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Purpose: The overuse of laboratory tests contributes to impair health systems effectiveness, tumor markers (TMs) being a paradigmatic example. In the present study we applied indicators of TMs appropriateness developed from administrative datasets to appraise regionwide overordering in the clinical practice., Patients and Methods: TMs ordered to outpatients in the Veneto Region over 6 years were obtained from the eletronic Outpatients' Records of Diagnostic and Therapeutic Procedures. TMs orders were examined as aggregated data or stratified according to disease codes, gender, age, and requests per patient. TMs recommended only for specific malignancies were examined using epidemiological data obtained from Veneto Tumor Registry., Results: A total of 5,821,251 TMs were ordered in 4,382,159 patients over 6 years. Overall, 3,252,389 (55.9%) TMs were ordered without appropriate disease codes (ranging from 77.0% for PSA to 17.5% for CA15.3). TM orders declined over 6 years (-13.4%), with a noticeable reduction of orders without appropriate disease codes (-21.3%). Orders decreased sharply from 2015 to 2016, after the enactment of a national Decree-Law aimed at improving appropriateness, and remained stable thereafter. However, the rate of inappropriate TMs requests still remained elevated (44.4%) in the last year of observation, with orders of TMs being much higher than expected on the basis of prevalence and incidence figures of specific malignancies., Conclusions: Indicators developed from administrative datasets were effective in assessing the overordering of TMs and the impact of interventions to improve appropriateness. The developed indicators could be considered for other diagnostic tests.

The role of biomarkers is crucial in oncology for both early diagnosis and the personalization of cancer treatments. Tissue biomarkers have gained a central role as predictors of the response to an increasing number of anticancer agents; conversely, the clinical role of circulating biomarkers (c-TMs) is limited and has remained almost unchanged over the years. The position of guidelines is summarized and discussed with reference to the potential usefulness of c-TMs in those areas of application that cannot be covered by tissue biomarkers. The pipeline of translational research on biomarkers is briefly described; the differences among analytical validation, clinical validation, and clinical utility are discussed, emphasizing that the assessment of clinical utility is the ultimate step toward clinical use. The role of monitoring of appropriateness as a proxy indicator of how the research pipeline has actually worked is discussed, and data and c-TMs overordering rates are reported. The role and limits of guidelines to influence appropriate c-TMs ordering are discussed. The design of primary studies on c-TMs is examined, underlining that they mainly focus on clinical validation rather than on clinical utility. The role of regulatory boards is also briefly presented and discussed.

Laboratory tests are frequently overused and have elevated inappropriateness rates. We previously developed a model to investigate the rate of utilization of tumor markers (TMs) in outpatients as an indirect indicator of inappropriateness. The model was based on the comparison between the number of actually ordered and expected tests, with the latter estimated on the basis of both epidemiological data and recommendations of available clinical practice guidelines.In this paper we propose an algorithm to distinguish prevalent cases without evidence of disease from those with metastatic spread, on the basis of both epidemiological and clinical information. The algorithm allows for a more precise prediction of the expected TM requests per year, to be compared with the actual number of requested TMs in order to assess possibly inappropriate overordering rates. Moreover, the implementation of the algorithm renders the epidemiologically based model more flexible to develop accurate indicators for appropriateness in the use of TMs in different stages of disease and for different clinical questions. A practical application with CA15.3 requests in breast cancer is presented.

Rationale, Aims, and Objectives: Although the issue of monitoring appropriateness of tumour markers (TMs) request in outpatients remains crucial, proper indicators are still demanding. The present study developed and explored indicators of inappropriate TM ordering in outpatients through the data mining of electronic health records (EHRs)., Methods: Carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific antigen (PSA) ordered in outpatients during a year were examined by mining EHRs of a Local Health Authority in Italy. Evidence-based criteria were used to develop performance indicators. Demographic and clinical information associated with TM orders were examined., Results: A total of 80 813 TMs were ordered in 52 536 outpatients (1.54 markers/patient). Indicators related to disease codes, gender, age, and TM repetitions were developed, and their application showed that (1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and 65.6%) whereas the other TMs are largely requested also in patients without cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are negligible; (3) although requests in people older than 80 years are relevant (16.4% of total), the highest rate of request of all markers occurs in patients aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69 years; (5) <50% of PSA orders are associated with cancer code for all age intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA are prevalent in cancer patients or benign diseases to which TMs are appropriate, whereas PSA repetitions occur mainly in patients without cancer., Conclusions: The developed indicators resulted suitable to monitor TM overordering in outpatients through the mining of EHRs. The present study is a first approach towards the use of big-data mining for TM appropriateness evaluation purposes., (© 2017 John Wiley & Sons, Ltd.)

Background: Evaluation of appropriateness of laboratory tests on the basis of individual requests remains a serious problem as the clinical question is usually not reported with the test order. This study explored the comparison of the rate of tumor marker orders with cancer prevalence as a putative indicator of inappropriateness., Methods: Tumor marker orders (2011 and 2012) were obtained from the Ministry of Health and cancer prevalence from the Italian Association of Cancer Registries. The rate of tumor marker orders was matched with demographic data and tumor prevalence and examined by using the confidence interval approach. Region-to-region and year-to-year variations were also examined. Focus was placed on CEA, CA125, CA19.9 and CA15.3., Results: Tumor markers ordered in Italy were 13,207,289 in 2012 (221.3/1000 individuals). Given an estimated prevalence of 2,243,953 cancer cases, 7.04 tumor markers appear to be requested for each prevalent case of epithelial cancer per year. The rate of requests of CEA, CA125, CA19.9 and CA15.3 (in aggregate 5,834,167 requests in 2012, 44.2% of total) from the first and the last ranked region (96 and 244/1000 individuals) are significantly different (p<0.01). Region-to-region differences do not correspond to any known variation of prevalence in the different regions., Conclusions: The developed approach provides a proxy indicator of inappropriateness showing that tumor markers are overused in Italy and their ordering pattern is not related to tumor prevalence. The model is suitable to be validated in other laboratory tests used in diseases whose prevalence is known.

Background and Aim: Hepatocellular carcinoma (HCC) is a multifactorial disease driven by both genetic and epigenetic factors. Infection, inflammation and the immune response against hepatitis B virus and hepatitis C virus have been shown to play an important role in increasing cancer risk and promoting tumor development. In order to investigate the genetic component influencing HCC development, we analyzed 50 single nucleotide polymorphisms (SNP) spanning 34 different genes in 230 Italian patients affected by HCC and 230 controls., Methods: Genes were selected on the basis of their known biological function and their possible involvement in the progression or in the susceptibility to HCC was considered. SNP genotyping was performed using allelic-specific fluorescent probes., Results: For most SNP, no differences were identified between HCC patients and controls, with the exception of rs2304052, localized on the secreted protein acidic and rich in cysteine (SPARC) gene, which was significantly associated to the disease. The C allele was significantly more frequent in the HCC patients than in the healthy controls (23% vs 10%, corrected P < 0.001), as well as the CC genotype (13% vs 1%, corrected P < 0.001)., Conclusion: Since the presence of the rs2304052 C allele is associated with an increased risk (odds ratio: 2.76) of developing hepatocarcinoma, our results allowed us to identify a SNP in the SPARC gene correlating to HCC susceptibility.

Background: Tumour markers are frequently used in clinical practice and the reason for ordering varies considerably and often seems to be inappropriate. We carried out a survey of Italian laboratories on their current pattern of use., Methods: Forty-four laboratories located in health-care institutions with inpatient beds were surveyed about the organizational, clinical and methodological aspects of tumour markers ordering., Results: Thirty-one laboratories (70%) filled in and returned the questionnaire. Overall, 977,786 tumour marker tests were scrutinized. The pattern of tumour marker use did not seem to be influenced by the institutional setting, by availability of oncology facilities or by adoption of clinical guidelines. In addition, the information flow from clinicians to the laboratory and vice versa was poor and informal., Conclusions: Monitoring tumour marker pattern use can provide valuable information for health-care decision makers, highlighting potential inadequacies in laboratory services but also identifying problems in other areas of health-care delivery that could benefit from educational programmes.

The free-to-total prostate-specific antigen ratio (F/T PSA) is associated with the presence of prostate cancer and is thus used as an indicator for suspicion of prostate cancer and as a determinant for biopsy. We reviewed a recent retrospective series of 966 consecutive prostate biopsies where F/T PSA was blindly determined and did not influence biopsy indication. We simulated the association of F/T PSA with biopsy outcome and its impact as a biopsy determinant. When adopting an F/T PSA cutoff of 10%, 13%, 16% or 20% among random sextant biopsies in the 4-10 ng/mL total PSA range, the sensitivity was 15%, 37%, 55% and 72% and the specificity 89%, 80%, 64% and 44%, respectively. Using F/T PSA as a biopsy determinant, from 1.7 to 2.6 cancer biopsies would have been delayed to avoid 10 benign biopsies. As this balance is not acceptable, F/T PSA has no role as a biopsy indicator and its clinical use is questionable.