Transitioning from transrectal to transperineal prostate biopsy using a freehand cognitive approach.

OBJECTIVES: To report a single-centre experience of a complete transition from transrectal (TR) to transperineal (TP) prostate biopsy under local anaesthesia using a freehand cognitive coaxial approach and without use of antibiotic prophylaxis. PATIENTS AND METHODS: Analysis was performed of a prospective database of patients undergoing prostate biopsy performed by four surgeons between 1 June 2018 and 31 May 2022. Outcomes of interest were complications, cancer detection rate, inter-operator reliability, and tolerability. RESULTS: Overall, 1915 patients underwent 2337 separate prostate biopsy sessions. Only 2.4% patients in the TP group received antibiotic prophylaxis, while 100% received antibiotics in the TR group. The complication rate was significantly lower in the TP group compared to the TR group (0.3% vs 5.0%, P < 0.001). In contrast to the TR group, there were no cases of urosepsis or admissions to intensive care in the TP group. The total cancer detection rate by TP biopsy was 70% and the overall pathology detection rate was 88.4%. There was no difference in cancer or pathology detection between operators. A stable level of cancer detection was reached early on for both Prostate Imaging-Reporting and Data System 4 and 5 lesions. All cases performed were performed successfully without need for early termination. CONCLUSION: Implementing a complete transition from TR to TP biopsy can result in a significant reduction in complications and hospital re-admissions. A cognitive freehand coaxial technique is well tolerated by patients and achieves a high cancer detection rate.

Measuring quality of life in patients with kidney stone disease: is it the future in endourology?

PURPOSE OF REVIEW: Kidney stone disease is recognized to negatively impact quality of life. This pertains to acute episodes, surgical interventions and even during asymptomatic periods. Over time there has been increased attention towards assessing this subjective parameter, including as a determinant of treatment success. Our aim was to evaluate the current status and emerging trends in this field. RECENT FINDINGS: Patient groups most affected appear to be recurrent stone formers, cystine stone formers, women, younger populations, non-Caucasians and low-income populations. Several stone specific patient reported outcome measures are now available of which, WISQol has been implemented the most in clinical research studies. More invasive interventions such as percutaneous nephrolithotomy impede quality of life to greater extent than alternatives such as shockwave lithotripsy. SUMMARY: There are certain patient groups who are more vulnerable to the negative impact of kidney stone disease on their quality of life. Urologists can improve patient care by recognizing these particular populations as well as by implemented patient reported outcome measures in their routine clinical practice and when performing research.

A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.

Identifying possible biomarkers of lower urinary tract symptoms using metabolomics and partial least square regression.

INTRODUCTION: The objective of this study was to explore potential novel biomarkers for moderate to severe lower urinary tract symptoms (LUTS) using a metabolomics-based approach, and statistical methods with significant different features than previous reported. MATERIALS AND METHODS: The patients and the controls were selected to participate in the study according to inclusion/exclusion criteria (n = 82). We recorded the following variables: International prostatic symptom score (IPSS), prostate volume, comorbidities, PSA, height, weight, triglycerides, glycemia, HDL cholesterol, and blood pressure. The study of 41 plasma metabolites was done using the nuclear magnetic resonance spectroscopy technique. First, the correlations between the metabolites and the IPSS were done using Pearson. Second, significant biomarkers of LUTS from metabolites were further analysed using a multiple linear regression model. Finally, we validated the findings using partial least square regression (PLS). RESULTS: Small to moderate correlations were found between IPSS and methionine (-0.301), threonine (-0.320), lactic acid (0.294), pyruvic acid (0.207) and 2-aminobutyric-acid (0.229). The multiple linear regression model revealed that only threonine (p = 0.022) was significantly associated with IPSS, whereas methionine (p = 0.103), lactic acid (p = 0.093), pyruvic acid (p = 0.847) and 2-aminobutyric-acid (p = 0.244) lost their significance. However, all metabolites lost their significance in the PLS model. CONCLUSION: When using the robust PLS-regression method, none of the metabolites in our analysis had a significant association with lower urinary tract symptoms. This highlights the importance of using appropriate statistical methods when exploring new biomarkers in urology.

Current status of patient-reported outcome measures and other subjective assessment grading tools in bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is characterised by chronic pain in the bladder area accompanied by urgency and/or frequency without the presence of other confusable diseases. Owing to a lack of gold standard diagnostic tests and definitive cure it is paramount to define treatment goals and validated measurements of outcomes. Patient-reported outcome measures (PROMs) are validated questionnaires completed by patients that can help to reduce ambiguity in the BPS patient treatment pathway, but they are currently underutilised. We present to our knowledge the first summary and analysis of all available PROMs in BPS patients. METHODS: Review and critical evaluation of all relevant BPS guidelines presented in English language and a systematic search for PubMed database articles relating to PROMs and subjective assessment grading tools in BPS, interstitial cystitis and chronic pelvic pain syndrome. RESULTS: The ideal PROMs for BPS should assess urinary symptoms, pain, quality of life and sexual health. There are five PROMs designed specifically for BPS patients. The most universally used and quoted is the O'Leary-Sant questionnaire followed by the Pelvic Pain and Urgency Score and the Wisconsin Interstitial Cystitis scale. However, there is no single PROM for BPS that is ideal, and for comprehensive assessment several questionnaires are often used simultaneously. CONCLUSIONS: Patient-reported outcome measures are a valuable tool for use in the long-term management of patients burdened with BPS. There are now several disease-specific PROMs in use that have their respective advantages and disadvantages. Their use should be encouraged in future research as well as continued efforts to develop new PROMs that can address current shortcomings.

Outcomes Associated with the Endourological Management of Stent Encrustation: Findings from a Literature Review on Behalf of the EAU YAU Urolithiasis Group.

PURPOSE OF REVIEW: Double J ureteric stents (DJs) are useful aids for urinary drainage in case of stones or tumour causing ureteric obstruction. Prolonged dwelling time such as when forgotten can lead to encrustation. Our aim was to perform a literature review to evaluate outcomes associated with endourological management of encrusted stents (ES). RECENT FINDINGS: There now exist validated tools which can aid in grading the severity of encrustation and aid operative planning such as the total number of surgeries that may be required. Evaluation of different treatment strategies remains under reported. Removal of encrusted stent is a challenging problem, and it typically requires a multimodal endourological approach.

Holmium and Thulium Fiber Laser Safety in Endourological Practice: What Does the Clinician Need to Know?

PURPOSE OF REVIEW: To summarise the literature on laser safety during endourological practice. RECENT FINDINGS: Holmium and Thulium Fiber laser are the two main energy sources in the current clinical practice. The latter may have superior properties, but more clinical studies are needed to formally establish this. Laser injury to urothelium is more dependent on user experience rather than laser type. Smaller laser fibres allow for lower intra-renal temperature profiles. Operators should pay close attention to laser technique including maintaining the safety distance concept and only firing the laser when tip is clearly in view. When adjusting laser settings, pay close attention to resultant power given the associated heat changes. Prolonged periods of laser activation are to be avoided for the same reason. Outflow can be manipulated such as with access sheath to mitigate temperature and pressure changes. There is still limited evidence to support the mandate for compulsory use of eye protection wear during laser lithotripsy. Lasers are the gold standard energy source for stone lithotripsy. However, the safe clinical application of this technology requires an understanding of core principles as well as awareness of the safety and technical aspects that can help in protecting patient, surgeon and operating staff.

IPSS "bother question" score predicts health-related quality of life better than total IPSS score.

OBJECTIVE: The objective of this study was to investigate the role of bothersomeness of urinary symptoms on the general health-related quality of life (HRQoL) of patients with benign prostatic hyperplasia. We hypothesised that a higher International Prostate Symptom Score (IPSS) would be associated with a higher score on the IPSS bother question (IPSS-BQ), and a higher IPSS-BQ score would be the dominant factor associated with poorer general HRQoL. MATERIALS AND METHODS: A case-control, cross-sectional study design was used. Patients were selected according to strict inclusion and exclusion criteria and stratified by IPSS severity group (controls: IPSS < 8; moderately symptomatic: IPSS = 8-18; and severely symptomatic: IPSS > 18). The IPSS-BQ was used to analyse bothersomeness of urinary symptoms. A standardised, multidimensional measure of HRQoL (RAND-36) was used. Data were collected on prostate size, uroflowmetry parameters, prostate specific antigen and comorbidities that were quantified using the Charlson Index and the American Association of Anaesthesiologists (ASA) score. Multiple linear regression models were used to assess the impact of bothersomeness of urinary symptoms on physical and mental HRQoL. Cohen's d was used to determine the effect size. RESULTS: We included 83 patients in the statistical analysis. Linear regression analyses showed that the IPSS was not an independent predictor of HRQoL. Only the highest IPSS-BQ score was associated with both worse physical (P = 0.021) and mental (P = 0.011) HRQoL in the final model. The effect sizes were small to moderate. CONCLUSION: The IPSS-BQ score is an important predictor of HRQoL. The IPSS-BQ score as a proxy should be regarded as a standard outcome measure and reported in all LUTS-related research.

Rules and regulations for a pregnant endourologist: the European perspective.

INTRODUCTION: Working in surgery while pregnant is challenging. Navigating this period safely is of paramount importance. Anecdotal observation suggests that there exists great variation among European nations in regard to maternity leave and radiation safety. The aim of this article was to gain insight into policy patterns and variations across Europe regarding these issues. METHODS: A series of core question items was distributed to representatives across 12 nations Austria, Belgium, Germany, Greece, Iceland, Italy, Netherlands, Norway, Poland, Republic of Ireland, Spain and the United Kingdom). RESULTS: The total number of weeks with full pay ranged from as little as 4 weeks in Belgium to 32 and Iceland. All countries included in this study give the option of additional weeks beyond the initial period, however at reduced pay. Some offer unpaid leave beyond this. Only 5/12 countries had a specific policy on when the pregnant surgeon should come off the on-call rota. Only Austria, Italy and Poland stipulate a requirement for the pregnant clinician to be replaced or be completely exempt in cases involving radiation. Only Germany, Iceland, Norway and Poland highlight the need to limit radiation dose in the first trimester. Beyond this, Germany alone provides written guidance for reduction in gown weight and along with Poland, display arguably the most forward-thinking approach to resting. CONCLUSION: There is a marked range in maternal leave policies across Europe. There also exists a lack of universal guidance on radiation safety for the pregnant urologist. There is urgent need for this void to be addressed.

Management of Kidney Stone Disease in Pregnancy: A Practical and Evidence-Based Approach.

PURPOSE OF REVIEW: Suspected kidney stone disease during pregnancy is a difficult condition for health professionals to manage. This is partly due to the more limited range of diagnostic and therapeutic strategies, which can be safely applied. A comprehensive review of literature was performed to identify evidence to develop a practical guide to aid clinicians. RECENT FINDINGS: Ultrasound remains the recommended first line option for imaging. Complicated cases, such as suspected infected obstructed system, require urgent decompression such as in the form of percutaneous nephrostomy. This article highlights the pharmacotherapeutic agents, which are considered safe for use in pregnancy. Where surgical intervention is indicated, evidence supports ureteroscopy to be a safe option as long as infection has been treated. Ureteroscopy can offer definitive clearance of the stone(s) and can be less burdensome regarding bothersome symptoms compared to indwelling ureteral stent or nephrostomy, which also require regular exchange due to the high propensity for encrustation in pregnancy. A multidisciplinary approach is fundamental to safely manage suspected kidney stone disease in pregnancy. Adoption of a locally agreed pathway as suggested in this article supports improved patient care.

Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma.

BACKGROUND: Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS: A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group. No significant differences in response rate or progression-free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS: Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).

Serum levels of the IL-6 family of cytokines predict prognosis in renal cell carcinoma (RCC).

PURPOSE: An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival. METHODS: A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. The patients were followed-up for 10 years. The morning before surgery blood was sampled and serum frozen, with levels of IL-6, IL-27, IL-31, OSM, CNTF, IL-6Rα and gp130 determined. RESULTS: Among patients with the highest quartile of IL-6 (> 8 pg/ml) (n = 29), six of nine who had metastasis at diagnosis had such high IL-6 values. Among presumed radically treated patients, a high IL-6 and IL-27 strongly predicted recurrence. In particular, the predictions among patients with large (diameter > 7 cm) tumors were excellent regarding both IL-6 and IL-27 values. High gp130 serum levels predicted an overall survival (OS) among RCC patients with large tumors. Patients with a high IL-6 exhibited a strong expression of IL-6 in endothelial- and vascular smooth muscle cells. Moreover, the level of intra-tumoral CD3-positive cells predicted survival. CONCLUSIONS: IL-6 and IL-27 seem to play a role in RCC biology. IL-6 enables the pinpointing of metastatic condition at diagnosis, as well as together with IL-27, the predicting of survival and recurrence. Endothelial cells and vascular smooth muscle cells are both suggested as important sources of IL-6.

The levels of IL-6 and soluble IL-33R are increased in the renal vein during surgery for clear cell renal cell carcinoma.

PURPOSE: The main aim was to map serum levels of IL-1/IL-6 family cytokines and relevant receptors from serum samples taken across treatment in patients with Renal Cell Carcinoma (RCC). Additionally, we explored the possible interactions between these measurements, immunohistochemistry and intratumoral blood flow. METHODS: We included 40 patients undergoing open surgery for renal tumors. Blood samples were collected before, during (taken simultaneously from a peripheral site and the renal vein (RV) before clamping) and after surgery. Samples were analyzed for IL-6, IL-27, IL-31, OSM, TNF-α, serum (s)-gp130, s-IL-6Rα, s-IL-33R, IL-1Rα and VEGF. All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. Immunohistochemistry for the CCRCC group included expression of IL-6/IL-6R. Intratumoral blood flow was determined by calculating intratumoral contrast enhancement on preoperative computerized tomography (CT) imaging. RESULTS: In the CCRCC patients, the intraoperative RV concentration of IL-6 was significantly higher than in both the preoperative and postoperative samples (p = 0.005 and p = 0.032, respectively). Furthermore, the intraoperative ratio showed significantly higher levels of IL-6 in the RV than in the simultaneously drawn peripheral sample. Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. Increased blood flow in the CCRCC tumors predicted increased IL-6 levels in the RV (p < 0.001). The other cytokines and receptors showed an overall stability across the measurements. However, the intraoperative ratios of IL-33R and gp130 showed significantly higher levels in the RV. CONCLUSION: Serum levels of IL-6 increased during surgery. Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. Other studied cytokines/receptors were remarkably stable across all measurements.

AGAP2-AS1 as a prognostic biomarker in low-risk clear cell renal cell carcinoma patients with progressing disease.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and one of the most common cancers. While survival for localized ccRCC is good, the survival of metastatic disease is not, and thirty percent of patients with ccRCC develop metastases during follow-up. Although current scoring methods accurately identify patients at low progression risk, a small subgroup of those patients still experience metastasis. We therefore aimed to identify ccRCC progression biomarkers in "low-risk" patients who were potentially eligible for adjuvant treatments or more intensive follow-up. METHODS: We assembled a cohort of ccRCC patients (n = 443) and identified all "low-risk" patients who later developed progressing tumors (n = 8). Subsequently, we performed genome-wide expression profiling from formalin-fixed samples obtained at initial surgery from these "low-risk" patients and 16 matched patients not progressing to recurrence with metastasis. The patients were matched for Leibovich sore, creatinine, age, sex, tumor size and tumor stage. Key results were confirmed with qPCR and external data from The Cancer Genome Atlas. RESULTS: Principal component analysis indicated that systematic transcriptomic differences were already detectable at the time of initial surgery. One thousand one hundred sixty-seven genes, mainly associated with cancer and immune-related pathways, were differentially expressed between progressors and nonprogressors. A search for a classifier revealed that overexpression of AGAP2-AS1, an antisense long noncoding RNA, correctly classified 23 of 24 samples, years (4.5 years average) in advance of the discovery of metastasis and without requiring larger gene panels. Subsequently, we confirmed AGAP2-AS1 gene overexpression by qPCR in the same samples (p < 0.05). Additionally, in external data from The Cancer Genome Atlas, overexpression of AGAP2-AS1 is correlated with overall unfavorable survival outcome in ccRCC, irrespective of other prognostic predictors (p = 2.44E-7). CONCLUSION: AGAP2-AS1 may represent a novel biomarker identifying high-risk ccRCC patients currently classified as "low risk" at the time of surgery.

Current status of thulium fibre laser lithotripsy: an up-to-date review.

OBJECTIVE: To perform an up-to-date review to scope the current status of the thulium fibre laser (TFL) in the setting of stone lithotripsy and provide a guide for the clinical urologist. METHODS: A review of world literature was performed to identify original articles on TFL for stone lithotripsy. Our clinical experiences of using the technology have also been shared. RESULTS: To date there have been 11 clinical studies published on TFL for stone lithotripsy. Three of these have been in the setting of miniaturised percutaneous nephrolithotomy (mini-PCNL) and the remainder have been on ureteroscopy (URS). There has only been one randomised study on this technology, which has been for URS. For URS, the range of settings has been 0.1-4 J × 7-300 Hz for both URS and mini-PCNL. Stones ranging from 0.4-3.2 and 1.5-3 cm have been treated with URS and mini-PCNL, respectively. The final stone-free rate for TFL has ranged from 66.6% to 100% and 85-100% for URS and mini-PCNL, respectively. The average length of stay ranged from 0.5 to 2.4 days in the URS group, but no studies have been reported this for mini-PCNL. Operative times in all the studies (both URS and mini PCNL) were <60 min. CONCLUSION: Initial clinical studies reveal that TFL appears to be efficacious in the setting of stone lithotripsy. However, further randomised trials are warranted to delineate its formal position, as well as determine the optimal settings for use in clinical practice.

Should patients with low-risk renal cell carcinoma be followed differently after nephron-sparing surgery vs radical nephrectomy?

OBJECTIVE: To investigate whether pT1 renal cell carcinoma (RCC) should be followed differently after partial (PN) or radical nephrectomy (RN) based on a retrospective analysis of a multicentre database (RECUR). SUBJECTS: A retrospective study was conducted in 3380 patients treated for nonmetastatic RCC between January 2006 and December 2011 across 15 centres from 10 countries, as part of the RECUR database project. For patients with pT1 clear-cell RCC, patterns of recurrence were compared between RN and PN according to recurrence site. Univariate and multivariate models were used to evaluate the association between surgical approach and recurrence-free survival (RFS) and cancer-specific mortality (CSM). RESULTS: From the database 1995 patients were identified as low-risk patients (pT1, pN0, pNx), of whom 1055 (52.9%) underwent PN. On multivariate analysis, features associated with worse RFS included tumour size (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14-1.39; P < 0.001), nuclear grade (HR 2.31, 95% CI 1.73-3.08; P < 0.001), tumour necrosis (HR 1.5, 95% CI 1.03-2.3; P = 0.037), vascular invasion (HR 2.4, 95% CI 1.3-4.4; P = 0.005) and positive surgical margins (HR 4.4, 95% CI 2.3-8.5; P < 0.001). Kaplan-Meier analysis of CSM revealed that the survival of patients with recurrence after PN was significantly better than those with recurrence after RN (P = 0.02). While the above-mentioned risk factors were associated with prognosis, type of surgery alone was not an independent prognostic variable for RFS nor CSM. Limitations include the retrospective nature of the study. CONCLUSION: Our results showed that follow-up protocols should not rely solely on stage and type of primary surgery. An optimized regimen should also include validated risk factors rather than type of surgery alone to select the best imaging method and to avoid unnecessary imaging. A follow-up of more than 3 years should be considered in patients with pT1 tumours after RN. A novel follow-up strategy is proposed.

Higher than expected and significantly increasing incidence of upper tract urothelial carcinoma. A population based study.

PURPOSE: To register all cases of urothelial cancer and renal cell carcinoma (RCC) in Norway during 1999-2018 to obtain the contemporary incidence of UTUC and UTUC incidence relative to other urothelial cancers and RCC. Further to analyse possible changes over time regarding UTUC incidence, UTUC patient characteristics, tumour characteristics and survival. METHODS: 3502 cases registered with ICD code C65 and C66 during 1999-2018 at the Norwegian cancer registry were entered into a database. After a selection process 3096 cases were included in the study. The crude incidences of UTUC were calculated for each year adjusting for the corresponding population data. Age-standardized rates adjusting to the European standard population (2013) were calculated. Comparisons were made with other cases of urothelial cancer and RCC. For changes over time, the material was split into 5-year periods. Regression analysis was used to calculate yearly changes and for assessing statistical significance. Survival outcomes were calculated using the Kaplan-Meier method. RESULTS: The overall age-standardized incidence rate was 3.88, increasing from 3.21 to 4.70 from first to last 5-year periods. The increase affected all ages except those < 60 years of age, and were observed regardless of gender or anatomical location. UTUC constituted 11.8% of all urothelial cancers, increasing from 9.9 to 12.8%. Mean patient age at diagnosis increased from 71.5 to 73.4 years. The 5-years Cancer-specific survival improved from 57.4 to 65.4%. CONCLUSION: The incidence of UTUC was higher than expected and increasing. Patient age at diagnosis was increasing.

Pattern, timing and predictors of recurrence after surgical resection of chromophobe renal cell carcinoma.

PURPOSE: Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death. METHODS: Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015-2019) and the international collaborative database RECUR (15 institutes, 2006-2011). Kaplan-Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source. RESULTS: 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (< 24 months) was observed in 8 cases, all staged ≥ pT2b. 30 deaths occurred, of which 11 were attributed to chRCC. Sarcomatoid differentiation was rare (n = 4) but associated with recurrence and cancer-specific death on univariate analysis. On multivariate analysis, UICC/AJCC T-stage ≥ pT2b, presence of coagulative necrosis, and positive surgical margins were predictors of recurrence and cancer-specific death. CONCLUSION: Recurrence and death after surgically resected chRCC are rare. For completely excised lesions ≤ pT2a without coagulative necrosis or sarcomatoid features, prognosis is excellent. These patients should be reassured and follow-up intensity curtailed.

Tumour architecture, grade and location remain predictors of non-organ-confined upper tract urothelial carcinoma at time of radical nephroureterectomy: results from a multicenter Norwegian external validation study.

PURPOSE: Selecting patients for intensified treatment for upper tract urothelial carcinoma can be challenging, partly due to the lack of accurate preoperative staging tools. Several preoperative staging models for upper tract urothelial carcinoma have been presented, but none have been externally validated. The aim of the current study was to perform an external validation of the Margulis nomogram for predicting non-organ-confined upper tract urothelial carcinoma at time of nephroureterectomy. METHODS: 209 patients from two high-volume centres in Norway were treated with radical nephroureterectomy during the period 2005-2017. 163 patients with complete data necessary for external validation of the Margulis nomogram were included in the study. All relevant covariates were analysed with uni- and multivariate regression analysis to assess their ability to predict non-organ-confined disease. The Margulis nomogram was applied on the present cohort to calculate predicted risk of non-organ-confined disease. This was compared to the observed risk to assess model calibration. The Margulis nomogram accuracy was measured as the area under the curve in a receiver operator characteristics curve to evaluate model discrimination. RESULTS: Tumour grade (OR 28.1, p = 0.001) and architecture (OR 4.72, p < 0.001) were independent predictors of non-organ-confined disease. There was a high concordance between predicted and observed risk quantified with a Cronbach alpha of 0.96. The Margulis nomogram had an area under the curve of 0.83 in predicting non-organ-confined disease when applied on the current cohort. CONCLUSIONS: We consider the Margulis nomogram validated for clinical use.

Magnetic resonance radiomics for prediction of extraprostatic extension in non-favorable intermediate- and high-risk prostate cancer patients.

BACKGROUND: To investigate whether magnetic resonance (MR) radiomic features combined with machine learning may aid in predicting extraprostatic extension (EPE) in high- and non-favorable intermediate-risk patients with prostate cancer. PURPOSE: To investigate the diagnostic performance of radiomics to detect EPE. MATERIAL AND METHODS: MR radiomic features were extracted from 228 patients, of whom 86 were diagnosed with EPE, using prostate and lesion segmentations. Prediction models were built using Random Forest. Further, EPE was also predicted using a clinical nomogram and routine radiological interpretation and diagnostic performance was assessed for individual and combined models. RESULTS: The MR radiomic model with features extracted from the manually delineated lesions performed best among the radiomic models with an area under the curve (AUC) of 0.74. Radiology interpretation yielded an AUC of 0.75 and the clinical nomogram (MSKCC) an AUC of 0.67. A combination of the three prediction models gave the highest AUC of 0.79. CONCLUSION: Radiomic analysis combined with radiology interpretation aid the MSKCC nomogram in predicting EPE in high- and non-favorable intermediate-risk patients.