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Background Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs). Methods PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a ‘Trial within cohorts’ studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician. Trial registration Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620). Discussion PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.

Background Cancer survivors’ perspectives on a successful return to work (RTW) may not be captured in the common measure of RTW, namely time until RTW. Objective The purpose of this study was therefore to develop an RTW outcome measure that reflects employed cancer survivors’ perspectives, with items that could be influenced by an employer, i.e. the Successful Return-To-Work questionnaire for Cancer Survivors (I-RTW_CS), and to assess its construct validity and reproducibility. Methods First, three focus groups with cancer survivors ( n  = 14) were organized to generate issues that may constitute successful RTW. Second, a two-round Delphi study among 108 cancer survivors was conducted to select the most important issues. Construct validity of the I-RTW_CS was assessed using correlations with a single-item measure of successful RTW and the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS; n  = 57). Reproducibility (test–retest reliability) was assessed using the intraclass correlation coefficient (ICC; n  = 50). Results Forty-eight issues were generated, of which seven were included: ‘enjoyment in work’; ‘work without affecting health’; ‘confidence of employer without assumptions about work ability’; ‘open communication with employer’; ‘feeling welcome at work’; ‘good work–life balance’; and ‘joint satisfaction with the situation (employer and cancer survivor)’. Correlations with single-item successful RTW and QWLQ-CS were 0.58 and 0.85, respectively. The reproducibility showed an ICC of 0.72. Conclusions The I-RTW_CS provides an RTW outcome measure that includes cancer survivors’ perspectives and weights its items on an individual basis, allowing a more meaningful evaluation of cancer survivors’ RTW. This study provides preliminary evidence for its construct validity and reproducibility.

The clinical presentation of renal cell cancer (RCC) is shifting towards incidental and early detection, creating new challenges in RCC diagnosis. Overtreatment might be reduced with the development of new diagnostic biomarkers to distinguish benign from malignant small renal masses (SRMs). Differently from tissue biopsies, liquid biopsies are obtained from a patient’s blood or urine and, therefore, are minimally invasive and suitable for longitudinal monitoring. The most promising types of liquid biopsy biomarkers for RCC diagnosis are circulating tumour cells, extracellular vesicles (EVs) and cell-free DNA. Circulating tumour cell assays have the highest specificity, with low processing time and costs. However, the biological characteristics and low sensitivity limit the use of these markers in SRM diagnostics. Cell-free DNA might complement the diagnosis of high-volume RCC, but the potential for clinical application in SRMs is limited. EVs have the highest biological abundance and the highest sensitivity in identifying low-volume disease; moreover, the molecular characteristics of these markers make EVs suitable for multiple analytical applications. Thus, currently, EV assays have the greatest potential for diagnostic application in RCC (including identification of SRMs). All these liquid biomarkers have potential in clinical practice, pending validation studies. Biomarker implementation will be needed to also improve characterization of RCC subtypes. Last, diagnostic biomarkers might be extended to prognostic or predictive applications.In this Review, the authors provide an overview of currently available diagnostic liquid biopsy biomarkers for renal cell carcinoma, comparing clinical potential and limitations of the three most promising liquid biomarkers: circulating tumour cells, extracellular vesicles and cell-free DNA.

Key Points High-evidence-level recommendations for diagnosis, treatment and follow-up monitoring of patients with upper tract urothelial carcinomas (UTUCs) are lacking, but radical nephroureterectomy should no longer be considered the gold-standard treatment in all patients Tumour grade and pathological stage are the main predictors of treatment outcome and the diagnostic challenge is selecting those patients with low-grade and low-stage tumours eligible for kidney-sparing therapy Preoperative tumour staging is difficult with currently available imaging modalities but clinical variables have been identified to enable risk stratification and distinguishing high-risk and low-risk tumours Available urine tests and markers show increased sensitivity for detection of urothelial carcinoma in the lower urinary tract compared with cytology but evidence of their benefits in the upper tract is lacking Endoscopic evaluation of the urinary tract together with histological evaluation of the tumour using biopsy samples are the best diagnostic instruments currently available for tumour grading Developments in real-time (optical) diagnostic techniques, such as optical coherence tomography, confocal laser endomicroscopy and endoluminal ultrasonography, can potentially improve diagnosis and treatment selection for patients with UTUC Recommendations based on high-level evidence for diagnosis, treatment and follow-up monitoring of upper tract urothelial carcinomas (UTUCs) are lacking and decision-making is often based on data from lower tract urothelial carcinoma. Here, Baard et al . review diagnostic tests for UTUC, describe efforts to improve lesion visualization, and propose an algorithm that integrates diagnosis, treatment, and clinical risk-stratification. Upper tract urothelial carcinoma (UTUC) is a rare condition and recommendations based on a high level of evidence for diagnosis, treatment and follow-up monitoring are lacking. Current decision-making is often based on evidence from trials investigating urothelial carcinoma of the lower tract. Radical nephroureterectomy has been the standard of care for UTUC but kidney-sparing treatment using endoscopic approaches has been established for a select patient group with low-grade and low-stage disease. Optimal treatment choice requires correct tumour characterization. According to available recommendations, diagnostic work-up of UTUC includes evaluation by CT urography or MRI urography, cystoscopy and urine cytology. Ureterorenoscopy and lesion biopsy are grade C recommendations in patients with suspected UTUC. When kidney-sparing treatment is planned, ureterorenoscopy and biopsy should be considered and are the procedures of choice in most cases. These diagnostics have limitations and their accuracy varies in defining tumour characteristics and predicting grade and stage. Urinary tests have higher sensitivity than cytology for detection of lower tract urothelial carcinoma but evidence of their benefit in UTUCs is lacking. New optical and image enhancement techniques are being developed to facilitate real-time diagnostics with increased accuracy. A new diagnostic algorithm for patients with suspected UTUC that integrates the diagnosis, treatment and clinical risk stratification is required.

PurposeTo systematically review the published literature on surgical margins as a risk factor for local recurrence (LR) in patients undergoing partial nephrectomy (PN) for pT1 renal cell carcinomas (RCC).Evidence acquisitionA systematic literature search of relevant databases (MEDLINE, Embase and the Cochrane Library) was performed according to the PRISMA criteria up to February 2022. The hypothesis was developed using the PPO method (Patients = patients with pT1 RCC undergoing PN, Prognostic factor = positive surgical margins (PSM) detected on final pathology versus negative surgical margins (NSM) and Outcome = LR diagnosed on follow-up imaging). The primary outcome was the rate of PSM and LR. The risk of bias was assessed by the QUIPS tool.Evidence synthesisAfter assessing 1525 abstracts and 409 full-text articles, eight studies met the inclusion criteria. The percentage of PSM ranged between 0 and 34.3%. In these patients with PSM, LR varied between 0 and 9.1%, whereas only 0–1.5% of LR were found in the NSM-group. The calculated odds ratio (95% confident intervals) varied between 0.04 [0.00–0.79] and 0.27 [0.01–4.76] and was statistically significant in two studies (0.14 [0.02–0.80] and 0.04 [0.00–0.79]). The quality analysis of the included studies resulted in an overall intermediate to high risk of bias and the level of evidence was overall very low. A meta-analysis was considered unsuitable due to the high heterogeneity between the included studies.ConclusionPSM after PN in patients with pT1 RCC is associated with a higher risk of LR. However, the evidence has significant limitations and caution should be taken with the interpretation of this data.

Purpose To evaluate the impact of the COVID-19 pandemic on renal cell carcinoma (RCC) care in the Netherlands. Methods Newly diagnosed RCCs between 2018 and 2021 were selected from the Netherlands Cancer Registry; 2020–2021 was defined as COVID period and 2018–2019 as reference period. Numbers of RCCs were evaluated using 3-week-moving averages, overall and by disease stage and age. Changes in treatment were evaluated with logistic regression analyses. To evaluate possible delays in care, time to start of treatment was assessed. The cumulative number of metastatic RCC (mRCC) over time was assessed to evaluate stage shift. Results During the 1st COVID wave (weeks 9–22, 2020), the number of new RCC diagnoses decreased with 15%. Numbers restored partially in 2020, but remained 10% lower compared to 2018/2019. The decline was mostly due to a drop in T1a/T1b RCCs and in age > 70 years. 2021 showed similar numbers of new RCC diagnoses compared to 2018/2019 without an increase due to previously missed RCCs. Treatment-related changes during the 1st COVID wave were limited and temporarily; less surgery in T1a RCCs in favor of more active surveillance, and in mRCC targeted therapy was preferred over immunotherapy. Time to start of firstline treatment was not prolonged during the 1st COVID wave. No increase in mRCC was found until the end of 2021. Conclusions The COVID-19 pandemic resulted in fewer RCC diagnoses, especially T1a/T1b tumors. Treatment-related changes appeared to be limited, temporarily and in accordance with the adapted guidelines. The diagnostic delay could lead to more advanced RCCs in later years but there are no indications for this yet.

The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities can result in damage to vital structures in the vicinity of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE) is a novel ablation modality based on the principle of electroporation or electropermeabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostate.

Due to the growing field of digital pathology, more and more digital histology slides are becoming available. This improves the accessibility, allows teleconsultations from specialized pathologists, improves education, and might give urologist the possibility to review the slides in patient management systems. Moreover, by stacking multiple two-dimensional (2D) digital slides, three-dimensional volumes can be created, allowing improved insight in the growth pattern of a tumor. With the addition of computer-aided diagnosis systems, pathologist can be guided to regions of interest, potentially reducing the workload and interobserver variation. Digital (3D) pathology has the potential to improve dialog between the pathologist and urologist, and, therefore, results in a better treatment selection for urologic patients.

Introduction: Percutaneous cryoablation (PCA) can be a valid alternative to partial nephrectomy for patients with cT1a renal tumors. A potential disadvantage of PCA is radiation exposure for patients, though the exact significance of this is unknown. This study aims to uncover the degree of radiation exposure during PCA and what factors are of influence. Methods: This is a retrospective analysis of a prospectively maintained database of patients who underwent CT-guided PCA for cT1 renal cell carcinoma (RCC) between January 2014 and September 2024. The median effective dose (mSV) of PCA was calculated and compared to the expected cumulative radiation exposure during follow-up. Multivariate linear regression was performed to identify factors predictive of higher radiation exposure (mSV). Results: A total of 164 PCAs were performed, with radiation data available for 133 cases. Mean age was 65 (±11) years and the mean tumor diameter was 28 (±9.6) mm. Median effective dose of the CA procedures was 26 mSV (IQR 18–37). The estimated cumulative effective dose of follow-up CT scans according to 2016 and 2024 European Association of Urology guidelines was 158 (IQR 117–213) and 105 mSV (IQR 78–142), respectively. Multivariate linear regression analysis identified BMI (OR 1.723, p < 0.001), the number of needles used (OR 4.060, p < 0.001), and the necessity for additional procedures (OR 8.056, p < 0.001) as significant predictors of a higher effective dose. Conclusions: We found a median effective dose of 26 mSV for PCA, which is relatively low compared to the cumulative radiation exposure associated with CT scans during follow-up of patients post-ablation according to the guidelines. Furthermore, increased BMI, a higher number of required needles and the execution of additional procedures are all associated with a higher effective dose.

PurposeTo assess the difference between renal mass biopsy (RMB) performed either before or during the ablation procedure.MethodsA retrospective multicenter study was performed in patients with a cT1 renal mass treated with ablation between January 2007 and July 2019, including a search in the national pathology database for patients with a RMB planned for ablation. Patient and tumor characteristics and information on malignant, benign, and non-diagnostic biopsy results were collected to establish rates of overtreatment and number of ablations avoided in case of benign or non-diagnostic histology.ResultsRMB was performed in 714 patients, of which 231 patients received biopsy before planned ablation, and 483 patients at the time of ablation. Pathology results before ablation were malignant in 63% (145/231), benign in 20% (46/231) and non-diagnostic in 17% (40/231). Pathology results at the time of ablation were malignant in 67.5% (326/483), benign in 16.8% (81/483) and non-diagnostic in 15.7% (76/483), leading to a total of 32.5% of ablation of benign or non-diagnostic lesions. Of the patients with a benign biopsy obtained before ablation, 80.4% (37/46) chose not to undergo ablation. Patients with inconclusive biopsy before planned ablation chose an informed individualized approach including ablation, repeated biopsy, or no intervention in 56%, 34% and 10%.ConclusionThis study emphasizes the importance of obtaining a biopsy prior to the ablation procedure in a separate session to lower the rate of potentially unnecessary ablations.