The pan-cancer analysis of whole genomes The expansion of whole-genome sequencing studies from individual ICGC and TCGA working groups presented the opportunity to undertake a meta-analysis of genomic features across tumour types. To achieve this, the PCAWG Consortium was established. A Technical Working Group implemented the informatics analyses by aggregating the raw sequencing data from different working groups that studied individual tumour types, aligning the sequences to the human genome and delivering a set of high-quality somatic mutation calls for downstream analysis (Extended Data Fig. 1). Given the recent meta-analysis

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials.

We reviewed the scientific literature for factors affecting men's choice and adherence to active surveillance (AS) for low-risk prostate cancer. Our findings suggest that the use of AS could be increased by addressing a variety of factors such as information, psychosocial support, clinician education, and standardised guidelines.

In the last decade, active surveillance (AS) has emerged as an acceptable choice for low-risk prostate cancer (PC), however there is discordance amongst large AS cohort studies with respect to entry and monitoring protocols. We systematically reviewed worldwide AS practices in studies reporting ≥5 years follow-up. We searched PubMed and Medline 2000-now and identified 13 AS cohorts. Three key areas were identified: (I) patient selection; (II) monitoring protocols; (III) triggers for intervention—(I) all studies defined clinically localised PC diagnosis as T2b disease or less and most agreed on prostate-specific antigen (PSA) threshold (<10 µg/L) and Gleason score threshold (3+3). Inconsistency was most notable regarding pathologic factors (e.g., number of positive cores); (II) all agreed on PSA surveillance as crucial for monitoring, and most agreed that confirmatory biopsy was required within 12 months of initiation. No consensus was reached on optimal timing of digital rectal examination (DRE), general health assessment or re-biopsy strategies thereafter; (III) there was no universal agreement for intervention triggers, although Gleason score, number or percentage of positive cancer cores, maximum cancer length (MCL) and PSA doubling time were used by several studies. Some also used imaging or re-biopsy. Despite consistent high progression-free/cancer-free survival and conversion-to-treatment rates, heterogeneity exists amongst these large AS cohorts. Combining existing evidence and gathering more long-term evidence [e.g., the Movember’s Global AS database or additional information on use of magnetic resonance imaging (MRI)] is needed to derive a broadly supported guideline to reduce variation in clinical practice.

Objective• To describe a protocol for transperineal sector biopsies (TPSB) of the prostate and present the clinical experience of this technique in a UK population. Patients and Methods• A retrospective review of a single-centre experience of TPSB approach was undertaken that preferentially, but not exclusively, targeted the peripheral zone of the prostate with 24-38 cores using a 'sector plan' . Procedures were carried out under general anaesthetic in most patients.• Between January 2007 and August 2011, 634 consecutive patients underwent TPSB for the following indications: prior negative transrectal biopsy (TRB; 174 men); primary biopsy in men at risk of sepsis (153); further evaluation after low-risk disease diagnosed based on a 12-core TRB (307). Results• Prostate cancer was found in 36% of men after a negative TRB; 17% of these had disease solely in anterior sectors.• As a primary diagnostic strategy, prostate cancer was diagnosed in 54% of men (median PSA level was 7.4 ng/mL).• Of men with Gleason 3+3 disease on TRB, 29%were upgraded and went on to have radical treatment.• Postoperative urinary retention occurred in 11 (1.7%) men, two secondary to clots. Per-urethral bleeding requiring hospital stay occurred in two men. There were no cases of urosepsis. Conclusions• TPSB of the prostate has a role in defining disease previously missed or under-diagnosed by TRB. The procedure has low morbidity.

Bilateral neurovascular bundle preservation was attempted in 58% of patients. The transfusion rate was 3%. The conversion and re-intervention rates were 1% and 2%, respectively. There were eight complications, six of which were in the initial 26 cases, i.e. bladder neck stenosis (two), and rectal injury, laparotomy for bleeding, premature drain removal leading to urinary peritonitis, ulnar nerve neuropraxia, port-site hernia and paralytic ileus in one each. The positive surgical margin rate was 16%. All patients had a PSA level of £ 0.1 ng/mL at 3 months. By 1 year 90% of patients were pad-free and 62% operated on using a bilateral nerve-sparing technique had erections. There were no biochemical failures. The mean (range) follow-up was 9.8 (1-24) months. Conclusion The present results are similar to those reported by other centres with greater experience and confirm that LRP is an effective, safe and precise technique. Once intial experience has been gained it offers advantages over open surgery in the form of a dry and magnified operative site, and a lower likelihood of blood transfusion, in addition to the generic advantages of laparoscopy.

The 2 procedures are equivalent in terms of operative, postoperative and pathological data. Each surgeon has to choose considering personal experience, training and standardization.

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