Proposal for a predictive model of erectile function after permanent (125)I prostate brachytherapy for localized prostate cancer.

To determine the risk factors for EDin men treated by prostate brachytherapy (PB) for localized prostate cancer and to propose a model to predict post-implant erectile function. Out of a series of 270 sexually active men treated by PB, 241 (89%) (mean age=66 years (range, 43-80)) accepted to participate in a mail-based study on erectile function. The risk factors for erectile dysfunction were determined by regression analysis and a predictive model was proposed. The performance of the model was determined in this population and subsequently verified in a population of 50 men treated by PB in another treatment center. The risk factors for ED after PB were age, the pre-implant IIEF score and prostate volume. In the studied population, the final model to predict a post-treatment IIEF-5 score, using these factors, had a sensitivity of 69% and a specificity of 68% associated to an area under the ROC curve (AUC) of 0.75. The same performance was obtained in another treatment center. Age, pre-implant IIEF-5 score and prostate volume may be used to predict post-implant erectile function in patients treated by PB.

[Analysis of the evolution of surgery for the treatment of primary renal tumors during the period 2006-2010: report of 458 consecutive surgeries]. / Analyse de l'évolution des pratiques chirurgicales pour la prise en charge des tumeurs primitives du rein dans la période 2006-2010: à propos d'une série de 458 chirurgies consécutives.

OBJECTIVE: Most of small renal masses are accessible to conservative surgery, which has proved to maintain carcinological outcome, with a lower cardiovascular morbidity, hospital stay and mortality. Current international guidelines for the management of renal tumours recommend that partial nephrectomy be the new standard of treatment of T1 tumours. In this study, the authors assessed evolutive trends in the surgical management of renal tumours in the period 2006 to 2010 in a university hospital. PATIENTS AND METHODS: Retrospective analysis of a cohort of 446 consecutive patients treated for renal tumour between 2006 and 2010. RESULTS: Overall, 458 surgeries were performed, divided in 184 (40.2%) partial nephrectomy and 274 (49.8%) radical nephrectomy. During the study period, the number of partial nephrectomy increased significantly, with a mean annual increase rate of 10% in T1a tumours (P=0.002). We also observed a non significant increasing trend for conservative surgery in T1b tumours. Furthermore, the number of laparoscopic partial nephrectomy increased significantly, with a mean annual increase rate of 8% (P=0.02). At the end of the study period, one in two patients, whatever the stage, was treated by partial nephrectomy. This change in practice occurred without any increase in per- and postoperative morbidity (P=0.39). CONCLUSION: Analysis of this cohort of patients operated for renal tumour between 2006 and 2010 in our university hospital did not highlight underuse of conservative surgery, taking into account the current international guidelines. This trend for more partial nephrectomy did not underscore an increase in surgical morbidity or decrease in carcinological outcome. However, the higher rate of positive surgical margins in the laparoscopic partial nephrectomy group should incite to caution.

DNA replication stress response involving PLK1, CDC6, POLQ, RAD51 and CLASPIN upregulation prognoses the outcome of early/mid-stage non-small cell lung cancer patients.

Lung cancer is the leading cause of cancer deaths worldwide. Clinical staging classification is generally insufficient to provide a reliable prognosis, particularly for early stages. In addition, prognostic factors are therefore needed to better forecast life expectancy and optimize adjuvant therapeutic strategy. Recent evidence indicates that alterations of the DNA replication program contribute to neoplasia from its early stages and that cancer cells are frequently exposed to endogenous replication stress. We therefore hypothesized that genes involved in the replication stress response may represent an under-explored source of biomarkers. Expressions of 77 DNA replication-associated genes implicated in different aspects of chromosomal DNA replication, including licensing, firing of origins, elongation, replication fork maintenance and recovery, lesion bypass and post-replicative repair were determined in primary tumors and adjacent normal tissues from 93 patients suffering from early- or mid-stage non-small cell lung cancer (NSCLC). We then investigated a statistically significant interaction between gene expressions and survival of early-stage NSCLC patients.The expression of five genes, that is, POLQ, PLK1, RAD51, CLASPIN and CDC6 was associated with overall, disease-free and relapse-free survival. The expression levels are independent of treatment and stage classification. Except RAD51, their prognostic role on survival persists after adjustment on age, sex, treatment, stage classification and conventional proliferation markers, with a hazard ratio of 36.3 for POLQ (95%CI 2.6-517.4, P=0.008), 23.5 for PLK1 (95%CI 1.9-288.4, P=0.01), 20.7 for CLASPIN (95%CI 1.5-275.9, P=0.02) and 18.5 for CDC6 (95%CI 1.3-267.4, P=0.03). We also show that a five-gene signature including POLQ, PLK1, RAD51, CLASPIN and CDC6 separates patients into low- and high-risk groups, with a hazard ratio of 14.3 (95% CI 5.1-40.3, P<0.001). This 'replication stress' metamarker may be a reliable predictor of survival for NSCLC, and may also help understand the molecular mechanisms underlying tumor progression.