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This review summarises the treatment strategies of the last five decades for metastatic urothelial cancer. The introduction of combination chemotherapy in the mid-1980s led to clinically significant response rates and prolonged survival. Two years ago, the results of a phase-3 clinical trial with the PD1 inhibitor pembrolizumab for second-line treatment of metastatic urothelial carcinoma were published. These data were the first to show an overall survival benefit in comparison with a conventional chemotherapy with vinflunine, docetaxel or paclitaxel. Currently, PD1/PD-L1 inhibitors are also tested within randomized phase-3-trials for first-line treatment using different approaches either as a monotherapy or a combination with conventional chemotherapy or CTLA-4 inhibitors. Whereas data from single-arm phase-2 clinical trials have already been published, first phase-3 data are expected in 2019., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

The approval of immune checkpoint inhibitors has started a new era in the treatment of urothelial carcinoma, which, so far, has been a disease with limited treatment options. However, in the current German S3 guideline for bladder cancer the remarkable improvements provided by immune checkpoint inhibitors have not been reflected. As cancer immunotherapy is a novel approach, there are several questions related to the daily clinical routine: What clinical data was used as the basis for the approval of the individual substances? What does this mean for previous treatment algorithms? What issues must be considered in the management of adverse events? What side-effects may occur and how can they be recognised and treated? The present paper provides an overview of the new treatment options regarding their relevance as well as recommendations for their application in clinical practice., Competing Interests: Prof. Kurt Miller: Advisor für BMS, MSD, Roche Prof. Jürgen Gschwend: Berater- und Vortragshonorare von AstraZeneca, Astellas, Bayer, BMS, Janssen, MSD, Novartis, Roche Prof. Axel Merseburger: klinische Studien: Amgen, Astellas, Bayer, Ferring, Ipsen, Janssen, Roche, BMS, Merck, MSD; Referent, Speaker, Vorträge: Amgen, BMS, AstraZeneca, Astellas, Bayer, Ferring, MSD, Ipsen, Janssen, Roche, Sanofi, TEVA; Beratertätigkeit: GBA, TEVA, UEG, Ipsen, Janssen, BMS, Merck, Astra Zeneca, Roche, Sanofi, MSD Prof. Margitta Retz: Advisor/Speaker für Astellas, AstraZeneca, BMS, Janssen-Cilag, MSD, Pfizer, Roche Prof. Arnulf Stenzl: AdBoard/Consultant: MSD; AdBoard: Bristol-Myers Squibb; Speaker: Ipsen Pharma; klinische Studien: Roche, CureVac, (© Georg Thieme Verlag KG Stuttgart · New York.)

Data published in November 2016 showed a significant survival benefit for the PD-1 antibody Pembrolizumab in the second-line treatment of metastatic urothelial cancer in comparison to standard chemotherapy. Other PD-1/PD-L1 antibodies are being tested in advanced clinical trials. This class of substances will become standard of care from the time of their approval which is expected for 2017 and will replace vinflunine, which is currently recommended in the German guideline. PD-1/PD-L1 directed substances are also being tested as a first line treatment of metastatic urothelial carcinoma. Monotherapy is evaluated as well as combination treatments with CTLA-4 inhibitors of conventional chemotherapy. First data are expected at the end of 2017.A new strategy is the application of PD-1/PD-L1 directed substances in the perioperative treatment of patients with a muscle-invasive urothelial carcinoma after complete surgical resection (cystectomy or nephroureterectomy). Two international phase III trials evaluate an adjuvant immunotherapy with nivolumab and atezolizumab. Recruitment will be completed in 2018., Competing Interests: Interessenkonflikt: Thomas Horn: MSD Mitarbeit, Berater- und Vortragstätigkeit Jansson, Astellas, Medac, BMSMargitta Retz: Astellas, AstraZeneca, Bayer, BMS, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-AventisRobert Tauber: Berater- und Vortragstätigkeit Astellas, Bayer, BMS, Ipsen, Janssenn, Novartis, Pierre-Fabre, Pfizer, Roche, Sanofi-Aventis, (© Georg Thieme Verlag KG Stuttgart · New York.)

The prognosis of advanced penile carcinomas is extremely poor. Low numbers of available studies on chemotherapy over a long time, decentralized treatment as well as rareness of disease have not improved the prognosis. This article focuses on important clinical trials and developments for chemotherapy in penile cancer. Considering the latest study data there is a strong recommendation for multimodal approaches, including lymph node dissection and perioperative treatments with cisplatin/taxane-based chemotherapy. A systematic, centralized registration and evaluation by the "Rostocker-AUO-Register" for penile cancer should improve conditions for affected patients. Furthermore, molecular targeted therapy might be a promising therapeutic option but until now only very few case reports have been published. Further prospective clinical trials are necessary to establish these agents in the therapeutic landscape of penile cancer. Decision for palliative chemotherapy in advanced penile cancer should be well considered and depends on the patient's age and general condition particularly regarding possible adverse events of chemotherapy. Notably, best supportive care might be an important alternative for some patients and should be taken in consideration., (© Georg Thieme Verlag KG Stuttgart · New York.)

Medical treatment of advanced urothelial carcinoma of the bladder consists of perioperative treatments as well as palliative chemotherapy in advanced stages. This article focuses on important clinical trials and developments of the last two years, with a review of literature and proceedings of the relevant meetings (ASCO, GU-ASCO, EAU, AUA). The general benefit of perioperative chemotherapy is confirmed. Chemotherapy with Gemcitabin/Cisplatin remains the therapy of choice in the palliative setting. So far, targeted therapies did not show convincing results., (Georg Thieme Verlag KG Stuttgart · New York.)