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Objective: The aim of this article is to review and illustrate the attributes that analyze the performance of a predictive model, suchas discrimination, calibration and clinical utility. Material and methods: To illustrate a biomarkervalidation process, we analyzed 216 patientsrecruited in the Miguel Servet University Hospital Zaragoza, Spain. The outcome of the study was clinicallysignificant prostate cancer (Gleason ≥ 7). A newbiomarker was built using logistic regression modelfrom age, prostate-specific antigen, prostate volumeand digital rectal exam variables. To analyze the discriminationability, the receiver operating characteristiccurve, its area under the curve (AUC), and Youdenindex were estimated. In addition, the calibration wasanalyzed through calibration curve, intercept and slope;and the clinical utility was studied by means of decisionand clinical utility curves. Results: The discrimination ability was good:AUC 0.790 (0.127-0.853 95% C.I.), Youden index cutoffpoint 0.431 (specificity 0.811, sensitivity 0.697).The Intercept was 0 and Slope 1 showing a perfect calibration.Decision curve showed good net benefit in athreshold probability range 25%-80%. Clinical utilitycurve showed that for a 18% cutoff point, a minimum4.5% of CsPCa patients are wrongly classified belowthe cutoff point, saving 18.5% biopsies. Conclusions: A complete validation process isnecessary to analyze the performance of a biomarkerin oncology, based on their discrimination ability, theconcordance between predicted and actual occurrenceof the outcome, and its applicability in clinical practice.
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This chapter aims to introduce the moleculartechnologies that have been optimized for theanalysis of biomarkers in recent years and that are currentlybeing applied in clinical practice.The chapter is divided into three blocks, which dealwith the concepts and techniques of molecular biology related to DNA-, RNA- and proteins-based biomarkers.In addition, real case examples in which these moleculartechnologies are used in clinical routine are given.
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Objective: To review the current situationof biomarkers used in the diagnosis, prognosis,treatment response and relapse of testicular cancer. Methods: A non systematic review was performedof clinical guidelines and articles published within thelast years regarding biomarkers in testicular cancer. Results: The most commonly used biomarkersare alphafetoprotein (AFP) and beta human corionicgonadotropin (β-HCG).The enzyme lactate dehydrogenase (LDH) is presentin multiple tissues and is elevated in advancedgerminal tumors. A few micro molecules of RNA (micro-RNA) have demonstrated to be specifically elevatedin testicular germinal tumors. However, its clincalbenefit, as well as its standardization is currently underinvestigation. Conclusions: Classic biomarkers AFP, β-HCG,and LDH are of some utility confirming the diagnosisif they are elevated. However, its limited sensibility isnot enough to rely the diagnosis on themselves. Thereare promising results with Micro-RNA but its daily usedoes not seem imminent.
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The natural history of renal cell canceris unpredictable and despite the increased knowledgeof this disease, the incidence has been increasing in recent years. Renal cancer represents a tumor withsignificant mortality and efforts to understand its behaviorhavenot yet translated into a decrease in mortality.In the study of renal cell cancer, the knowledge ofmolecular pathways is very important, since they arethe basis for the development of new therapies. Thisknowledge has made it possible to reclassify these tumorsand the current challenge is the search for biomarkersthat allow to establish an adequate diagnosisand prognosis and predict the response to a certaintype of treatment.In the present manuscript we carry out a review ofthe main markers studied and their potential value inrenal cell cancer.
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Bladder cancer (BCa) represents the 7thmost frequent cancer in the male population worldwideand the 10th when both genders are considered.Due its high prevalence, result of high incidence andlow cancer specific mortality in low grade disease, BCarepresents a significant clinical and financial burden.Despite our knowledge of the natural history of thedisease and of the risk factors associated with BCa(age, gender, smoking history and certain chemicals)and, the evidence that outcomes, related directly tothe stage of the disease, are affected by delays in thediagnosis, "screening" is not even considered by mosturological societies and relevant international urologicalguidelines.The aim of the present article is to provide the readerwith an up to date, non-systematic, narrative reviewof the most relevant articles focussed on the useof urinary biomarkers (UBMs) in the screening of BCaboth, mass and high risk population screening, theeconomic assessment of the cost-effectiveness of suchprogrammes, as well as, potential innovations for thefuture of BCa screening.
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Introduction: Bladder cancer is thefifth most common tumor in the world. Moreover, it isone of the most expensive due to its high recurrencerate. Urinary biomarkers for surveillance of non muscleinvasive bladder cancer is a promising and growingfield due to the invasiveness of the actual methods, basedon cystoscopy and cytology. Although current EuropeanGuidelines only consider the use of biomarkersin the low risk scenario as an alternative to cystoscopywhen the patient declines invasive methods for the follow-up after surgery, there is increasing evidence oftheir safety in high risk tumors. Material and methods: We have performeda review of the main urinary biomarkers, includingFDA-approved ones, protein-based and genetic biomarkers.We have also described the different options to incorporatethe biomarkers in the clinical practice. Results: There are not randomized control trialscomparing any biomarker with the gold standard follow-up. Most of the papers published so far are cohortstudies, limitating the evidence of the results. Biomarkerscan be used as an alternative of cystoscopy, in a noninvasive follow-up, or alternating both tests. There arefew economical studies comparing both options, but theevidence supports the efficiency of the main biomarkers. Conclusions: Cystoscopy and cytology are the goldstandard for non muscle invasive bladder cancer surveillance.2021 European Guidelines suggest, for the firsttime, an alternative use of biomarkers in a concrete lowgrade scenario to avoid invasive explorations to patientswith low risk of progression. Paradoxically, biomarkers(mainly genetic ones) have a very good profile of sensitivityand negative predictive value in the high risk scenario.Although there is increasing evidence to supporttheir implementation, the lack of fase IV trials hinderstheir daily use.
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Predicting response to definitive treatmentsis a fascinating challenge which develops throughthe evolution of a panel of convincing molecularbiomarkers capable of adding in clinical decissionsdespite interpatient and intratumoral heterogenicity.Muscle-invasive bladder cancer (MIBC) can be locallytreated either with radical cystectomy (RC) with or withoutneoadyuvant chemotherapy or bladder preservationapproaches such as trimodal therapy (TMT) includingmaximal transurethral resection of bladder tumor(TURBt) followed by external beam radiotherapy withconcurrent systemic radio-sensitizing chemotherapy.Conventional or novel/targeted systemic agents areessential parts of perioperative multidisciplinary managementconsidering both neoadjuvant and adjuvantsetting. Advances in molecular biology such as next generation sequencing and whole genome or transcriptomicanalysis, provided novel insights to achieve a fullunderstanding of the biology behind MIBC helping toidentify emerging predictive signatures. Although severalprogresses have been made, real-world applicationof molecular biomarkers in MIBC scenario is hinderedby lack of standardization, and low reproducibility. Inthis review we aim to present the emerging role of novelmolecular biomarkers in predicting response to localtreatments and systemic agents in MIBC.
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PSA is the most widely used diagnosticand prognostic biomarker in prostate cancer (PCa).However, its lack of specificity has generated the needto search for new complementary markers. In thisscenario, blood plasma constitutes one of the sourcesof search for new markers, which have been tried tobe combined with PSA and other clinical variables inorder to develop tests that increase their diagnosticspecificity.This narrative review of the literature provides anoverview of commercially available plasma biomarkers and tests for use in different clinical settingsfor PCa. The most studied markers to help select theappropriate patients for initial and / or repeat biopsyhave been: PHI, 4K, STHLM3. These markers havebeen oriented towards the diagnosis of the so-calledclinically signifi cant PCa, trying to validate and calibratetheir algorithms in different populations. Giventhe development and evolution in the diagnosis of PCa,there is still a lack of evidence of the impact of magneticresonance imaging (MRI) when used in combinationwith these new markers, as well as its possiblerole in the screening of the disease and not only in theearly diagnosis process. Furthermore, there are only asmall number of studies that have directly comparedthese tests with each other and with PSA, so there isnot enough evidence to know which test has the bestproperties in each clinical scenario. In order to clarifythe true diagnostic role of these new biomarkers, newprospective, comparative studies in different populationsare absolutely necessary to evaluate their clinicalutility in combination with MRI and fusion biopsy.
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Introduction: The use of prostatespecific antigen (PSA) is useful for the diagnosis ofprostate cancer. Its main limitation is its low specificity,which has led to the search for new biomarkersin order to identify clinically significant prostatecancer and to reduce overdiagnosis and overtreatment.The aim of this article is to summarize the currentliterature on urinary biomarkers used in thediagnosis of prostate cancer.A PubMed-based literature search was conductedup to December 2020. We selected the most recentand relevant original articles, clinical trials and reviewsthat have provided relevant information onthe use of biomarkers.In this review, we have discussed four importanturinary biomarkers useful for prostate cancer diagnosis:PCA3, Select MDX, ExoDX, TMPRSS2:ERG. Conclusion: The use of urinary biomarkers hasimproved of clinically significant prostate cancerdiagnosis. Their use reduces the number of unnecessarybiopsies and avoids overtreatment of indolentprostate cancer.
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Introduction and objectives: Active surveillance (AS) is currently a therapeuticstrategy recommended by all Clinical Guidelines forthe initial management of very low-risk, low-risk, andsome intermediate-risk prostate cancer (PCa). However,a high percentage of cases will present the need for active treatment and a quarter of them will presentunfavorable anatomopathological characteristics. Methods: review of the biomarkers' literature oncircumscribed to the inclusion and follow-up of patientsin AS. Results: PSA and its variants remain the most widelyused and most cost-effective biomarker in AS. Inparticular, the use of PSA density based on the prostatevolume detected by mpMRI has gained much weight.Different multipanel biomarkers in blood and urineare commercially available to predict progressionto PCa ≥3 + 4 (GG2), but they have not clearly beenprospectively tested in AS cohorts. Tissue biomarkersanalyze gene panels that offer predictive informationindependent of classical clinicopathological variablesand may play a role in controversial indications for AS.Lastly, risk calculators are cost-effective and validatedfor their care use in AS and are probably underused. Conclusions: Although there is no specific biomarkerfor the optimization of AS, its rational use togetherwith mpMRI may in the future optimize the inclusionof patients in AS and follow-up differentiatedby risk groups.
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Introduction: Prostate cancer is themost prevalent and deadliest neoplasm in men, with adiverse clinical presentantion and oncological outcomes.The diagnosis and treatment remains a challenge.New essays about biomarkers show their potential asa tool that may influence in clinical decision making,risk stratification and management of the disease. Methods: we performed a literature review abouttissue biomarkers in the diagnosis and treatment ofprostate cancer. Results: Within the last years, a wide number ofdiagnostic and prognostic tests in tissue have been developed(ConfirmMDx, Promark, Oncoytype DX, Decipher),creating an opportunity to improve the diagnosis,prognosis and treatment of prostate cancer. Conclusions: Since prostate cancer is the mostprevalent neoplasm in men, it is mandatory to stratifypatients correctly to prevent unnecessary biopsiesand overtreatment in low risk patients, as well as designthe best strategy in those with high risk disease.Tissue biomarkers may become a useful tool in precisionmedicine to guide decision making.
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Whole exome sequencing studies haverevealed the molecular landscape of metastatic CastrateResistant Prostate Cancer (mCRPC) providingnew information about prognostic and predictive factorsof response to therapies. These studies highlightedpotentially actionable targets leading to the beginingof the biomarker-driven era in prostate cancer.Alterations in androgen receptor (AR), DNA repair genes,PI3K-AKT-MTOR pathway or in genes involved incell cycle are frequently observed in mCRPC patientsand may be relevant in the resistance induced mechanismto approve therapy in this setting. Poly(ADP-ribose)polymerase (PARP) inhibitor in BRCA mutatedpatients, pembrolizumab (inmune checkpoint inhibitors)in mCRPC patients with mismatch repair genedefects and microsatellite instability and ipatasertib(AKT inhibitor) in patients with loss of function inPTEN are examples on how molecular information canbe useful to improve treatment selection. Nonethelessthe heterogeneity of advanced PC, the lack of consensusregarding the optimal biological source of analysisand the optimal time and technique for the analisysare still challenges that need to be defined in the nextfuture. The aim is to review the current literature concerningprognostic and predictive marker of responseto therapies in the mCRPC setting.
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In the recent years, research in oncologyhas focused on liquid biopsies, which rely on thedetection of cancer-derived components, includingcirculating tumor cells (CTCs), circulating tumor DNA(ctDNA), circulating free RNA (cfRNA), and extracellularvesicles (EVs), in the biofluids of patients, providinggenomic, epigenetic and transcriptomic, informationabout tumors and metastatic sites. In this reviewwe collect current evidence regarding the potentialof liquid biopsies for the diagnosis and follow-up ofuro-oncology patients, as well as the advantages andlimitations of these approaches. Although promising,the way in which this methodology must be incorporatedinto the clinical routine needs to be still definedboth at the pre-analytical and analytical level beforetheir clinical utility is demonstrated.
