Urinary biomarkers for bladder cancer diagnosis and NMIBC follow-up: a systematic review.

BACKGROUND: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations. OBJECTIVE: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt®, Xpert®Bladder, BTA stat®, BTA TRAK™, NMP22 BC®, NMP22® BladderChek® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit®, Cxbladder, ADXBLADDER, Urodiag®) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up. METHODS: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy. RESULTS: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction. CONCLUSION: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed.

Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

CONTEXT: Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. OBJECTIVE: This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). EVIDENCE ACQUISITION: All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. EVIDENCE SYNTHESIS: The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. CONCLUSIONS: Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. PATIENT SUMMARY: We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the prognostic parameters currently used by clinicians.

Radium 223 dichloride for prostate cancer treatment.

Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo®) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases. In this review, first we summarize the interplay between prostate tumor cells and bone microenvironment; then, we discuss radium-223 dichloride mechanism of action and present the results of the available clinical trials and future developments for this new drug.

[uPA/PAI-1, Oncotype DX™, MammaPrint(®). Prognosis and predictive values for clinical utility in breast cancer management]. / uPA/PAI-1, Oncotype DX™, Mammaprint(®). Valeurs pronostique et prédictive pour une utilité clinique dans la prise en charge du cancer du sein.

CONTEXT AND AIMS: Breast cancer prognosis and predictive biomarkers development would allow sparing some patients from chemotherapy or identifying patients for whom chemotherapy would be indicated. In this context, in 2009, the French National Cancer Institute, a National Health and Science Agency dedicated to cancer, in collaboration with the French society of senology and breast pathology (SFSPM) published a report on the assessment of the prognostic and the predictive clinical validity of tissular biomarkers, uPA/PAI-1, Oncotype DX™ and MammaPrint(®), in breast cancer management. They concluded that only the uPA/PAI-1 prognosis value reached the highest level of evidence (LOE I according to Hayes 1998 classification). In 2012, it was decided to update this report since new data have emerged and because information disparities among clinicians have been identified. This article aims to present the main conclusions together with the levels of evidence associated with those conclusions. METHODS: The updating process was based on literature published since 2009 appraisal and on multidisciplinary and independent experts' opinion. The levels of evidence (LOE) used are those of the classification defined by Simon in 2009 (updated Hayes 1998 classification): LOE IA and LOE IB: high level of evidence; LOE IIB and LOE IIC: intermediate level of evidence; LOE IIIC and LOE IV-VD: low level of evidence. CONCLUSIONS: Among patients without lymph-node involvement, uPA/PAI-1, invasion process biomarkers, reach the highest level of evidence for 10 years recurrence free survival prognosis (LOE IA according to Simon). The predictive value to anthracyclins chemotherapy remains to be confirmed. Oncotype DX™ and MammaPrint(®) prognosis and predictive value do not reach the LOE I level. This updating' process confirms the 2009 levels of evidence for all the three biomarkers prognosis value. Besides, concerning Oncotype DX™ and MammaPrint(®), new data do not allow to conclude neither to their complementary clinical information to other clinicopathological existing biomarkers nor to a favorable cost-efficiency ratio in therapeutic decision making and this because of the methodological weakness and uncertainty that are identified in the selected studies. Practically, beyond the prognosis and predictive biomarkers validity, the clinical utility of a new biomarker for chemotherapy indication depends on its clinical added information with regard to validated biomarkers (HR, HER2 and Ki67) and to clinicopathological parameters. Since they are the sole validated biomarkers of the invasion process, uPA/PAI-1 could complete clinical information of other clinicopathological factors and consequently could confer an added clinical value. However, data concerning the impact of this information on chemotherapy clinical indication are lacking.

2008 French national guidelines for the treatment of venous thromboembolism in patients with cancer: report from the working group.

Venous thromboembolism (VTE) is a major therapeutic issue in cancer patients. Advances in this field and heterogeneities in clinical practices prompted us to establish guidelines in the management of VTE in cancer patients according to the SOR (Standards, Options and Recommendations) methodology. A literature review of the studies published on this topic between 1999 and 2007 was performed. The guidelines were developed from the analysis of 38 out of 418 publications selected. They were peer-reviewed by 65 independent experts. The treatment of VTE in patients with cancer, including those with intracranial malignancies, should be based on low-molecular-weight heparins administered at therapeutic doses for at least 3 months. In the event of recurrent VTE, pulmonary embolism with hemodynamic failure or contra-indication to anticoagulant treatment, the indications and usages of vena cava filters and thrombolytic drugs should be the same as in non-cancer patients.

2007 Standards, Options, and Recommendations: use of erythropoiesis-stimulating agents (ESA: epoetin alfa, epoetin beta, and darbepoetin) for the management of anemia in children with cancer.

The Standards, Options, and Recommendations (SOR) project undertaken by the French National Federation of Cancer Centers (FNCLCC) to develop and disseminate clinical practice guidelines in oncology has now been taken over by the French National Cancer Institute. In 2007, the SOR updated the information related to the use of erythropoiesis-stimulating agents (ESA) in anemic children with cancer. Updates were based on a review of the most reliable scientific data available, followed by critical appraisal by a multidisciplinary group of experts and validation by independent experts. The literature review identified four randomized trials likely to provide reliable new information on the use of ESA in children. This review confirmed four points: treatment increases hemoglobin levels and decreases the need for blood transfusions; no quality-of-life and no survival benefit has been demonstrated; treatment does not seem associated with significantly more side effects; impact on thromboembolic events and patient quality of life remains unclear. The main result of the study was the elaboration of a new standard of care unavailable at the time of the 2003 version. Systematic administration of ESA is not recommended for the prevention or treatment of anemia in pediatric cancer patients. However, treatment decision must be made on a case-by-case basis and, when treatment is considered, the intravenous route must be preferred. The full French document is available at www.sor-cancer.fr.

[Recommendations for venous thromboembolic events treatment and central venous catheter thrombosis management in cancer patients]. / Traitement curatif de la maladie thromboembolique veineuse et prise en charge des thromboses veineuses sur cathéter chez les patients atteints de cancer Méthode SOR.

The "Standards, Options: Recommendations" (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) and is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. In order to answer questions related to venous thromboembolic events (VTE) treatment and to central venous catheter thrombosis (CVCT) management in cancer patients, the SOR elaborated national guidelines, here presented in a short report. It results of a collaborative work with members from three learned societies (<< Société nationale française de médecine interne >> : SNFMI, << Société française de médecine vasculaire >> : SFMV and << Société française d'anesthésie-réanimation >> : SFAR).

[2008 Standards, Options: Recommendations for venous thromboembolic events(VTE)treatment and central venous catheter thrombosis(CVCT) management in cancer patients]. / Standards, Options : Recommandations 2008. Traitement curatif de la maladie thromboembolique veineuse, prevention et traitement des thromboses veineuses sur catheter chez les patients atteints de cancer.

The Standards, Options: Recommendations (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. In order to answer questions related to venous thromboembolic events(VTE) treatment and to central venous catheter thrombosis (CVCT) management in cancer patients, the SOR elaborated national guidelines, here presented in a short report. It results of a collaborative work with members from three learned societies("société nationale française de médicine interne": SNFMI, "société française de médicine vasculaire": SFMV and "société française dEanesthésie-réanimation:SFAR).

[2008 Standards, Options: recommendations for venous thromboembolic events (VTE) treatment and central venous catheter thrombosis (CVCT) management in cancer patients]. / Standards, Options : Recommandations 2008. Traitement curatif de la maladie thromboembolique veineuse, prévention et traitement des thromboses veineuses sur cathéter chez les patients atteints de cancer.

The <> (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. In order to answer questions related to venous thromboembolic events (VTE) treatment and to central venous catheter thrombosis (CVCT) management in cancer patients, the SOR elaborated national guidelines, here presented in a short report. It results of a collaborative work with members from three learned societies ("société nationale française de médicine interne": SNFMI, "société française de médicine vasculaire": SFMV and "société française d'anesthésie-réanimation": SFAR).

[Standards & options: recommendations for the use of erythropoiesis-stimulating agents (ESA) in anaemic cancer patients undergoing radiotherapy (2007 update)]. / Standards, Options : recommandations 2007 indication des agents stimulant l'érythropièse (ASE) dans la prise en charge de l'anémie induite par la radiothérapie (mise à jour).

INTRODUCTION: Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Option and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA(epoetin alfa, epoetin bêta, darbepoetin) in anaemic patients with cancer. This article presents the updated Recommendations set up in 2007. METHODS: This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. On the basis of analysis of literature, the conclusions and their level of evidence are established. Then, the conclusions accompanied by experts' judgement lead to the Recommendations. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers. RESULTS: New data, relative to the "use of ESA in anaemic cancer patients undergoing radiotherapy", didn't lead to update the latest Recommendations validated in 2003. However, new data relative to the "use of ESA in anaemic prophylaxis among adult patients with cancer" and to the "use of iron with ESA in cancer patients" were sufficient to generate either major or minor modifications to the initial Recommendations. CONCLUSIONS: Thus, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in two years.

[Clinical Practice guidelines for the use of erythropoiesis-stimulating agents (ESA: epoetin alfa, epoetin bêta, darbepoetin) in anaemic patients with cancer: 2007 update (summary report)]. / Standards, Options: recommandations 2007. Indication des agents stimulant l'érythropoïèse (ASE: époétine alpha, époétine bêta et darbépoétine) dans la prise en charge de l'anémie en cancérologie (mise à jour), rapport abrégé.

UNLABELLED: Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Options and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA in anaemic patients with cancer. This article presents a short version of the Recommendations updated in 2007. METHODS: This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. There are two levels of gradation for the Recommendations: Standards and Options. Their setting takes into account the organisational context of care, the particular situation of the patient and the expression of his preferences. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers. RESULTS: New data are sufficiently important to update the latest Recommendations validated in 2003. Thus, five clinical questions were updated. The resulting modifications were either major (new Options or new Standards) or minor (increased level of evidence). It should be noted that for the clinical question--use of ESA in radiotherapy--new data are not sufficient to generate modifications in the initial Recommendations which remain valid. CONCLUSIONS: Because of the important new data published on the subject between 2003 and 2007, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in 2 years.