Identification of pathologically insignificant prostate cancer is not accurate in unscreened men.

BACKGROUND: Identification of men harbouring insignificant prostate cancer (PC) is important in selecting patients for active surveillance. Tools have been developed in PSA-screened populations to identify such men based on clinical and biopsy parameters. METHODS: Prospectively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre. Tumour volume was assessed by pathological examination. For each tool, receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared. Comparison of accuracy in screened and unscreened populations was performed. RESULTS: Of 848 patients, 415 had Gleason 3+3 disease on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded. One had positive lymph nodes. Two hundred and six (24% of cohort) were D'Amico low risk. Of these, 143 had more than two biopsy cores involved. None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden. Accuracy is low in PSA-screened and -unscreened populations. CONCLUSIONS: In our unscreened population, tools designed to identify insignificant PC are inaccurate. Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy

Mining Human Prostate Cancer Datasets: The “camcAPP” Shiny App

Core CRUK funding: MD, AGL, ADL. Academy of Medical Sciences Clinical Lecturer Starter Grant SGCL11 (prinicipal funder of this work): ADL

Elevated levels of FOXA1 facilitate androgen receptor chromatin binding resulting in a CRPC-like phenotype.

Castration-resistant prostate cancer (CRPC) continues to pose a significant clinical challenge with new generation second-line hormonal therapies affording limited improvement in disease outcome. As the androgen receptor (AR) remains a critical driver in CRPC, understanding the determinants of its transcriptional activity is important for developing new AR-targeted therapies. FOXA1 is a key component of the AR transcriptional complex yet its role in prostate cancer progression and the relationship between AR and FOXA1 are not completely resolved. It is well established that FOXA1 levels are elevated in advanced prostate cancer and metastases. We mimicked these conditions by overexpressing FOXA1 in the androgen-responsive LNCaP prostate cancer cell line and observed a significant increase in AR genomic binding at novel regions that possess increased chromatin accessibility. High levels of FOXA1 resulted in increased proliferation at both sub-optimal and high 5α-dihydrotestosterone (DHT) concentrations. Immunohistochemical staining for FOXA1 in a clinical prostate cancer cohort revealed that high FOXA1 expression is associated with shorter time to biochemical recurrence after radical prostatectomy (hazard ratio (HR) 5.0, 95% confidence interval (CI) 1.2-21.1, P=0.028), positive surgical margins and higher stage disease at diagnosis. The gene expression program that results from FOXA1 overexpression is enriched for PTEN, Wnt and other pathways typically represented in CRPC gene signatures. Together, these results suggest that in an androgen-depleted state, elevated levels of FOXA1 enhance AR binding at genomic regions not normally occupied by AR, which in turn facilitates prostate cancer cell growth

Analysis of heterogeneity in T2_2-weighted MR images can differentiate pseudoprogression from progression in glioblastoma

$\textbf{Purpose}$ To develop an image analysis technique that distinguishes pseudoprogression from true progression by analyzing tumour heterogeneity in $T_2$-weighted images using topological descriptors of image heterogeneity called Minkowski functionals (MFs). $\textbf{Methods}$ Using a retrospective patient cohort ($n$ = 50), and blinded to treatment response outcome, unsupervised feature estimation was performed to investigate MFs for the presence of outliers, potential confounders, and sensitivity to treatment response. The progression and pseudoprogression groups were then unblinded and supervised feature selection was performed using MFs, size and signal intensity features. A support vector machine model was obtained and evaluated using a prospective test cohort. $\textbf{Results}$ The model gave a classification accuracy, using a combination of MFs and size features, of more than 85% in both retrospective and prospective datasets. A different feature selection method (Random Forest) and classifier (Lasso) gave the same results. Although not apparent to the reporting radiologist, the $T_2$-weighted hyperintensity phenotype of those patients with progression was heterogeneous, large and frond-like when compared to those with pseudoprogression. $\textbf{Conclusion}$ Analysis of heterogeneity, in $T_2$-weighted MR images, which are acquired routinely in the clinic, has the potential to detect an earlier treatment response allowing an early change in treatment strategy. Prospective validation of this technique in larger datasets is required.Funded by Medical Research Council/ Royal College of Radiologists (UK) Clinical Research Fellowship (G1000265); Cancer Research UK Clinical Research Fellowship; Addenbrookes Charitable Trust Award to TCB. Cancer Research UK Programme grant (C197/ A3514) to KMB

Show the data, don't conceal them

Data presentation and statistical analysis in scientific writing are agreed to be in need of improvement, despite the profusion of advice and instruction. Recent evidence supports the need for better planning and analysis of animal experiments. This series of short articles aims to provide advice in small easily digested pieces, on a variety of topics, both basic and more specialized, that are relevant to readers of the journal. The present article encourages authors to present data clearly, preferably as a dot plot, so that the distribution of the values can be recognized. The use of different measures of distribution of a population, and different measures of precision of an estimate is contrasted

Prevalence, Characteristics and Outcomes of People Aged 65 Years and Over with an Incidental Rise in Cardiac Troponin I. An observational prospective cohort study

Background: Cardiac troponin I (cTnI) is a sensitive and specific marker of acute cardiac damage. We examined the prevalence, characteristics and outcome of incidental cTnI rises in older patients. Methods: One hundred and eighty-seven consecutive patients aged 65 years or over with a raised cTnI on admission at least 8 h after symptom onset were categorised into: (1) ST-elevation myocardial infarction, (2) other acute coronary syndromes (ACS), (3) other recognised non-ACS causes of cTnI rise and (4) non-ACS with no other identifiable cause (an incidental finding). The number of readmissions and deaths for each group was measured at 30 and 90 days. Results: Age range = 65–98 years. Male = 55.6%. Fifty-four percent had a raised cTnI due to non-ACS illnesses, whilst in 18% it was an incidental finding. The latter group was relatively older and had a significantly lower degree of cTnI rise (U = 1718.5, p = 0.002), but a higher readmission and mortality rate compared to the other groups (categories 1–3) for both follow-up periods. Conclusions: Incidental cTnI rise is common in older patients and is associated with a poorer prognosis compared to ACS or a recognised non-ACS condition. Future research should attempt to evaluate the significance of such incidental rises in elderly patients

First 500 cases of robotic-assisted laparoscopic radical prostatectomy from a single UK centre: learning curves of two surgeons.

OBJECTIVE: • To study the outcomes and learning curve of robotic-assisted laparoscopic radical prostatectomy (RALP) in a single centre by two surgeons. PATIENTS AND METHODS: • In total, 500 consecutive patients underwent RALP between 2005 and 2009 carried out by two surgeons. Using an ethically-approved database, prospective data collection of demographic, surgical, oncological and functional outcomes (patient reported) was performed, with up to 4 years of follow-up. • The learning curves of both surgeons were analyzed and, in addition, the first 100 and last 100 patients were compared to determine the effect of surgeon experience. RESULTS: • The mean age of the patients was 61.5 years and mean preoperative prostate-specific antigen was 7.0 µg/L. Clinical stages were T1 in 63.2%, T2 in 33.8% and T3 in 3.0% of patients. Median (range) operating time was 170 (63-420) min and median (range) blood loss was 200 (20-3000) mL, with significant improvements for both surgeons with increasing experience (P < 0.001 and P= 0.029, respectively). • Pathological stages were pT2 in 53.4%, pT3a in 41.6%, pT3b in 4.0% and pT4 in 0.6% of patients. Overall, the positive margin rate (PMR) was 24.0% and stage-specific rates were 16.1%, 30.4%, 55.0% and 100.0% for pT2, pT3a, pT3b and pT4 disease, respectively. In the last 50 cases performed by each surgeon, the PMRs for pT2 and pT3a disease were 8.0% and 19.1% (surgeon 1) and 12.9% and 23.5% (surgeon 2). • At 12 months of follow-up, 91.3% of patients were continent and, by 48 months of follow-up, 75% of men with preoperative potency who underwent bilateral nerve-sparing RALP were potent. CONCLUSION: • This is the first report of two surgeons' learning curves in a single centre and shows that key learning curve outcomes continued to improve during the series, suggesting that the learning curve for RALP may be longer than has been previously suggested