Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.

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 + 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. RESULTS: 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 < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction 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). CONCLUSIONS: 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.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.

National and international variation in the registration of bladder cancer.

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.

The influence of histological diagnosis on the postoperative complication rate following trans-urethral resection of prostate (TURP).

BACKGROUND: A number of studies have shown that the early mortality following TURP is higher for patients with prostate cancer than those with benign disease. This study examines the effect of the histological diagnosis on the predischarge complication rate following TURP. METHODS: Information on the postoperative, predischarge complications of 3036 patients, who underwent TURP over the last decade at our institution, was collated from the urology department database (AuditBase for Windows). The information on this database is collected prospectively, at the point of care and validated at monthly audit meetings. Statistical analyses were performed using chi2 and difference of proportion where n > 60. Statistical significance was taken as P < 0.05. RESULTS: The postoperative, predischarge major complication rate for patients with benign disease was 2.1%. This was not statistically different from the 2.3% complication rate seen in patients with malignant disease. Patients suffering a postoperative complication stayed in hospital significantly longer than those who had a straightforward postoperative course (P < 0.001); however, patients with malignant histology suffering a postoperative complication did not stay statistically significantly longer than those with benign histology suffering a postoperative complication (P < 0.1). CONCLUSIONS: Patients undergoing TURP for prostate cancer do not suffer more postoperative, predischarge complications or stay in hospital longer than patients undergoing TURP for benign disease.