The impact of the COVID-19 pandemic on renal cancer care.

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 Impact of a Multidisciplinary Tumor Board (MTB) on Treatment Decision Making for Patients With Renal Cell Carcinoma (RCC): 5-Year Data Analysis.

OBJECTIVE: To describe the impact of a multidisciplinary tumor board (MTB) for renal cell carcinoma (RCC) patients in a locoregional renal cancer network by evaluating shared decision making (SDM) and adherence to MTB recommendations. DESIGN, SETTING AND PARTICIPANTS: This prospective cohort study included all cases from a Dutch renal cancer network with suspicion of or histologically confirmed RCC discussed in MTBs between 2017-2022. Main endpoints were distribution of cases presented, proportion of recommendations with multiple treatment options enabling shared decision making (SDM), definite treatment after SDM and adherence to MTB recommendations. Further endpoints were definite treatment per tumor stage stratified by age and inclusion in clinical trials. Outcomes were displayed as means and proportions (%). Pearson's Chi-Squared test was used to analyze the effect of age on definite treatment advice. RESULTS: Overall, 2651 cases were discussed, of which 1900 (72%) were new referrals and 751 (28%) rediscussions. Majority of cases were cT1a-b tumors (46%) and 22% were local recurrences or metachronous metastatic. Adherence to MTB recommendation was 96% and in 30% multiple treatment options were recommended, allowing for SDM. In 45% of cases with cT1a tumors multiple treatment options were recommended by the MTB, resulting in (cryo)ablation (32%) and AS (30%) as most frequent definite treatments after SDM. Among patients with cT3-4 tumors the inclusion rate in clinical trials was 47%. CONCLUSIONS: A network MTB creates opportunity to discuss multiple treatment options and clinical trials in SDM with patients at a high rate of adherence to MTB recommendation.

Diagnostic liquid biopsy biomarkers in renal cell cancer.

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.

Indications and Outcomes for Deferred Cytoreductive Nephrectomy Following Immune Checkpoint Inhibitor Combination Therapy: Can Systemic Therapy be Withdrawn in Patients with No Evidence of Disease?

Background: Upfront cytoreductive nephrectomy (CN) is no longer the standard of care for patients with metastastic renal cell carcinoma (mRCC) with intermediate or poor prognosis according to the International mRCC Database Consortium categories. Objective: To investigate indications for CN following first-line ipilimumab-nivolumab, and assess management and outcomes for patients achieving no evidence of disease (NED) after CN. Design setting and participants: This was a retrospective cohort study among 125 patients with synchronous mRCC who received ipilimumab-nivolumab treatment between March 2019 and June 2022 at four European centres. At one of the four centres, nivolumab was stopped following NED. Outcome measurements and statistical analysis: We measured complete response of metastases (mCR) according to Response Evaluation Criteria in Solid Tumours 1.1; near-complete response of mestastases (mnCR) was defined as a >80% reduction in cumulative metastatic volume. Treatment-free survival (TFS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS) were determined. Results and limitations: At median follow-up of 25 mo, 23/125 patients (18%) had undergone deferred CN. Of 26 patients (21%) with mCR or mnCR, 19 (73%) underwent CN to achieve NED, of whom 11 (58%) discontinued nivolumab, with median TFS of 21 mo. For patients who continued (n = 8, 42%) versus discontinued nivolumab following NED, 2-yr DFS was 83% versus 60% (p = 0.675) and 3-yr CSS was 100% versus 70% (p = 0.325). Four patients underwent CN because of a dissociated response of the primary tumour and were still alive at median follow-up of 5 mo. Conclusions: CN can result in NED, durable DFS, and substantial time off systemic therapy. More collaborative data are required to ascertain the benefits of treatment discontinuation versus oncologic safety. Patient summary: In our study using real-world data, 18% of patients treated with immunotherapy underwent deferred kidney surgery. The majority were free of disease after 3 years. Half of the patients who stopped immunotherapy after surgery have been off therapy for 21 months or longer. Larger studies are needed to investigate the effect of kidney surgery and discontinuation of immunotherapy on survival.

The PRO-RCC study: a long-term PROspective Renal Cell Carcinoma cohort in the Netherlands, providing an infrastructure for 'Trial within Cohorts' study designs.

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.

Surgical margins after partial nephrectomy as prognostic factor for the risk of local recurrence in pT1 RCC: a systematic review and narrative synthesis.

PURPOSE: To 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 ACQUISITION: A 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 SYNTHESIS: After 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. CONCLUSION: PSM 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.

Multidisciplinary integrated care pathway for von Hippel-Lindau disease.

BACKGROUND: Clinical pathways are care plans established to describe essential steps in the care of patients with a specific clinical problem. They translate (inter)national guidelines into local applicable protocols and clinical practice. The purpose of this article is to establish a multidisciplinary integrated care pathway for specialists and allied health care professionals in caring for individuals with von Hippel-Lindau (VHL) disease. METHODS: Using a modified Delphi consensus-making process, a multidisciplinary panel from 5 Dutch University Medical Centers produced an integrated care pathway relating to the provision of care for patients with VHL by medical specialists, specialized nurses, and associated health care professionals. Patient representatives cocreated the pathway and contributed quality criteria from the patients' perspective. RESULTS: The panel agreed on recommendations for the optimal quality of care for individuals with a VHL gene mutation. These items were the starting point for the development of a patient care pathway. With international medical guidelines addressing the different VHL-related disorders, this article presents a patient care pathway as a flowchart that can be incorporated into VHL expertise clinics or nonacademic treatment clinics. CONCLUSIONS: Medical specialists (internists, urologists, neurosurgeons, ophthalmologists, geneticists, medical oncologists, neurologists, gastroenterologists, pediatricians, and ear-nose-throat specialists) together with specialized nurses play a vital role alongside health care professionals in providing care to people affected by VHL and their families. This article presents a set of consensus recommendations, supported by organ-specific guidelines, for the roles of these practitioners in order to provide optimal VHL care. This care pathway can form the basis for the development of comprehensive, integrated pathways for multiple neoplasia syndromes.

Renal biopsies performed before versus during ablation of T1 renal tumors: implications for prevention of overtreatment and follow-up.

PURPOSE: To assess the difference between renal mass biopsy (RMB) performed either before or during the ablation procedure. METHODS: A 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. RESULTS: RMB 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%. CONCLUSION: This 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.

Identification of Meaningful Data for Providing Real-Time Intraoperative Feedback in Laparoscopic Surgery Using Delphi Analysis.

Background. Surgeons are at risk of being overwhelmed with information while performing surgery. Initiatives focusing on the use of medical data in the operating room are on the rise. Currently, these initiatives require postprocessing of data. Although highly informative, data cannot be used to influence preventable error in real time. Ideally, feedback is provided preemptive. Aims. First, to identify which information is considered to be relevant for real-time feedback during laparoscopic surgery according to surgeons. Second, to identify the optimal routing for providing such feedback, and third, to decide on optimal timing for feedback to alarm users during laparoscopic surgery. Methods. A Delphi study of 3 iterations was conducted within the Amsterdam UMC, location AMC. A total of 25 surgeons and surgical residents performing laparoscopy were surveyed using 5-point Likert scales. Consensus was obtained when 80% of answers fitted the same answering category. Results. Delphi round 1 resulted in 198 unique ideas within 5 scenarios. After round 3, consensus was obtained on 102 items. Feedback most relevant during laparoscopic surgery refers to equipment like the gas insufflator, diathermy, and suction device. Feedback should be delivered via an additional monitor. Surgeons want to be instantly alarmed about aberrations in patients' vital parameters or combinations of vital parameters, preferably via a designated section on a monitor in their field of vision. Conclusions. Surgeons performing laparoscopy are uniform in their opinion that they need to be alarmed immediately when patients' vital parameters are becoming aberrant. Surgeons state that information regarding supporting equipment is best displayed on an additional monitor.

The Successful Return-To-Work Questionnaire for Cancer Survivors (I-RTW_CS): Development, Validity and Reproducibility.

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.

Laparoscopic cryoablation for small renal masses: Oncological outcomes at 5-year follow-up.

Objective: To evaluate the oncological outcome at 5-year follow-up after laparoscopic cryoablation (LCA) for small renal masses (SRMs), as there is an increasing interest in ablative therapy for cT1a renal tumours due to the rising incidence of SRMs, the trend towards minimally invasive nephron-sparing treatments, and the ageing population. Patients and methods: Between 2004 and 2015, 233 consecutive LCA were performed in 219 patients for SRMs at two referral centres. We only included those patients with ≥5 years of follow-up (n = 165) in a prospectively maintained database. A descriptive analysis was conducted for pre-, peri- and postoperative characteristics. A Kaplan-Meier analysis assessed overall (OS), disease-specific (DSS), and recurrence-free survival (RFS). Results: The median (interquartile range [IQR]) age of our patient cohort was 68 (60.5-76) years. The median (IQR) body mass index was 26.2 (23.8-29) kg/m2, and the median (IQR) Charlson Comorbidity Index score corrected for age was 4 (2.5-6). The median (IQR) tumour diameter was 28 (21-33) mm. In all, 15% developed a complication in the first 30 days after LCA, of which 1% had a major complication (Clavien-Dindo Grade ≥III). The median (IQR) preoperative estimated glomerular filtration rate (eGFR) was 82.5 (65-93.75) mL/min/1.73 m2. The median eGFR decreased by 16.4% and 15.2% at the 3-month and 5-year follow-up, respectively. Persistence was found in 1%, local recurrence in 2%, and systemic progression in 4%. The OS, DSS, and RFS were 74%, 96.9% and 95.4%, respectively. Conclusion: LCA is a safe and effective treatment for SRMs in selected cases and shows good oncological outcomes after 5 years of follow-up, with only 1% developing a major complication.

Feasibility and safety of irreversible electroporation (IRE) in patients with small renal masses: Results of a prospective study.

BACKGROUND: Irreversible electroporation (IRE) has the potential to overcome limitations of thermal ablation, enabling small renal mass (SRM) ablation near vital structures. PURPOSE: To assess feasibility and safety of percutaneous IRE for the treatment of SRMs. MATERIALS AND METHODS: This prospective study is a phase 2 trial (NCT02828709) of IRE for patients with SRMs. Primary endpoints are feasibility and safety. Device- and procedural-adverse events were assessed by Clavien-Dindo and Common Terminology Criteria for Adverse Events version 4.0 grading systems. Technical feasibility was assessed by recording the technical success of the procedures. Technical success was evaluated by performing a CT immediately after ablation where complete tumor coverage and nonenhancement were evaluated. Tumor charcateristics and patient characteristics, procedural and anesthesia details, postprocedural events, and perioperative complications were recorded. RESULTS: Ten SRMs were included with a mean tumor size of 2.2 cm (range 1.1-3.9 cm) were treated with IRE. Renal mass biopsies revealed 7 clear cell and 1 papillary renal cell carcinoma. Two renal mass biopsies were nondiagnostic. The median follow-up was 6 months (range 3-12 months). Technical success was achieved in 9 out of 10 cases. One patient had a grade 3 Clavien-Dindo complication (1/10, 95% Confidence interval (CI) 0.0179-0.4041). Mean anesthesia time was 3.7 hours (range 3-5 hours), mean procedural time was 2.1 hours (range 1 hour 45 minutes-2 hours 30 minutes) and mean ablation time was 50 minutes (range 20 minutes-1 hour 45 minutes). The creatinine preoperative and postoperative (1 week, 3 months, 6 months, and 12 months) did not significantly differ. In total, 8 out of 10 cases did not experience postoperative pain. CONCLUSION: IRE in SRMs is safe and feasible. Renal function is not affected by IRE and postoperative pain is rare. Anesthesia time and procedural time are a potential concern.

Ex-vivo study in nephroureterectomy specimens defining the role of 3-D upper urinary tract visualization using optical coherence tomography and endoluminal ultrasound.

Minimal invasive endoscopic treatment for upper urinary tract urothelial carcinoma (UUT-UC) is advocated in patients with low-risk disease and limited tumor volume. Diagnostic ureterorenoscopy combined with biopsy is the diagnostic standard. This study aims to evaluate two alternative diagnostic techniques for UUT-UC: optical coherence tomography (OCT) and endoluminal ultrasound (ELUS). Following nephroureterectomy, OCT, ELUS, and computed tomography (CT) were performed of the complete nephroureterectomy specimen. Visualization software (AMIRA®) was used for reconstruction and coregistration of CT, OCT, and ELUS. Finally, CT was used to obtain exact probe localization. Coregistered OCT and ELUS datasets were compared with histology. Coregistration with three-dimensional CT makes exact data matching possible in this ex-vivo setting to compare histology with OCT and ELUS. In OCT images of normal-appearing renal pelvis and ureter, urothelium, lamina propria, and muscularis were visible. With ELUS, all anatomical layers of the ureter could be distinguished, besides the urothelial layer. ELUS identified suspect lesions, although exact staging and differentiation between noninvasive and invasive lesions were not possible. OCT provides high-resolution imaging of normal ureter and ureter lesions. ELUS, however, is of limited value as it cannot differentiate between noninvasive and invasive tumors.

Histopathology: ditch the slides, because digital and 3D are on show.

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.

An In-vivo Prospective Study of the Diagnostic Yield and Accuracy of Optical Biopsy Compared with Conventional Renal Mass Biopsy for the Diagnosis of Renal Cell Carcinoma: The Interim Analysis.

BACKGROUND: Lack of accuracy in preoperative imaging leads to overtreatment of benign renal masses (RMs) or indolent renal cell carcinomas (RCCs). Optical coherence tomography (OCT) is real time and high resolution, enabling quantitative analysis through attenuation coefficient (µOCT, mm-1). OBJECTIVE: To determine the accuracy and diagnostic yield of OCT and renal mass biopsy (RMB) for the differentiation of benign RMs versus RCC and oncocytoma versus RCC. DESIGN, SETTING, AND PARTICIPANTS: From October 2013 to June 2016, 95 patients with solid enhancing RMs on cross-sectional imaging were prospectively included. All patients underwent subsequent excision or ablation. INTERVENTION: Percutaneous, image-guided, needle-based OCT followed by RMB in an outpatient setting under local anaesthesia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Accuracy and diagnostic yield, µOCT correlated to resection pathology or second biopsy during ablation. Tables (2×2) for RMB, receiver operating characteristic curve for OCT. Mann-Whitney test to differentiate µOCT of RMs. RESULTS AND LIMITATIONS: RMB diagnostic yield was 79% with sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 100%, 89%, 99%, and 100%, respectively. Diagnostic yield and added value of OCT to differentiate RCC from benign was 99% and 15%, respectively. Significant difference was observed in median µOCT between benign RMs (3.2mm-1, interquartile range [IQR]: 2.65-4.35) and RCCs (4.3mm-1, IQR: 3.70-5.00), p=0.0171, and oncocytomas (3.38mm-1, IQR: 2.68-3.95) and RCCs (4.3mm-1, IQR: 3.70-5.00), p=0.0031. OCT showed sensitivity, specificity, positive predictive value. and NPV of 91%, 56%, 91%, and 56%, respectively, to differentiate benign RMs from RCCs and 92%, 67%, 95%, and 55%, respectively, to differentiate oncocytoma from RCC. Limitations include two reference standards and heterogeneity benign RMs. CONCLUSIONS: Compared with RMB, OCT has a higher diagnostic yield. OCT accurately distinguishes benign RMs from RCCs, and oncocytoma from RCCs, although specificity and NPV are lower. PATIENT SUMMARY: Optical coherence tomography, a new optical scan, exhibits similar sensitivity and positive predictive value than renal mass biopsy, although lower specificity and negative predictive value. Optical coherence tomography has a higher diagnostic yield for diagnosing renal cell carcinoma.

Irreversible Electroporation for the Ablation of Renal Cell Carcinoma: A Prospective, Human, In Vivo Study Protocol (IDEAL Phase 2b).

BACKGROUND: Irreversible electroporation (IRE) is an emerging technique delivering electrical pulses to ablate tissue, with the theoretical advantage to overcome the main shortcomings of conventional thermal ablation. Recent short-term research showed that IRE for the ablation of renal masses is a safe and feasible treatment option. In an ablate and resect design, histopathological analysis 4 weeks after radical nephrectomy demonstrated that IRE-targeted renal tumors were completely covered by ablation zone. In order to develop a validated long-term IRE follow-up study, it is essential to obtain clinical confirmation of the efficacy of this novel technology. Additionally, follow-up after IRE ablation obliges verification of a suitable imaging modality. OBJECTIVE: The objectives of this study are the clinical efficacy and safety of IRE ablation of renal masses and to evaluate the use of cross-sectional imaging modalities in the follow-up after IRE in renal tumors. This study conforms to the recommendations of the IDEAL Collaboration and can be categorized as a phase 2B exploration trial. METHODS: In this prospective clinical trial, IRE will be performed in 20 patients aged 18 years and older presenting with a solid enhancing small renal mass (SRM) (≤4 cm) who are candidates for ablation. Magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) will be performed at 1 day pre-IRE, and 1 week post-IRE. Computed tomography (CT), CEUS, and MRI will be performed at 3 months, 6 months, and 12 months post-IRE. RESULTS: Presently, recruitment of patients has started and the first inclusions are completed. Preliminary results and outcomes are expected in 2018. CONCLUSIONS: To establish the position of IRE ablation for treating renal tumors, a structured stepwise assessment in clinical practice is required. This study will offer fundamental knowledge on the clinical efficacy of IRE ablation for SRMs, potentially positioning IRE as ablative modality for renal tumors and accrediting future research with long-term follow-up. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02828709; https://clinicaltrials.gov/ct2/show/NCT02828709 (archived by WebCite at http://www.webcitation.org/6nmWK7Uu9). Dutch Central Committee on Research Involving Human Subjects NL56935.018.16.

Diagnostic dilemmas in patients with upper tract urothelial carcinoma.

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.

Current position of diagnostics and surgical treatment for upper tract urothelial carcinoma.

BACKGROUND: The applicability of urinary biomarkers and optical diagnostics in upper urinary tract carcinoma (UUT-UC) are increasingly debated. To receive insight in the opinion of the urological community involved in this field, a survey was sent out to identify the most promising techniques and understand the need for new diagnostics. Primary objective of this study was to provide an overview of current diagnostics in upper urinary tract urothelial carcinoma. Secondary objectives of this study was to assess the need for additional diagnostic techniques in the current diagnostic work-up for UUT-UC and to assess knowledge of novel techniques. METHODS: An electronic survey was distributed to all participants of the upper urinary tract tumor registration study by the Clinical Research Office of the Endourological Society. Additionally, based on publications, experts in the field were contacted. Analysis was performed on the results overviewed by the survey monkey website. RESULTS: In total 81 of the 112 invited individuals responded resulting in a response rate of 72.3%. Most urologists involved in the treatment of upper urinary tract tumors follow the guidelines in their diagnostic work-up of patients suspected for UUT-UC. 61.4% of all responders consider current available diagnostic methods insufficient to select patient candidates for conservative renal sparing surgery. According to the responders, digital endoscopes for retrograde intrarenal surgery (RIRS) including narrow-band imaging (NBI) are best known and most likely to be beneficial compared to all evaluated diagnostic tools currently available. CONCLUSIONS: Urologists consider current diagnostic techniques for upper urinary tract tumors insufficient for optimal patient selection for conservative renal sparing surgery. Among the new techniques, NBI and digital RIRS are best known and considered to be beneficial in the diagnostic work-up.

Irreversible electroporation: state of the art.

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.

Prostate cancer diagnosis by optical coherence tomography: First results from a needle based optical platform for tissue sampling.

The diagnostic accuracy of Optical Coherence Tomography (OCT) based optical attenuation coefficient analysis is assessed for the detection of prostate cancer. Needle-based OCT-measurements were performed on the prostate specimens. Attenuation coefficients were determined by an earlier described in-house developed software package. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.56 mm(-1) ; 3.85 mm(-1) ; p < 0.0001) for all patients combined. The area under the ROC curve was 0.64. In order to circumvent the effect of histopathology mismatching, we performed a sub-analysis on only OCT data in which tumor was visible in two subsequent histopathological prostate slices. This analysis could be performed in 3 patients. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.23 mm(-1) ; 4.11 mm(-1) ; p < 0.0001) for all patients grouped together. The area under the ROC curve was 0.89. Functional OCT of the prostate has shown to differentiate between cancer and healthy prostate tissue. The optical attenuation coefficient in malignant tissue was significantly higher in malignant tissue compared to benign prostate tissue. Further studies are required to validate these initial results in a larger group of patients with a more tailored histopathology matching protocol.