Nivolumab in patients with advanced renal cell carcinoma in France: interim results of the observational, real-world WITNESS study.

BACKGROUND: Nivolumab is the first immune checkpoint inhibitor approved in Europe for the treatment of advanced renal cell carcinoma (aRCC) in patients resistant to prior antiangiogenic therapy. WITNESS is an ongoing, prospective, observational study designed to evaluate the effectiveness and safety of nivolumab in patients with aRCC treated in real life (or routine practice) in France (ClinicalTrials.gov identifier: NCT03455452). PATIENTS AND METHODS: This study includes adult patients with a confirmed diagnosis of aRCC who have initiated nivolumab after 1-2 prior lines of antiangiogenic therapy. Endpoints include overall survival (OS), progression-free survival (PFS), duration of treatment (DOT), duration of response (DOR), overall response rate (ORR), subgroup analyses, and treatment-related adverse events (TRAEs). Results after a median follow-up of 12.3 months are presented here. RESULTS: A total of 325 patients with aRCC were included, of whom 38.2% had a Karnofsky score <80, 77.8% received nivolumab as second-line therapy, and 69.5% had undergone a previous nephrectomy. In the overall population, median OS was 20.5 [95% confidence interval (CI) 17.6-25.0] months and median PFS was 5.2 (95% CI 4.5-5.9) months. ORR was 34.5%, median DOT was 3.8 months, and median DOR was 16.5 months. Nivolumab was effective in different subgroups including patients with bone or glandular metastases and those receiving baseline corticosteroids. Moreover, effectiveness was observed irrespective of prior nephrectomy and line of treatment. No new safety signals were identified; TRAEs of any grade were reported in 32.0% of patients, grade ≥3 and serious TRAEs in 11.1% each, and TRAEs leading to discontinuation in 8.9%. CONCLUSIONS: Preliminary results of the ongoing WITNESS study confirm the real-world effectiveness and safety of nivolumab monotherapy in previously treated patients with aRCC. Treatment benefits were similar to those observed in the pivotal phase III CheckMate 025 randomized clinical trial, despite a broader, real-life study population.

Implementation of the GAA 'healthy clubs project' in Ireland: a qualitative study using the Consolidated Framework for Implementation Research.

The sports clubs' role in promoting health has been acknowledged by policy makers and researchers, but there is little evidence on how sports clubs implement health-related interventions. The present article investigates the Gaelic Athletic Association Healthy Club Project (HCP) implementation process (mechanisms, barriers, leverages) over a 10-year timeframe. A case study design helped to produce and compare a data synthesis for five clubs involved since 2013. A qualitative iterative data collection, including document analysis was conducted through 20 focus groups with Healthy Club Officers, coaches, participants and members. The Consolidated Framework for Implementation Research was used in the deductive analysis process, conducted by the first author. Results have shown the success of the HCP in placing health promotion on the agenda of sports clubs leading to informal policy for health promotion, even if activities and recognition are directed toward and coming from the community. This study also underlines the virtuous cycle of the settings-based approach in enhancing membership and volunteer recognition through health promotion actions, and the importance of social good and corporate social activities for sports clubs. Nevertheless, the HCP still relies on limited human resources, is not recognized by competitive oriented adult playing members. and acknowledged as a resource by some coaches, limiting its rootedness in the core business of sports clubs. Future research should empower the HCP community to focus on organizational changes and develop outcomes for individuals, for the club as a whole as well as for the local community.

Gastrointestinal metastases in renal cell carcinoma: A retrospective multicenter GETUG (Groupe d'Étude des Tumeurs Uro-Génitales) study.

BACKGROUND: Among patients with renal cell carcinoma (RCC), bone and visceral metastases have a poor prognosis, while endocrine gland metastases have a more favorable prognosis. Gastrointestinal metastases (GIMs) are rare, and their prognosis is still poorly understood. OBJECTIVES: To report clinical presentations, patient characteristics, therapeutic strategies, and prognosis of GIMs from RCC. METHODS: We retrospectively collected data from RCC patients presenting GIMs, in 10 French GETUG centers, between 2000 and 2021. RESULTS: We identified 74 patients with 87 GIMs, mostly gastric or duodenal. The median age at GIM diagnosis was 69 years and 76% of patients already had other metastases. GIMs occurred after a median duration of 5.4 years (IC95%=[4.2-7.1]) and 1.9 years (IC95%=[1.2-3.8]) from RCC diagnosis and first metastasis, respectively. GIMs were symptomatic in 52 patients (70%), with anemia in 41 patients (55%) and/or gastrointestinal bleeding in 31 patients (42%). Only 22 asymptomatic patients (30%) were fortuitously diagnosed. GIM management consisted of systemic treatment only in 29 GIMs (33%), local treatment only in 23 GIMs (26%), and both local and systemic treatment in 18 GIMs (21%). For 17 GIMs (20%), there was no therapeutic modification. After diagnosis of GIM, median overall survival was 19 months. CONCLUSION: We report the largest retrospective cohort of GIMs in RCC patients. They should be suspected in case of anemia or gastrointestinal bleeding in any patient with a history of RCC. Their management varies widely depending on their location in the digestive tract and whether or not they are symptomatic.

Evaluation of local control after percutaneous microwave ablation versus partial nephrectomy: A propensity score matched study.

INTRODUCTION: The incidence of small renal tumors (≤4cm) is on the rise. The gold standard treatment is partial nephrectomy (PN) but focal therapy can be a good alternative. We evaluated oncological control after treatment of T1a renal tumors by microwave ablation (MWA) compared to PN. METHODS: This is a retrospective, single-center study of all patients treated for TNM stage T1a renal tumors by either PN or MWA between 2010 and 2020. A propensity score was calculated and patients were matched 2:1 to compare recurrence-free survival, metastasis-free survival and overall survival between groups. We also compared postoperative complications using the Clavien-Dindo classification. RESULTS: After matching and propensity score, the two groups (41 MWA and 82 PN) were comparable. The median follow-up was 23 months (interquartiles, 9-48 months). Recurrence-free survival was higher in the PN group compared to MWA, with a recurrence rate of 17.1% in the MWA group vs 4.9% in the PN group (P=0.003). MWA treatment was a risk factor for tumor recurrence (P=0.002), but there was no significant difference in terms of metastasis-free survival (P=0.549) or overall survival (P=0.539). MWA was associated with fewer postoperative complications (P=0.0005). CONCLUSION: This study shows that MWA was associated with higher risk of recurrence but similar metastasis-free survival and overall survival compared to PN. Recurrence was treated with new MWA or active surveillance. MWA may be an interesting alternative to PN for small renal tumors. LEVEL OF EVIDENCE: Grade C.

Circulating Biomarkers in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus in the Pre-nephrectomy Setting.

Many drugs are available in renal cell carcinoma (RCC), yet clinicians are still looking for predictive biomarkers of disease recurrence or progression supporting more personalised treatments. An assessment of circulating biomarkers over time was carried out in this French, open-label, single-arm, multicentre trial conducted in 25 patients with either locally advanced (n = 14) or metastatic RCC (n = 11) who received everolimus (10 mg daily) for 6 weeks prior to nephrectomy (NEORAD, NCT01715935). Circulating biomarkers, including circulating tumour cells, haematopoietic and endothelial cells, plasma angiogenesis and inflammatory markers were quantified at baseline, upon everolimus and post-nephrectomy. We assessed tumour burden, objective response rate upon RECIST1.1, disease-free survival (DFS) and progression-free survival (PFS). The correlation between circulating biomarkers was evaluated with multiple factor analysis and biomarker association with DFS/PFS by Cox regression. No objective response rate was obtained before nephrectomy. Upon everolimus, neutrophils, platelets and sVEGFR2 significantly decreased. We did not find any association between circulating biomarkers and DFS/PFS, but patients with the highest tumour burden at baseline had significantly higher plasma levels of interleukin-6, an inflammatory circulating biomarker, and lower levels of sVEGFR2, related to angiogenesis. Further understanding of the link between these circulating biomarkers could help to optimise drug combinations in RCC.

Impact of blood transfusion on survival after nephrectomy for localized or locally advanced renal cancer.

OBJECTIVE: Several studies have reported blood transfusion were associated with a decrease of survival after oncological surgery. For kidney cancer, the effect of blood transfusion is still debated. The objective of this study was to determine the effect of blood transfusion after oncological nephrectomy on overall, specific and recurrence-free survival in a retrospective cohort of localized or locally advanced kidney cancer. MATERIAL AND METHODS: We performed a monocentric retrospective analysis of all patients managed by surgery for localized or locally advanced renal cancer between January 2000 and December 2016. We compared overall and specific survival and recurrence-free survival between two groups: patients transfused and not transfused. Demographic, surgical and tumor characteristics were compared. Survival analyses were performed using univariate Cox regression and multivariate Cox proportional regression test. RESULTS: We included 382 patients in this study: 320 (83.8%) were not transfused and 62 (16.2%) were transfused. Transfused patients were significantly older (P=0.001) and had a lower pre-operative hemoglobin level (P=0.008). Operative and oncological characteristics were also different between both groups. In univariate analysis, we showed that blood transfusion was associated with lower overall survival (P<0.001), specific survival (P<0.001), and recurrence-free survival (P<0.001). In multivariate analysis, we found that blood transfusion was not associated with overall survival, or specific survival, but it was associated with lower recurrence-free survival (HR: 1.967, CI95% [1.024-3.780], P=0.042). CONCLUSIONS: Perioperative blood transfusion is an independent risk factor that increases tumor recurrence among patients treated with nephrectomy for renal cancer.

An analysis of health-related quality of life in the phase III PROSELICA and FIRSTANA studies assessing cabazitaxel in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Men with metastatic castration-resistant prostate cancer (mCRPC) are living longer, therefore optimizing health-related quality of life (HRQL), as well as survival outcomes, is important for optimal patient care. The aim of this study was to assess the HRQL in patients with mCRPC receiving docetaxel or cabazitaxel. PATIENTS AND METHODS: PROSELICA (NCT01308580) assessed the non-inferiority of cabazitaxel 20 mg/m2 (C20) versus 25 mg/m2 (C25) in patients with mCRPC after docetaxel. FIRSTANA (NCT01308567) assessed the superiority of C25 or C20 versus docetaxel 75 mg/m2 (D75) in patients with chemotherapy-naive mCRPC. HRQL and pain were analyzed using protocol-defined, prospectively collected, Functional Assessment of Cancer Therapy-Prostate (FACT-P) and McGill-Melzack questionnaires. Analyses included definitive improvements in HRQL, maintained or improved HRQL, and HRQL over time. RESULTS: In total, 2131 patients were evaluable for HRQL across the two studies. In PROSELICA, 38.8% and 40.5% of patients receiving C20 and C25, respectively, had definitive FACT-P total score (TS) improvements. In FIRSTANA, 43.4%, 49.7%, and 44.9% of patients receiving D75, C20, and C25, respectively, had definitive FACT-P TS improvements. In both trials, definitive improvements started after cycle 1 and were maintained for the majority of subsequent treatment cycles. More than two-thirds of patients maintained or improved their FACT-P TS. CONCLUSIONS: In PROSELICA and FIRSTANA, >40% of the 2131 evaluable patients with mCRPC had definitive FACT-P TS improvements; improvements occurred early and were maintained. More than 75% of patients maintained or improved their FACT-P TS.

Building health-promoting sports clubs: a participative concept mapping approach.

OBJECTIVES: The potential of sports clubs to promote health beyond physical activity has been acknowledged by researchers and policy-makers. This study gathered stakeholder ideas on support sports clubs need to increase health promotion efforts and prioritize them based on importance and feasibility. STUDY DESIGN: The study design used in this study is a mixed-methods concept mapping approach. METHODS: French sports and public health stakeholders (n = 45) were invited to participate. Steps included are as follows: (1) formulating a focus prompt, (2) brainstorming statements in response to the focus prompt, (3) sorting statements into themed piles, and (4) rating statements based on indicators. Multidimensional scaling and hierarchical cluster analysis were used to produce visual cluster maps, and descriptive statistics generated Go-Zone graphs based on mean importance and feasible ratings. RESULTS: Participants generated 62 statements from the focus prompt: 'What assistance would benefit sports clubs to become a health-promoting setting?'. Final sorting produced 9 clusters: Tools for health promotion, Communication tools, Stakeholder training courses, Diagnostic and Financing, Awareness and Mobilization, Advocacy, Policies and Methods, Sharing and Networking, as well as Communication and Dissemination. Participant ratings produced 34 statements within the Go-Zone graphs. CONCLUSION: Understanding stakeholders' needs to increase health promotion activities in sports clubs is crucial to planning and implementing sustainable health promotion policies and practice. Priority areas include increasing awareness of health promotion benefits, mobilizing actors, advocating for support, and educating sports club actors.

Perceptions of barriers and levers of health-enhancing physical activity policies in mid-size French municipalities.

BACKGROUND: Policy is one of the levers for initiating structural change to foster the promotion of health-enhancing physical activity (HEPA). To this end, policy-makers have to deal with complex ecosystems embedded in specific contexts. However, limited research has been conducted on this topic at the local level. The purpose of this study was to identify the perceived barriers and levers of HEPA policies according to department heads and elected officials across various sectors in mid-size French municipalities. METHODS: This study used a mixed method primarily based on an adaptation of the concept mapping approach. A list of statements completing the sentence: 'In a mid-size municipal context, to develop HEPA policies, it is necessary to …' was submitted to key informants of 17 mid-sized French cities. Key informants in each municipality first rated the importance of each statement without considering their local context; they then rated the feasibility of each statement given their local context. In both cases, they used a Likert scale ranging from 1 to 6. RESULTS: A total of 23 municipal department heads and 10 elected officials from the sport (n = 14), health (n = 10) and social (n = 9) sectors in 11 mid-size French cities participated in this study. A list of 84 statements, sorted into 16 categories, was rated by participants according to their importance (M = 4.52, SD = 0.86) and their feasibility (M = 3.77, SD = 0.74). Potential barriers to (n = 10) and levers of (n = 38) HEPA policy development were identified. These results varied according to the position and sector of the participants. CONCLUSIONS: The results suggest that local contextual factors can affect the development of HEPA policies in mid-size French municipalities. The different perceptions of the potential levers and barriers according to sector might affect intersectoral collaboration. This study contributes by enhancing understanding of how local HEPA policies are developed in the French context.

[Radiotherapy of oligometastases: Sequences and interactions with systemic therapies, example of kidney cancer]. / Radiothérapie des oligométastases : interactions/séquences avec thérapies systémiques, exemple du cancer du rein.

This article is a review of the literature that aims to clarify the place of systemic and locoregional treatments, with a focus on radiotherapy and surgery in the management of patients with oligometastatic kidney cancer. We have selected articles of interest published in Medline indexed journals. We have also analysed the related guidelines: National Comprehensive Cancer Network (NCCN) 2019, European Association of Urology (EAU) 2019, European Society of Medical Oncology (ESMO) 2019, Association française d'urologie (Afu) 2018 as well as some abstracts of international congresses. The main treatments evaluated were surgery and radiotherapy. We defined the different scenarios conventionally encountered in clinical practice. The evolution of systemic therapies (increased overall survival and response rate) is likely to increase the number of patients potentially accessible to locoregional treatments. The complete analysis of the literature underlines the place of locoregional treatments whatever the scenarios mentioned. Data on stereotactic radiotherapy found a local control rate consistently above 70% in all studies with a maintained response and positive impact on overall survival and progression-free survival. The improvement of overall survival by sequential use of the various therapeutic classes confirms the need for optimization of locoregional treatments in the model of oligometastatic kidney cancer. The dogma of radioresistance must definitely be set aside with current irradiation techniques.

How do mobile health applications support behaviour changes? A scoping review of mobile health applications relating to physical activity and eating behaviours.

OBJECTIVE: The objective of this review was to analyse how researchers conducting studies about mobile health applications (MHApps) effectiveness assess the conditions of this effectiveness. STUDY DESIGN: A scoping review according to PRIMSA-ScR checklist. METHODS: We conducted a scoping review of efficacy/effectiveness conditions in high internal validity studies assessing the efficacy of MHApps in changing physical activity behaviours and eating habits. We used the PubMed, Web of Science, SPORTDiscus and PsycINFO databases and processed the review according to the O'Malley and PRISMA-ScR recommendations. We selected studies with high internal validity methodologies (randomised controlled trials, quasi-experimental studies, systematic reviews and meta-analyses), dealing with dietary and/or physical activity behaviours; covering primary, secondary or tertiary prevention and dealing with behaviour change (uptake, maintenance). We excluded articles on MHApps relating to high-level sport and telemedicine. The process for selecting studies followed a set protocol with two authors who independently appraised the studies. RESULTS: Twenty-two articles were finally selected and analysed. We noted that the mechanisms and techniques to support behaviour changes were poorly reported and studied. There was no explanation of how these MHApps work and how they could be transferred or not. Indeed, the main efficacy conditions reported by authors refer to practical aspects of the tools. Moreover, the issue of social inequalities was essentially reduced to access to the technology (the shrinking access divide), and literacy was poorly studied, even though it is an important consideration in digital prevention. All in all, even when they dealt with behaviours, the evaluations were tool-focused rather than intervention-focused and did not allow a comprehensive assessment of MHApps. CONCLUSION: To understand the added value of MHApps in supporting behaviour changes, it seems important to draw on the paradigms relating to health technology assessment considering the characteristics of the technologies and on the evaluation of complex interventions considering the characteristics of prevention. This combined approach may help to clarify how these patient-focused MHApps work and is a condition for improved assessment of MHApps in terms of effectiveness, transferability and scalability.

[Oligometastatic prostate cancer management]. / Prise en charge du cancer de la prostate oligo-métastatique.

OBJECTIVE: To review biology and management of oligometastatic prostate cancer. MATERIAL AND METHODS: Relevant publications were identified through Medline (www. ncbi.nlm.nih.gov), Embase (www.embase.com) and the US National Library of Medicine (www.clinicaltrials.org) databases using the following keywords, alone or in association, «prostate cancer; metastasis; oligo-metastasis¼. Articles were selected according to methods, language of publication and relevance. After careful selection 99 publications were eligible for our review. RESULTS: Oligometastatic prostate cancer is a new entity including prostate cancer with a limited number of metastasis. This particular state becomes more frequent with the imaging progresses especially with the common use of new PET imaging with Choline or PSMA. There is no consensus about a strict definition of oligometastatic prostate cancer, number and sites of metastasis vary widely in the literature. Moreover, oligometastatic state can be observed de novo at the time of prostate cancer diagnosis as well as in case of recurrence after a primary treatment. There is actually an important lack of evidence-based medicine and no guidelines regarding treatment can be found. In de novo oligo-metatastatic prostate cancer, treatment of the primary tumor in association with androgen deprivation therapy seems to increase survival in selected patients but this needs to be confirmed by ongoing prospective clinical trials. In recurrent prostate cancer, metastasis directed therapy with or without androgen deprivation therapy is now routinely performed but its impact needs also to be analyzed. CONCLUSION: In absence of consensus or guidelines, management of prostate cancer should be an individualized, patient-based management taking into account primary tumor stage and grade, number and types of metastasis and patient characteristics.

A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy.

BACKGROUND: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. PATIENTS AND METHODS: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. RESULTS: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). CONCLUSIONS: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. CLINICALTRIALS: gov identifier NCT01732549.

[Impact of obesity on pathologic outcomes and biochemical reccurence after radical prostatectomy]. / Effets de l'obesité sur les résultats anatomopathologiques de la prostatectomie totale et sur la survie sans recidive biologique.

OBJECTIVE: To determine whether obesity is associated with adverse pathologic characteristics, positive surgical margins and the biochemical recurrence free survival (bRFS) after primary treatment with radical prostatectomy (RP). PATIENTS AND METHODS: Medical charts of patients managed with RP between 1999 and 2011 for localized prostate cancer (PCa) were retrospectively reviewed. Population study was split into two groups according to the body mass index (BMI): non obese (BMI< 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)). Correlations between obesity and adverse pathological features or bRFS were assessed using univariable and multivariable analyses. RESULTS: Overall, 328 patients were included in the present study: 278 (84.8%) obese and 50 (15.2%) non obese. In multivariable analysis, obesity was associated with positive surgical margins (P=0.014), extracapsular extension (P=0.004) and pathologic Gleason score ≥ 7 (P=0.048). Obesity was not associated with seminal vesicle invasion (P=0.636) and lymph node metastasis (P=0.132). After a mean follow-up of 60.51 ± 28.82 months, no statistical difference in terms of bRFS was observed between the two groups (P=0.186). Furthermore, obesity was not an independent predictor of bFS in multivariable analysis. CONCLUSION: Obesity was associated with adverse pathologic characteristics and positive surgical margins but no statistical correlation was found with bRFS. LEVEL OF EVIDENCE: 5.

[Neoadjuvant before surgery treatments: state of the art in prostate cancer]. / Traitements néoadjuvants préopératoires : mise au point dans le cancer de la prostate.

GOAL: To study the impact of systemic treatment in neoadjuvant strategy before surgery in prostate cancer. MATERIALS: Literature reviews with data analysis from PubMed search using the keywords "neoadjuvant", "chemotherapy", "hormonal therapy", "prostate surgery", "radical prostatectomy", but also reports from ASCO and ESMO conferences. The articles on neoadjuvant treatment before radiotherapy were excluded. RESULTS: First studies with former therapy are more than 15-years-old and with questionable methodology: lack of power to have a clear idea of the impact on survival criteria such as overall survival or relapse-free survival. However, the impact of neoadjuvant hormone therapy on the classic risk factors for relapse (positive margins, intraprostatic disease, positive lymph nodes) was demonstrated by these studies and a Cochrane meta-analysis. The association with hormone therapy seems mandatory in comparison to treatment based solely on chemotherapy and/or targeted therapy. Promising data on the use of new drugs and their combinations arise: abiraterone acetate combined with LHRH analogue showed a fast PSA decrease and higher rates of pathologic complete response. Other results are promising with hormonal blockages at various key points. CONCLUSION: Studies with 2nd generation anti-androgene agents or enzyme inhibitors seem to show very promising results. To provide answers about the effectiveness of current neoadjuvant strategy in terms of survival, other studies are needed: randomized phase III or phase II exploring predictive biomarkers. The design of such trials requires a multidisciplinary approach with urologists, oncologists, radiologists and methodologists.

[Existence of pattern 5 on radical prostatectomy: poor prognostic factor associated with a lower biochemical recurrence-free survival]. / Existence de grade 5 sur pièce de prostatectomie totale: facteur de mauvais pronostic associé à une moindre survie sans récidive biologique.

OBJECTIVES: To analyze the impact of the existence of Gleason grade 5 on the adverse pathology and biochemical recurrence-free survival of patients. PATIENTS: Three hundred and seventy-two prostatectomies were performed between 1999 and 2011 in our institution for localised prostate adenocarcinoma. We examined the existence of grade 5 of the specimen to determine the reliability of prostate biopsies in the diagnosis of grade 5 and the association of grade 5 with other histoprognostic factors. Biochemical recurrence-free survival was analyzed according to the presence of grade 5 in the final specimen. RESULTS: In total, all histological data and biochemical recurrence-free survival were available for 321 patients who were included in the study. Sixty-eight had Gleason grade 5 (majority or third minority pattern) on the specimen while 253 had not. Grade 5, rarely diagnosed on biopsy (sensitivity=26.47 %) was correlated independently with the extracapsular extension (OR=2.1; CI 95 [1.1-3.9]), the seminal vesicle invasion (OR=3.8; CI 95 [1.7-8.7]) and positive surgical margins (OR=2.0; CI 95 [1.1-3.6]). Overall survival was similar in both groups but the biochemical recurrence-free survival was statistically lower in the presence of grade 5 (HR=3.7; CI 95 [1.8-7.6]). Biochemical recurrence-free survival was not different than grade 5 is predominant or third minority pattern (HR=1.01; CI 95 [0.3-2.8]). On multivariate analysis, grade 5 was an independent risk factor for biochemical recurrence (P=0.005) as well as seminal vesicle invasion (P=0.047). CONCLUSION: The existence of grade 5 in the surgical specimen whatever the percentage was a poor prognostic factor associated with increased tumor aggressiveness and reduced biochemical recurrence-free survival. LEVEL OF EVIDENCE: 5.

Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma.

PURPOSE: Everolimus has demonstrated its efficacy in metastatic renal cell carcinoma (mRCC). Preliminary studies have shown high variability of everolimus blood concentrations (EBC). In other settings, its activity was correlated with EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess its influence on oncologic outcomes. PATIENTS AND METHODS: Our study analyzed first 3 months' trough EBC levels in 42 patients treated in 4 French oncologic centers between March 2010 and August 2013. Patients presented a histologically confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies. RESULTS: Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The median trough concentration was 14.1 µg/L (range 2.6-91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 µg/L were free from progression at 6 months (p = 0.06). Median progression-free survival was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33-1.31; p = 0.23), and the median overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28-1.37; p = 0.24), for patients above or below the median value of trough concentrations, respectively. CONCLUSION: Impact of drug exposure for AA tyrosine kinase inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC variability was confirmed in the present study, and the results suggest a relationship between initial EBC within the first 3 months and the drug activity. It underlines the need to prospectively include EBC monitoring in future clinical trials to determine the need of its implementation in routine use.

[Treatment of bladder outlet obstruction in locally advanced prostate cancer]. / Désobstruction prostatique a la phase avancée du cancer de prostate.

Bladder outlet obstruction (BOO) is one of the major complication of the locally advanced prostate cancer. Its impact on prostate cancer prognosis is low and remains controversial but its impact on patient quality of life is real. We performed a systematic search to find relevant publications from Medline and wrote a mini-review on the different therapeutic approaches to relieve obstructive symptoms.

Phase II study assessing lapatinib added to letrozole in patients with progressive disease under aromatase inhibitor in metastatic breast cancer-Study BES 06.

This trial evaluated the effect of adding lapatinib to letrozole after clinical resistance to aromatase inhibitor (IA) treatment in hormone receptor-positive metastatic breast cancer. Postmenopausal women received daily letrozole plus lapatinib (1,500 mg). The primary end point was objective rate response (ORR) at week 12. Secondary objectives included time to response, duration of response, clinical benefit (CB), progression-free survival (PFS), overall survival, and safety. Twenty-four human epidermal growth factor receptor 2 (HER2)-negative patients were included with secondary resistance to IA. ORR at 12 weeks was 4 % (95 % confidence interval (CI), 0.7-20). Stable and progression diseases were reported in 25 % (95 % CI, 12-45) and 71 % (95 % CI, 51-85) of cases, respectively. At 24 weeks, the ORR increased to 8 %. CB was 21 % (95 % CI, 9-40). At a median follow-up of 27 months, median PFS was 3.4 months (95 % CI, 2.8-5.4). Grade 3 or 4 adverse events were rarely reported. No clinical cardiac toxicity was observed. Lapatinib was discontinued in two patients due to severe diarrhea. This trial was prematurely closed due to low recruitment. These preliminary results suggest that the addition of lapatinib to letrozole has a favorable safety profile and could overcome tumoral resistance to letrozole among HER2-negative tumors.