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Patients with larger (T1b,4 cm) renal cell carcinoma (RCC) not suitable for surgery have few treatment options because thermal ablation is less effective in this setting. We hypothesize that SABR represents an effective, safe, and nephron-sparing alternative for large RCC.Individual patient data from 9 institutions in Germany, Australia, USA, Canada, and Japan were pooled. Patients with T1a tumors, M1 disease, and/or upper tract urothelial carcinoma were excluded. Demographics, treatment, oncologic, and renal function outcomes were assessed using descriptive statistics. Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards regression were generated for oncologic outcomes.Ninety-five patients were included. Median follow-up was 2.7 years. Median age was 76 years, median tumor diameter was 4.9 cm, and 81.1% had Eastern Cooperative Oncology Group performance status of 0 to 1 (or Karnofsky performance status ≥70%). In patients for whom operability details were reported, 77.6% were defined as inoperable as determined by the referring urologist. Mean baseline estimated glomerular filtration rate (eGFR) was 57.2 mL/min (mild-to-moderate dysfunction), with 30% of the cohort having moderate-to-severe dysfunction (eGFR45mL/min). After SABR, eGFR decreased by 7.9 mL/min. Three patients (3.2%) required dialysis. Thirty-eight patients (40%) had a grade 1 to 2 toxicity. No grade 3 to 5 toxicities were reported. Cancer-specific survival, overall survival, and progression-free survival were 96.1%, 83.7%, and 81.0% at 2 years and 91.4%, 69.2%, 64.9% at 4 years, respectively. Local, distant, and any failure at 4 years were 2.9%, 11.1%, and 12.1% (cumulative incidence function with death as competing event). On multivariable analysis, increasing tumor size was associated with inferior cancer-specific survival (hazard ratio per 1 cm increase: 1.30; P .001).SABR for larger RCC in this older, largely medically inoperable cohort, demonstrated efficacy and tolerability and had modest impact on renal function. SABR appears to be a viable treatment option in this patient population.

The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel performed a protocol-driven systematic review (SR) on thermal ablation (TA) compared with partial nephrectomy (PN) for T1N0M0 renal masses, in order to provide evidence to support its recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed, and only comparative studies published between 2000 and 2019 were included. Twenty-six nonrandomised comparative studies were included, recruiting a total of 167 80 patients. Risk of bias (RoB) assessment revealed high or uncertain RoB across all studies, with the vast majority being retrospective, observational studies with poorly matched controls and short follow-up. Limited data showed TA to be safe, but its long-term oncological effectiveness compared with PN remains uncertain. A quality assessment of pre-existing SRs (n=11) on the topic, using AMSTAR, revealed that all SRs had low confidence rating, with all but two SRs being rated critically low. In conclusion, the current data are inadequate to make any strong and clear conclusions regarding the clinical effectiveness of TA for treating T1N0M0 renal masses compared with PN. Therefore, TA may be cautiously considered an alternative to PN for T1N0M0 renal masses, but patients must be counselled carefully regarding the prevailing uncertainties. We recommend specific steps to improve the evidence base based on robust primary and secondary studies. PATIENT SUMMARY: In this report, we looked at the literature to determine the effectiveness of thermoablation (TA) in the treatment of small kidney tumours compared with surgical removal. We found that TA could cautiously be offered as an option due to many remaining uncertainties regarding its effectiveness.

To systematically assessed the diagnostic performance of contrast-enhanced computed tomography (CT) compared to other imaging modalities for diagnosing and staging renal-cell carcinoma in adults.A comprehensive literature search was conducted through various electronic databases. Data from the selected studies were extracted and pooled, and median sensitivity and specificity were calculated wherever possible. Forty studies analyzing data of 4354 patients were included. They examined CT, magnetic resonance imaging (MRI), positron emission tomography-CT, and ultrasound (US).For CT, median sensitivity and specificity were 88% (interquartile range [IQR] 81%-94%) and 75% (IQR 51%-90%), and for MRI they were 87.5% (IQR 75.25%-100%) and 89% (IQR 75%-96%). Staging sensitivity and specificity for CT were 87% and 74.5%, while MRI showed a median sensitivity of 90% and specificity of 75%. For US, the results varied greatly depending on the corresponding technique. Contrast-enhanced US had a median diagnostic sensitivity of 93% (IQR 88.75%-98.25%) combined with mediocre specificity. The diagnostic performance of unenhanced US was poor. For positron emission tomography-CT, diagnostic accuracy values were good but were based on only a small amount of data. Limitations include the strong heterogeneity of data due to the large variety in imaging techniques and tumor histotypes. Contrast-enhanced CT and MRI remain the diagnostic mainstay for renal-cell carcinoma, with almost equally high diagnostic and staging accuracy.For specific questions, a combination of different imaging techniques such as CT or MRI and contrast-enhanced US may be useful. There is a need for future large prospective studies to further increase the quality of evidence.

Renal medullary carcinoma (RMC) is one of the most aggressive renal cell carcinomas. It predominantly afflicts young adults and adolescents with sickle cell trait and other sickle hemoglobinopathies, and is refractory to targeted and antiangiogenic therapies used in patients with clear-cell renal cell carcinoma. Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. On the basis of recent advances in the diagnosis, management, and clinical trial development for RMC, a panel of experts met in October 2017 and developed updated consensus recommendations to inform clinicians, researchers, and patients. Because RMC often aggressively recurs while patients are still recovering from nephrectomy, upfront chemotherapy should be considered for most patients, including those with localized disease. After safety and dosing information has been established in adults, phase II and III trials enrolling patients with RMC should allow patients aged 12 years and older to be accrued. Patients with the very rare unclassified renal cell carcinoma with medullary phenotype variant should be included in RMC trials. Medical providers should be aware that RMC can afflict subjects of all races, and not only those of African descent, and that the presence of sickle cell trait, or of other sickle hemoglobinopathies, can affect drug responses and toxicity.

Papillary renal cell carcinoma (PRCC) is currently divided in 2 subtypes. We reviewed a large cohort of PRCC and correlated subtype, morphological features and diagnostic marker expression with overall survival (OS) to uncover differences between the 2 subtypes. Three hundred seventy-six renal tumors initially diagnosed as PRCC with clinical and survival data were collected from the participating centers. Two hundred forty-six tumors were classified as PRCC1 (65.4%) and 130 as PRCC2 (34.6%) and graded according to the 2016 World Health Organization/International Society of Urological Pathology grading system. Morphological features (abundant cytoplasm, necrosis, fibrous stroma, foamy macrophages and psammoma bodies) were noted. Immunohistochemical stains (MIB1, p53, Racemase, EMA, CK7, CK20, E-Cadherin) were performed using tissue microarrays. χ2-Tests, log-rank tests and uni- and multivariate Cox regression analysis were performed. Both subtypes displayed different morphological features and immunohistochemical profiles: abundant cytoplasm was more frequent in PRCC2, while foamy macrophages were more common in PRCC1. Abundant cytoplasm and presence of psammoma bodies were associated with poorer OS. PRCC1 showed more frequent CK7 expression, PRCC2 more frequent E-Cadherin, p53 and higher MIB1 expression (>15%). Expression of Racemase and CK7 was associated with better OS, while high MIB1 (>15%) was associated with poorer OS. In multivariate analysis, the only independent predictors of OS were proliferation (MIB1), tumor stage, metastasis and age at surgery. Subtype was not an independent prognostic factor. Therefore, PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2.

Context Management of locally recurrent renal cancer is complex. Objective In this systematic review we analyse the available literature on the management of local renal cancer recurrence. Evidence acquisition A systematic search (PubMed, Web of Science, CINAHL, Clinical Trials, and Scopus) of English literature from 2000 to 2017 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Evidence synthesis The search identified 1838 articles. Of those, 36 were included in the evidence synthesis. The majority of the studies identified were retrospective and not controlled. Local recurrence after thermal ablation (TA) may be managed with repeat TA. Alternatively, salvage nephrectomy is possible. However, a higher rate of complications should be expected than after primary nephrectomy. Salvage nephrectomy and TA represent treatment options for local recurrence after partial nephrectomy. Local retroperitoneal recurrence after radical nephrectomy is ideally treated with surgical resection, for which minimally invasive approaches might be applicable to select patients. For large recurrences, addition of intraoperative radiation may improve local control. Local tumour destruction appears to be more beneficial than systemic therapy alone for local recurrences. Conclusions Management of local renal cancer relapse varies according to the clinical course and prior treatments. The available data are mainly limited to noncontrolled retrospective series. After nephron-sparing treatment, TA represents an effective treatment with low morbidity. For local recurrence after radical nephrectomy, the low-level evidence available suggests superiority of surgical excision relative to systemic therapy or best supportive care. As a consequence, surgery should be prioritised when feasible and applicable. Patient summary In renal cell cancer, the occurrence and management of local recurrence depend on the initial treatment. This cancer is a disease with a highly variable clinical course. After initial organ-sparing treatment, thermal ablation offers good cancer control and low rates of complications. For recurrence after radical nephrectomy, surgical excision seems to provide the best long-term cancer control and it is superior to medical therapy alone.

IntroductionBecause “real-life” patients often do not meet the strict eligibility criteria of clinical trials, we assessed the trial eligibility of patients with advanced or metastatic renal cell carcinoma (mRCC) in routine practice and compared the survival of “trial-ineligible” and potentially “trial-eligible” patients.Patients and MethodsThe present prospective, multicenter German cohort study is recruiting patients from 110 oncology/urology outpatient centers and hospitals at initiation of systemic first-line treatment. The demographic, clinical, treatment, and survival data were collected. We defined patients as “trial-ineligible” when ≥ 1 exclusion criterion (Karnofsky performance status < 80%, hemoglobin less than the lower limit of normal, non–clear cell carcinoma histology) was documented. Otherwise, the patients were considered “trial-eligible”.ResultsOf 732 patients included, 57% were classified as “trial-ineligible”. Overall, the median first-line progression-free survival (PFS) was 7.9 months (95% confidence interval [CI], 6.9-8.9 months). The median first-line PFS of “trial-eligible” and “trial-ineligible” patients was 11.0 months (95% CI, 9.6-13.1 months) and 5.3 months (95% CI, 4.6-6.5 months), respectively. The median OS of the “trial-eligible” and “trial-ineligible” patients was 26.0 months (95% CI, 22.1-29.7 months) and 12.6 months (95% CI, 10.6-15.8 months), respectively.ConclusionOur data suggest that patients in routine practice differ from patients treated in clinical trials and that almost 60% of mRCC patients in German routine practice would be ineligible for participation in clinical trials. While their first-line PFS and OS were shorter than those of “trial-eligible” patients, the PFS and OS of “trial-eligible” patients were comparable with the results from clinical trials. Physicians should be aware of these differences when discussing treatment options and outcome expectations with patients.

Metanephric adenoma (MA) describes a rare renal tumor and is generally considered a benign lesion. However, there are cases with regional lymphogenic and distant metastases. Noninvasive diagnosis of MA using conventional imaging remains challenging. Here, we describe a case of histologically verified MA with additional advanced molecular imaging consisting of 18F-PSMA-1007 PET/CT, 99mTc-Sestamibi SPECT and contrast-enhanced ultrasound.

Background: Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols. Objective: To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes. Design, setting, and participants: Nonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI). Intervention: Primarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation. Outcome measurements and statistical analysis: Incidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used. Results and limitation: Of 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n = 53), intermediate- (n = 105), and high-risk (n = 128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p = 0.004). Median OS was longer in PC compared with that in PI patients (p< 0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort. Conclusions: Low-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested. Patient summary: We analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies. Renal cell carcinoma recurrences are rare in low-risk patients. Potentially curable recurrences are more frequent in high-risk patients, but local treatment is unlikely to be curative. Competing risk analyses suggest age and risk score as important factors in developing follow-up strategies.

Background Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) play a decisive role as prognostic markers in clear-cell renal cell carcinoma (RCC). To date, the role of PD-1/PD-L1 as a prognostic marker in papillary RCC (pRCC) remains scarce. Patients and Methods Patients’ sample collection was a joint collaboration of the nationwide PANZAR consortium – a multicenter study. Medical history and tumor specimens were collected from 245 and 129 patients with pRCC types 1 and 2, respectively. Expression of PD-1 and PD-L1 was determined by immunohistochemistry in pRCC and tumor-infiltrating mononuclear cells. Results Of 374 pRCC specimens, 204 type 1 and 97 type 2 were evaluable for PD-1 and PD-L1 expression analysis. In total, PD-1 and PD-L1 expression were found in 8 (4.9%) of 162 and 12 (7.2%) of 166 evaluable pRCC type 1 specimens. Comparably, PD-1 and PD-L1 expression were found in 2 (2.4%) of 83 and 5 (6.2%) of 81 evaluable pRCC type 2 specimens. Hardly any clinically relevant associations between PD-1 and PD-L1 positivity and clinicopathologic or clinical courses were observed, neither in pRCC type 1 nor type 2. Conclusion The analysis of a large pRCC cohort from a multicenter consortium revealed no impact of PD-1/PD-L1 expression on prognosis in patients with pRCC with predominantly limited disease status, neither for type 1 nor type 2. However, the impact of PD-1 and PD-L1 in more advanced pRCC disease needs further elucidation.

Background Digital biomarkers allow for continuous remote patient monitoring and will potentially change the way healthcare is provided and clinical trials are designed. We conducted a study to identify current preferences and interest in digital biomarkers in patients with advanced urological cancers. Methods We included 80 patients undergoing systemic therapy for advanced urologic malignancies at our institution. A questionnaire was developed to survey the current access to online information and digital technologies and to rate preferences on a scale from 1 (does not apply) to 5 (fully applies). Statistical analysis was performed by Chi-square test and unpaired t-test. Results 26% of the cohort presented with prostate cancer (PC), 38% with urothelial cancer (UC) and 36% with renal cell carcinoma (RCC). 69% of patients researched medical information about their disease online, 85% of PC patients, 72% of RCC patients, and 53% of UC respectively. 63% of all patients use smartphones and 9% wearables. Smartphone usage is most common in RCC patients (76%) followed by PC (66%) and UC (46%) patients while wearables are used by 7% of RCC, 5% of PC, and 13% of UC patients, respectively. In our cohort RCC patients are younger (Mean 63.3 years) than PC patients (Mean 69.3 years) and UC patients (Mean 68.3 years). The percentage of patients seeking information online and using smartphones or wearables is significantly higher in patients under the age of 75 (p Conclusions Our study demonstrates a high engagement of patients in digital technologies. Even though there is a lower penetration rate for digital technologies in older people, interest in digital biomarker data is high in regardless of age group. Legal entity responsible for the study Severin Rodler. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background In the S-TRAC trial, adjuvant sunitinib (SU) prolonged disease-free survival (DFS) versus placebo (PBO) in patients (pts) with loco-regional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy. We previously applied the 16-gene Recurrence Score and confirmed its prognostic value (Clin Cancer Res 2018;15:4407). Here, we report the results of retrospective exploratory genomic and transcriptomic analyses using nephrectomy biospecimens from the S-TRAC trial. Methods Formalin-fixed paraffin-embedded tumor tissue blocks from patients who provided informed consent were used for whole exome (WES) and whole transcriptome (RNAseq) sequencing (Personalis, Menlo Park, CA; Genome Med. 2015;7:71) to examine somatic mutations and analyze relevant gene expression signatures (GES) in relation to clinical outcome. GES analyses included published signatures [effector T-cell (Teff), angiogenesis (Angio), myeloid inflammation (Minf)] among others. Cox proportional analyses of DFS were performed for each genotype or signature in SU versus PBO groups and between genotypes or signatures within each treatment group. Estimates of related parameters were reported. Results In all, 171 pts (SU, n = 91; PBO, n = 80) were genotyped and 133 (SU, n = 72; PBO, n = 61) were included in the GES analyses. Differences in DFS were observed relative to wildtype when mutations in genes such as ARID1A, MTOR, or ROBO3 were present; presence or absence of mutation in BAP1, SETD2 or PBRM1, however, did not distinguish pts with respect to DFS. Low tumor mutational burden (TMB) was associated with longer DFS in PBO as compared to high TMB (hazard ratio (HR) 0.253; 95% CI: 0.119, 0.541), but not in SU. Low-Angio GES showed a modest association with shorter DFS vs high-Angio GES in PBO (HR 1.912; 95% CI: 0.829, 4.409) but did not differentiate DFS in SU. Pts with low-Minf GES in SU had longer DFS vs those with high-Minf GES (HR 0.304; 95% CI: 0.132, 0.702). Conclusions These findings define molecular features that differentiate SU-specific outcomes in adjuvant RCC and may inform personalized therapy strategies for pts at high risk of recurrence. Independent validation studies are needed to confirm these findings. Clinical trial identification NCT00375674. Editorial acknowledgement Vardit Dror and David Cope Engage Scientific Solutions, funded by Pfizer. Legal entity responsible for the study Pfizer. Funding Pfizer. Disclosure A. Ravaud: Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses, lecture fees: Ipsen; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Merck Sharp & Dohme. J. Martini: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. K. Ching: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. M. Staehler: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Exelixis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. A. Magheli: Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Astellas; Speaker Bureau / Expert testimony: Janssen. B. Escudier: Advisory / Consultancy, lecture fees: Pfizer; Advisory / Consultancy, lecture fees: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Roche. X.J. Mu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. O. Valota: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. X. Lin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer. R.J. Motzer: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): GlaxoSmithKline.

Recent work by Gershman and colleagues adds to collective data favoring partial nephrectomy to optimize functional preservation while maintaining oncological equipoise in the management of T1 renal cancer, and should not be over-interpreted as an endorsement to preferentially perform radical nephrectomy.

Background Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit. Objectives To prospectively evaluate sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC. Design, setting, and participants The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate). Intervention Patients were randomised to sorafenib 400mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50mg once daily (4 wk on, 2 wk off) (So-Su), or vice versa (Su-So). Outcome measurements and statistical analysis The primary endpoint was improvement in progression-free survival (PFS) with So-Su versus Su-So, assessed from randomisation to progression or death during second-line therapy. Secondary endpoints included overall survival (OS) and safety. Results and limitations In total, 365 patients were randomised (So-Su, n =182; Su-So, n =183). There was no significant difference in total PFS between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio [HR] 1.01; 90% confidence interval [CI] 0.81–1.27; p =0.5 for superiority). OS was similar for So-Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77–1.30; p =0.5 for superiority). More So-Su patients than Su-So patients reached protocol-defined second-line therapy (57% vs 42%). Overall, adverse event rates were generally similar between the treatment arms. The most frequent any-grade treatment-emergent first-line adverse events were diarrhoea (54%) and hand-foot skin reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for sunitinib. Conclusions Total PFS was not superior with So-Su versus Su-So. These results demonstrate that sorafenib followed by sunitinib and vice versa provide similar clinical benefit in mRCC. Patient summary We investigated if total progression-free survival (PFS) is improved in patients with advanced/metastatic kidney cancer who are treated with sorafenib and then with sunitinib (So-Su), compared with sunitinib and then sorafenib (Su-So). We found that total PFS was not improved with So-Su compared with Su-So, but both treatment options were similarly effective in patients with advanced/metastatic kidney cancer. Trial registration ClinicalTrials.gov identifier NCT00732914, www.clinicaltrials.gov

Local treatment of metastases such as metastasectomy or radiotherapy remains controversial in the treatment of metastatic renal cell carcinoma. To investigate the benefits and harms of various local treatments, we did a systematic review of all types of comparative studies on local treatment of metastases from renal cell carcinoma in any organ. Interventions included metastasectomy, radiotherapy modalities, and no local treatment. The results suggest that patients treated with complete metastasectomy have better survival and symptom control (including pain relief in bone metastases) than those treated with either incomplete or no metastasectomy. Nevertheless, the available evidence was marred by high risks of bias and confounding across all studies. Although the findings presented here should be interpreted with caution, they and the identified gaps in knowledge should provide guidance for clinicians and researchers, and directions for further research.

Background For patients (pts) with advanced or metastatic renal cell carcinoma (mRCC), approval of novel therapies led to continuous changes in treatment options. The Tumour Registry Renal Cell Carcinoma (TNK) analysed treatment and outcome of pts treated in Germany from 2007-2017. CARAT is the successor registry, which continues to assess longitudinal real world clinical outcome, incl. patient-reported outcomes (PROs) and decentralized biobanking. Today, we introduce CARAT and report on current changes of the treatment landscape in mRCC in Germany. Methods Since Dec 2017 150 pts have been enrolled in CARAT, expanding the previous TNK (2007-17, 1500 pts). CARAT is an observational, prospective, open, multicentre clinical research platform aiming to enrol 1000 pts by 150 sites. Pts with mRCC who start systemic 1stline treatment are eligible. Treatment characteristics, clinical outcome and physician-reported factors on treatment decision making are collected. Overall survival (OS) is assessed by the KM-method. Changes of the treatment landscape are shown descriptively. Results By April 2019 >1650 pts with mRCC have been recruited. Median age is 68 years. 60% had intermediate risk (MSKCC) at start of 1st-line. Median OS for pts with start of 1st-line 2007-17 is 19 months (>60% events). If selected by trial eligibility criteria, the median OS is 27 months. Pts who started treatment in 2018 mostly received pazopanib or sunitinib (38%/34%). Since the approval (May 2018) 18% are treated with cabozantinib. Preferred 2nd-line treatment changed from sorafenib/temsirolimus (35%/21%, 2007-09), everolimus (33% 2010-12), everolimus/axitinib/sunitinib (29%/19%/18%, 2013-15) to nivolumab (>60% since 2016). The impact of new treatment options on OS will be analysed. Conclusions Pts in routine care in Germany are older and have inferior prognosis than trial-eligible pts. CARAT complements results of RCTs with prospective data on clinical and PROs for pts with mRCC in routine care. CARAT will show changes in the choice of treatment due to new approvals, applied sequences and investigate the effectiveness in a “real world” setting. For the first time, these data will be combined with PROs and a decentralized biobank for translational research. Legal entity responsible for the study IOMEDICO. Funding Ipsen. Disclosure P.J. Goebell: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self): IOMEDICO. M. Bogemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Astellas; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ipsen; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Eusa Pharma; Honoraria (self), Advisory / Consultancy: ABX; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Amgen. S. Dorfel: Shareholder / Stockholder / Stock options: IOMEDICO. N.W. Marschner: Advisory / Consultancy, Leadership role, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: IOMEDICO; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ipsen. M. Staehler: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): GSK; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche. V. Grunwald: Honoraria (self), Research grant / Funding (self), Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: MSD; Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self), Shareholder / Stockholder / Stock options: AstraZeneca; Honoraria (self), Research grant / Funding (self), Shareholder / Stockholder / Stock options, Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: Merck Serono; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Lilly; Honoraria (self), Non-remunerated activity/ies: PharmaMar; Honoraria (self): Nanobiotix; Honoraria (self): Janssen. All other authors have declared no conflicts of interest.

Purpose To investigate a multiparametric magnetic resonance imaging (MRI) approach comprising diffusion-weighted imaging (DWI), blood oxygen–dependent (BOLD), and dynamic contrast-enhanced (DCE) MRI for characterization and differentiation of primary renal cell carcinoma (RCC). Material and Methods Fourteen patients with clear-cell carcinoma and four patients with papillary RCC were examined with DWI, BOLD MRI, and DCE MRI at 1.5T. The apparent diffusion coefficient (ADC) was calculated with a monoexponential decay. The spin-dephasing rate R2* was derived from parametric R2* maps. DCE-MRI was analyzed using a two-compartment exchange model allowing separation of perfusion (plasma flow [FP] and plasma volume [VP]), permeability (permeability surface area product [PS]), and extravascular extracellular volume (VE). Statistical analysis was performed with Wilcoxon signed-rank test, Pearson's correlation coefficient, and receiver operating characteristic curve analysis. Results Clear-cell RCC showed higher ADC and lower R2* compared to papillary subtypes, but differences were not significant. FP of clear-cell subtypes was significantly higher than in papillary RCC. Perfusion parameters showed moderate but significant inverse correlation with R2*. VE showed moderate inverse correlation with ADC. Fp and Vp showed best sensitivity for histological differentiation. Conclusion Multiparametric MRI comprising DWI, BOLD, and DCE MRI is feasible for assessment of primary RCC. BOLD moderately correlates to DCE MRI–derived perfusion. ADC shows moderate correlation to the extracellular volume, but does not correlate to tumor oxygenation or perfusion. In this preliminary study DCE-MRI appeared superior to BOLD and DWI for histological differentiation.

Objective: To determine the safety and feasibility after image-guided single fraction robotic stereotactic radiosurgery (SRS) in patients with bone metastases of prostate cancer. Materials and methods: Forty patients with 64 bone metastases of prostate cancer were prospectively enrolled in a single center study and underwent 54 consecutive outpatient single session SRS procedures during a 4-year period. F-18 choline PET/CT in addition to standard CT imaging was done prior to SRS in all patients. Nineteen patients were under anti-androgen therapy, 8 patients had undergone chemotherapy before SRS. Overall survival and freedom from local tumor recurrence was analyzed with the Kaplan-Meier method. Results: Mean follow-up was 14 months (3– 48 months). Seventy-five percent of patients had a single bone metastasis. The median tumor volume was 13 cc. The mean prescribed tumor dose was 20.2 Gy (16.5–22 Gy). Eight patients had died at the time point of the data analysis. The actuarial 6-months, 12-months, and 24-months local tumor control rate was 95.5% (95% CI: 83.0 –98.8) as measured by MRI and PET CT imaging. The median initial PSA before SRS was 5.4 ng/dl (CI: 1.4 – 8.2) and dropped to 2.7 ng/dl (CI: 0.14 –10) after 3 months. One case of progressive neurological deficits was documented. Conclusions: This first report on single session, image-guided robotic SRS documents a safe, feasible, and patient-friendly treatment option in selected patients with bone metastases of prostate cancer. © 2011 Elsevier Inc. All rights reserved.

CONTEXT: While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown. OBJECTIVE: To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC. EVIDENCE ACQUISITION: Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken. EVIDENCE SYNTHESIS: The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03-1.92 and 1.41, 95% CI: 0.88-2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67-2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9-2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91-1.86). Sunitinib was associated with more Grade 3-4 adverse events than everolimus, although this was not statistically significant. CONCLUSIONS: This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed. PATIENT SUMMARY: We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.

Objective Imaging-based monitoring of molecular therapies in oncology remains a challenge. Molecular therapies might have more pronounced effects on lesion density than on lesion size. We analyzed changes in lesion diameter and density in patients with metastasized renal cell cancer (mRCC) in the early follow-up of targeted therapy and compared size-based measurements according to Response Evaluation Criteria in Solid Tumors (RECIST) with size- and density-based response evaluations according to the Choi criteria. Patients and methods A total of 22 patients treated with sorafenib (800 mg/d) were retrospectively analyzed. Relative changes (in %) in the greatest diameter and density of defined neoplastic “target lesions” were determined 8 weeks and 1 year after start of therapy in relation to a pretherapeutic baseline investigation. Data were analyzed according to RECIST (ver. 1.0), and results were compared with the response assessment based on Choi. Median survival was determined for all subgroups according to Choi or RECIST at the 8-week and 1-year follow-up. Results Applying RECIST, 18 patients (82%) demonstrated stable disease (SD) 8 weeks after the start of targeted therapy, 3 patients (14%) partial response (PR), and 1 patient (4%) progressive disease (PD). Partial responders at 8 weeks had a median survival of 48 months. After 1 year, 59% of all patients still showed SD. Applying Choi, 15 patients (68%) showed PR 8 weeks after the start of therapy, 5 patients (23%) SD, and 2 patients (9%) PD. After 1 year, PR was still the predominant response group (64% of the patients). Partial responders after 8 weeks had a median survival of 18 months. Conclusion Choi defined more patients as partial responders at early stages of therapy than RECIST, but this was not an effective selection for patients with prolonged median survival. Evaluation of a larger patient cohort will further clarify the role of combined size- and density-based follow-up strategies in targeted therapy of mRCC.

Background The outcome of patients with advanced renal cell carcinoma (RCC) under systemic therapy shows remarkable variability, and there is a need to identify prognostic parameters that allow individual prognostic stratification and selection of optimal therapy. Artificial neural networks (ANN) are software systems that can be trained to recognize complex data patterns. In this study, we used ANNs to identify poor prognosis of patients with RCC based on common clinical parameters available at the beginning of systemic therapy. Patients and Methods Data from patients with RCC who started systemic therapy were collected prospectively in a single center database; 175 data sets with follow-up data (median, 36 months) were available for analysis. Age, sex, body mass index, performance status, histopathologic parameters, time interval between primary tumor and detection of metastases, type of systemic therapy, number of metastases, and metastatic sites were used as input data for the ANN. The target variable was overall survival after 36 months. Logistic regression models were constructed by using the same variables. Results Death after 36 months occurred in 26% of the patients in the tyrosine kinase inhibitors group and in 37% of the patients in the immunotherapy group ( P = .22). ANN achieved 95% overall accuracy and significantly outperformed logistic regression models (78% accuracy). Pathologic T classification, invasion of vessels, and tumor grade had the highest impact on the network's decision. Conclusion ANN is a promising approach for individual risk stratification of patients with advanced RCC under systemic therapy, based on clinical parameters, and can help to optimize the therapeutic strategy.

Background The aim of this single-center study was to analyze factors predicting long-term outcomes following surgical resection of pulmonary metastases in patients with renal cell carcinoma. Methods Two hundred two consecutive patients entered the study. Overall survival was analyzed by the Kaplan-Meier method. Multivariate analysis was performed using Cox regression models. Results In 175 cases (87%), curative resection of the pulmonary metastases was achievable, with median survival of 43 months. Multivariate analysis revealed complete metastasectomy (R0), metastasis size >3 cm, positive nodal status of the primary tumor, synchronous metastases, pleural infiltration, and tumor-infiltrated hilar or mediastinal lymph nodes as independent prognostic factors for survival. On the basis of these findings, a new scoring system (the Munich score) was established to predict survival, which discriminates 3 groups with low, intermediate, and high risk for poor outcomes (median survival, 90, 31, and 14 months, respectively, P Conclusions The aim of the Munich score is to define patients with low, intermediate, and high risk for poor survival and will help identify patients who may benefit from further adjuvant therapy.

e16101Background: Checkpoint-inhibitors have recently been introduced in the treatment of patients with genitourinary cancers. However, the use in elderly patients is controversial due to putative ...

Background It is unknown if discontinuation of targeted therapy (TT) and readministration in case of recurrence is feasible in patients with metastatic renal cell carcinoma (mRCC) in which complete response (CR) is achieved by TT alone or no evidence of disease (NED) with additional resection of residual metastases. Patients and methods Patients in whom TT was discontinued after CR to TT alone or NED after additional metastasectomy were included in this retrospective analysis. Outcome criteria evaluated were time off TT, recurrence of metastases and response to re-exposure to TT. Univariate and multivariate analyses were carried out to identify variables potentially predictive of outcome. Results In 36 patients with CR or NED under TT with sunitinib (22), sorafenib (11), bevacizumab/interferon (2) and temsirolimus (1), TT was discontinued. Recurrence was observed in 24 patients (66.7%). Re-exposure to TT was effective in 86.9% of these cases. Twelve patients (33.3%) remained recurrence free at a median follow-up of 12 months (range 3–31). Median time off TT was 7 months (range 1–31). Factors that correlate with outcome could not be identified. Conclusions In the majority of patients with mRCC and CR or NED, discontinuation of TT was followed by recurrence, but re-exposure to TT was effective.

Objectives In this study, clinically available pulsed laser systems emitting either in the infrared (IR)- or visible (VIS) spectral region were compared in a standardized manner with respect to their impact on phantom stones in an underwater laboratory set-up.

Renal cell carcinoma (RCC) is the most deadly urological malignancy with only 62% of all patients surviving 5 years in all stages. Approximately 20–30% present initially with metastatic disease as well as 20–40% of patients who will develop systemic spread after surgery. New insights in angiogenesis lead to the development of new drugs directed against receptors and downstream signaling molecules of angiogenetic regulation mechanisms. The results of clinical trials with these drugs will lead to a change of paradigm in the systemic treatment of RCC patients. Specially Sutent, Sorafenib and Temsirolimus proved efficacy in metastatic disease and should be added substantially to the therapeutic armamentarium when surgery of the primary or metastases is impossible.

Acute urinary retention (AUR) is a serious complication in patients with benign prostatic hyperplasia (BPH). It is defined as the sudden inability to pass urine which results in painful distension of the bladder and necessitates immediate decompression by catheterization. In the understanding of the natural history of BPH considerable progress has been achieved. In primary prevention of AUR it is crucial to identify the clinical profile of patients with a progressive disease and thus provide appropriate and individual treatment. Several studies indicate the potential of alpha-blockers after an episode of AUR to improve the chance of a successful trial without catheter (TWOC) which should be performed 2 to 7 days after AUR. Long-term studies are needed to clarify whether treatment with alpha-blockers can avoid or delay relapse of AUR. On the other hand, high PSA values (≥6 ng/ml), elevated post-TWOC residual urine (>90 ml), prostate size (>20 ml), history of prior AUR and the degree of intravesical prostatic protrusion seem to be major risk factors for AUR relapse and thus may require non-conservative treatment options. Since numerous studies addressing the issue of AUR have been published recently, this review focuses primarily on the literature published in Medline in 2005.

The European Association of Urology renal cancer guidelines panel recommends nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of vascular endothelial growth factor-targeted therapy. New data have recently become available showing a survival benefit for cabozantinib.