Characteristics of Patients in SPCG-15-A Randomized Trial Comparing Radical Prostatectomy with Primary Radiotherapy plus Androgen Deprivation Therapy in Men with Locally Advanced Prostate Cancer

Background: There is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. Objective: To describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design, setting, and participants: This study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. Intervention: Radical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysis: Cause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitations: The distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45-75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. Conclusions: We have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summary: This study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.Peer reviewe

From food to pest: Conversion factors determine switches between ecosystem services and disservices

Ecosystem research focuses on goods and services, thereby ascribing beneficial values to the ecosystems. Depending on the context, however, outputs from ecosystems can be both positive and negative. We examined how provisioning services of wild animals and plants can switch between being services and disservices. We studied agricultural communities in Laos to illustrate when and why these switches take place. Government restrictions on land use combined with economic and cultural changes have created perceptions of rodents and plants as problem species in some communities. In other communities that are maintaining shifting cultivation practices, the very same taxa were perceived as beneficial. We propose conversion factors that in a given context can determine where an individual taxon is located along a spectrum from ecosystem service to disservice, when, and for whom. We argue that the omission of disservices in ecosystem service accounts may lead governments to direct investments at inappropriate targets

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Short-term morbidity and mortality following radical cystectomy: a systematic review

Objective To study short-term (<90 days) morbidity and mortality following radical cystectomy (RC) for bladder cancer and identify modifiable risk factors associated with these.Design Systematic review.Methods The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed and EMBASE were searched for relevant papers on 11 June 2019 and rerun on 27 May 2020. Studies reporting complications, reoperations, length of stay and mortality within 90 days were included. Studies were reviewed according to criteria from the Oxford Centre for Evidence-Based Medicine and the quality of evidence was assessed using the Newcastle–Ottawa Scale.Results The search retrieved 1957 articles. Sixty-six articles were included. The quality of evidence was poor to good. Most studies were retrospective, and no randomised clinical trials were identified. Of included studies a median of 6 Martin criteria for reporting complications after surgery were fulfilled. The Clavien-Dindo classification for grading complications was most frequently used. The weighted overall complication rate after RC was 34.9% (range 28.8–68.8) for in-house complications, 39.0% (range 27.3–80.0) for 30-day complications and 58.5% (range 36.1–80.5) for 90-day complications. The most common types of complications reported were gastrointestinal (29.0%) and infectious (26.4%). The weighted mortality rate was 2.4% (range 0.9–4.7) for in-house mortality, 2.1% (0.0–3.7) for 30-day mortality and 4.7% (range 0.0–7.0) for 90-day mortality. Age and comorbidity were identified as the best predictors for complications following RC.Conclusion Short-term morbidity and mortality are high following RC. Reporting of complications is heterogeneous and the quality of evidence is generally low. There is a continuous need for randomised studies to address any intervention that can reduce morbidity and mortality following RC.PROSPERO registration number 104937

Compton polarimetry with a 36-fold segmented HPGe-detector of the AGATA-type

The calibration of a highly-segmented AGATA-type HPGe-detector as a gamma-ray Compton polarimeter and a method for (quasi-)continuous angle Compton polarimetry are presented. The high granularity, combined with the large detection efficiency of the AGATA-type HPGe-crystals, offers a significant advantage for polarization measurements of gamma-radiation. A polarization-directional correlation experiment with gamma-rays from a Co-60 source with an activity of about 680 kBq was used to determine the polarization sensitivity of a single AGATA-type HPGe-crystal at 1173 and 1332 key and to demonstrate the method. The polarization measurement was based on segment information. In our set-up a polarization sensitivity of 19% at 1332 keV has been achieved