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The aim of the current research was to investigate the prognostic significance of pretreatment hemoglobin-to-red cell distribution width ratio (HRR) in patients with renal cell carcinoma (RCC). The neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio (LMR) and HRR were analyzed retrospectively to assess their prognostic value using Kaplan-Meier curves and Cox regression analysis in 198 patients with RCC. High HRR (0.72) and high LMR (2.43) were found to be associated with longer progression-free survival and overall survival. A multivariate analysis identified International Metastatic Renal Cell Carcinoma Database Consortium prognostic score, tumor stage, node stage, LMR and HRR as independent prognostic factors for progression-free survival, as well as International Metastatic Renal Cell Carcinoma Database Consortium score, neutrophil-to-lymphocyte ratio and HRR for overall survival. HRR is a an independent prognostic parameter predicting the progression and survival of patients with RCC.Lay abstract Hemoglobin-to-red cell distribution width ratio (HRR) may be associated with lifespan in patients with cancer, as shown in previous studies of solid organ malignancy. The present study investigates the prognostic significance of pretreatment HRR in patients with renal cell carcinoma. A higher HRR was associated with longer survival in the present study, indicating the value of HRR as a predictor of survival and prognosis in renal cancer.

Purpose: To assess the healthcare resources’ consumption and integrated costs of patients with renal cancer and new metastasis (mRCC), in the perspective of the Italian National Health System (NHS). Methods: From the ReS database, through the administrative data record linkage, adults with a primary/secondary hospital (ordinary/daily admissions) diagnosis (ICD9-CM code) of renal cancer and lymph node and/or distant metastases in the same hospital discharge (index date) were selected in 2015. Metastases were defined new if they were absent in the 2 previous years. Patients were described in terms of gender, age (mean ± SD) and comorbidities of interest. The 2-year survival and annual pharmacological treatments, hospitalization, outpatient specialist services and costs were analysed. Results: Out of >6 million adults in the 2015 ReS database, 133 (2.1 × 100,000) were hospitalized with a diagnosis of RCC and metastasis. Patients with new metastases were 63.2% (1.4 × 100,000; 73.8% males; mean age 68 ± 13). Hypertension was the most common comorbidity (70.2% of mRCC patients). The 2-year survival of mRCC patients was 26.2%. During 1-year follow-up, at least a drug was prescribed to 88.1% of mRCC patients (on average € 12,095/patient), 91.7% were hospitalized (€ 8,897/patient) and 82.1% entrusted the outpatient specialist care (€ 1,075/patient). The mean overall expenditure for the NHS was € 22,067 per capita. Conclusions: This study shows the mRCC burden on the Italian real clinical practice and its economic impact in the perspective of the NHS. Real-world analyses prove to be useful to concretely estimate the overall healthcare responsibility on patients affected by mRCC.

Tumor lysis syndrome is uncommon in solid tumors but with the use of immunotherapy (checkpoint inhibitors) their incidence is increasing. Physicians need to take adequate precautions while treating patients with immunotherapy. The findings of our case report will help improve our current understanding of tumor lysis syndrome specially in solid tumors and will help in developing multidisciplinary treatment and prophylaxis strategies for this uncommon, but potentially fatal complication.

The authors report cases of metastatic renal cell carcinoma with level III-IV tumour thrombi in the inferior vena cava (IVC). Cases were treated with three courses of neoadjuvant sunitinib to reduce the thrombus level before surgery. Nephrectomy and tumour thrombectomy were performed, and sunitinib treatment continued after the operation. Cases 1 and 3 showed regression of lung metastases, but the size of the primary renal tumour and thrombus remained the same. The progression-free survival of the cases was 35 months and 24 months, respectively. In case 2, the primary renal tumour, metastases and thrombus showed regression. The upper limit of the thrombus decreased by 3 cm. In this case, the progression-free survival was 15 months, and the cancer-specific survival was 18 months. The neoadjuvant sunitinib treatment had a limited effect on downsizing the extent of tumour thrombi in the IVC.

Resume But Definir les amenagements du traitement medical par les anti-angiogeniques, l’inhibiteur de mTOR ou les immunotherapies systemiques lors de la prise en charge du cancer du rein metastatique chez les patients âges. Methode Recherche bibliographique a partir de la base de donnees bibliographiques Medline (NLM outil Pubmed) et Embase a partir des mots-cles suivants : cancer du rein metastatique, personne âge, traitement. Resultats Les criteres de selections du traitement medical du cancer du rein metastatique chez les patients âges sont le score IMDC necessairement complete par le performance status, le profil de tolerance du traitement, les interactions medicamenteuses plus frequentes, l’observance du traitement, la capacite de gestion de ses effets secondaires et la preference des patients. Chacun de ces criteres est detaille de maniere critique. Conclusion L’efficacite et la tolerance de traitements medicaux du cancer du rein metastatique n’ont pas ete rapportees comme differentes en fonction de l’âge. Aucune adaptation posologique n’est recommandee de principe. Toutefois, la prevention et le traitement precoce des effets secondaires des traitements doivent etre renforces chez les patients âges.

Background: Available treatments for metastatic RCC (mRCC) are usually non-curative. In the last decade, novel targeted therapies have significantly improved mRCC outcome. The objective in this study was to describe outcomes in patients with mRCC in Morocco.Methods: 100 patients with mRCC were recruited between January 2008 and December 2018 in the Hassan II University Hospital of Fez. Data were retrospectively collected. Kaplan-Meier survival analysis was used to determine overall survival (OS) and progression free survival (PFS).Results: Mean age of the patients was 58.6 years(±12). Sixty seven percent of patients were male. Clear cell carcinoma was the most common histological subtype (78%). According to the IMDC scoring, 72% of patients were in the intermediate and 18% in the poor risk groups. Seventy patients received targeted therapy. Overall response rate (according to RECIST criteria version 1.0) was 38.6%. The median PFS was 7.0 months (95% CI, 4.6 to 9.4). The median OS was 11.6 months (95% CI, 7.9 to 15.3). In the multivariate analysis, cancer specific mortality was impacted by treatment with VEGFR inhibitors (HR: 0.2; 95% CI, 0.1 to 0.4; p =0.001) and IMDC score (intermediate risk group HR: 3.5 (95% CI, 1.4 to 9.1; p =0.009); and poor risk group HR: 5.5 (95% CI, 1.9 to 16.1; p =0.002)).Conclusion: This is the first report from clinical practice in an African country of OS data in mRCC. The study showed high mortality rates. However, outcomes of VEGFR inhibitors are consistent with studies investigating these treatments.

Background Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow‐growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature. Methods This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient‐related outcomes. Wilcoxon 2‐sample rank‐sum tests and χ2 tests were used to assess differences between ST and AS cohorts in continuous and categorical variables, respectively. Kaplan‐Meier survival curves were used to assess survival. Results Of 504 patients, mRCC was initially managed by AS (n = 143) or ST (n = 305); 56 patients were excluded from the analysis. Disease was present in 69% of patients who received AS, whereas the remaining 31% had no evidence of disease. At data cutoff, 72 of 143 patients (50%) in the AS cohort had not received ST. The median overall survival was not reached (95% CI, 122 months to not estimable) in patients who received AS versus 30 months (95% CI, 25‐44 months) in those who received ST. Quality of life at baseline was significantly better in patients who were managed with AS versus ST. Conclusions AS occurs frequently (32%) in real‐world clinical practice and appears to be a safe and appropriate alternative to immediate ST in selected patients., This prospective observational study followed patients with metastatic renal cell carcinoma who were managed by active surveillance before treatment. The approach is used frequently in clinical practice and appears to be a safe and appropriate option for some patients.

Background Liver metastases are present in 20.3% of metastatic kidney cancers. The aim of this literature review was to assess the efficacy of surgical treatment for hepatic metastasis from kidney cancer. Methods An extended web search of the literature was independently performed in March 2018 by two authors according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Results Through electronic searches, we identified 935 potentially relevant citations. Thirteen articles were finally included in the systematic review. Median survival after resection ranged from 15 to 142 months while the 1-, 3- and 5-year overall survival ranged from 69% to 100%, 26% to 83.3% and 0% to 62%, respectively. Median disease-free survival ranged from 7.2 to 27 months. Conclusion Surgical treatment of hepatic metastases is performed in approximately 1% of patients with liver metastases and in select patients may be potentially curative. Surgical resection of liver metastases from kidney cancer represents a valid option for selected patients with metastatic renal cancer.

INTRODUCTION AND OBJECTIVE:Previous studies have shown a survival advantage for patients with high body mass index (BMI) and metastatic renal cancer. In prostate cancer patients, findings regarding...

Objectives To analyze the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. Material and methods We evaluated 32 consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analyzed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan–Meier curves. The learning curve was analyzed with the cumulative sum (CUSUM) methodology. Results In our series, the median time to the withdrawal of the first-line treatment was 11 months (95% CI 4.9–17.1). The mean time to progression was 30.4 months (95% CI 22.7–38.1), and the mean overall survival was 34.9 months (95% CI 27.8–42). By applying the CUSUM methodology, we obtained a graph for the CUSUM value of the time to withdrawal of the first-line treatment (CUSUM TW), observing 3 well-differentiated phases: phase 1 or initial learning phase (1–15), phase 2 (16–26) in which the management of the drug progressively improved and phase 3 (27–32) of maximum experience or mastery of the management of these drugs. The number of treated patients needed to achieve the proper management of these patients was estimated at 15. Conclusions Despite the limitations of the sample size and follow-up time, we estimated (in 15 patients) the number needed to reach the necessary experience in the management of these patients with tyrosine kinase inhibitors. We observed no relationship between the time to the withdrawal of the first-line treatment for any cause and progression.

Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers and metastatic renal cancer. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events that may be life threatening if not anticipated and managed appropriately. This new family of dysimmune toxicities remains largely unknown to the broad oncology community. We propose here some practical guidelines for the oncologist to help in the clinical care of patients under immune checkpoint molecules.

Background Pazopanib is a multitarget tyrosine kinase inhibitor used in the treatment of renal cancer and soft tissue sarcoma. Its use is commonly associated with a number of side effects, such as hemorrhagic diathesis, neutropenia, leukopenia, thrombocytopenia, nausea, vomiting, abdominal pain, increased serum aspartate aminotransferase, increased serum alanine aminotransferase, decreased serum glucose, increased serum bilirubin, decreased serum phosphate and magnesium, fatigue, hypertension, diarrhea, anorexia, proteinuria, and hypothyroidism. Abscesses of metastases caused by pazopanib administration are rarely reported in the literature. Case presentation We report a case of abscesses of lung metastases related to pazopanib in a patient with metastatic renal cancer. The patient was a 53-year-old Caucasian man who developed abscesses of lung metastases during the first 3 months of treatment with pazopanib. The abscesses resolved after 1 month by stopping pazopanib and administering adequate antibiotic therapy. Conclusions We conclude that abscesses of metastases could be a rare side effect occurring during treatment with pazopanib in patients with renal cancer.

Introduction: Metastatic renal cell carcinoma (mRCC) in recent years has been one of the diseases in the oncology that has experienced the greatest development of targeted therapies.Area covered: On one hand, more and more refined acquisitions of molecular biology are allowing a better sub-classification of this tumor, identifying new and peculiar biological profiles of patients with metastatic renal cancer that will soon be destined for increasingly tailored treatments. On the other hand, immunotherapy has, in a short time, redesigned the perimeter of our knowledge, entering clinical practice in an overpowering and convincing way. Monoclonal antibodies targeting immune checkpoint inhibitors have now entered clinical trials and have demonstrated promising antitumor effect for refractory metastatic renal cancer.Expert opinion: This review summarizes the results of published and reported studies of immune checkpoint inhibitors targeted therapies enrolling patients with metastatic renal cancer.

Locally recurrent renal cell carcinoma following either partial or radical nephrectomy presents a complex set of technical and therapeutic challenges to clinicians. That there is a role for aggressive surgical resection in these clinical scenarios is clear. Retrospective evidence demonstrates the feasibility of salvage surgery and the potential benefit to oncologic outcomes. However, clear trade-offs exist between the possible oncologic benefits of surgical extirpation and the high-risk nature of salvage renal surgery. Similarly, local recurrence following primary ablative therapy can be challenging to diagnose on cross-sectional imaging, and salvage surgery is technically demanding. Verification of local recurrence in this situation is critical prior to embarking upon surgical intervention. Additionally, metastatic disease presents unique and complex challenges of its own. Metastasectomy has been demonstrated to have a role in the management of these patients but again must be undertaken with a clear understanding of the risks of surgery. Several retrospective series have demonstrated excellent survival in well-selected patients undergoing surgical management of metastatic disease. Broadly speaking, appropriate patient selection and risk evaluation are paramount to successful surgical management of both locally recurrent disease and metastatic disease. As the contemporary era of targeted therapy and immunotherapy continues to evolve, further evaluation of the role and timing of surgery will be necessary to infer meaningful standards of care.

The treatment landscape in metastatic renal cell carcinoma has changed fundamentally over the last decade by the development of antiangiogenic agents, mammalian target of rapamycin inhibitors and immunotherapy. Outside of the context of a clinical trial, the treatments are used sequentially. We describe results under real-life conditions of a sequential treatment strategy, before the era of immunotherapy. All patients were treated according to their prognostic score (either Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium) for advanced renal cell carcinoma. A treatment strategy involving 1 to 4 lines was determined including a rechallenge criterion for the repeat use of a treatment class. Three hundred forty-four patients were included over 3 years. Overall survival was 57 months in patients with good or intermediate prognosis and 19 months in patients with poor prognosis. In the former group, the proportions of patients treated with 2 to 4 treatment lines were 70%, 38% and 16%, respectively. The best objective response rates for lines 1 to 4 were 46%, 36%, 16% and 17%, respectively. Grade III/IV toxicity did not appear to be cumulative. The recommended strategy was followed in 68% of patients. A large proportion of patients with good or intermediate prognosis who progress after two lines of treatment still have a performance status good enough to receive a systemic treatment, which justifies such a strategy. Overall survival of patients with good and intermediate prognosis was long, suggesting a benefit from the applied approach. These results might be used as selection criterion for the treatment of patients in the era of immune checkpoint inhibitors.

Objective: To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme. Patients and Methods: Patients with metastatic renal cell cancer (mRCC) previously treated with agents targeting the vascular endothelial growth factor pathway were eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Results: A total of 389 patients were enrolled between July 2015 and April 2016, of whom 18% were aged ≥75 years, 6.7% had non-clear cell RCC, 49.6% had bone and 8.2% brain metastases, and 79% had received ≥2 previous lines of therapy. The most common any-grade treatment-related AEs were fatigue (13%) and rash (9%). Twenty-two patients (5.7%) discontinued treatment because of AEs. There were no treatment-related deaths. The objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% confidence interval 3.7–6.2) and the 12-month overall survival rate was 63%. Similar survival rates were reported among patients with non-clear-cell histology, elderly patients, those with bone and/or brain metastases, and those who had received prior first-line sunitinib or pazopanib, or prior everolimus. Conclusion: The safety and efficacy observed were consistent with those reported in the pivotal Checkmate 025 trial. Results in patients with non-clear-cell mRCC who were elderly, pretreated with everolimus, and had bone and/or brain metastases encourage the use of nivolumab in these categories of patients. © 2018 The Authors BJU International

To evaluate whether sunitinib and pazopanib treatments are associated with change in skeletal muscle area (SMA) and total lean body mass (LBM) as well as to compare their efficacies and safety profiles in patients with metastatic renal cell cancer (mRCC). Thirty-six patients treated with a tyrosine kinase inhibitor were included. Eighteen of them received sunitinib and the rest/remaining received pazopanib in the first line of mRCC treatment. Baseline and follow-up computed tomography studies of the patients were performed to measure cross-sectional areas (cm2) of muscle tissues. About 69% of patients were male and median age was 60 (49–68) years. Median time interval between two CT imagings was 6.1 (3.1–7.7) months and it was similar between the two groups (for sunitinib, 4.9 (2.5–6.9) months vs for pazopanib, 7.3 (3.2–9.5) months, p = 0.16, respectively). Disease control rate was 77.7% in all patients. Of these, 66.6% in sunitinib group was consisted of four partial responses and eight stable diseases. In addition, 88.8% in pazopanib group was consisted of three partial responses and 13 stable diseases. A significant decrease in SMA and LBM was observed after sunitinib therapy, whereas SMA and LBM values of pazopanib group did not change significantly (p = 0.02 and p = 0.70, respectively). No significant differences were observed between patients with sunitinib, and pazopanib group median PFS [11.9 (95% CI 6.1–17.6) vs 8.1 months (95% CI 7.2–9.1), respectively; p = 0.28] and median OS [28.6 (95% CI 24.3–32.9) vs 25.5 months (95% CI 18.9–52.7), respectively; p = 0.42]. Dose-limiting toxicities were significantly more frequent in sunitinib group than in pazopanib group (66.7% vs 22.2%, p = 0.02, respectively). Loss of SMA and LBM with sunitinib was more substantial than with pazopanib. Treatment efficacies of both drugs were similar, but dose-limiting toxicity was more frequent in sunitinib group. Loss of SMA had no significant association with prognosis. Further studies are needed to clarify the possible association between SMA and prognosis in mRCC patients who receive sunitinib or pazopanib.

We present an unusual case of a metastatic renal cell carcinoma (RCC) mimicking trigeminal schwannoma. The patient, with no prior history of RCC, presented with clinical symptoms and imaging consistent with trigeminal neuralgia secondary to trigeminal schwannoma. Magnetic resonance imaging of the brain showed a large bilobed cystic/solid mass primarily in the cerebellopontine angle cistern, with extension into the left middle cranial fossa, Meckel cave, and left cavernous sinus. Following surgical excision, histopathology revealed the tumor to be an RCC infiltrating into the trigeminal nerve fascicles. Further imaging and investigation revealed widespread metastasis to the vertebral bodies and long bones. Metastatic RCC to the trigeminal nerve is rare. Despite the development of more effective treatment modalities, the prognosis of metastatic RCC remains poor. To our knowledge, this is the first reported case of RCC metastasizing to the trigeminal nerve fascicles.

In patients with metastatic renal cell carcinoma, risk stratification according to the Memorial Sloan Kettering Cancer Center or the International Metastatic Renal Cell Carcinoma Database Consortium classification systems is a crucial part of clinical assessment and essential for guiding management. New research has now demonstrated that disagreement in risk-group classification is common and prognostically relevant.

706 Background: The introduction of first line immune combination or immune/VEGF therapy in metastatic renal cancer has changed treatment landscape. Here we compare outcomes of these combinations with patients treated with first line sunitinib. The focus is on the impact of subsequent treatments. Methods: This retrospective analysis was performed at Barts Cancer Institute for consecutive patients from April 2015 when front line immune therapy was first used at our institution. Only patients enrolled on reported prospective trials were included to avoid selection bias. Patients were treated with VEGF targeted therapy (n=35) (group V), PD-1 + CTLA4 (n=15) (group I/I) or a combination of PD-L1 + VEGF TKI inhibitor (n=29) (group I/V). The primary analysis focused on the proportion of patients who received second line therapy and their outcome. Results: 79 patients received first line therapy for clear cell RCC. IMDC good, intermediate and poor risk occurred in 27.8%, 60.8% and 11.4% respectively. Front line response rates for V, I/I and I/V groups were 34.3%, 46.7% and 65.5% and PFS in V, I/I and I/V groups were 11mo (95%CI 6-16), 18mo (95% CI 0-41) and 36mo (95% CI 13-59), respectively (P= 0.016). OS in the 3 groups were immature but not significantly different. Second line therapy occurred in 87.5%, 92.9% and 81.8% in the V, I/I and I/V groups respectively (in those who progressed after initial therapy). Second line response rate post first line V, I/I and I/V were 11%, 0% and 0% respectively as per RECIST 1.1. 63% of patients receiving VEGF front line therapy subsequently received immune therapy. 95% of patients receiving first line immune/immune or immune/VEGF combination therapy received VEGF therapy in the second line. Only 70% of patients who progressed on second line therapy got 3rd line therapy across all arms. Conclusions: Response rates after front line immune combination therapy are modest. The sequencing of PD-1 therapy after VEGF monotherapy appears particularly relevant in outcomes. A high proportion of patients are sequencing therapy and reaching third line which may help improve outcomes.

CARMENA, a trial comparing the efficacy of sunitinib alone to that of nephrectomy followed by sunitinib in patients with primary metastatic renal cell carcinoma who require targeted therapy has demonstrated the non-inferiority of systemic therapy alone. The data provided by this and other studies argue for a lesser role of surgery in the management of these patients.

e16087 Background: Several studies, the majority on melanoma and lung cancer, have addressed the value of gender with respect to immune check point inhibitors outcome as compared to standard therapy, showing conflicting results. Nevertheless, few focused on gender-related clinical outcome and toxicity in renal cell carcinoma (RCC) patients. Methods: This analysis evaluated the effect of gender on overall survival and adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 in an expanded access programme of nivolumab 3 mg/kg once every 2 weeks in second-line and beyond metastatic RCC. Only patients assuming at least one dose of nivolumab were analyzed. Results: Of 389 patients analyzed, 25.2% were female. On study entry, no differences were found in women as compared to men in terms of age, on average 64 years, p = 0.91; overweight/obesity, 45 versus (vs) 49%, p = 0.47; LDH , mean U/L 391 vs 32, p = 0.17); and neutrophils/lymphocytes ratio> 3 (62 vs 63%, p = 0.87). Disease presentation was similar according to gender, although women tended to present less lung (66% vs 76%, p = 0.06) and bone metastases (42% vs 52%, p = 0.07). Notably, there was no differences in the IDMC prognostic model by gender (p = 0.94). Any drug related AEs (38 vs 30%, p 0.15), grade 3-4 (6% vs 6%) and median number of drug doses 12 (53% vs50%, p = 0.58 ) did not differ between gender. After adjusting for known prognostic variables, multivariate analysis showed that women had similar overall survival as compared to men (hazard ratio 0.81, 95% confidence interval 0.56-1.17, p = 0.26). Conclusions: Women demonstrate similar overall survival than men in metastatic RCC treated with secondal line and beyond nivolumab, with no differences observed in serious AEs and dose administered.

4508 Background: Carmena was a randomized phase III trial, testing the benefit of CN followed by sunitinib (arm A) vs sunitinib alone (arm B), with stratification by MSKCC risk groups in 450 mRCC patients. Based on this trial, CN is not anymore recommended in mRCC (NEJM, Mejean et al, 2018). However there are questions about which patients could still benefit from CN, especially in intermediate risk group. In the present study, we investigated different subgroups from the Carmena trial to answer these questions. Methods: Carmena trial was initially stratified according to MSKCC risk groups. For the purpose of this analysis, we reclassified the patients based on IMDC risk groups. We also analyzed patients with one metastatic site vs more than one, as well as patients with secondary nephrectomy in arm B. Overall survival (OS) was the primary endpoint. Results: With a updated median FU of 61.5 months (mo), the median OS by ITT analysis was 15.6 vs 19.8 mo in arm A and B respectively stratified on MSKCC (HR 0.933 ; 95% CI [0.76- 1.15]) / stratified on IMDC (HR 0.957 ; 95% CI [0.78- 1.18]). Using IMDC risk group factors, 58.6% patients were intermediate and 41.4 % were poor risk. When looking at intermediate risk group only, 48.1% had only one risk factor (interval between diagnosis and treatment < 1y), with a median OS of 30.5 and 25.2 mo in arm A and B respectively (HR 1.24 [0.81 – 1.90]). By contrast, 51.9 % had two risk factors (mostly low hemoglobin, high corrected calcium or neutrophils), with a median OS of 16.6 and 31.2 mo in arm A and B respectively (HR 0.61 [0.41 – 0.91] p = 0.015). Regarding number of metastatic sites, 33% had only one metastatic site. Median OS was 23.6 and 22.7 mo in arm A and B respectively (HR 1.08 [0.75 – 1.57]. Finally, 40 patients had a secondary nephrectomy in arm B, with median OS of 48.5 mo [CI 95%: 27.9-64.4] vs 15.7 mo [CI 95%: 13.3-20.5] in patients who never had surgery. Conclusions: With longer FU, Carmena trial confirms that CN is not superior to sunitinib alone in ITT population, both with MSKCC and IMDC risk groups. However for patients with only one IMDC risk factor, CN might be beneficial. Number of metastatic site is not helpful to define good candidates for surgery. Finally, patients with secondary nephrectomy have very long OS, supporting this strategy. Clinical trial information: NCT00930033.

The sequencing of targeted therapy is well established in metastatic renal cancer. Switching between different vascular endothelial growth factor (VEGF)-targeted therapies or VEGF-targeted therapies and mammalian target of rapamycin (mTOR) inhibitors are both of proven benefit. The optimal sequence remains unclear. Unfortunately, there is a lack of biomarkers to drive decision making. In this article we review the current data and describe the treatment options for patients.

Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib–axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93–7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6–17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib (≤ vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39–13.40 months) vs. 5.46 months (95% CI 4.04–6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95–10.51 months, p = 0.01) and 8.67 (95% CI 4.0–13.33 months, p = 0.008) vs. 2.97 (95% CI 0.65–5.27 months, p = 0.01) and 2.97 months (95% CI 0.66–5.28 months, p = 0.01), respectively. Overall Axitinib at standard schedule of 5 mg bid, was well-tolerated. The most common adverse events of all grades were fatig (25.6%), hypertension (22.6%), gastro-intestinal disorders (25.9%), and hypothyroidism (16.1%). The sequence Sunitinib–Axitinib was well-tolerated without worsening in side effects, with a median OS of 34.7 months (95% CI 18.4–51.0 months). Our results are consistent with the available literature; this retrospective analysis confirms that Axitinib is effective and safe in routine clinical practice.

Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a real-world study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included Objective Response Rate (ORR), Disease Control Rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9-18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6-39.9 months); the observed ORR and DCR were 30.3% and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR=0.05 [95% CI, 0.05-055], p=0.01; HR=0.10 [95% CI, 0.02-0.43], p=0.002 respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p= 0.2) and with a high tumor burden (number of metastatic sites 6) (p= 0.08). Worst OS was observed in patients age >70 years old (HR=6.91 [95% CI, 1.49-31.91], p=0.01). The treatment was well tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR=0.22 [95% CI, 0.05-0.8], p=0.03) and thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR=0.12 [95% CI, 0.02-0.78], p=0.02). Our results are consistent with those reported in prospective phase III trials and the published retrospective real world experiences. This analysis confirms the safety and efficacy of pazopanib in first-line setting, both in frail patients with multiple co-morbidities and Karnofsky PS

Overview: Treatment monitoring for solid tumors in general and for metastatic renal cancer in particular has been dominated by assessment of tumor burden via cross-sectional imaging. This poses a special problem for the mammalian target of rapamycin and vascular endothelial growth factor pathway-directed agents used in this disease. The standard RECIST metrics used to categorize “response” and “progression” are arbitrary and do not adequately capture the effect of these agents. Other approaches, including use of relative RECIST measures as a continuous variable, volumetric measurements, and functional assessments, such as dynamic contrast-enhanced magnetic resonance imaging-based quantitative variables and fluorodeoxyglucose-positron emission tomography, have been proposed as alternatives, but the data do not support their routine clinical use. Even fewer data are available on the use of baseline imaging characteristics to choose a specific therapy. Therefore, until further research on imaging predictive and intermediate biomarkers matures, a combination of standard cross-sectional imaging and clinical judgment is the most pragmatic option for treatment decision making for patients with metastatic renal cancer.

Treatment of metastatic renal cell carcinoma (mRCC) has evolved dramatically within the past 10 years with the advent of therapy targeting the angiogenesis and mammalian target of rapamycin (mTOR) pathways. These therapies rapidly supplanted immunotherapy as a first-line systemic treatment option. Response rates, however, continue to vary, largely due to mRCC's clinical and molecular heterogeneity. This article reviews current understanding of mRCC biology and available treatments, discusses novel biomarkers that improve prognostication and may be able to predict response, and integrates available literature on surgical and systemic therapies into an individualized strategy.

INTRODUCTION: Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Republic of Moldova, Romania, Russian Federation, Serbia, Slovakia, Slovenia and the Ukraine represent a collection of Central and Eastern European (CEE) countries in which the epidemiology and treatment of cancer varies greatly between and within countries. Current challenges include non-adherence to current treatment guidelines, restrictions in access and reimbursement for new therapies, and a lack of basic oncology programs. Metastatic renal cell carcinoma (mRCC) is a malignancy with historically poor prognosis. In CEE countries, the incidence and mortality rates of mRCC are among the highest in the world. Fortunately, mRCC represents a cancer for which a number of new targeted therapies have recently demonstrated benefit, resulting in new evidence-based treatment guidelines. Incorporating these mRCC treatment recommendations into the routine care of patients with mRCC in CEE countries would represent a major step forward for cancer care in this region. AREAS COVERED: This review discusses the unique challenges faced by the aforementioned Eastern European countries in the treatment of metastatic renal cell cancer, in an attempt to assist health-care providers in providing the best care possible for their European patients. EXPERT OPINION: Despite a wealth of clinical trial data supporting the use of targeted therapies for first-line treatment of mRCC, cytokine-based immunotherapy is still used in some of these European countries. With implementation and adherence to existing guidelines, treatment can be clinically and economically optimized in patients with mRCC from this region.

With the advent of targeted therapy for the treatment of metastatic renal cancer, the routine use of cytoreductive nephrectomy has been questioned. However, available data suggest that cytoreductive nephrectomy remains an integral part of treatment in properly selected patients. This review details the rationale for the continued use of cytoreductive nephrectomy in acceptable surgical candidates in the era of targeted therapy.

Les auteurs mettent au point a travers un cas clinique des metastases pulmonaires secondaires a un cancer renal, la place des antiangiogeniques en tant que therapeutiques ciblees dans le traitement du cancer renal metastatique. L’evolution de ce cas sous traitement avec le sorafenib etait marquee par une nette regression des metastases pleuropulmonaires sur la radiographie thoracique et le scanner thoracique de controle apres un an de traitement, et la survie actuellement dans ce cas est de 15 mois, et aucun effet secondaire n’a ete notifie. Cette classe therapeutique commence a prendre une place dans les strategies therapeutiques de la prise en charge adjuvante du cancer du rein chimioresistant, ce qui apparait comme une avancee surtout que ce domaine connaissait peu de therapeutique efficace.

Since sexual disorders were not specifically studied in the principal series, epidemiological data is scarce. Nevertheless, in practice, when sexuality is dealt with during the monitoring of patients undergoing targeted therapies, more than half of the patients questioned say that they attach importance to their quality of sex life, despite the severity of their metastatic renal cancer. At the start of treatment, it is therefore important to inform patients of the possible occurrence of problems and to encourage them to report them. During treatment, screening for sexual disorders by questioning is desirable: desire, lubrication, dyspareunia, erectile dysfunction. In the event of the onset of a sexual disorder during treatment, it is not usually necessary to stop or modify the treatment. Therapeutic measures depend on the discomfort felt and are under the control of the specialist: erectile dysfunction, male libido disorders, vaginal dryness and vulvovaginitis. A consultation with an oncology psychologist and/or sex therapist is useful, if possible with the partner, based on the impact of the sexual problems.

Background The safety and efficacy of upfront sunitinib, before nephrectomy in metastatic clear cell renal cancer (mCRC), has not been prospectively evaluated. Methods Two prospective single-arm phase II studies investigated either two cycles (study A: n = 19) or three cycles (study B: n = 33) of sunitinib before nephrectomy in mCRC. Results Overall, 38 of 52 (73%) of patients obtained clinical benefit (by RECIST) before surgery. The partial response rate of the primary tumour was 6% [median reduction in longest diameter of 12% (range 8%-35%)]. No patients became ineligible due to local progression of disease. A nephrectomy was carried out in 37 (71%) of patients. Necrosis (>50%) was a prominent feature at nephrectomy in 49%. Surgical complications (Clavien–Dindo classification) occurred in 10 (27%) patients, including one death (3%). The median blood loss and surgical time were 725 (90–4200) ml and 189 (70–420) min, respectively. The median progression-free survival was 8 months (95% confidence interval 6–15 months). A comparison of two versus three pre-surgery cycles showed no significant difference in terms of surgical complications or efficacy. Conclusions Nephrectomy after upfront sunitinib can be carried out safely. It obtains control of disease. Randomised studies are required to address if this approach is beneficial.

588 Background: Data on 1st line treatment with tyrosine kinase inhibitors (TKI) in elderly patients(pts) with metastatic renal cell carcinoma (mRCC) is controversial, and there is rationale for inferior outcomes due to multiple comorbidities and polypharmacy. We aimed to compare the efficacy and safety between the elderly (E) and non-elderly (NE) in 1st line therapy, and to explore factors influencing survival and toxicity. Methods: We retrospectively reviewed all medical records of mRCC pts treated with 1st line TKI at our institution (2007 – 2018). Categorial variables were compared by Fisher’s exact test and continuous, Mann–Whitney. Survival was estimated by Kaplan-Maier method, prognostic factors adjusted by Cox regression model. Results: From 171 eligible pts, 64 (37.4%) had ≥ 65years old, with median age of 70.5 for E and 56 for NE. In both groups most were male, had clear cell histology, good/intermediate IMDC risk, prior nephrectomy and > 1 metastatic (mets) site. Sites of mets were evenly distributed. E pts had more diabetes (35.9 vs16.8%, p.009) , hypertension (67.2 vs 46.7%, p.01), cardiovascular disease (15.6 vs 6.5%, p.06), moderate/severe renal dysfunction (62.5 vs 28.8%, p < 0001), high Charlson Comorbidities Index (CCI≥3, 48.4% vs 20.8%, p < .0001), polypharmacy (34.4 vs15.9%, p.008), worst ECOG (≥2, 28.2 vs 12.3%, p.01), and a trend to worst nutrition (weight loss 35.9 vs 22.5%, p.07). Sunitinib was used for 60.9 vs 79.4%, Pazopanib 35.9 vs 18.7%, Sorafenib 3.1 vs 1.9%, comparing E and NE pts. Median overall survival (OS) and progression free survival (PFS) was 23.7 vs 25.6m (p.8) and 9.3 vs 10.9m (p.7), respectively. After adjusting for prognostic factors, age continues not to influence OS (HR 1.17, IC95 0.77-1.78, p.45). Grade (G) 3/4 toxicity was seen in 59.4 vs 53.3%, dose reduction in 54.7 vs 53.3% and suspension due to toxicity 25 vs 13.3% for E and NE, respectively. In the E, none of the comorbidities, CCI or polypharmacy impaired OS or toxicity, but pts using sunitinibe had greater G3/4 toxicity than with pazopanib (71.8 vs 39.1%, p.02). Conclusions: Elderly had similar outcomes to NE pts, despite greater comorbidities and polypharmacy, hence efficacious therapies shouldn’t avoided. Pazopanib seems to be safer in this subgroup.

644 Background: The introduction of tyrosine kinase inhibitors (TKI) and recently immunotherapy has brought major survival benefits for metastatic renal cancer (mRCC) patients (pts). In Brazil, there is no approved 2nd line treatment for mRCC in the Public Health System (PHS). Our center is unique, because it provides care for both PHS and Private System (PrS) population, enabling us to make the comparison of overall survival (OS) of these pts. Methods: We retrospectively reviewed medical records of all mRCC pts treated with 1st line TKI at our service from 2007 to 2018. Categorial variables were compared by Fisher’s exact test and continuous by Mann–Whitney. Survival was estimated by Kaplan-Maier method, prognostic factors adjusted by Cox regression model. Results: 171 pts were eligible, 37 (21.6%) PHS and 134 (78.4%) PrS pts. Between the two groups, there was no differences in age, gender, number and sites of metastasis (mets). PHS pts had worst ECOG (≥2, in 35.1 vs 13.5%, p .007), a trend towards more poor IMDC risk (IMDC favorable 16.2 vs 26.6%, intermediate 51.4 vs 57%, poor 32.4 vs 16.4%, p.09), had less nephrectomies (73 vs 92.5%, p.008) and more non clear cell histology (32.4 vs 12.7%, p.01). Median lines of therapy were 1 for PHS vs 2 for PrS pts (p.03). Sunitinib was the 1st line agent for 91.9 vs 67.2%, and pazopanib 8.1 vs 29.9%, of the PHS and PrS pts, respectively. Median time from diagnosis of mets to treatment start was 2.29 vs 1.79 m (p.59). Median OS was 16.5 vs 26.5 m (p.0002) and progression free survival, 8.4 vs 11 m (p.01), for the PHS vs PrS. On multivariate analysis, after adjusting for factors that were present before the beginning of treatment and were statistically significant for OS in the univariate model, PHS pts still had higher risk of death (HR 1.85, IC 95 1.2-2.9, p.01), probably due to having received fewer lines of therapy (≥2 lines of therapy vs 1, HR 0.51, IC95 0.4-0.7, p .001). Conclusions: Brazilian PHS pts had significant worse OS compared to PrS pts, in part due to less access to drugs. Access to cancer drugs is a challenge worldwide, and in Brazil effort has to be done to change this reality.

In its attempt to recruit patients with late-stage and metastatic renal cancer for a new trial of an experimental cancer treatment, Oxford Biomedica took the standard form of asking and answering an array of imagined patient questions in its patient pamphlet. The trial was organized as a standard randomized control trial (RCT), in which one group of patients would receive the new treatment and the other group would be given the standard treatments. No one would know which group they were in until the end of the trial, at which time the survivors would be counted, the side effects measured, and a decision made about whether to take the drug to the next stage of testing. Among the questions appears one that addresses the key issue patients must struggle with when considering signing up themselves, and their caretakers, for a trial that will take a great deal of time and energy at what will likely be the end of their lives. The pamphlet puts the question in this form: “What happens if I get placebo and TroVax® is then shown to work?” Although the five-year survival rate for metastatic renal cancer is less than 5 percent, the answer to the question is given as: “If the study shows TroVax® prolongs survival and you received the placebo, you will be given the opportunity to be treated with TroVax®, following regulatory approval.”1 As with the vast majority of such trials, the drug was

Integration of surgery and systemic therapies represents the best management option for most patients with metastatic renal cell carcinoma. Cytoreductive nephrectomy, metastasectomy, and consolidative surgery can all play a vital role in this challenging patient population. Relevant issues in this era relate to the timing of surgery, the role of cytoreduction as systemic therapies become more effective, management of the residual mass, and surgical safety after targeted therapy.

For patients with metastatic renal cancer, prognostic factors defined in systemic therapy clinical trials stratify patients into good, intermediate, and poor risk groups with median survival varying from 4 to 13 months. These same factors also stratify patients whose renal cancers were initially resected completely and who then developed subsequent metastatic disease. Metastasectomy performed in low-risk patients was significantly associated with enhanced survival when compared with low-risk patients not undergoing metastasectomy. Two randomized, prospective clinical trials demonstrated a modest survival advantage of approximately 6 months for patients undergoing cytoreductive nephrectomy followed by interferon alfa-2b. Once effective systemic agents are developed, both metastasectomy and cytoreductive nephrectomy will play greater roles in consolidating clinical responses.

Pazopanib and sunitinib are treatment options for metastatic renal cell cancer (mRCC), with similar efficacy, and minor differences in their toxicity profile. Our experience has suggested that pazopanib-induced alopecia may be a potentially significant but previously under-reported toxicity. For this reason we performed a retrospective review of the clinical records of all patients with mRCC treated with pazopanib at the Royal Marsden Hospital from European licensing until June 2013, and all patients treated with sunitinib over the same period. We found that 36 patients with mRCC were treated with pazopanib and 85 patients with sunitinib. Four of the 36 (11%) patients treated with pazopanib developed alopecia severe enough to warrant a wig, versus none of 85 patients treated with sunitinib (p = 0.007). In conclusion, grade 2 pazopanib-induced alopecia was reported at significantly higher rates when compared to sunitinib-induced alopecia. Hence, in our view, patients should be informed about this potential toxicity when discussing the treatment options for metastatic renal cell cancer.

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.