgical planning and can be omitted.
European Urology Open Science, Volume 28, pp 43-46; doi:10.1016/j.euros.2021.04.004
The prevalence of prostate cancer (PCa) is increasing. As the prognosis of PCa continues to improve, the increasing follow-up requirements after radical prostatectomy or radiotherapy puts significant pressure on health care systems. Follow-up is typically conducted by treating urologists, specialized nurses, or general practitioners. Despite the increase in patient numbers, resources are not likely to increase in proportion. Furthermore, the ongoing COVID-19 pandemic has led to a paradigm shift in our thinking towards telehealth solutions, primarily to avoid or limit physical contact and to spare resources. Here we report our novel telehealth solution for PCa follow-up, called Mobile PSA. Currently, more than 4500 PCa patients have been using Mobile PSA follow-up in our center. Mobile PSA can increase follow-up accuracy, as all biochemical relapses will be detected in a timely manner, can significantly reduce delays in reporting prostate-specific antigen results to patients, and can significantly reduce costs. We assessed a new telehealth information system for prostate cancer follow-up that does not use an app. More than 4500 prostate cancer patients in our center have used this system, called Mobile PSA, for follow-up. The system significantly reduces delays in reporting prostate-specific antigen (PSA) test results to patients, increases the accuracy of detecting recurrence of elevated PSA, and reduces costs.
European Urology Open Science, Volume 28, pp 47-51; doi:10.1016/j.euros.2021.04.002
Two nomograms have been developed to predict the outcome of positron emission tomography (PET)/computed tomography (CT) imaging with68Ga-labeled ligands for prostate-specific membrane antigen (68Ga-PSMA) for patients with rising prostate-specific antigen after radical prostatectomy (RP). These nomograms quantify the ability of PSMA PET/CT to detect prostate cancer recurrences, and therefore provide critical information in determining the optimal timing for PSMA PET/CT in guiding salvage therapies. We validated the ability of these nomograms to accurately predict PET/CT outcome using another ligand tracer, 18F-DCFPyL. The external validation cohort consisted of 157 men from the Prostate Cancer Network Netherlands who underwent 18F-DCFPyL PET/CT to guide salvage therapies after RP. The nomogram of Rauscher et al (predicting a positive scan) showed accurate prediction of 50–80% (discrimination 0.68, 95% confidence interval [CI] 0.59–0.76). The nomogram of Luiting et al (predicting recurrence outside the prostatic fossa) showed accurate prediction for predicted probability values between 15% and 65%, with a small degree of overestimation for predicted probability values between 30% and 50% (discrimination 0.74, 95% CI 0.28–1.24). According to calibration curves, discrimination results, and decision curve analysis, we conclude that clinicians can use these 68Ga-PSMA–based nomograms to predict 18F-DCFPyL PET/CT outcome. These nomograms improve shared decision-making in determining the optimal time to initiate PSMA PET/CT–guided salvage therapies. Prediction tools developed for prostate scans (positron emission tomography, PET) using one type of radioactive tracer (chemicals labeled with gallium-68) are also accurate in predicting scan findings with another tracer (a chemical labeled with fluorine-18). Our study confirms that these tools can be used to guide decisions on the timing of treatments for prostate cancer recurrence.
European Urology Open Science, Volume 27; doi:10.1016/s2666-1683(21)00066-5
European Urology Open Science, Volume 27, pp 88-93; doi:10.1016/j.euros.2021.03.006
The underlying cause of a urethral stricture can sometimes be obscure. It is possible that an injury to the urethra induces an immunological cascade that generates scar tissue and fibrosis, eventually resulting in a stricture. If such immunological reactions could be better elucidated, immunological therapies could possibly emerge. To evaluate if ectopic germinal centres exist in urethral stricture disease. Resected stricture specimens from 45 patients undergoing open bulbar urethroplasty with excision and anastomosis were assessed. Histopathological characteristics, such as fibrosis (grade I–III), inflammation, and sclerosis, were evaluated using immunostaining for CD3 (T cells), CD20 (B cells), and CD21 (follicular dendritic cells). The primary outcome measure was the presence or absence of a germinal centre. The secondary outcome was evaluation of any correlation between the degree of fibrosis and germinal centres. Fisher’s exact test was used for univariate analysis. In six patients, ectopic germinal centres were found. In ten patients, there was no inflammation at all. There was no correlation found between the degree of fibrosis and the abundance of immunohistochemically detected immune cells. Ectopic germinal centres, with B and T cells as well as follicular dendritic cell networks, do exist in urethral stricture disease. This finding may open up for novel research avenues on the possibility of adopting immunological treatments for urethral stricture disease. In patients with a narrowing of the urethra due to any kind of trauma, we looked for the presence of centres of immunological reaction in urethral tissue. We identified these immunological centres (also called germinal centres) in some patients. This intriguing finding suggests that immunological treatments may have potential for men with scar tissue in a narrowed urethra.
European Urology Open Science, Volume 27, pp 65-72; doi:10.1016/j.euros.2021.03.005
During robotic surgeries, kinematic metrics objectively quantify surgeon performance. To determine whether clinical factors confound the ability of surgeon performance metrics to anticipate urinary continence recovery after robot-assisted radical prostatectomies (RARPs). Clinical data (patient characteristics, continence recovery, and treatment factors) and surgeon data from RARPs performed between July 2016 and November 2018 were prospectively collected. Surgeon data included 40 automated performance metrics (APMs) derived from robot systems (instrument kinematics and events) and summarized over each standardized RARP step. The data were collected from two high-volume robotic centers in the USA and Germany. Surgeons from both institutions performed RARPs. The inclusion criteria were consecutive RARPs having both clinical and surgeon data. RARP with curative intent to treat prostate cancer. The outcome was 3- and 6-mo urinary continence recovery status. Continence was defined as the use of zero or one safety pad per day. Random forest (SAS HPFOREST) was utilized. A total of 193 RARPs performed by 20 surgeons were included. Of the patients, 56.7% (102/180) and 73.3% (129/176) achieved urinary continence by 3 and 6 mo after RARP, respectively. The model anticipated continence recovery (area under the curve = 0.74, 95% confidence interval [CI] 0.66–0.81 for 3-mo, and area under the curve = 0.67, 95% CI 0.58–0.76 for 6 mo). Clinical factors, including pT stage, confounded APMs during prediction of continence recovery at 3 mo after RARP (Δβ median –13.3%, interquartile range [–28.2% to –6.5%]). After adjusting for clinical factors, 11/20 (55%) top-ranking APMs remained significant and independent predictors (ie, velocity and wrist articulation during the vesicourethral anastomosis). Limitations included heterogeneity of surgeon/patient data between institutions, although it was accounted for during multivariate analysis. Clinical factors confound surgeon performance metrics during the prediction of urinary continence recovery after RARP. Nonetheless, many surgeon factors are still independent predictors of early continence recovery. Both patient factors and surgeon kinematic metrics, recorded during robotic prostatectomies, impact early urinary continence recovery after robot-assisted radical prostatectomy.
European Urology Open Science, Volume 27, pp 43-52; doi:10.1016/j.euros.2021.03.003
Salvage robot-assisted radical prostatectomy (sRARP) is a potential treatment option for locally recurrent prostate cancer (PCa) after nonsurgical primary treatment. There are minimal data comparing outcomes between propensity-matched sRARP and primary robot-assisted radical prostatectomy (RARP). The primary objective is to compare perioperative, oncological, and functional outcomes of sRARP with primary RARP, and the secondary is to compare outcomes between sRARP after whole and focal gland therapy. A 1:1 propensity-matched comparison was carried out of 135 sRARP cases with primary RARP cases from a cohort of 3852 consecutive patients from a high-volume tertiary centre. Perioperative, oncological, and functional outcomes including complication rates, positive surgical margins, biochemical recurrence (BCR), continence, and erectile dysfunction (ED) were retrospectively collected. There were no significant differences in patient characteristics between sRARP and primary RARP groups. In the salvage and primary groups, median (interquartile range) follow-up periods were 521 (304–951) and 638 (394–951) d, grade III–V Clavien-Dindo complication rates were 1.5% and 0% (p = 0.310), BCR rates were 31.9% and 14.1% (p < 0.001) at the last follow-up, pad-free continence rates were 78.8% and 84.3% at 2 yr (p = 0.337), and ED rates were 94.8% and 76.3% (p < 0.001), respectively. Comparing the whole and focal gland groups, BCR rates were 36.7% and 29.1% (p = 0.687) at follow-up, pad-free continence rates were 53.1% and 89.3% at 2 yr (p < 0.001), and ED rates were 98% and 93% (p = 0.214), respectively. Salvage RARP has similar perioperative outcomes to primary RARP with inferior potency rates. Post–focal therapy sRARP has similar recurrence and continence rates to primary RARP. Post–whole gland therapy, complication, and recurrence rates are higher, and there is a higher risk of urinary incontinence. We report the largest propensity-matched comparison of salvage robot-assisted radical prostatectomy (RARP) after focal and whole gland therapy. Salvage RARP is a feasible procedure for the treatment of locally recurrent prostate cancer in high-volume centres; however, patients should be counselled appropriately as to the different outcomes.
European Urology Open Science, Volume 27, pp 53-60; doi:10.1016/j.euros.2021.03.004
Prostate magnetic resonance imaging (MRI) is increasingly used in the detection, image-guided biopsy, and active surveillance of prostate cancer. The accuracy of prostate MRI may differ based on factors including imaging technique, patient population, and reader experience. To determine whether the accuracy of prostate MRI varies with reader experience. We rescored regions of interest from 194 consecutive patients who had undergone MRI/ultrasonography fusion biopsy. Original prostate MRI scans had been interpreted by one of 33 abdominal radiologists (AR group). More than 14 mo later, rescoring was performed by two blinded, prostate MRI radiologists (PR group). Likert scoring was used for both original MRI reports and rescoring. Test performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of prostate MRI was defined for the AR and PR groups. A Likert score of 4–5 was considered test positive and clinically significant prostate carcinoma (csPCa; Gleason grade group [GGG] ≥2) was considered outcome positive. MRI-positive lesions (Likert 4–5) scored by the PR group resulted in csPCa more frequently than those scored by the AR group (64.9% vs 39.3%). MRI-negative lesions (Likert 2–3) were more likely to result in a clinically insignificant biopsy (benign pathology or GGG 1) when scored by the PR versus the AR group (91.8% vs 76.6%). Sensitivity and specificity of MRI to detect csPCa were higher for the PR group than for the AR group (sensitivity 85.9% vs 70.7%; specificity 77.3% vs 46.8%). Overall diagnostic accuracy was higher for the PR group than for the AR group (80.1% vs 54.6%). Sensitivity, specificity, PPV, and NPV of prostate MRI were higher for the PR group than for the AR group. We examined the accuracy of prostate magnetic resonance imaging (MRI) in two groups of radiologists. Experienced radiologists were more likely to detect clinically significant prostate cancer on MRI.
European Urology Open Science, Volume 27, pp 19-28; doi:10.1016/j.euros.2021.02.008
The optimal management of oligometastatic prostate cancer (PCa) is still debated. The purpose of the present systematic review and meta-analysis is to collect the available evidence to date to better define the role of stereotactic body radiotherapy (SBRT) in selected patients with oligorecurrent PCa. Study methodology complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). All prospective studies including PCa patients with nodal and/or bone oligometastases (one to five lesions) were considered eligible. Heterogeneity between study-specific estimates was tested using chi-square statistics and measured with the I2 index. A pooled estimate was obtained by fitting both fixed-effect and DerSimonian and Laird random-effect model. Overall, six works (two randomized and the remainder observational) published between 2013 and 2020 were considered eligible. Globally, data from 445 patients were incorporated, of whom 396 were treated with SBRT (329 in observational studies and the remaining 67 in randomized ones). Regarding local progression-free survival (PFS), five studies reported values close to 100%, while one reported a value of 80% in the observation arm. The benefit in terms of biochemical PFS brought by SBRT was evident in all considered studies. Such a difference in cumulative probabilities between the intervention arm and the comparator arm is maintained even 24 mo after the baseline. All studies but one considered toxicity among the endpoints of interest. Most events were classified as either G1 or G2, and the only G ≥ 3 adverse event was reported in one trial. SBRT is highly cost effective, safe, and with an almost inexistent toxicity risk that makes it the perfect candidate for the optimal management of PCa oligometastatic patients. However, more solid data and a higher level of evidence are needed to affirm its role in the management of these patients. In this work, we reviewed available evidence on the use of stereotactic body radiotherapy in treating oligometastatic prostate cancer patients. We found good evidence that radiotherapy brings important benefits in overall treatment efficacy without major side effects.
European Urology Open Science, Volume 27, pp 33-42; doi:10.1016/j.euros.2021.02.007
Extracorporeal shock wave lithotripsy (ESWL) of kidney stones is losing ground to more expensive and invasive endoscopic treatments. This proof-of-concept project was initiated to develop artificial intelligence (AI)-augmented ESWL and to investigate the potential for machine learning to improve the efficacy of ESWL. Two-dimensional ultrasound videos were captured during ESWL treatments from an inline ultrasound device with a video grabber. An observer annotated 23 212 images from 11 patients as either in or out of focus. The median hit rate was calculated on a patient level via bootstrapping. A convolutional neural network with U-Net architecture was trained on 57 ultrasound images with delineated kidney stones from the same patients annotated by a second observer. We tested U-Net on the ultrasound images annotated by the first observer. Cross-validation with a training set of nine patients, a validation set of one patient, and a test set of one patient was performed. Classical metrics describing classifier performance were calculated, together with an estimation of how the algorithm would affect shock wave hit rate. The median hit rate for standard ESWL was 55.2% (95% confidence interval [CI] 43.2–67.3%). The performance metrics for U-Net were accuracy 63.9%, sensitivity 56.0%, specificity 74.7%, positive predictive value 75.3%, negative predictive value 55.2%, Youden’s J statistic 30.7%, no-information rate 58.0%, and Cohen’s κ 0.2931. The algorithm reduced total mishits by 67.1%. The main limitation is that this is a proof-of-concept study involving only 11 patients. Our calculated ESWL hit rate of 55.2% (95% CI 43.2–67.3%) supports findings from earlier research. We have demonstrated that a machine learning algorithm trained on just 11 patients increases the hit rate to 75.3% and reduces mishits by 67.1%. When U-Net is trained on more and higher-quality annotations, even better results can be expected. Kidney stones can be treated by applying shockwaves to the outside of the body. Ultrasound scans of the kidney are used to guide the machine delivering the shockwaves, but the shockwaves can still miss the stone. We used artificial intelligence to improve the accuracy in hitting the stone being treated.
European Urology Open Science, Volume 27, pp 73-76; doi:10.1016/j.euros.2021.03.007
We report on a pediatric case of hemorrhagic cystitis due to BK virus in a patient with acute lymphoblastic leukemia who had undergone bone marrow transplantation. A very large hematoma that almost completely filled the bladder was aspirated using a morcellator via suprapubic percutaneous access, and a thulium laser was then used to cauterize extensive areas of diffuse uroepithelial bleeding. This combined minimally invasive procedure was successful in clearing the bladder hematoma and achieving hemostasis.
European Urology Open Science, Volume 27, pp 77-87; doi:10.1016/j.euros.2021.03.002
Several liquid- and tissue-based biomarker tests (LTBTs) are available to inform the need for prostate biopsies and treatment of localised prostate cancer (PCa) through risk stratification, but translation into routine practice requires evidence of their clinical utility and economic impact. To review and summarise the health economic evidence on the ability of LTBTs to inform decisions on prostate biopsies and treatment of localised PCa through risk stratification. A systematic search was performed in the EMBASE, MEDLINE, Health Technology Assessment, and National Health Service Health Economic Evaluation databases. Eligible publications were those presenting health economic evaluations of an LTBT to select individuals for biopsy or risk-stratify PCa patients for treatment. Data on the study objectives, context, methodology, clinical utility, and outcomes were extracted and summarised. Of the 22 studies included, 14 were focused on test-informed biopsies and eight on treatment selection. Most studies performed cost-effectiveness analyses (n = 7), followed by costing (n = 4) or budget impact analyses (n = 3). Most (18 of 22) studies concluded that biomarker tests could decrease health care costs or would be cost-effective. However, downstream consequences and long-term outcomes were typically not included in studies that evaluated LTBT to inform biopsies. Long-term effectiveness was modelled by linking evidence from different sources instead of using data from prospective studies. Although studies concluded that LTBTs would probably be cost-saving or -effective, the strength of this evidence is disputable because of concerns around the validity and transparency of the assumptions made. This warrants prospective interventional trials to inform health economic analyses to ensure collection of direct evidence of clinical outcomes based on LTBT use. We reviewed studies that evaluated whether blood, urine, and tissue tests can reduce the health and economic burden of prostate cancer. Results indicate that these tests could be cost-effective, but clinical studies of long-term outcomes are needed to confirm the findings.
European Urology Open Science, Volume 27, pp 61-64; doi:10.1016/j.euros.2021.03.001
Urinary incontinence remains a significant postprostatectomy sequala. While it has been found that many patient and technical factors contribute to postprostatectomy incontinence, the impact of anatomical differences by races has not been studied. Shorter preoperative membranous urethral length (MUL) on prostate magnetic resonance imaging has been associated with a higher risk of postprostatectomy incontinence. We compared MUL between Asian and non-Asian men and their postprostatectomy urinary function using the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). We found that MUL was significantly shorter for Asian (7.9 mm, 95% confidence interval [CI] 7.5–8.3) than for non-Asian men (10.9 mm, 95% CI 10.2–11.7), with a mean difference of 3.0 mm (95% CI 2.15–3.87; p < 0.01). In addition, Asian men had significantly worse EPIC-CP urinary scores ≥12 mo after prostatectomy (3.82, 95% CI 2.47–5.17) in comparison to non-Asian men (1.95, 95% CI 1.11–2.79), with a mean difference of 1.87 (95% CI 0.32–3.42; p = 0.022). Confirmatory studies are needed to explore racial differences in MUL and its effect on postprostatectomy incontinence. We compared the length of a specific section of the urethra (called the membranous urethra) and urinary function after removal of the prostate between Asian and non-Asian men. We found that the membranous urethra is significantly shorter in Asian men and they have worse urinary continence after removal of the prostate. More studies are needed to confirm our findings.
European Urology Open Science, Volume 27; doi:10.1016/s2666-1683(21)00068-9
European Urology Open Science, Volume 27, pp 1-9; doi:10.1016/j.euros.2021.02.004
The incidence of cancer is higher among patients with end-stage renal disease but it remains uncertain whether a mild decrease in renal function affects cancer. To measure the effect of impaired renal function, represented by the estimated glomerular filtration rate (eGFR), personal health behaviors, and long-term exposure to fine particulate matter (PM2.5) on the risk of urothelial carcinoma (UC) incidence. We performed a population-based cohort study of 372 008 participants aged ≥30 yr with no prior cancer history using the MJ health examination database (2000–2015) and UC diagnosis data from the Taiwan Cancer Registry database. Cox proportional hazards models were used to quantify the association between eGFR and UC incidence. We detected 383 UC cases during a median follow-up of 10.3 yr. Low eGFR was significantly associated with UC (p value for trend <0.01): compared to eGFR ≥90 ml/min/1.73 m2, the adjusted hazard ratio (HR) was 1.36 (95% confidence interval [CI] 0.98–1.88), 1.86 (95% CI 1.22–2.84), and 1.95 (95% CI 1.06–3.56) for eGFR strata of 60–89, 45–59, and <45 ml/min/1.73 m2, respectively. The risk remained elevated after stratifying the follow-up duration to check for reverse causality, and the dose-response relationship was stronger for women than for men. Current smoking (HR 1.34, 95% CI 1.02–1.77) and long-term exposure to PM2.5 concentrations ≥25.1 μg/m3 (HR 1.54, 95% CI 1.14–2.09) both significantly increased the risk of UC incidence. A significant dose-response relationship between PM2.5 and UC was also noted (ptrend < 0.01). Limitations include the retrospective design and limited information on medical history. Lower renal function showed a dose-response relationship in elevating UC risk. Long-term exposure to PM2.5 is also a possible UC risk factor. People with kidney function that is lower than normal should monitor the health of their kidneys and other organs in the urinary system. Our study confirmed that as well as smoking, exposure to fine particulate matter in the air may be a risk factor for cancers of the urinary system.
European Urology Open Science, Volume 27, pp 10-18; doi:10.1016/j.euros.2021.02.005
Intravesical bacillus Calmette-Guérin (BCG) instillation is a standard treatment for non–muscle-invasive bladder cancer (NMIBC); however, not all patients benefit from BCG therapy. Currently, no surrogate marker exists to predict BCG efficacy, and thereby, identify patients who will benefit from this treatment. To evaluate the utility of urine Mycobacterium tuberculosis complex polymerase chain reaction (MTC-PCR) assay as a predictive marker for recurrence and progression following BCG therapy. A prospective analysis was carried out for of intermediate- or high-risk NMIBC patients who received BCG instillation for the first time. Urine samples, for MTC-PCR assay, were collected at baseline and annually for up to 10 yr after the last BCG instillation, including induction and maintenance therapy. The first postoperative sample for MTC-PCR was taken at 1 yr from the last instillation. A survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence and progression after BCG treatment were assessed using Cox regression analysis. During follow-up (median: 57 mo), 468/521 samples (89.8%) were MTC-PCR positive, and 108/123 patients (87.8%) exhibited MTC-PCR positivity at least once. Five-year recurrence- and progression-free survival in patients who were not MTC-PCR positive was significantly lower than in patients who were MTC-PCR positive at least once (p < 0.001). Using multivariable Cox regression analysis, MTC-PCR positivity at least once was a significant prognostic factor for recurrence (hazard ratio [HR]: 36.782, p < 0.001) and progression (HR: 47.209, p < 0.001). Patients who were not MTC-PCR positive, even once after BCG therapy, were extremely likely to exhibit recurrence and progression. Urine MTC-PCR may be an extremely useful, noninvasive surrogate marker to predict recurrence and progression following BCG therapy. Urine Mycobacterium tuberculosis complex polymerase chain reaction may be a novel biomarker capable of identifying patients at risk of recurrence and progression after bacillus Calmette-Guérin (BCG) immunotherapy.
European Urology Open Science, Volume 27, pp 29-32; doi:10.1016/j.euros.2021.02.006
Transitional cell carcinoma of the bladder is a common malignancy with an estimated 549 393 new cases occurring in 2018 alone. Both non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) show high recurrence and progression rates, and therefore impose a great burden on patients and health care systems. Current risk stratification and therapy strategies are predominantly based on clinical and histopathological findings for tumor stage and grade. The chemoresistance and metastasis of low-grade tumors suggest an incomplete understanding of disease mechanisms, despite numerous studies on differentiating molecular subtypes of bladder cancer to identify tumor drivers and potential therapeutic targets. We present a highly unusual course for a low-grade bladder tumor leading to metastasis and death, for which we used postmortem histopathological and molecular analyses to evaluate targetable alterations in key signaling pathways driving the underlying tumor biology.
European Urology Open Science, Volume 27; doi:10.1016/s2666-1683(21)00067-7
European Urology Open Science, Volume 26, pp 64-71; doi:10.1016/j.euros.2021.01.015
En bloc resection (ERBT) is a valid alternative to piecemeal resection for non–muscle-invasive bladder cancer (NMIBC), guaranteeing pathological outcomes. However, very few studies investigated long-term oncological outcomes of ERBT. To report long-term oncological outcome of ERBT. This is a retrospective analysis of prospectively collected data. We included patients who underwent ERBT from June 2010 to February 2014, and were diagnosed with NMIBC at pathology evaluation. The primary study endpoint was recurrence-free survival at 5 yr. Secondary outcomes were presence of detrusor muscle, recurrence rate at the first follow-up cystoscopy, progression to muscle-invasive bladder cancer (MIBC) at 5 yr, and factors associated with long-term oncological outcomes. Kaplan-Meier curves were used to describe recurrence-free survival time. A univariate analysis was used to investigate factors associated with recurrence. Overall, 74 patients were included in this study. The median age was 71 (66–76) yr. Most of the patients presented with only one bladder tumor, and the median tumor diameter was 2 (interquartile range [IQR] 1–2.5) cm. After histopathological examination, eight, 35, and 31 patients were diagnosed with low-, intermediate-, and high-risk disease, respectively. All the en bloc resected tumors showed the presence of detrusor muscle. The median follow-up was 72 (IQR 66–90) mo. The recurrence rate at the first follow-up cystoscopy was 5.4% (four out of 74 patients). Overall, 57 (77%) patients were free of recurrence at 5 yr. No progression to MIBC was observed: progression-free survival was 100%. Limitations include retrospective design and small size. Our findings showed that ERBT for NMIBC presents an optimal long-term oncological outcome. Further studies with larger cohorts are necessary for confirming our preliminary results and for a direct comparison with the traditional piecemeal resection. In case of superficial bladder tumors, transurethral resection of the entire tumor and its base in one piece seems to provide good long-term results in terms of recurrence and progression rates.
European Urology Open Science, Volume 26, pp 55-63; doi:10.1016/j.euros.2021.01.011
Observational data has indicated improved survival after radical prostatectomy (RP) compared with definitive radiotherapy (RT) in men with high-risk prostate cancer (PCa). To compare PCa-specific mortality (PCSM) and overall mortality (OM) in men with high-risk PCa treated with RP or RT, providing information on target doses and fractionations. This is an observational study from the Cancer Registry of Norway. Patients were diagnosed with high-risk PCa during 2006–2015, treated with RP ≤12 mo or RT ≤15 mo after diagnosis, and stratified according to RP or RT modality; external beam radiotherapy (EBRT; 70–<74, 74–<78, or 78 Gy), hypofractionated RT or EBRT combined with brachytherapy (BT-RT). Competing risk and Kaplan-Meier methods estimated PCSM and OM, respectively. Multivariable Cox regression models evaluated hazard ratios (HRs) for PCSM and OM. In total, 9254 patients were included (RP 47%, RT 53%). RT patients were older, had poorer performance status and more unfavorable disease characteristics. With a median follow-up time of seven and eight yrs, the overall 10-yr PCSM was 7.2% (95% confidence interval [CI] 6.4–8.0) and OM was 22.9% (95% CI 21.8–24.1). Compared with RP, EBRT 70–<74 Gy was associated with increased (HR 1.88, 95% CI 1.33–2.65, p < 0.001) and BT-RT with decreased (HR 0.49, 95% CI 0.24–0.96, p = 0.039) 10-yr PCSM. Patients treated with EBRT 70–78 Gy had higher adjusted 10-yr OM than those treated with RP. In men with high-risk PCa, treatment with EBRT <74 Gy was associated with increased adjusted 10-yr PCSM and OM, and BT-RT with decreased 10-yr PCSM, compared with RP. In this study, we compared mortality after radical prostatectomy (RP) and radiotherapy (RT) in men with high-risk prostate cancer (PCa); the results suggest that men receiving lower-dose RT have higher, and patients receiving brachytherapy may have lower, risk of death from PCa than patients treated with prostatectomy.
European Urology Open Science, Volume 26, pp 10-13; doi:10.1016/j.euros.2021.01.008
This study describes technical implications and compares short-term outcomes after a dorsal versus ventral approach for double-face augmentation urethroplasty (DFAU) for treating a near-obliterated bulbar urethral stricture (BUS). This was a retrospective evaluation of a prospectively collected database of patients with BUS (<2 cm) who underwent DFAU. The choice between the approaches depended on (1) landmark identification (the relation between the bulbospongiosus muscle and the distal end of the stricture) and (2) corpus spongiosum width. In DFAU, inlay augmentation was at the level of the narrowed urethral plate (<6 Fr). Patient follow-up data (symptom score and uroflowmetry) were assessed every 3 mo for the first year, and every 6 mo thereafter. A successful outcome was defined as a normal urinary flow rate without obstructive voiding symptoms. Fifty-two patients underwent DFAU for BUS (dorsal approach, n = 30; ventral approach, n = 22). The maximum flow rate and symptom scores significantly improved in both groups. The overall success rates (86%) were similar. In conclusion, a dorsal approach for DFAU is versatile and can be considered in all circumstances. A ventral approach should be performed in patients with proximal BUS. The short-term outcomes were similar for both approaches. We assessed whether double-face augmentation urethroplasty is a suitable option for treating near-obliterated bulbar urethral strictures using two free grafts for augmentation to improve the urinary flow. This operation can be performed using two methods and both techniques were safe with similar short-term outcomes.
European Urology Open Science, Volume 26; doi:10.1016/s2666-1683(21)00054-9
European Urology Open Science, Volume 26, pp 27-34; doi:10.1016/j.euros.2021.01.013
Postoperative urinary retention (POUR) is a known complication in the postanesthesia care unit (PACU). The variations in catheterization thresholds contribute to unnecessary invasive procedures. In the current study, we implemented an algorithm for a sterile intermittent catheterization (SIC) threshold of 800 ml with volume-dependent bladder scan intervals and compared the incidence of SIC with that of a matched patient cohort threshold of 400 ml. This comparative study of two prospective historical cohorts represented two thresholds for POUR, set at 400 ml without a standardized bladder scan protocol and 800 ml with a volume-dependent bladder scan protocol. The primary outcome was the frequency of catheterization during the PACU stay. Secondary outcomes evaluated patient safety aspects in occurrence of thresholds above 400/800 ml. The study was set at the PACU under the Department of Anesthesia, Center for Cancer and Organ Diseases, Rigshospitalet, Denmark. In total, 741 patients were consecutively included, with 307 in the POUR-400 and 434 in the POUR-800 group, and with comparable group characteristics. Significantly fewer patients fulfilled the SIC/catheter a’ demeure (CAD) criteria in the POUR-800 (5.0%) versus POUR-400 (14.3%) group, equivalent to a 65.0% relative reduction in SIC. Implementation of a standardized ultrasound-guided protocol with volume-dependent scan intervals and an evidence-based catheterization threshold of 800 ml decreases the need for SIC by >65%, without increasing the need for urinary catheterization at the wards. In this study, we implemented an algorithm for a sterile intermittent catheterization threshold of 800 ml with volume-dependent bladder scan intervals. A marked reduction was seen in catheterization in the postanesthesia care unit, without increasing catheterization rates at the ward.
European Urology Open Science, Volume 26, pp 35-43; doi:10.1016/j.euros.2021.01.009
It is important to understand the implications of reduced bacillus Calmette-Guérin (BCG) treatment intensity, given global shortages and early termination of the NIMBUS trial. To assess the association of partial versus complete BCG induction with outcomes. This is a retrospective cohort study of veterans diagnosed with high-risk non–muscle-invasive bladder cancer (NMIBC; high grade [HG] Ta, T1, or carcinoma in situ) between 2005 and 2011 with follow-up through 2014. Patients were categorized into partial versus complete BCG induction (one to five vs five or more instillations). Partial BCG induction subgroups were defined for comparison with the NIMBUS trial. Propensity score–adjusted regression models were used to assess the association of partial BCG induction with risk of recurrence and bladder cancer death. Among 540 patients, 114 (21.1%) underwent partial BCG induction. Partial versus complete BCG induction was not significantly associated with the risk of recurrence in HG Ta (cumulative incidence [CIn] 46.6% vs 53.9% at 5 yr, p = 0.38) or T1 (CIn 47.1% vs 56.7 at 5 yr, p = 0.19) disease. Similarly, we found no increased risk of bladder cancer death (HG Ta: CIn 4.7%7vs 5.4% at 5 yr, p = 0.87; T1: CIn 10.0% vs 11.4% at 5 yr, p = 0.77). NIMBUS-like induction was associated with an increased risk of recurrence in patients with HG Ta disease, although not statistically significant. Unmeasured confounding is a limitation. Cancer outcomes were similar among high-risk NMIBC patients who underwent partial versus complete BCG induction, suggesting that future research is needed to determine how to optimize BCG delivery for the greatest number of patients, especially during global shortages. Outcomes were similar between patients receiving partial and complete courses of bacillus Calmette-Guérin (BCG) therapy. Future research is needed to determine how to best deliver BCG to the greatest number of patients, particularly during medication shortages.