Search

Background Abiraterone acetate received licencing for use in only "high-risk" metastatic hormone-naive prostate cancer (mHNPC) following the LATITUDE trial findings. However, a "risk"-related effect was not seen in the STAMPEDE trial. There remains uncertainty as to whether men with LATITUDE "low-risk" M1 disease benefit from androgen deprivation therapy (ADT) combined with abiraterone acetate and prednisolone (AAP). Objective Evaluation of heterogeneity of effect between LATITUDE high- and low-risk M1 prostate cancer patients receiving ADT + AAP in the STAMPEDE trial. Design, setting, and participants A post hoc subgroup analysis of the 2017 STAMPEDE "abiraterone comparison". Staging scans for M1 patients contemporaneously randomised to ADT or ADT + AAP within the STAMPEDE trial were evaluated centrally and blind to treatment assignment. Stratification was by risk according to the criteria set out in the LATITUDE trial. Exploratory subgroup stratification incorporated the CHAARTED criteria. Outcome measurements and statistical analysis The primary outcome measure was overall survival (OS) and the secondary outcome measure was failure-free survival (FFS). Further exploratory analysis evaluated clinical skeletal-related events, progression-free survival (PFS), and prostate cancer-specific death. Standard Cox-regression and Kaplan-Meier survival estimates were employed for analysis. Results and limitations A total of 901 M1 STAMPEDE patients were evaluated after exclusions. Of the patients, 428 (48%) were identified as having a low risk and 473 (52%) a high risk. Patients receiving ADT + AAP had significantly improved OS (low-risk hazard ratio [HR]: 0.66, 95% confidence interval or CI [0.44–0.98]) and FFS (low-risk HR: 0.24, 95% CI [0.17–0.33]) compared with ADT alone. Heterogeneity of effect was not seen between low- and high-risk groups for OS or FFS. For OS benefit in low risk, the number needed to treat was four times greater than that for high risk. However, this was not observed for the other measured endpoints. Conclusions Men with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for "risk" or "volume". Patient summary Coadministration of abiraterone acetate and prednisolone with androgen deprivation therapy (ADT) is associated with prolonged overall survival and disease control, compared with ADT alone, in all men with metastatic disease starting hormone therapy for the first time.

PURPOSE SORCE is an international, randomized, double-blind, three-arm trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) found to be at intermediate or high risk of recurrence. PATIENTS AND METHODS We randomly assigned participants (2:3:3) to 3 years of placebo (arm A), 1 year of sorafenib followed by 2 years of placebo (arm B), or 3 years of sorafenib (arm C). The initial sorafenib dose was 400 mg twice per day orally, amended to 400 mg daily. The primary outcome analysis, which was revised as a result of external results, was investigator-reported disease-free survival (DFS) comparing 3 years of sorafenib versus placebo. RESULTS Between July 2007 and April 2013, we randomly assigned 1,711 participants (430, 642, and 639 participants in arms A, B, and C, respectively). Median age was 58 years, 71% of patients were men, 84% had clear cell histology, 53% were at intermediate risk of recurrence, and 47% were at high risk of recurrence. We observed no differences in DFS or overall survival in all randomly assigned patients, patients with high risk of recurrence, or patients with clear cell RCC only. Median DFS was not reached for 3 years of sorafenib or for placebo (hazard ratio, 1.01; 95% CI, 0.83 to 1.23; P = .95). We observed nonproportional hazards; the restricted mean survival time (RMST) was 6.81 years for 3 years of sorafenib and 6.82 years for placebo (RMST difference, 0.01 year; 95% CI, −0.49 to 0.48 year; P = .99). Despite offering treatment adaptations, more than half of participants stopped treatment by 12 months. Grade 3 hand-foot skin reaction was reported in 24% of participants on sorafenib. CONCLUSION Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence after nephrectomy and is the appropriate control of our current international adjuvant RCC trial, RAMPART.

Background\ud \ud 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.\ud \ud \ud \ud Methods\ud \ud We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + 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.\ud \ud \ud \ud Results\ud \ud Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).\ud \ud \ud \ud Conclusions\ud \ud The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

Background SORCE is a randomised, double-blind trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) at intermediate or high risk of recurrence (Leibovich classification). Methods We recruited patients from 147 sites in the UK, Australia, France, Belgium, Denmark, The Netherlands and Spain and randomised them (2:3:3) between three years of placebo (A), one year of sorafenib followed by two years of placebo (B) and three years of sorafenib (C). The initial sorafenib dose was 400mg twice per day orally, amended during trial recruitment to a reduced starting dose of 400mg daily. The primary outcome is investigator-reported disease-free survival (DFS). Given the results of the ASSURE and S-TRAC trials, and blinded to SORCE outcomes, we revised the primary analysis to compare three years of sorafenib (arm C) vs placebo (arm A) to focus on the question of longer exposure to sorafenib. Results Between July 2007 and April 2013, we randomised 1711 patients; 430, 642, and 639 to arms A, B, and C respectively. Median age was 58 years; 71% male, 84% clear cell histology, 53% at intermediate risk of recurrence and 47% at high risk of recurrence. We observed no differences in DFS or OS in any of our pre-planned and pre-powered analyses: all randomised patients, high-risk patients only, and patients with clear cell RCC only. Median DFS was not reached for three years sorafenib or for placebo (HR 1.01, 95% CI 0.83 -1.23, p=0.95). We observed non-proportional hazards: restricted mean survival time (RMST) was 6.81 years for three years of sorafenib and 6.82 years for placebo, RMST difference 0.01, 95% CI -0.49 – 0.48, p=0.99. Despite offering treatment adaptations, over half of patients stopped treatment early. Grade 3 hand-foot syndrome was reported in 24% of patients on sorafenib. Conclusions Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence following nephrectomy; it is the appropriate control of our current international adjuvant RCC trial, RAMPART. Clinical trial identification ISRCTN38934710; EudraCT: 2006-006079-19; NCT00492258. Legal entity responsible for the study University College London (UCL). Funding Cancer Research UK, UK Medical Research Council, Educational Grants and Drug Supply from Bayer, Cancer Australia Support for Cancer Clinical Trials Program and University College London. Disclosure T.Q.G. Eisen: Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self), Research grant / Funding (self): Pfizer; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): GSK; Honoraria (self): AVEO; Honoraria (self): Astellas; Honoraria (self): Boehringer Ingelheim. I.D. Davis: Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche / Genentech; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bristol-Myers Squibb. M.R. Stockler: Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Binomics; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Tilray. J.M.G. Larkin: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Achilles Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Covance; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Aveo; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: Eisai; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Imugene; Advisory / Consultancy: Incyte; Advisory / Consultancy: iOnctura. A. Bex: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy, Non-remunerated activity/ies: BMS; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eusa; Non-remunerated activity/ies: Roche. S. Joniau: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas ; Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ferring; Speaker Bureau / Expert testimony: GSK; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MDX Health; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: Sanofi. J. Bellmunt: Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): Takeda; Shareholder / Stockholder / Stock options: Biocline. All other authors have declared no conflicts of interest.

Background We sought to determine the survival benefits that patients judged sufficient to warrant adjuvant therapy with sorafenib for 1 year, or for 3 years after resection of renal cell carcinoma in the SORCE trial. Methods SORCE participants from all sites in Australia and New Zealand, and selected sites in the UK, completed a validated preferences questionnaire at months 0, 3, 15, and 42 to elicit the minimum survival benefits they judged sufficient to warrant adjuvant sorafenib for 1 year (versus observation), or for 3 years (versus 1 year). The questionnaires used reference survival times of 5 and 15 years; and reference survival rates at 5 years of 65% and 85%. Results The 233 participants had a median age of 57 years (range 29–78) and 71% were male. For 1 year of sorafenib versus no adjuvant therapy, the median benefits in survival times judged sufficient to warrant treatment were an extra 9 months beyond 5 years and an extra 1 year beyond 15 years; the median benefit in survival rates were an extra 4% beyond 65% and an extra 3% beyond 85% at 5 years. For 3 years of sorafenib versus 1 year of sorafenib, the median benefit in survival time judged sufficient to warrant extended treatment was an extra 1 year beyond both 5 and 15 years. Participants randomly allocated to treatment with sorafenib judged larger benefits necessary than those allocated to placebo. Participants' preferences were not associated with their baseline characteristics or the interval from randomisation. Conclusion Most participants judged an extra year of survival necessary to warrant 1 year of adjuvant sorafenib worthwhile, and an additional year of survival to warrant extending the duration of sorafenib from 1 to 3 years. Patients' preferences are important in shared decision making. SORCE trial clinical trials number NCT00492258.

Madam — Tanguay and colleagues presented data on patients treated with docetaxel [1]. We agree that the reported rates of neutropenia-based toxicities vary across the trials, as do the categories against which toxicities are reported.

MPORTANCE:\ud \ud The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. Furthermore, no clinical trial has assessed the role of RT in patients with node-positive (N+) M0 disease. The STAMPEDE Trial includes such individuals, allowing an exploratory multivariate analysis of the impact of radical RT.\ud OBJECTIVE:\ud \ud To describe survival and the impact on failure-free survival of RT by nodal involvement in these patients.\ud DESIGN, SETTING, AND PARTICIPANTS:\ud \ud Cohort study using data collected for patients allocated to the control arm (standard-of-care only) of the STAMPEDE Trial between October 5, 2005, and May 1, 2014. Outcomes are presented as hazard ratios (HRs) with 95% CIs derived from adjusted Cox models; survival estimates are reported at 2 and 5 years. Participants were high-risk, hormone-naive patients with newly diagnosed M0 prostate cancer starting long-term HT for the first time. Radiotherapy is encouraged in this group, but mandated for patients with node-negative (N0) M0 disease only since November 2011.\ud EXPOSURES:\ud \ud Long-term HT either alone or with RT, as per local standard. Planned RT use was recorded at entry.\ud MAIN OUTCOMES AND MEASURES:\ud \ud Failure-free survival (FFS) and overall survival.\ud RESULTS:\ud \ud A total of 721 men with newly diagnosed M0 disease were included: median age at entry, 66 (interquartile range [IQR], 61-72) years, median (IQR) prostate-specific antigen level of 43 (18-88) ng/mL. There were 40 deaths (31 owing to prostate cancer) with 17 months' median follow-up. Two-year survival was 96% (95% CI, 93%-97%) and 2-year FFS, 77% (95% CI, 73%-81%). Median (IQR) FFS was 63 (26 to not reached) months. Time to FFS was worse in patients with N+ disease (HR, 2.02 [95% CI, 1.46-2.81]) than in those with N0 disease. Failure-free survival outcomes favored planned use of RT for patients with both N0M0 (HR, 0.33 [95% CI, 0.18-0.61]) and N+M0 disease (HR, 0.48 [95% CI, 0.29-0.79]).\ud CONCLUSIONS AND RELEVANCE:\ud \ud Survival for men entering the cohort with high-risk M0 disease was higher than anticipated at study inception. These nonrandomized data were consistent with previous trials that support routine use of RT with HT in patients with N0M0 disease. Additionally, the data suggest that the benefits of RT extend to men with N+M0 disease.

OBJECTIVE To determine whether variations exist in the methods by which different cancer registries record information on bladder cancers. METHODS The registration practices of the various cancer registries within the UK, Europe and the USA were investigated by consulting the available publications and by correspondence with registry staff. In addition, a telephone survey was carried out within the UK to determine whether the national guidelines on bladder cancer coding were being followed. RESULTS There is variation in the registration of bladder cancers both among regions within the UK and between the UK and other regions. The telephone survey showed that only four of the 11 UK regional registries were correctly following the national bladder cancer coding guidelines. Bladder cancer registration also varies between the cancer registries within mainland Europe. When comparing registration practices in the UK and the USA the major difference is that cases of bladder carcinoma in situ and pTa transitional cell carcinoma are included in the North American cancer statistics but not in the British cancer statistics. CONCLUSION Much needs to be done before it can be claimed that the registration of bladder cancers has been standardized either nationally or internationally. In particular, the differences in registration practices between the UK and the USA will tend to give a falsely low impression of British incidence and survival rates compared with the equivalent North American figures. This confounding factor must be considered if these incidence and survival values are to be compared.

There are compelling reasons to study the addition of both enzalutamide and abiraterone, in combination, to standard-of-care for hormone-naïve prostate cancer. Through a protocol amendment, this will be assessed in the STAMPEDE trial, with overall survival as primary outcome measure. © 2014 European Association of Urology.

Background Sorafenib is an orally available kinase inhibitor with activity at Raf, PDGFβ and VEGF receptors that is licensed for the treatment of advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Current evidence-based post-nephrectomy management of individuals with localized RCC consists of surveillance-based follow up. The SORCE trial is designed to investigate whether treatment with adjuvant sorafenib can reduce recurrence rates in this cohort. Case presentation Here we report an idiosyncratic reaction to sorafenib resulting in fatal hepatotoxicity and associated renal failure in a 62 year-old man treated with sorafenib within the SORCE trial. Conclusion This is the first reported case of sorafenib exposure associated fatal toxicity in the adjuvant setting and highlights the unpredictable adverse effects of novel adjuvant therapies.

N.D. James, M.R. Sydes, M.D. Mason, N.W. Clarke, D.P. Dearnaley, M.R. Spears, R. Millman, C.C. Parker, A.W.S. Ritchie, J.M. Russell, J. Staffurth, R.J. Jones, R. Cathomas, A. Robinson, S. Chowdhury, D. Tsang, S. Brock, O. Parikh, J.D. Graham, M.K.B. Parmar. Warwick University, Clinical Trials Unit, Coventry, United Kingdom; Medical Research Council Clinical Trials Unit at UCL, Institute for Clinical Trials and Methodology, London, United Kingdom; Cardiff University, School of Medicine, Cardiff, United Kingdom; The Christie NHS Foundation Trust, Department of Urology, Manchester, United Kingdom; The Institute of Cancer Research and Royal Marsden Hospital NHS Trust, Academic Unit of Radiotherapy, London, United Kingdom; Medical Research Council Clinical Trials Unit at UCL, Patient Representative, NA, United Kingdom; The Royal Marsden Hospital, Department of Radiotherapy, London, United Kingdom; Beatson West of Scotland Cancer Centre, Institute of Cancer Sciences, Glasgow, United Kingdom; Cardiff University and Velindre NHS Trust, School of Medicine, Cardiff, United Kingdom; Kantonsspital Graubunden, Department of Oncology, Chur, Switzerland; Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, United Kingdom; Guy’s Hospital, Department of Medical Oncology, London, United Kingdom; Southend & Basildon Hospitals, Department of Oncology, Southend, United Kingdom; Poole Hospital NHS Foundation Trust and Royal Bournemouth Hospital NHS Foundation Trust, Department of Oncology, Poole, United Kingdom; East Lancashire Hospitals NHS Trust, Department of Oncology, Blackburn, United Kingdom; Musgrove Park Hospital, Oncology and Haematology Clinical Trials Unit, Taunton, United Kingdom

Aim The natural history of patients (pts) with newly diagnosed high-risk non-metastatic (M0) prostate cancer receiving androgen deprivation therapy (ADT) either alone or with standard of care radiotherapy (RT) at 6 to 9 months is not well documented. Further, no RCT has tested RT in N + M0 patients; none are planned. The STAMPEDE RCT (NCT00268476; MRC PR08; CRUK/06/019) includes such pts & allows exploratory multivariate analysis of radical RT's impact. We report data from trial pts. We hypothesised that planning RT in N + M0 pts improves survival outcomes. Methods Newly diagnosed pts with confirmed M0 disease in the control arm (standard of care = ADT planned for >2yr), diagnosed

5012 Background: STAMPEDE (www.stampedetrial.org) recruits men with newly-diagnosed or rapidly relapsing prostate cancer (PCa) that is metastatic (M1) or high-risk locally advanced, all commencing long-term androgen ablation therapy (AAT) for the first time. This is now the largest therapeutic RCT in PCa. We report survival outcomes for newly-diagnosed M1 control arm men in order to inform future trials in this setting. Methods: Newly-diagnosed men with M1 disease in the trial’s control arm (standard of care: AAT alone for at least 2yr), diagnosed up to 6 months prior to randomisation, were identified from trial records in Dec-2012. We report overall survival (OS) and failure-free survival (FFS) from randomisation by primary disease characteristics. Results: 3703 men were recruited to STAMPEDE Oct-2005 to Dec-2012, including a control arm cohort of 630 M1 men with newly-diagnosed disease. This cohort has median age at randomisation 66yr (quartiles 60-71), median PSA 105 (quartiles 34-379) IU/l; metastases to bone only (B) 393 (62%), soft tissue only (ST) 78 (13%) or bone and soft tissue (B+ST) 159 (25%). ST was mainly lymph nodes. Median time from diagnosis to randomisation is 69 days (max 180 days). Median duration of AAT prior to randomisation is 46 days (max 105 days). There were 129 deaths, of which 111 were from PCa. Median OS from randomisation is 42 months, with 2-yr OS 74% (95%CI 68, 78) in this cohort; B 77% (95%CI 71, 83), ST 85% (95%CI 70, 93), B+ST 57% (95%CI 45, 68). Median FFS is 12 months, driven by rising PSA; 2-yr FFS 32% (95%CI 27-37). Median time from FFS event to death was 22 months. Additional data on relapse therapies will be presented. Conclusions: Survival, and particularly FFS, remains relatively poor for men presenting with M1 disease starting long-term AAT, despite potential access when castration-resistant (CRPC) to docetaxel and other newer therapies. Better first-line therapy is required; STAMPEDE will report many comparisons in the future. Different M1 patterns may vary prognostically. Men with M1 disease will now spend most time in a state of CRPC, which has important implications for clinicians and trialists. Clinical trial information: NCT00268476.

The techniques of flow cytometry are being increasingly used to classify lymphocytes according to their surface antigens. Accurate analyses depend on the exclusion of non-lymphocytic contaminant cells. Using a fluorescence-activated cell sorter (FACS IV), virtually complete separation of human lymphocytes from monocytes and granulocytes can be achieved by means of wide-angle (90 degrees) light scatter. The technique described is simple and suitable for routine use. Used in conjunction with fluorescein-labelled monoclonal antibodies and logarithmic amplification of the fluorescence signals, it improves the accuracy of lymphocyte subset analysis. Its use is particularly necessary in the study of subjects such as renal allograft recipients, who have a high or variable contaminant cell:lymphocyte ratio.

Background:\ud Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa—the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)—includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort.\ud \ud Objective:\ud Describe survival outcomes, along with current treatment standards and factors associated with prognosis, to inform future trial design in this patient group.\ud \ud Design, setting, and participants@\ud STAMPEDE trial control arm comprising men newly diagnosed with M1 disease who were recruited between October 2005 and January 2014.\ud \ud Outcome measurements and statistical analysis:\ud Overall survival (OS) and failure-free survival (FFS) were reported by primary disease characteristics using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (CIs) were derived from multivariate Cox models.\ud \ud Results and limitations:\ud A cohort of 917 men with newly diagnosed M1 disease was recruited to the control arm in the specified interval. Median follow-up was 20 mo. Median age at randomisation was 66 yr (interquartile range [IQR]: 61–71), and median prostate-specific antigen level was 112 ng/ml (IQR: 34–373). Most men (n = 574; 62%) had bone-only metastases, whereas 237 (26%) had both bone and soft tissue metastases; soft tissue metastasis was found mainly in distant lymph nodes. There were 238 deaths, 202 (85%) from PCa. Median FFS was 11 mo; 2-yr FFS was 29% (95% CI, 25–33). Median OS was 42 mo; 2-yr OS was 72% (95% CI, 68–76). Survival time was influenced by performance status, age, Gleason score, and metastases distribution. Median survival after FFS event was 22 mo. Trial eligibility criteria meant men were younger and fitter than general PCa population.\ud \ud Conclusions:\ud Survival remains disappointing in men presenting with M1 disease who are started on only long-term ADT, despite active treatments being available at first failure of ADT. Importantly, men with M1 disease now spend the majority of their remaining life in a state of castration-resistant relapse.\ud \ud Patient summary:\ud Results from this control arm cohort found survival is relatively short and highly influenced by patient age, fitness, and where prostate cancer has spread in the body.

For the past ten years or so the natural killer (NW) cell has masqueraded as the cell par excellence in immunosurveillance 1 . In this article Keith James and Alistair Ritchie discuss the evidence (both direct and indirect) for NK cells' influence on the differentiation, proliferation and activity of B cells.