SummaryBackgroundLong-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.MethodsStandard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).Findings2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23–184). Median follow-up was 43 months (IQR 30–60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79–1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66–0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69–0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3–5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.InterpretationZoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompa...

Background: STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.Methods: We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC þ docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.

isrctn.com Identifier: ISRCTN12808747.

Testicular germ cell tumours (TGCTs) are the most common cause of cancer in men between the ages of 15 and 40 years, and, overall, the majority of patients should expect to be cured. The European Germ Cell Cancer Consensus Group has provided clear guidelines for the primary treatment of both seminoma and nonseminomatous germ cell tumours. There is, however, no international consensus on how best to follow patients after their initial management. This must promptly and reliably identify relapses without causing further harm. The standardising of follow-up would result in optimising risk-benefit ratios for individual patients, while ensuring economic use of resources. We have identified the seven common scenarios in managing seminomas and nonseminomas of the various stages and discuss the pertinent issues around relapse and follow-up. We review the available literature and present our comprehensive TGCT follow-up guidelines. Our protocols provide a pragmatic, easily accessible user-friendly basis for other centres to use or to adapt to suit their needs. Furthermore, this should enable future trials to address specific issues around follow-up giving meaningful and useful results. BackgroundTesticular germ cell tumours (TGCTs) are uncommon malignancies but the most common cause of cancer in men between the ages of 15 and 40 years. The peak incidence for nonseminomatous germ cell tumour (NSGCT) is between 20 and 30 years of age, and for seminoma between 30 and 40 years. In the United Kingdom, the incidence rate is only 1 : 100 000 men per year with a lifetime risk of developing a TGCT of 1 in 400 and 1900 new cases per year (Horwich, 2002). There has, however, been a steady increase in the incidence of TGCTs in European countries in the last two decades (Bergstrom et al, 1996). The reasons for this increasing incidence and the aetiology of TGCTs remain unknown. The European Germ Cell Cancer Consensus Group has provided clear guidelines for the primary treatment of both seminoma tumour and NSGCT (Schmoll et al, 2004). There is, however, a lack of clear consensus on how to follow patients after primary treatment, and a number of issues dictate that follow-up should be carefully thought out and rigorously adhered to. Here, we discuss these factors as they pertain to male germ cell tumour (GCT) practice and describe our recently developed protocols. Rational for follow-upDetecting relapse In general, detecting relapse is the major reason for maintaining follow-up and is the main focus of this review. The management of testicular cancer has been a major oncological success story, and provides a model for the management of curative solid tumours (Horwich et al, 2006). The use of platinumbased chemotherapy schedules has resulted in high cure rates for all stages of the disease (International Germ Cell Cancer Collaborative Group, 1997). The fact that the majority of young men treated for testicular cancer have a durable response to primary treatment has resulted in the accumulation of significant data on both the patterns ...

TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer Declared competing interests of authors: Professor James reports trial support (free trial drug for the Phase II part of the trial and a grant awarded to investigation sites for recruitment of Phase III patients with trial numbers 301-700) and lecturing fees from Sanofi-aventis. He also reports free trial drug for the Phase II part of the trial followed by a trial-linked discount for sites ordering trial drug for Phase III patients and lecturing fees from Novartis Pharmaceuticals UK Ltd. In addition, there was a trial-linked discount for sites ordering trial drug from GE Healthcare. Professor James also reports trial support, consultancy work and lecture fees from Sanofi-aventis and Novartis Pharmaceuticals UK Ltd who were directly related and consultancy work and lecture fees from Bayer HealthCare, Algeta, Amgen, Janssen, Astellas Pharma and Affinity OncoGeneX Pharmaceuticals Inc. who were related to prostate cancer but not the drugs in this study. Dr Pope reports trial support (free trial drug for the Phase II part of the trial and a grant awarded to investigation sites for recruitment of Phase III patients with trial numbers 301-700) from Sanofi-aventis; trial support (free trial drug for the Phase II part of the Phase III patients) from Novartis Pharmaceuticals UK Ltd; and trial support (trial-linked discount for sites ordering trial drug) from GE Healthcare from GP Health Care, during the conduct of the study. Dr Parker reports personal fees from Bayer HealthCare, BN ImmunoTherapeutics Inc. (BNIT), Astellas Pharma, Janssen, Sanofi-aventis and Takeda UK Ltd, outside the submitted work. Dr Stanley reports that Teva Pharmaceutical Industries Ltd supported his attendance at European Society for Medical Oncology, he received personal fees from Calgene, Inc., and Amgen, Inc. supported part of his attendance at British Oncology Pharmacy Association, outside the submitted work. Dr Brown reports personal fees and non-financial support from Novartis Pharmaceuticals UK Ltd for advisory board in different cancer and writing assistance for different cancer outside the submitted work. Dr Billingham reports personal fees from Eli Lilly, and from Pfizer, both for expenses paid for contributing to educational events, outside the submitted work. This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www.publicationethics.org/).Editorial contact: nihredit@southampton.ac.ukThe full HTA archive is freely available to view online at www.journalslibrary.nihr.ac.uk/hta. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www.journalslibrary.nihr.ac.uk Criteria for inclusion in the Health Technology Assessment journalReports are published in Health Technology Assessment (HTA) if (1) they have resulted from work for th...