Interpretation of composite endpoints in urology: an analysis of citation quality.

OBJECTIVE: To investigate how urological studies using composite endpoints as the primary outcome were cited. MATERIALS AND METHODS: In this quality analysis of citations, three randomized clinical trials each investigating oncological and non-oncological urology were selected for citation analysis based on pre-defined criteria. In total, 531 papers citing the selected studies were reviewed; citations were evaluated based on whether they correctly referred to the composite endpoint and if singleton endpoints were defined and/or discussed. RESULTS: Among the citations, 223/531 (42%) referred to the composite endpoint, of which 217/223 (97.3%) correctly cited the composite endpoint. However, only 91/217 (41.9%) defined and/or discussed the singleton endpoints of the composite endpoint. The lack of a validated instrument for citation analysis was a limitation of this study. Meanwhile, the main strength is the large number of individually analyzed citations. CONCLUSIONS: The composite endpoints of urological randomized clinical trials are generally cited without referring to the composite endpoint; when cited, the composite endpoints are described correctly. However, in most cases, without defining or discussing the singleton endpoints.

Fatigue, quality of life and metabolic changes in men treated with first-line enzalutamide versus abiraterone plus prednisolone for metastatic castration-resistant prostate cancer (HEAT): a randomised trial protocol.

INTRODUCTION: Enzalutamide and abiraterone acetate plus prednisolone (AAP) are used in combination with androgen-deprivation therapy to further suppress the androgen stimulation of metastatic castration-resistant prostate cancer (mCRPC). First-line mCRPC treatment with enzalutamide and AAP yields similar overall survival and radiographic progression-free survival in phase III trials. Thus, treatment selection relies on patient choice, cost and side effects. The aim of this randomised trial is to investigate differences in fatigue, health-related quality of life (HRQoL) and metabolic side effects in men with mCRPC treated with first-line enzalutamide versus AAP. METHODS AND ANALYSIS: In this ongoing open-label randomised (1:1) clinical trial, enzalutamide is compared with AAP as first-line treatment for men with mCRPC. The primary endpoint is fatigue assessed with the questionnaire Functional Assessment of Chronic Illness Therapy-Fatigue version 4. Secondary endpoints are changes in body composition (ie, fat mass, visceral adipose tissue, subcutaneous adipose tissue and lean body mass assessed with dual energy X-ray absorptiometry), glucose metabolism assessed with a 2-hour oral glucose tolerance test, serum lipids, blood pressure and HRQoL assessed with the questionnaire Functional Assessment of Cancer Therapy-Prostate (FACT-P). All study endpoints are assessed at baseline and 12-week postintervention. Blood and urine samples are collected at baseline and at time of progression on allocated treatment for future investigation of predictive and prognostic biomarkers in prostate cancer treatment. The planned sample size is 170 participants. All participants are recruited from Herlev and Gentofte Hospital, Denmark. Estimated last patient's last visit is February 2020. ETHICS AND DISSEMINATION: The study received project approval from the National Committee on Health Research Ethics and Danish Data Protection Agency and Danish Medicines Agency (EudraCT no.: 2017-000027-99). The results of the study will be published in peer-reviewed international journals and will be presented at national and international conferences and symposiums. TRIAL REGISTRATION NUMBER: Clinicaltrialsregister.eu (2017-000099-27).

Salvage cryotherapy for local recurrence after radiotherapy for prostate cancer.

OBJECTIVE: The aim of this study was to present the outcome of patients treated with salvage cryotherapy after radiotherapy for prostate cancer at one institution. MATERIALS AND METHODS: Consecutive patients treated between 2007 and 2013 with transperineal cryotherapy for biopsy-verified local recurrence after radiotherapy were investigated. An external reviewer retrieved outcome data retrospectively from medical records. Complications were graded according to the Clavien classification. One patient with less than 1 year of follow-up was excluded from the analysis of side-effects. RESULTS: Thirty patients were included, 29 of whom had a follow-up of at least 1 year. The median follow-up was 2.7 years (range 1-6.5 years). Eleven of the 23 patients without hormonal treatment at the time of cryotherapy reached a prostate-specific antigen (PSA) nadir of less than 0.5 ng/ml. At the end of follow-up five of these 23 patients still had a PSA below 0.5 ng/ml and 10 were free from recurrence according to the Phoenix definition. Clinical recurrence (verified with imaging or biopsies) was detected in 13 patients, six of which were local. One patient died from prostate cancer. Eleven patients had urinary incontinence grade 1-2 and three had grade 3-4, seven had pelvic pain, three had severe but transitory tissue sloughing, three developed a urethral stricture or had prolonged urinary retention, and one developed a urinary fistula 4.5 years after cryotherapy. CONCLUSIONS: Salvage cryotherapy should be considered as an alternative to hormonal treatment and surgery for local recurrence after radiotherapy for prostate cancer. The results compare well to those reported from centres with longer experience.