Background/Objectives: This work introduces accuracy- and precision-ROC curves in addition to SS– and PV–ROC curves and shows a novel means of profiling biomarker characteristics for validation of optimal cutoffs in clinical diagnostics and decision making. Methods: This investigation included 91 patients with a confirmed bladder cancer diagnosis and 1152 patients without evidence of cancer. The study performed a quantitative investigation of used-up test cassettes from the visual UBC® Rapid qualitative point-of-care assay, which had already been applied in routine diagnostics. Using a photometric reader, quantitative data could also be obtained from the test line of the used cassettes. The ROC curves were constructed using different thresholds or cutoff levels to determine the TP/TN and FP/FN values for each threshold at concentrations of 5, 10, 30, 50, 90, 110, 250 and 300 µg/L. The resulting TP/TN and FP/FN values were used to calculate the sensitivity/specificity, accuracy, precision and predictive values in order to plot the ROC curves with integrated cutoff value distributions and their index cutoff diagrams. Results: A common, optimal cutoff value for all the diagnostic parameters was derived with the aid of an ROC index cutoff diagram. It includes higher specificity and an acceptable number of NPVs. As a result, use of a sensitivity–specificity ROC curve and the Youden index only permits the selection of a maximal threshold value or cutoff point for the biomarker of interest but disregards the clinical status of the patient, whereas the precision, accuracy and predictive values give information related to the disease. Conclusions: This work’s novelty compared to the existing methodology includes the first international publication of accuracy- and precision-ROC curves. It enables the investigation of the relationship among the sensitivity, specificity, precision, accuracy and predictive values at varied cutoff levels within a bioassay, presenting these in a single graph consisting of selected receiver operating characteristic (ROC) curves for each parameter, including cutoff distribution curves. This is a transparent method to identify appropriate cutoffs for multiple diagnostic parameters. According to the results, the single-sided use of a sensitivity–specificity ROC curve including the maximal Youden index value as an optimal cutoff or single-point determinations for predictive values cannot provide diagnostic information of the same quality as that given by a multi-parameter diagnostic profile and a multi-parameter cutoff-index-diagram-derived optimal value as presented within this work. The proposed multi-parameter cutoff-index diagram includes novel index cutoff AOX. It is a new different method that allows a quantitative comparison of the results from multi-parameter ROC curves, which cannot be performed with the AUC. However, the methods are different and do not exclude each other.

Background: This investigation is both a study of potential non-invasive diagnostic approaches for the bladder cancer biomarker UBC® Rapid test and a study including novel comparative methods for bioassay evaluation and comparison that uses bladder cancer as a useful example. The objective of the paper is not to investigate specific data. It is used only for demonstration, partially to compare ROC methodologies and also to show how both sensitivity/specificity and predictive values can be used in clinical diagnostics and decision making. This study includes ROC curves with integrated cut-off distribution curves for a comparison of sensitivity/specificity (SS) and positive/negative predictive values (PPV/NPV or PV), as well as SS-J index/PV-PSI index–ROC curves and SS-J/PV-PSI index cut-off diagrams (J = Youden, PSI = Predictive Summary Index) for the unified direct comparison of SS-J/PV results achieved via quantitative and/or qualitative bioassays and an identification of optimal separate or unified index cut-off points. Patients and Methods: According to the routine diagnostics, there were 91 patients with confirmed bladder cancer and 1152 patients with no evidence of bladder cancer, leading to a prevalence value of 0.073. This study performed a quantitative investigation of used-up test cassettes from the visual UBC® Rapid qualitative point-of-care assay, which had already been applied in routine diagnostics. Using a photometric reader, quantitative data could also be obtained from the test line of the used cassettes. Interrelations between SS and PV values were evaluated using cumulative distribution analysis (CAD), SS/PV–ROC curves, SS-J/PV-PSI index–ROC curves, and the SS-J/PV-PSI index cut-off diagram. The maximum unified SS-J/PV-PSI index value and its corresponding cut-off value were determined and calculated with the SS-J/PV-PSI index cut-off diagram. Results: The use of SS/PV–ROC curves with integrated cut-off concentration distribution curves provides improved diagnostic information compared to “traditional” ROC curves. The threshold distributions integrated as curves into SS/PV–ROC curves and SS-J/PV-PSI index–ROC curves run in opposite directions. In contrast to the SS–ROC curves, the PV–ROC and the novel PV-PSI index–ROC curves had neither an area under the curve (AUC) nor a range from 0% to 100%. The cut-off level of the qualitative assay was 7.5 µg/L, with a sensitivity of 65.9% and a specificity of 63.3%, and the PPV was 12.4% and the NPV was 95.9%, at a threshold value of 12.5 µg/L. Based on these set concentrations, the reader-based evaluation revealed a graphically estimated 5% increase in sensitivity and a 13% increase in specificity, as compared to the visual qualitative POC test. In the case of predictive values, there was a gain of 8% for PPV and 10% for NPV. The index values and cut-offs were as follows: visual SS-J index, 0.328 and 35 µg/L; visual PV-PSI index, 0.083 and 5.4 µg/L; maximal reader Youden index, 0.0558 and 250 µg/L; and maximal PV-PSI index, 0.459 and 250 µg/L, respectively. The maximum unified SS-J/PV-PSI index value was 0.32, and the cut-off was 43 µg/L. The reciprocal SS-J index correctly detected one out of three patients, while the reciprocal PV-PSI index gave one out of twelve patients a correct diagnosis. Conclusions: ROC curves including cut-off distribution curves supplement the information lost in “traditionally plotted” ROC curves. The novel sets of ROC and index–ROC curves and the new SS/PV index cut-off diagrams enable the simultaneous comparison of sensitivity/specificity and predictive value profiles of diagnostic tools and the identification of optimal cut-off values at maximal index values, even in a unifying SS/PV approach. Because the curves within an SS-J/PV-PSI index cut-off diagram are distributed over the complete cut-off range of a quantitative assay, this field is open for special clinical considerations, with the need to vary the mentioned clinical diagnostic parameters. Complete or partial areas over the x-axis (AOX) can be calculated for summarized quantitative or qualitative effectivity evaluations with respect to single and/or unified SS-J and PV-PSI indices and with respect to single, several, or several unified assays. The SS-J/PV-PSI index-AOX approach is a new tool providing additional joint clinical information, and the reciprocal SS-J indices can predict the number of patients with a correct diagnosis and the number of persons who need to be examined in order to correctly predict a diagnosis of the disease. These methods could be used in applications like medical or plant epidemiology, machine learning algorithms, and neural networks.

BACKGROUND:The synergy between in vitro and in vivo imaging was investigated in this study.PATIENTS AND METHODS:Comparison of fluorodeoxyglucose positron-emission tomography (FDG-PET) and computerised tomography (CT) included 62 patients (group 1), while that for comparison of FDG-PET and serum tumour markers included 26 patients (group 2).RESULTS:In group 1, FDG-PET had positive and negative predictive values of 81% and 80% respectively, compared to 73.7% and 71.4% for CT, respectively. Combined imaging showed 100% sensitivity and 100% specificity. In group 2, FDG-PET and CEA were both positive in 42.9%, and only CEA was falsely negative in all other cases. FDG-PET and TPA were both positive in 47.6%, and in 52.4% only FDG-PET was positive. NSE and SCC had 100% specificity; their sensitivity was 38% and 25%, respectively.CONCLUSION:FDG-PET diagnosis was improved by CT. Because the serum tumour markers were falsely negative in more than 50% and there were no falsely negative results for FDG-PET, combined imaging may allow reduction of cut-off values for conventional serum tumour markers.

Purpose of review Traditional morphologically based imaging modalities are now being complemented by positron emission tomography (PET)/computed tomography (CT) in prostate cancer. Metastatic prostate cancer is an attractive target for radioimmunotherapy (RIT) as no effective therapies are available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. Recent findings Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated further. However, 18F-choline and 11C-choline PET/CT have been demonstrated to be useful for detection of recurrence. 18F-choline and 18F-fluoride PET/CT are useful for detection of bone metastases. Prostate tumor antigens may be used as targets for RIT. Prostate-specific membrane antigen is currently under focus of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, which targets the extracellular domain of prostate-specific membrane antigen, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. Summary PET/CT in prostate cancer has proven to play a significant role, in particular for detection of prostate cancer recurrence and bone metastases. RIT of metastatic prostate cancer warrants further investigations.

Purpose of review Traditional morphologically based imaging modalities in uro-oncology are now being complemented by the functional and molecular imaging technique positron emission tomography (PET). This review highlights the most important recent developments. Recent findings 18 Prostate cancer: PET imaging with the new radiotracers (11)C-choline, (18)F-fluorocholine, and 11 C-acetate show promising results. The role of anti-1-amino-3-F-fluorocyclobutane-1-carboxylic acid remains to be elucidated further. (18)F-fluoride PET is useful for the detection of bone metastases. Bladder cancer: (18)F-fluorodeoxyglucose (FDG) PET/CT with delayed images after a diuretic and oral hydration may improve detection of locally recurrent or residual bladder tumours. Both (18)F-FDG PET and 11 C-choline PET may be useful for staging of bladder cancer. Renal cancer: (18)F-FDG PET has a role in staging and restaging of the disease. Recently, (124)I-cG250 PET has shown promising results in the detection of clear-cell renal carcinoma. Testicular cancer: (18)F-FDG PET is useful in staging and follow-up after treatment. There are no important recent developments with new radiopharmaceuticals in testicular cancer. Summary The utility of PET molecular imaging in uro-oncology expanded due to the new metabolic PET tracers with more favourable properties.

Purpose: Appropriate imaging in uro-oncology is a crucial component at primary diagnosis, followup and recurrence to achieve an accurate assessment of the disease and determine the most effective treatment. We summarize recent developments in positron emission tomography and positron emission tomography/computerized tomography for prostate, bladder and renal cancer.Materials and Methods: The recent published literature on positron emission tomography and positron emission tomography/computerized tomography in uro-oncology was searched and reviewed.Results: For prostate cancer F-18-fluorodeoxyglucose is not highly effective for primary diagnosis but it has a limited role in staging and recurrence detection. Promising results have been shown by C-11-choline, F-18-fluorocholine, C-11-acetate and F-18-fluoride. The role of C-11-methionine, F-18-fluoro-5-alpha-dihydrotestosterone and anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid remains to be elucidated. For bladder cancer F-18-fluorodeoxyglucose positron emission tomography is useful for identifying distant metastases but not for detecting primary tumors due to the urinary excretion of F-18-fluorodeoxyglucose. The role of C-11-choline and "C-methionine remains to be evaluated further in clinical studies. For renal cancer F-18-fluorodeoxyglucose is of limited use for primary diagnosis but it has a role in staging and restaging of the disease. More clinical data are needed to investigate the roles of F-18-fluoromisonidazole and F-18-fluorothymidine.Conclusions: Several advances in positron emission tomography and positron emission tomography/computerized tomography for urological cancer have been made in recent years. However, larger clinical trials are needed to establish the role of this imaging method for urological malignancy. In the near future the new radiotracers and further advancement in this imaging technique are expected to improve the performance of positron emission tomography/computerized tomography in uro-oncology.

Genomics, proteomics and metabolomics, which can be also summarized as 'omics', have become increasingly inter-related with imaging. Gene expression profiling may be assessed using high-density microarrays for the detection of overexpression patterns, followed by the development of histochemical assays. Next, antibodies to the gene-corresponding proteins (for example, receptors) can be produced, leading to serum immunoassays for follow-up, as well as antibody-guided in vivo imaging or therapy. In vivo imaging for cancer detection and/or therapy can be performed by applying nonlabeled antibodies, by using radiolabeled antibodies for detection using single-photon tomography or positron emission tomography (PET), or by other tracers, for example, for magnetic resonance imaging tomography (MRI, MRT). Protein profiles from protein chips can be derived from mass maps obtained through mass spectrometry (MS). Electrophoretic separation of proteins has also been combined with MS to produce a two-dimensional assignment of proteins within a complex mixture. Overexpression of tumor-related proteins can be used for the development of antibodies to develop noninvasive assays that can be used in the screening of risk groups as a basis for further investigation by invasive imaging methods. Metabolomic profiling by nuclear magnetic resonance spectroscopy can be applied for the detection of biomarkers of the metabolome. Metabolite profiles in cells, tissues, and organisms can be generated with nuclear magnetic resonance spectroscopy and MS. Metabolic information provided by magnetic resonance spectroscopic imaging (MRSI) combined with the anatomical information provided by MRI can significantly improve the assessment of cancer location and extent, and cancer aggressiveness. Biomarkers found by MRSI can lead to new PET tracers. This article provides examples and discusses some of the recent achievements to bring forward novel strategies for the diagnosis and therapy of cancer.

You have accessJournal of UrologyDiscussed Poster, Sunday, May 9, 2004, 8:00 am - 12:00 pm1 Apr 2004265: Non-Invasive Screening of Urinary Bladder Cancer - Is NMP22®Bladderchek™ Paving the a Venue? Peter Oehr Peter OehrPeter Oehr More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)37527-XAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "265: Non-Invasive Screening of Urinary Bladder Cancer - Is NMP22®Bladderchek™ Paving the a Venue?." The Journal of Urology, 171(4S), p. 70 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 70 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Peter Oehr More articles by this author Expand All Advertisement Loading ...

I: Basics.- Physical Principles, Dedicated/ Coincidence-PET.- Dual-Modality PET/CT Acquisition Systems for Clinical Oncology.- Transport and Metabolism of Glucose and FDG.- Radiopharmaceutical Production and Safety of [18F]FDG.- Image Fusion.- PET Scanner Quality Control.- II: Experimental Oncology.- to Experimental PET in Oncology.- PET in Cell Cultures: Oncology, Genetics, and Therapy.- Small-Animal PET in Oncology.- Small-Animal PET in Neuro-oncology and Gene Therapy.- III: Clinical Applications.- PET/CT: Clinical Considerations.- Brain Tumors.- Head and Neck Tumors.- Thyroid Carcinomas.- Lung Cancer.- Breast Cancer.- Pancreatic Cancer.- Gastro-Esophageal Cancer.- Liver Cancer.- Colorectal Cancer.- Ovarian Cancer.- Cancer of the Uterus.- PET in Bladder, Renal, and Prostate Cancer.- Testicular Tumors.- Malignant Melanoma.- Malignant Lymphomas.- Musculoskeletal Tumors.- Skeletal imaging with F-18.- PET in Surgery.- PET and Radiotherapy.- Cancer Screening with 18F FDG-PET.- Cost-Effectiveness Studies of PET in Oncology.- Reimbursement (EU and USA).- PET Reimbursement: Europe.- PET Reimbursement: United States.

Positron emission tomography (PET) using 18F-fluorodeoxy-glucose (18F- FDG) in oncology has become the predominant indication for clinical PET studies. In many cancers, 18F-FDG PET is the most accurate non-invasive method to detect and stage disease. This has major implications for treatment planning and avoiding unnecessary treatment with its associated morbidity and cost. This review outlines the current clinical evidence for PET in oncology. (non-author abstract)

From the contents: Basics Physical Principles.- Radiopharmaceutical Technology, Toxicity and Radiation Dosages.- Metabolism and Transport of Glucose and FDG.- Clinical Indications.- Malignant Melanoma.- Head and Neck Tumors.- Thyroid Carcinomas.- Pulmonary Nodules and Non-Small-Cell Bronchial Carcinoma.- Breast Cancer.- Pancreatic Cancer.- Colorectal Cancer.- Ovarian Cancer.- Testicular Tumors.- Hodgkin's Disease and Non-Hodgkin's Lymphomas.- Miscellaneous Tumors.- Cancer Screening with Whole-Body FDG PET.- PET in Radiotheraphy (part contents).