M. Peyromaure

Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients

Background:Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib.Methods:Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation.Results:Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25 kg m−2. Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25 kg m−2 experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3–13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009).Conclusion:Patients with sarcopenia and a BMI<25 kg m−2 experienced significantly more DLTs during the first cycle of treatment.

Recommandations en onco-urologie 2013 du CCAFU : Cancer de la prostate

OBJECTIVES The purpose of the guidelines national committee CCAFU was to propose updated french guidelines for localized and metastatic prostate cancer (PCa). METHODS A Medline search was achieved between 2013 and 2016, as regards diagnosis, options of treatment and follow-up of PCa, to evaluate different references with levels of evidence. RESULTS Epidemiology, classification, staging systems, diagnostic evaluation are reported. Disease management options are detailed. Recommandations are reported according to the different clinical situations. Active surveillance is a major option in low risk PCa. Radical prostatectomy remains a standard of care of localized PCa. The three-dimensional conformal radiotherapy is the technical standard. A dose of > 74Gy is recommended. Moderate hypofractionation provides short-term biochemical control comparable to conventional fractionation. In case of intermediate risk PCa, radiotherapy can be combined with short-term androgen deprivation therapy (ADT). In case of high risk disease, long-term ADT remains the standard of care. ADT is the backbone therapy of metastatic disease. In men with metastases at first presentation, upfront chemotherapy combined with ADT should be considered as a new standard. In case of metastatic castration-resistant PCa (mCRPC), new hormonal treatments and chemotherapy provide a better control of tumor progression and increase survival. CONCLUSIONS These updated french guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer.

Predictive Factors of Oncologic Outcomes in Patients Who do not Achieve Undetectable Prostate Specific Antigen after Radical Prostatectomy

PURPOSE We identified factors predicting oncologic outcomes in cases of persistently detectable prostate specific antigen. MATERIALS AND METHODS We reviewed the charts of patients treated with radical prostatectomy between 1998 and 2011 at a total of 14 centers. Study inclusion criteria were radical prostatectomy for presumed localized prostate cancer, absent positive nodes and detectable prostate specific antigen, defined as prostate specific antigen 0.1 ng/ml or greater 6 weeks postoperatively. Of the 9,735 radical prostatectomy cases reviewed 496 (5.1%) were eligible for analysis. Predictive factors for oncologic outcomes were assessed in time dependent analyses using the Kaplan-Meier method and Cox regression models. RESULTS At 6 weeks prostate specific antigen was 0.1 to 6.8 ng/ml. Biochemical progression was noted in 74.4% of patients and clinical metastasis was noted in 5%. The 2 most powerful predictors of general salvage treatment (vs radiotherapy) were postoperative prostate specific antigen greater than 1 ng/ml (OR 3.46, p=0.032) and prostate specific antigen velocity greater than 0.2 ng/ml per year (HR 6.01, p=0.001). Positive prostate specific antigen velocity was the single factor that independently correlated with the risk of failed salvage therapy (HR 2.6, p=0.001). The 5-year disease-free survival rate was 81.0% in patients with stable or negative prostate specific antigen velocity compared with 58.4% in those with positive prostate specific antigen velocity (p<0.001). CONCLUSIONS Patients with detectable prostate specific antigen after radical prostatectomy have a poor biochemical outcome. We identified postoperative prostate specific antigen and prostate specific antigen velocity as independent predictors of progression and failed salvage treatment. In addition to pathological prognostic factors, these factors should be considered early to better stratify patients for adjuvant therapy.

Gènes de fusion et cancer de la prostate. De la découverte à la valeur pronostique et aux perspectives thérapeutiques

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the prostate cancer tumorigenesis. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancer makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype, which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

Spécificités du cancer de la prostate avant l'âge de 50 ans

OBJECTIVE To report the characteristics of prostate cancer (PCa) in men less than 50-year-old and the results of different treatments of PCa in this population. METHOD A bibliographic research was performed using Pubmed database. The keywords that we used were: prostate cancer, age, young, radical prostatectomy, brachytherapy, radiotherapy, active surveillance. The studies which included a significant number of patients were selected. A total of 38 articles were used as bibliographic references. RESULTS PCa in young men does not seem to have different characteristics than in older men. Nevertheless, young men seem to have a lower risk of severe urinary and sexual sequelae, particularly following radical prostatectomy. CONCLUSIONS There is no recommendation regarding management of PCa in men less than 50-year-old. In case of localized cancer, two options may be considered. First option consists in decreasing the urinary and sexual complications of radical prostatectomy. A minimally-invasive treatment, such as brachytherapy or even active surveillance, may reach this objective. Second option consists in being more aggressive. To propose a radical prostatectomy offers to the patient the possibility of salvage radiation therapy in case of locally-advanced tumor or local recurrence.

Recommandations pour la prise en charge du cancer de la prostate chez l’homme âgé : un travail du comité de cancérologie de l’association française d’urologie

The increase in life expectancy combined with the increase in the global incidence of cancers will probably results in an increase in the number of cancers observed in the elderly. The increase in the incidence of prostate cancers in geriatric patients (45% of prostate cancers are diagnosed after 75 years old) is in sharp contrast with the lack of strong scientific data on the topic. By the meantime, oncogeriatrics has been developing for some years now under the guidance of the International Society of Oncogeriatrics. Such an approach aims at palliating the low quality of care of cancers in geriatric patients. The reasons for the low quality of care come from the characteristics of these patients and from the training of the care providers. The authors recall the principles of oncogeriatric evaluation and the classification of patients as it is actually proposed. They describe the main treatments and their results in the geriatric population and they describe the decision process concerning the choice of the treatment. They also suggest some guidelines on the diagnosis of prostate cancer, evaluation of the patients and the treatments of the disease in the elderly. Prostate cancer is almost the perfect model for oncogeriatrics. Urologists should remain the corner stone of its management, whatever the age of their patient.

Résultats de la prostatectomie totale chez le patient âgé

Resume Tres peu d’etudes ont ete publiees concernant les resultats de la prostatectomie totale (PT) chez le patient âge. Les rares donnees disponibles suggerent que l’âge avance n’augmente pas le taux de mortalite ou de morbidite postoperatoire, sous reserve d’une selection etroite des patients. De meme, les resultats carcinologiques de la PT sont comparables entre les patients de plus de 70 ans et les patients plus jeunes. Seul le risque d’incontinence semble accru, avec un impact potentiel sur la qualite de vie. Il n’existe pas d’etude comparant les differents traitements curatifs du cancer de la prostate (PT, radiotherapie externe, curietherapie, surveillance active) dans la population âgee. Le benefice en termes de survie ne peut etre precise.

Inhibiteurs des 5 alpha-réductases et cancer de la prostate : une mise au point du Comité de cancérologie de l’Association française d’urologie

INTRODUCTION Two randomised trials and negative conclusion of the FDA about inhibitors of 5 alpha-reductase in prevention of prostate cancer need a revision of the indications of these drugs. METHODS After description of fundamentals data, review of the literature in PubMed library was performed to analyse the indications of these drugs according to the different stages of prostate cancer. RESULTS Even if PCPT and REDUCE studies showed a decrease of cancers with the use of 5 alpha-reductase (5ARI) but with side effects, there is no indication for prostate cancer prevention by these drugs. In the same way, despite the results of REEDEM study, there is no indication of these drugs in active surveillance. CONCLUSION Despite the large interest of these drugs, no recommendation can be given for indications of 5ARI in prevention or treatment of prostate cancer.

Cystectomie totale chez les octogénaires

des greffons était diminué à 1 h et à 3mois après la transplantation. Dans le cortex total des greffons, il a été mis en évidence une augmentation du nombre de bifurcations des segments vasculaires et le développement d’un tissu fibreux qui participe au remodelage vasculaire (Fig. 1d). Conclusion Ce travail apporte des indications sur le spectre lésionnel de l’ischémie reperfusion rénale et permettra de développer des futures thérapies dans le but d’améliorer la préservation du réseau microvasculaire du greffon rénal.

Impact of sarcopenia (Sp) on early dose-limiting toxicity (DLT) and acute vascular toxicity in patients (pts) with metastatic renal cell carcinoma (mRCC) receiving sunitinib (SUT).

e15094 Background: mRCC pts with severe muscle wasting (Sp) are at increased risk of DLT during anti-VEGF therapy with sorafenib (Antoun et al., Ann Oncol 2010). We hypothesized that Sp could also predict SUT-induced toxicity. METHODS mRCC outpatients received SUT 50 mg OD (4/6 weeks) or 37.5 mg OD, from June 2006 to December 2010. From July 2008, SUT plasma levels were routinely monitored every 15 days. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by CT-scan, and Sp was defined using standardized thresholds. Blood pressure was monitored twice daily at home, and other toxicities were assessed every 15 days. The primary evaluation criterion was DLT during the first month. Secondary criteria were SUT AUC on day 28, acute vascular toxicities (thrombotic microangiopathy, TMA and reversible posterior leukoencephalopathy syndrome, RPLS) during treatment, and progression-free survival (PFS). RESULTS 45 pts (71.1% males, median age: 60.3 years, range 29-83) were eligible for CT-scan, toxicity and PFS analyses. Pharmacokinetic data were available for 16 pts. A total of 287 cycles (median/pt: 6, range 1-22) were given, for a median follow-up of 14.4 months (range: 1.5-51.3). During the first month, grade 3 hypertension (not dose-limiting) occurred in 11 pts (24.4%), and DLT occurred in 8 pts (17.8%), including grade 3 fatigue (3 pts, 6.7%), TMA and RPLS (2 pts each, 4.4%), grade 3 hand-foot syndrome and pulmonary embolism (1 pt each, 2.2%). 22 pts (48.9%) had Sp at baseline. Pts with Sp experienced significantly more DLTs during the first month of treatment (7/22 vs. 1/23, p = 0.02). SUT AUC on day 28 (median: 1599 vs. 1228 ng.h/ml, p = 0.12) and PFS (median: 8.0 vs. 8.5 months, p = 0.29) did not differ between pts with or without Sp. Of 7 pts who experienced TMA or RPLS during the whole treatment period, 6 (86%) had Sp at baseline. CONCLUSIONS mRCC pts with Sp receiving SUT are at higher risk of early DLT, and experience more frequently acute vascular toxicities (TMA and RPLS). Sp appears to be a marker of tissular vulnerability that deserves further validation on larger cohorts of pts receiving anti-VEGF agents.