Long-term outcome among men with conservatively treated localised prostate cancer

Optimal management of clinically localised prostate cancer presents unique challenges, because of its highly variable and often indolent natural history. There is an urgent need to predict more accurately its natural history, in order to avoid unnecessary treatment. Medical records of men diagnosed with clinically localised prostate cancer, in the UK, between 1990 and 1996 were reviewed to identify those who were conservatively treated, under age 76 years at the time of pathological diagnosis and had a baseline prostate-specific antigen (PSA) measurement. Diagnostic biopsy specimens were centrally reviewed to assign primary and secondary Gleason grades. The primary end point was death from prostate cancer and multivariate models were constructed to determine its best predictors. A total of 2333 eligible patients were identified. The most important prognostic factors were Gleason score and baseline PSA level. These factors were largely independent and together, contributed substantially more predictive power than either one alone. Clinical stage and extent of disease determined, either from needle biopsy or transurethral resection of the prostate (TURP) chips, provided some additional prognostic information. In conclusion, a model using Gleason score and PSA level identified three subgroups comprising 17, 50, and 33% of the cohort with a 10-year prostate cancer specific mortality of <10, 10–30, and >30%, respectively. This classification is a substantial improvement on previous ones using only Gleason score, but better markers are needed to predict survival more accurately in the intermediate group of patients

Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death

Prostate Cancer Foundation, American Cancer Society (RSG-15-067-01-TBG), Prostate Cancer Foundation, National Cancer Institute (R01 CA204749), Howard Hughes Medical Institute, National Institutes of Health (CA193837),(CA092629), (CA155169), (CA008748)

Ki-67 and outcome in clinically localised prostate cancer: analysis of conservatively treated prostate cancer patients from the Trans-Atlantic Prostate Group study

Treatment decisions after diagnosis of clinically localised prostate cancer are difficult due to variability in tumour behaviour. We therefore examined one of the most promising biomarkers in prostate cancer, Ki-67, in a cohort of 808 patients diagnosed with prostate cancer between 1990 and 1996 and treated conservatively. Ki-67 expression was assessed immunohistochemically, in two laboratories, by two different scoring methods and the results compared with cancer-specific and overall survival. The power of the biomarker was compared with Gleason score and initial serum prostate-specific antigen (PSA). Both methods showed that Ki-67 provided additional prognostic information beyond that available from Gleason score and PSA: for the semi-quantitative method, Δχ2 (1 d.f.)=24.6 (P<0.0001), overall survival χ2=20.5 (P<0.0001), and for the quantitative method, Δχ2 (1 d.f.)=15.1 (P=0.0001), overall survival χ2=10.85 (P=0.001). Ki-67 is a powerful biomarker in localised prostate cancer and adds to a model predicting the need for radical or conservative therapy. As it is already in widespread use in routine pathology, it is confirmed as the most promising biomarker to be applied into routine practice

The effect of low level laser on condylar growth during mandibular advancement in rabbits

<p>Abstract</p> <p>Introduction</p> <p>It has been shown that Low Level Laser (LLL) has a positive effect on bone formation. The aim of this study was to evaluate the effect of low level laser on condylar growth during mandibular advancement in rabbits.</p> <p>Materials and methods</p> <p>Continuous forward mandibular advancement was performed in fourteen male Albino rabbits with the mean age of 8 weeks and the mean weight of 1.5 ± 0.5 kg, with acrylic inclined planes. The rabbits were randomly assigned into two groups after 4 weeks. LLL (KLO3: wave length 630 nm) was irradiated at 3 points around the TMJ, through the skin in the first group. The exposure was performed for 3 minutes at each point (a total of 9 minutes) once a day for 3 weeks. The control group was not exposed to any irradiation. The rabbits in both groups were sacrificed after two months and the histological evaluation of TMJ was performed to compare fibrous tissue, cartilage, and new bone formation in condylar region in both groups. Disc displacement was also detected in both groups. Student's t-test, Exact Fisher and Chi square tests were used for the statistical analysis.</p> <p>Results</p> <p>The formation of fibrous tissue was significantly lower, while bone formation was significantly greater in lased group as compared with control group. The thickness of cartilage did not differ significantly between two groups.</p> <p>Conclusion</p> <p>Irradiation of LLL (KLO3) during mandibular advancement in rabbits, increases bone formation in condylar region, while neither increase in the cartilage thickness nor fibrous tissues was observed.</p

Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer

BACKGROUND: The discovery of ERG/ETV1 gene rearrangements and PTEN gene loss warrants investigation in a mechanism-based prognostic classification of prostate cancer (PCa). The study objective was to evaluate the potential clinical significance and natural history of different disease categories by combining ERG/ETV1 gene rearrangements and PTEN gene loss status. METHODS: We utilised fluorescence in situ hybridisation (FISH) assays to detect PTEN gene loss and ERG/ETV1 gene rearrangements in 308 conservatively managed PCa patients with survival outcome data. RESULTS: ERG/ETV1 gene rearrangements alone and PTEN gene loss alone both failed to show a link to survival in multivariate analyses. However, there was a strong interaction between ERG/ETV1 gene rearrangements and PTEN gene loss (P<0.001). The largest subgroup of patients (54%), lacking both PTEN gene loss and ERG/ETV1 gene rearrangements comprised a 'good prognosis' population exhibiting favourable cancer-specific survival (85.5% alive at 11 years). The presence of PTEN gene loss in the absence of ERG/ETV1 gene rearrangements identified a patient population (6%) with poorer cancer-specific survival that was highly significant (HR=4.87, P<0.001 in multivariate analysis, 13.7% survival at 11 years) when compared with the 'good prognosis' group. ERG/ETV1 gene rearrangements and PTEN gene loss status should now prospectively be incorporated into a predictive model to establish whether predictive performance is improved. CONCLUSIONS: Our data suggest that FISH studies of PTEN gene loss and ERG/ETV1 gene rearrangements could be pursued for patient stratification, selection and hypothesis-generating subgroup analyses in future PCa clinical trials and potentially in patient management