Screening, diagnosis and monitoring of sarcopenia: When to use which tool?

BACKGROUND & AIMS: Sarcopenia is a muscle disorder associated with loss of muscle mass, strength and function. Early screening, diagnosis and treatment may improve outcome in different disease conditions. A wide variety of tools for estimation of muscle mass is available and each tool has specific technical requirements. However, different investigational settings and lack of homogeneity of populations influence the definition of gold standards, proving it difficult to systematically adopt these tools. Recently, the European Working Group on Sarcopenia in Older People (EWGSOP) published a revised recommendation (EWGSOP-2) and algorithm for using tools for screening and diagnosing sarcopenia. However, agreement of the EWGSOP2 criteria with other classifications is poor and although an overview of available tools is valuable, for the purpose of clinical decision-making the reverse is useful; a given scenario asks for the most suitable tools. RESULTS: Tools were identified for screening, diagnostics and longitudinal monitoring of muscle mass. For each of these clinical scenarios the most appropriate tools were listed and for each technique their usability is specified based on sensitivity and specificity. Based on this information a specific recommendation is made for each clinical scenario. CONCLUSION: This narrative review provides an overview of currently available tools and future developments for different clinical scenarios such as screening, diagnosis and longitudinal monitoring of alterations in muscle status. It supports clinical decision-making in choosing the right tools for muscle mass quantification depending on the need within a given clinical scenario as well as the local availability and expertise.

Assessment of Xpert Bladder Cancer Monitor test performance for the detection of recurrence during non-muscle invasive bladder cancer follow-up.

PURPOSE: To assess the performance of the Xpert Bladder Cancer (BC) Monitor during the follow-up of patients with non-muscle invasive bladder cancer (NMIBC). METHODS: Patients with previously diagnosed NMIBC and followed up in clinical practice settings in two French urology departments between September 2017 and July 2019 were consecutively enrolled in this prospective observational study. Patients with a positive cystoscopy or computed tomography urogram underwent subsequent transurethral resection of the bladder, and/or biopsy, and the specimens were pathologically assessed. Cytology and Xpert BC Monitor tests were performed on urine samples. Xpert BC Monitor performance was assessed versus cystoscopy for disease-negative patients or versus histology for disease-positive patients, and was compared to that of cytology. RESULTS: Overall, 500 patients with a median age of 70.0 years were included. NMIBC recurrence was diagnosed in 44 cases (8.8%). Overall sensitivity, specificity, and negative predictive values (NPVs) were 72.7% (32/44), 73.7% (330/448) and 96.5% (330/342) for the Xpert BC Monitor, and 7.7% (2/26), 97.8% (310/317) and 92.8% (310/334) for cytology, respectively. The Xpert BC Monitor detected 92.3% (12/13) of the high-grade tumours and ruled out their presence in 99.7% (330/331) of cases. Analysis of the areas under the receiver operating characteristic curves demonstrated the superior performance of the Xpert BC Monitor over that of cytology. CONCLUSION: Xpert BC Monitor performance was superior to that of cytology in the follow-up of NMIBC. The exclusion of aggressive tumours with a very high NPV (99.7%) supports the use of this urinary test in daily practice.

RETRACTED: Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : cancer de la prostate French ccAFU guidelines ­ Update 2018­2020: Prostate cancer / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : cancer de la prostate.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). Cet article est retiré de la publication à la demande des auteurs car ils ont apporté des modifications significatives sur des points scientifiques après la publication de la première version des recommandations. Le nouvel article est disponible à cette adresse: DOI:10.1016/j.purol.2019.01.007. C'est cette nouvelle version qui doit être utilisée pour citer l'article. This article has been retracted at the request of the authors, as it is not based on the definitive version of the text because some scientific data has been corrected since the first issue was published. The replacement has been published at the DOI:10.1016/j.purol.2019.01.007. That newer version of the text should be used when citing the article.

[Prognostic value of PD-1/PD-L1 expression in upper tract urothelial carcinoma]. / Intérêt pronostique de l'expression de PD-1/PD-L1 dans les tumeurs de la voie excrétrice urinaire supérieure.

Current literature supports the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors for the treatment of urothelial carcinomas. While the prognostic value of PD-1 and PD-L1 levels has been comprehensively analyzed for urothelial carcinoma of the bladder, less is known for upper tract urothelial carcinoma. In addition, available data on the prognostic value of PD-1 and/or PD-L1 level in the tumor and/or peritumoral microenvironment are heterogeneous and even sometimes contradictory. In this article, we compared the methodologies of the various available studies in order to highlight the factors that can explain these discordant results.

Comprehensive molecular classification of localized prostate adenocarcinoma reveals a tumour subtype predictive of non-aggressive disease.

Background: Management of localized prostate cancer (PCa) is a major clinical challenge since most of these cancers would not evolve but a majority of patients will still undergo a life-changing radical surgery. Molecular studies have shown that PCa can be classified according to their genomic alterations but none of the published PCa molecular classifications could identify a subtype corresponding to non-evolutive tumours. Materials and methods: Multi-omics molecular profiling was carried out on post-radical prostatectomy material from a cohort of 130 patients with localized PCa. We used unsupervised classification techniques to build a comprehensive classification of prostate tumours based on three molecular levels: DNA copy number, DNA methylation, and mRNA expression. Merged data from our cohort and The Cancer Genome Atlas cohort were used to characterize the resulting tumour subtypes. We measured subtype-associated risks of biochemical relapse using Cox regression models and survival data from five cohorts including the two aforementioned. Results: We describe three PCa molecular subtypes associated with specific molecular characteristics and different clinical outcomes. Particularly, one subtype was strongly associated with the absence of biochemical recurrence. We validated this finding on 746 samples from 5 distinct cohorts (P = 3.41 × 10-8, N = 746 tumour samples), and showed that our subtyping approach outperformed the most popular prognostic molecular signatures to accurately identify a subset of patients with a non-evolutive disease. We provide a set of 36 transcriptomic biomarkers to robustly identify this subtype of non-evolutive cases whose prevalence was estimated to 22% of all localized PCa tumours. Conclusion: At least 20% of patients with localized PCa can be accurately predicted to have a non-evolutive disease on the basis of their molecular subtype. Those patients should not undergo immediate surgery and rather be placed under active surveillance.

[French ccAFU guidelines - Update 2018-2020: Prostate cancer]. / Recommandations françaises du Comité de Cancérologie de l'AFU ­ Actualisation 2018­2020 : cancer de la prostate.

OBJECTIVE: The purpose of the guidelines national committee ccAFU was to propose updated French guidelines for prostate cancer. METHODS: A Medline search was achieved between 2016 and 2018, as regards diagnosis, options of treatment and follow-up of prostate cancer, and to evaluate the different references specifying their levels of evidence. RESULTS: Epidemiology, classification, staging systems, diagnostic evaluation of prostate cancer 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≥76Gy 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 standard. In this situation, the combination of ADT and abiraterone acetate also becomes 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. CONCLUSION: These updated French guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer.

[Correlation of genetic and cytogenetic alterations in pathological aggressiveness urothelial carcinoma of the bladder: Performance of BCA-1, a mini-array comparative genomic hybridisation-based test]. / Corrélation des altérations génétiques à l'agressivité anatomo-pathologique des carcinomes urothéliaux de la vessie : performance du test BCA-1.

INTRODUCTION: Urothelial carcinomas are the fourth leading cause of cancer in humans. Their incidence is increasing by more than 50% in 25 years. The superficial forms (70% cases) require a close active surveillance to identify frequent recurrences and progression to invasive stage. Our main goal was to identify prognostic molecular markers for bladder cancer that could be used alone or in combination in routine clinical practice. In this aim, we evaluated the capability of the BCA-oligo test based on a CGH array to correctly classify tumoral grade/stage. METHOD: Urinary DNA was extracted from 81 patients with superficial bladder cancer and has been hybridized on the BCA-oligo array. The results from the molecular analysis were correlated with the tumoral grade and stage. RESULTS: Several chromosomal alterations were significantly more frequent in tumors of higher grade and more advanced stage. A significant association was observed between a high grade and the presence of one of these alterations: loss on 6p, gain on 8q or 13q, loss or gain on 9q or 11q, with an odds ratio of 6.91 (95% CI=2.20-21.64; P=0.0009). Moreover, a significant association was found between a more advanced stage (pT1) and the presence of one of these alterations: loss on 6p, gain on 8q, loss or gain on 5p, with an odds ratio of 15.2 (95% CI=3.71-62.58; P=0.0002). CONCLUSION: Our results showed that molecular analyses of superficial bladder cancers based on urinary DNA and the BCA-oligo test could be used as prognostic factor for the tumor evolution, allowing then a more adapted clinical management.

Comparison of semi-automated and manual methods to measure the volume of prostate cancer on magnetic resonance imaging.

PURPOSE: The purpose of this study was to determine the accuracy of manual semi-automated and volumetric measurements to assess prostate cancer volume on multiparametric magnetic resonance imaging (MP-MRI) using whole-mount histopathology for validation. MATERIALS AND METHODS: We evaluated 30 consecutive men (median age, 65.7 years; interquartile range [IQR], 61.5-70.9 years) with a median prostatic specific antigen of 8.5ng/dL (IQR, 5.5-10.5ng/dL), who underwent MP-MRI before radical prostatectomy. Index tumor volume was determined prospectively and independently on the basis of MRI and whole-mount section volumetric assessment using the maximum histologic diameter (MHD) and the histologic volume (HV). The MRI index tumor volume was determined by two independent radiologists using a single measurement of the maximum tumor dimension (MTD), a simplified MR ellipsoid volume (MREV) calculation and a MR region of interest volume (MROV) segmentation displayed by a commercially available OsiriX®. MTD was compared to MHD, whereas MREV and MROV were compared to HV. RESULTS: Thirty index lesions (median HV, 1.514 cm3; IQR, 0.05-3.780 cm3) were analyzed. The MREV, MROV and HD were significantly correlated with each other (r>0.5). Inter-observer agreement for measurements was good for each method (r>0.780). The MTD was the best predictor of maximum histologic diameter (r=0.980 and 0.791) and had an excellent inter-variability correlation (P<0.0001). CONCLUSION: Prostate cancer histologic volume can be assessed using MREV or MROV with a good accuracy and low inter-observer variability. MTD has the lowest inter-observer variability and provides best degrees of correlation with MHD. MTD should be used on MRI for selecting and following patients for active surveillance and staging before focal treatment of prostate cancer.

[Prevalence and diversity of management of prostate cancer patients classified as low risk using D'Amico group or Cancer of the Prostate Risk Assessment (CAPRA) score: A French multicenter study]. / Prévalence et diversité de la prise en charge des patients atteints de cancer de la prostate classés à faible risque selon la classification de d'Amico ou le score de CAPRA : étude française multicentrique.

OBJECTIVES: Currently, the French High Authority for Health does not recommend mass screening for prostate cancer (PCa), due to the risk of over-treatment, notably of low risk patients. Our study is intended to reflect the therapeutic attitudes for the management of patients classified as low risk of progression in French clinical centers. METHODS: For all positive prostate biopsies performed during 2012 and 2013 in five French departments of urology, clinicopathological characteristics required to calculate the d'Amico risk group and the Cancer of the Prostate Risk Assessment (CAPRA) score were filled. Information on the first treatment of "low risk" patients was collected. RESULTS: A total of 1035 patients were included, with a median age at diagnosis of 66 years old. According to d'Amico and CAPRA classifications, 30.4% and 35.0% of patients were at low, 34.5% and 33.2% at intermediate, 35.1% and 31.8% at high risk. The diagnosis severity increased with age (P<0.0001). The main treatment for low risk patients was radical prostatectomy (41.6% and 42.0% for d'Amico and CAPRA, respectively), but active surveillance was the most frequent treatment if diagnosed after 75 years old. The management of low risk patients varied significantly between centers (P<0.0001), according to the therapeutic platforms available within the hospital. CONCLUSIONS: In absence of strong progression predictor, the management of low risk PCa remains based on center habits and local therapeutic platforms. New predictive markers, such as multiparametric MRI or molecular tests, are needed to guide rational management of low risk PCa. LEVEL OF EVIDENCE: 4.

[CCAFU french national guidelines 2016-2018 on prostate cancer]. / Recommandations en onco-urologie 2016-2018 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. © 2016 Elsevier Masson SAS. All rights reserved.

International cancer seminars: a focus on kidney cancer.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

[Carcinogenic pathways and natural history of upper tract urothelial carcinomas: state-of-the-art review for the yearly scientific report of the French National Association of Urology]. / Voies de carcinogenèse et histoire naturelle des tumeurs de la voie excrétrice supérieure: état de l'art pour le rapport annuel de l'Association française d'urologie.

OBJECTIVE: To describe natural history and carcinogenesis of upper tract urothelial carcinoma (UTUC). METHODS: A systematic review of the scientific literature was performed in the Medline database (Pubmed) using different associations of the following keywords: upper tract urothelial carcinoma; clonality; carcinogenesis; mutation; chromosomal instability; Lynch syndrome; genetic polymorphism. RESULTS: Local development of UTUC is characterized by a highly prevalent multifocality that might be explained by the overlap of "field change" and "intraluminal seeding and implantation" theories. UTUC and bladder tumors share common carcinogenesis mechanisms such as mutations of FGFR3 and TP53 defining two distinct pathways of pathogenesis. Epigenetic alterations corresponding to the hypermethylation of different promoters regulating genes expression and chromosomal instability such as chromosome 9 deletions are also involved in UTUC carcinogenesis. Furthermore, specific genetic risk factors fro UTUC including Lynch syndrome and different polymorphisms might explain an individual susceptibility for developing these tumors. CONCLUSIONS: Significant advances have been done in the field of basic research in UTUCs in recent years and have been of particular interest to provide better descriptions of their natural history. Despite these important findings however, some carcinogenic mechanisms remains not elucidated and unknown in the field of UTUC so far.

Genetic susceptibility to urinary incontinence: implication of polymorphisms of androgen and oestrogen pathways.

PURPOSE: Although existence of genetic factors predisposing to urinary incontinence in women is widely admitted, precise molecular and genetic variations implicated are still unknown. Given the established influence of steroids metabolism in incontinence, we studied the correlation between polymorphisms of genes of oestrogen/androgen pathways and urinary incontinence in women, in order to raise evidence of genetic susceptibility. METHODS: A case-control study included 121 cases and 66 controls. Age, familial history of incontinence, gynaecologic history and age of menopause were collected. Patients were classified into three groups: control, urge urinary incontinence (UUI), stress urinary incontinence (SUI). Genetic polymorphisms were determined after amplification by PCR for the following genes: CYP-19, CYP17, androgen receptor (AR) and oestrogen receptor (ESR-1). Statistical analysis was performed to study correlation between genotype and presence of a subtype of incontinence. RESULTS: A total of 187 patients were analysed: 66 were controls, 30 presented UUI and 107 presented SUI. Patients presenting incontinence had significantly more often familial history of incontinence than controls. AR polymorphism (combination of 2 alleles containing more than 21 CAG repeats) is significantly associated with UUI (P = 0.02). Polymorphisms of ESR-1, CYP17 and CYP19 were not associated with any subtype of urinary incontinence. CONCLUSIONS: This study shows that AR polymorphism is linked to genetic susceptibility to urinary incontinence. This result suggests that this disease is partly gene-related and encourages larger studies to explore the genetics factors of urinary incontinence.

[Strategies for early diagnosis and prevention of prostate cancer]. / Stratégies de diagnostic précoce et de prévention du cancer de la prostate.

Prostate cancer (CaP) has become the most frequent cancer in France and represents the 4th cause of mortality by cancer. Main risk factors include age, family history, black ethnic origin and carcinogenesis results from interaction between environmental and endogen factors. This work aimed to review main data and strategic trends about evolution of prevention and early diagnosis of CaP. Research topics considered as priorities results from the main objective including definition of most efficient medico-economic strategies according to epidemiology, diagnostic and therapeutic modalities and ethno-sociologic particularities, including in the schema presently used (PSA/biopsies): 1) new markers (genetic, serum and urinary), measurable environmental risk factors and potential prevention actions; 2) functional imaging (new techniques including contrast echography, dynamic MRI, spectro-MRI) in order to avoid unnecessary biopsies (60-70% biopsies are negative); 3) optimization of biopsies technique in identifying tumor zones in order to decrease false negative biopsies (about 15% of CaP < 0,5 cm3 but of high grade are missed in the first set of biopsies) and in improving the representativity of the tumor sample biopsied (discordance of about 40% between biopsy data and complete pathological analysis of prostatectomy specimen); 4) development of predictive models in order to perform individual prediction taking into account several risk factors (clinical and molecular) and genes/environment interactions in order to offer rational help in diagnostic and primary prevention procedures.

[Genetic determinants of anatomical variants of the prostate]. / Facteurs génétiques déterminant les variations anatomiques de la prostate.

INTRODUCTION: The determinants of macroscopic and microscopic anatomical variants of the prostate during ageing are poorly defined. The authors evaluated the correlation between specific gene polymorphisms involved in androgen and oestrogen synthesis and gross (prostatic weight) and microscopic anatomy (stroma/epithelium ratio) of the prostate during ageing. METHODS: The prostatic weight and stromal surface area of an autopsy series of 85 men over the age of 50 were measured, then compared as a function of gene polymorphisms involved in androgen or oestrogen regulation. The following polymorphisms were studied: number of CAG repeats of the androgen receptor (AR), number of TA repeats and the V89L variant of the 5-alpha-reductase gene (SRD5A2) for androgens, and the A1A2 variant of 17-alpha-hydroxylase (CYP17) and number of TTTA repeats of the aromatase (CYP19) for oestrogens. RESULTS: No correlation was observed between the number of TA repeats of the SRD5A2 gene or TTTA repeats of the CYP19 gene and anatomical parameters of the prostate. A statistically significant positive correlation was observed between age and prostate weight (r=0.21, p=0.05) and a statistically significant negative correlation was observed between prostate weight and number of CAG repeats (r=-0.32, p=0.003). The group with less than 20 CAG repeats was associated with a higher prostate weight than the other group. The stromal surface area was greater in the [20-23] CAG repeat group (p=0.02), and in the A2A2 group of CYP17 (p=0.016) than in the other groups. CONCLUSION: A small number of CAG repeats is associated with a higher prostate weight. The mean number of CAG repeats of the androgen receptor and the A2A2 variant of the CYP17 gene are associated with a larger stromal surface area.

Prostate cancer genetics.

Prostate cancer (PC) is the most frequent malignant tumor among men over 50 years old. Its incidence varies according to countries and ethnic groups. Known risk factors are race and positive family history of the disease. Familial aggregation (at least 2 cases in the family) is observed in about 20% of cases and a hereditary form of PC, compatible with a Mendelian inheritance, in 5%. This proportion increases with younger age at diagnosis. Eight putative loci are already identified for hereditary PC but undoubtedly, others will be found in forthcoming studies. The genetic heterogeneity observed in hereditary PC reflects variety of origins of the studied families. Agreggation of PC and other cancers in some families suggests the involvement of common susceptibility genes. In other familial form and in sporadic cases, the genetic component should be polygenic: PC wouldn't result from segregation of a major gene mutation transmitted according to a monogenic inheritance, but rather to sharing of alleles at many loci, each contributing to a small increase in cancer risk. Indeed, several genetic polymorphisms were associated with an increased risk of developing PC and could explain the variations of PC incidence observed between populations.