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Patients with Barcelona Clinic Liver Cancer intermediate stage hepatocellular carcinoma (HCC) theoretically are an excellent group to consider downstaging using locoregional therapy (LRT) since they do not have extrahepatic spread or vascular invasion. Once successful, this can change the treatment strategy from palliative to curative intention. Although downstaging therapy is suggested in guidelines, it is still not widely accepted. Moreover, studies on downstaging are mainly performed in high-incidence HCC countries. Therefore, our aim was to gain insight in therapeutic strategies in patients with intermediate stage HCC and their impact on intention-to-treat survival in a real-life setting in a low-incidence HCC country. We retrospectively analyzed data from the national Dutch HCC registry. From this database, consisting of 1409 patients with a diagnosis of HCC between 2005-2013 in 5 Dutch tertiary referral centers, we identified 165 patients with intermediate stage HCC. Out of these patients, 63 (38%) were not offered LRT, whereas 102 (62%) did receive LRT. Subsequently, 50 (49%) of the 102 patients who received LRT were successfully downstaged. Eleven patients (22% of successfully downstaged patients) eventually underwent liver transplantation. Cox regression analysis showed that a lower MELD score, an AFP value <100 ng/ml, successful downstaging and liver transplantation (all ≤p = 0.01) were positively associated to overall survival. In conclusion, our results demonstrate that LRT is not routinely offered to intermediate stage HCC patients in the Netherlands. Nevertheless, we showed that patients with intermediate stage HCC who are successfully downstaged have a survival benefit compared to those who were not., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial., Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management., Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference., Setting: Online Delphi survey and consensus conference., Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management., Outcome Measurements and Statistical Analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus)., Results and Limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease., Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach., Patient Summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available., (Copyright © 2019 European Society of Medical Oncology and European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy., Objective: To evaluate the efficacy and safety of everolimus in elderly patients (those ≥ 65 and ≥ 70 yr of age) enrolled in RECORD-1., Design, Setting, and Participants: The multicenter randomized RECORD-1 phase 3 trial (Clinicaltrials.gov identifier, NCT00410124; http://www.clinicaltrials.gov) enrolled patients with mRCC who progressed during or within 6 mo of stopping sunitinib and/or sorafenib treatment (n=416)., Intervention: Everolimus 10mg once daily (n=277) or placebo (n=139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity., Measurements: Median progression-free survival (PFS), median overall survival (OS), and time to deterioration in Karnofsky performance status (TTD-KPS) were assessed using the Kaplan-Meier method; the log-rank test was used to compare treatment arms. Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety., Results and Limitations: In RECORD-1, 36.8% of patients were ≥ 65 yr and 17.5% were ≥ 70 yr of age. PFS, OS, TTD-KPS, reduction in tumor burden, and ORR were similar in the elderly and the overall RECORD-1 population. Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. The retrospective nature of the analyses was the major limitation., Conclusions: Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered., (Copyright © 2012. Published by Elsevier B.V.)

Context: The first therapeutic cancer vaccine demonstrating effectiveness in a phase 3 study was approved by the US Food and Drug Administration on 29 April 2010. The pivotal trial demonstrated overall survival (OS) benefit in patients treated with antigen-loaded leukapheresis cells compared with a control infusion. Results of other prostate cancer (PCa) vaccination strategies are awaited, as this approach may herald a new era in the care for patients with advanced PCa., Objective: Consider effectiveness and safety of vaccination strategies in the treatment of PCa., Evidence Acquisition: We searched three bibliographic databases (January 1995 through October 2010) for randomised phase 2 and 3 studies of vaccination strategies for PCa based on predetermined relevant Medical Subject Heading terms and free text terms., Evidence Synthesis: Data from 3 randomised phase 3 and 10 randomised phase 2 vaccination trials are discussed with respect to clinical outcome in terms of progression-free survival and OS, toxicity, prostate-specific antigen (PSA) response, and immunologic response. Three phase 3 trials (D9901, D9902A, and D9902B) that enrolled a total of 737 patients, all controlled and double-blinded, tested the efficacy of sipuleucel-T. The largest of these three trials, called Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT), has demonstrated safety and effectiveness of sipuleucel-T (now marketed as Provenge) as measured by prolonged survival of 512 asymptomatic patients with metastatic castration-resistant PCa (mCRPC). The study showed a 4.1-mo median survival benefit in the sipuleucel-T vaccine-treated group compared with the control group (25.8 vs 21.7 mo; hazard ratio [HR]: 0.78; 95% confidence interval [CI], 0.62-0.98; p=0.032) and extended 3-yr survival (31.7% vs 23.0%). In contrast, two phase 3 vaccination trials with a whole-tumour-cell mixture of two PCa cell lines (GVAX) and testing GVAX either alone or in combination with chemotherapy versus chemotherapy alone (VITAL1 and 2) were terminated prematurely based on futility and increased deaths. Other phase 2 vaccination trials testing different types of vaccines in castration-resistant PCa patients have been reported with variable outcomes. Notably, a controlled, double-blind, randomised phase 2 vaccine trial of PROSTVAC-VF, a recombinant viral vector containing complementary DNA encoding PSA, in 125 patients with chemotherapy-naïve, minimally symptomatic mCRPC also demonstrated safety but no significant effect on the time to disease progression. In comparison with controls (n=40), PROSTVAC-VF-treated patients (n=82) experienced longer median survival of 8.5 mo (25.1 vs 16.6 mo; HR: 0.56; 95% CI, 0.37-0.85; p=0.0061) and extended 3-yr survival (30% vs 17%). In general, PCa vaccines are perceived to have less toxicity compared with current cytotoxic or targeted therapies. Evaluation of clinical efficacy of different vaccination strategies (eg, protein-, peptide- and DNA-based vaccines) in the context of properly designed and controlled phase 3 studies is warranted., Conclusions: Cancer vaccines represent a new paradigm in the treatment of PCa. The IMPACT trial showed improved survival but no difference in time to disease progression in mCRPC patients with minimal tumour burden. Observations in phase 2 and 3 trials pave the way for other vaccination approaches for this disease, raise questions regarding the most appropriate clinical trial designs, and underscore the importance of identifying biomarkers for antitumour effect to better implement such therapies., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The use of cisplatin-based combination chemotherapy has led to a dramatic improvement in the cure rate of patients with metastatic germ cell tumors (GCTs). With high complete response (CR) rates achieved in approximately 80% of patients with advanced testicular cancer after standard first-line cisplatin-based chemotherapy. Thereafter, the goals of various trials were to reduce the chemotherapy toxicity by limiting the number of chemotherapy cycles, the duration of therapy, and reducing the doses of, or even omitting, individual cytotoxic drugs, while maintaining efficacy, or to investigate the potential role of carboplatin as single agent or combined with etoposide and bleomycin for advanced seminoma. From prospective randomized trials and available data from additional sources, a European standard has been defined in several consensus conferences,(1-3) with the most recent consensus conference published by the European Society for Medical Oncology Consensus Group.(4,5) These international guidelines were developed from the previous published guidelines and data from available current trials. The principles of evidence-based medicine were scored (score 1-4) using a modified version of the Oxford levels of evidence and are listed in the present report in brackets. Draft guidelines were presented at an International Consensus in Urological Disease (ICUD) meeting (Shanghai, November 2009). The writing committee compiled the results of the discussion. All participants agreed to this final update., (Copyright © 2011 Elsevier Inc. All rights reserved.)