Integrated pretreatment diffusion kurtosis imaging and serum squamous cell carcinoma antigen levels: a biomarker strategy for early assessment of radiotherapy outcomes in cervical cancer.

OBJECTIVE: This study aims to explore the utility of pretreatment DKI parameters and serum SCC-Ag in evaluating the early therapeutic response of cervical cancer to radiotherapy. MATERIALS AND METHODS: A total of 33 patients diagnosed with cervical cancer, including 31 cases of cervical squamous cell carcinoma and two cases of adenosquamous carcinoma, participated in the study. All patients underwent conventional MRI and DKI scans on a 3T magnetic resonance scanner before radiotherapy and after ten sessions of radiotherapy. The therapeutic response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were categorized into a response group (RG), comprising Complete Remission (CR) and Partial Remission (PR), and a non-response group (NRG), comprising Stable Disease (SD) and Progressive Disease (PD). LASSO was employed to select pretreatment DKI parameters, and ROC curves were generated for the selected parameters and serum SCC-Ag. RESULTS: Significant differences were observed in pretreatment MD, Da, Dr, MK, Ka, Kr, and SCC-Ag between the RG and NRG groups (P < 0.01). However, no significant differences were noted for FA and FAK (P = 0.441&0.928). The two selected parameters (MD and MK) demonstrated area under the curve (AUC), sensitivity, and specificity of 0.810, 0.769, 0.850 and 0.827, 0.846, 0.750, respectively. The combination of MD and MK exhibited an improved AUC of 0.901, sensitivity of 0.692, and specificity of 1.000, with a higher Youden index compared to the individual parameters. Conversely, the AUC, sensitivity, and specificity of the combination of MD, MK, and SCC-Ag were 0.852, 0.615, and 1.000, with a Youden index of 0.615. CONCLUSION: Pretreatment MD, MK, and SCC-Ag demonstrate potential clinical utility, with the combined application of MD and MK showing enhanced efficacy in assessing the early therapeutic response of cervical cancer to radiotherapy. The addition of SCC-Ag did not contribute further to the assessment efficacy.

Assessment of retroperitoneal lymph node status in locally advanced cervical cancer.

BACKGROUND: The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. METHODS: Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. RESULTS: The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD < 1.0 cm group (26.82%). The critical values of MAD and SCC-Ag in determining lymph node metastasis were 1.0 cm and 5.2 ng/mL, respectively. The accuracy, specificity, and Youden index of MAD ≥1.0 cm combined with SCC-Ag ≥ 5.2 ng/mL for evaluating lymph node metastasis were 75.71%, 100%, and 0.59, respectively, and were significantly different from the values for the MAD ≥1.0 cm (72.09%, 80.56%, and 0.47, respectively) and SCC-Ag ≥ 5.2 ng/mL (71.43%, 68.97%, and 0.42, respectively) groups. Correlation analysis showed that non-squamous cell carcinoma, pelvic lymph node (PLN) MAD ≥1.0 cm plus number ≥ 2, and 1 PLN MAD ≥1.0 cm with CILN and/or PALN MAD 0.5-1.0 cm were risk factors for CILN and/or PALN metastasis. CONCLUSION: Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD < 1.0 cm and SCC-Ag < 5.2 ng/mL may be treated with chemoradiotherapy directly based on imaging, given the low lymph node metastasis rate.

Assessment of Serum Tumor Markers for Predicting Ocular Metastasis in Lung Adenocarcinoma: A Retrospective Study.

The purpose of this study was to detect clinical variations between lung adenocarcinoma patients with and without ocular metastasis (OM) to identify risk factors for OM and assess the diagnostic values. We included 1153 patients with lung adenocarcinoma in this study. Independent t-tests and chi-square tests were used to compare patients' clinical characteristics. Statistically significant parameters were analyzed by binary logistic regression to detect risk factors of OM. The results showed that the OM group had increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21-1), carbohydrate antigen- (CA-) 125, CA-153, and total prostate-specific antigen (TPSA) compared with the NOM group. CYFRA21-1 is the most useful biomarker for detecting OM in this population.

Noninvasive Assessment of Liver Fibrosis: Current and Future Clinical and Molecular Perspectives.

Liver fibrosis is one of the risk factors for hepatocellular carcinoma (HCC) development. The staging of liver fibrosis can be evaluated only via a liver biopsy, which is an invasive procedure. Noninvasive methods for the diagnosis of liver fibrosis can be divided into morphological tests such as elastography and serum biochemical tests. Transient elastography is reported to have excellent performance in the diagnosis of liver fibrosis and has been accepted as a useful tool for the prediction of HCC development and other clinical outcomes. Two-dimensional shear wave elastography is a new technique and provides a real-time stiffness image. Serum fibrosis markers have been studied based on the mechanism of fibrogenesis and fibrolysis. In the healthy liver, homeostasis of the extracellular matrix is maintained directly by enzymes called matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs). MMPs and TIMPs could be useful serum biomarkers for liver fibrosis and promising candidates for the treatment of liver fibrosis. Further studies are required to establish liver fibrosis-specific markers based on further clinical and molecular research. In this review, we summarize noninvasive fibrosis tests and molecular mechanism of liver fibrosis in current daily clinical practice.

Assessment of associations between clinical and immune microenvironmental factors and tumor mutation burden in resected nonsmall cell lung cancer by applying machine learning to whole-slide images.

BACKGROUND: It is unclear whether clinical factors and immune microenvironment (IME) factors are associated with tumor mutation burden (TMB) in patients with nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: We assessed TMB in surgical tumor specimens by performing whole exome sequencing. IME profiles, including PD-L1 tumor proportion score (TPS), stromal CD8 tumor-infiltrating lymphocyte (TIL) density, and stromal Foxp3 TIL density, were quantified by digital pathology using a machine learning algorithm. To detect factors associated with TMB, clinical data, and IME factors were assessed by means of a multiple regression model. RESULTS: We analyzed tumors from 200 of the 246 surgically resected NSCLC patients between September 2014 and September 2015. Patient background: median age (range) 70 years (39-87); male 37.5%; smoker 27.5%; pathological stage (p-stage) I/II/III, 63.5/22.5/14.0%; histological type Ad/Sq, 77.0/23.0%; primary tumor location upper/lower, 58.5/41.5%; median PET SUV 7.5 (0.86-29.8); median serum CEA (sCEA) level 3.4 ng/mL (0.5-144.3); median serum CYFRA 21-1 (sCYFRA) level 1.2 ng/mL (1.0-38.0); median TMB 2.19/ Mb (0.12-64.38); median PD-L1 TPS 15.1% (0.09-77.4); median stromal CD8 TIL density 582.1/mm2 (120.0-4967.6);, and median stromal Foxp3 TIL density 183.7/mm2 (6.3-544.0). The multiple regression analysis identified three factors associated with higher TMB: smoking status: smoker, increase PET SUV, and sCEA level: >5 ng/mL (P < .001, P < .001, and P = .006, respectively). CONCLUSIONS: The IME factors assessed were not associated with TMB, but our findings showed that, in addition to smoking, PET SUV and sCEA levels may be independent predictors of TMB. TMB and IME factors are independent factors in resected NSCLC.

Serum cytokeratin 19 fragment 21-1 is a useful tumor marker for the assessment of extramammary Paget's disease.

Cytokeratin 19 fragment 21-1 (CYFRA 21-1) has been used as a tumor marker for several malignancies. However, to date, no studies have assessed whether CYFRA 21-1 could be a useful marker for extramammary Paget's disease (EMPD). The present study aimed to evaluate the significance of CYFRA 21-1 as a serum tumor marker for EMPD progression. Concentrations of serum CYFRA 21-1 and carcinoembryonic antigen (CEA) in 13 cases of EMPD were measured prior to undergoing treatment at Sapporo Medical University Hospital from January 2014 to May 2016. Four of the 13 patients had lymph node metastases at diagnosis, but none had distant metastases. Immunohistochemistry indicated that all 13 primary tumors and four metastatic tumors in lymph nodes were positive for cytokeratin 19. Although none of the 13 patients showed high serum CEA levels, six patients (46.2%) had elevated serum CYFRA 21-1. Furthermore, CYFRA 21-1 was reduced in association with post-treatment tumor reduction in all six patients. Among these six patients, four developed recurrence and metastasis during the follow-up period. CYFRA 21-1 was re-elevated in all four of these patients; however, serum CEA was elevated only in the patient with distant metastasis. These results suggest that CYFRA 21-1 is more sensitive compared with CEA, and can be useful as a tumor marker for evaluating tumor progression and treatment efficacy in patients with EMPD.

Assessment of Relationship Between CT Features and Serum Tumor Marker Index in Early-stage Lung Adenocarcinoma.

RATIONALE AND OBJECTIVES: The study aimed to assess the relationship between tumor marker index (TMI) and high-resolution computed tomography features in early-stage lung adenocarcinoma. MATERIALS AND METHODS: Seventy-four stage IA lung adenocarcinomas confirmed pathologically were retrospectively evaluated. Lung nodules were divided into two types: solid nodule (SN) and subsolid nodule (SSN). The maximum diameters on mediastinal window in axial imaging (Dm) and tumor shadow disappearance rate (TDR) were measured. Meanwhile, other computed tomography features of lung nodules were also recorded. TMI represents the geometric mean of normalized CEA and CYFRA 21-1 values, and the discriminatory value of TMI in this study was set at 1.0. The evaluation of discriminatory values for Dm and the TMI between SNs and SSNs was done with Mann-Whitney U-test. The relationship between TDR and TMI in SSNs was evaluated by Pearson correlation analysis. RESULTS: Of 74 cases, 40 cases (54.05%) showed SNs and 34 cases (45.95%) showed SSNs. Dm and TMI were higher in SNs than in SSNs (z = -4.782, P < 0.001; z = -2.647, P = 0.008). TDR demonstrated negative relationship with TMI in SSNs (r = -0.448, P = 0.008). Spiculation (odds ratio [OR] = 14.685; 95% confidence interval [CI]: 2.739-78.729; P = 0.002), nodule type (OR = 6.215; 95% CI: 1.531-25.228; P = 0.011), and gender (OR = 0.227; 95% CI: 0.062-0.833; P = 0.025) were independent factors associated with TMI. CONCLUSIONS: Early-stage lung adenocarcinoma with lower TDR coexisting with spiculation was associated with higher TMI, especially in patients with solid nodule, which tended to have poor prognosis.

Cancers Screening in an Asymptomatic Population by Using Multiple Tumour Markers.

BACKGROUND: Analytic measurement of serum tumour markers is one of commonly used methods for cancer risk management in certain areas of the world (e.g. Taiwan). Recently, cancer screening based on multiple serum tumour markers has been frequently discussed. However, the risk-benefit outcomes appear to be unfavourable for patients because of the low sensitivity and specificity. In this study, cancer screening models based on multiple serum tumour markers were designed using machine learning methods, namely support vector machine (SVM), k-nearest neighbour (KNN), and logistic regression, to improve the screening performance for multiple cancers in a large asymptomatic population. METHODS: AFP, CEA, CA19-9, CYFRA21-1, and SCC were determined for 20 696 eligible individuals. PSA was measured in men and CA15-3 and CA125 in women. A variable selection process was applied to select robust variables from these serum tumour markers to design cancer detection models. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, area under the curve, and Youden index of the models based on single tumour markers, combined test, and machine learning methods were compared. Moreover, relative risk reduction, absolute risk reduction (ARR), and absolute risk increase (ARI) were evaluated. RESULTS: To design cancer detection models using machine learning methods, CYFRA21-1 and SCC were selected for women, and all tumour markers were selected for men. SVM and KNN models significantly outperformed the single tumour markers and the combined test for men. All 3 studied machine learning methods outperformed single tumour markers and the combined test for women. For either men or women, the ARRs were between 0.003-0.008; the ARIs were between 0.119-0.306. CONCLUSION: Machine learning methods outperformed the combined test in analysing multiple tumour markers for cancer detection. However, cancer screening based solely on the application of multiple tumour markers remains unfavourable because of the inadequate PPV, ARR, and ARI, even when machine learning methods were incorporated into the analysis.

The assessment of the prognostic value of tumor markers and cytokines as SCCAg, CYFRA 21.1, IL-6, VEGF and sTNF receptors in patients with squamous cell cervical cancer, particularly with early stage of the disease.

The aim of this study is to determine the prognostic value of tumor markers, as squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragment (CYFRA 21.1) and interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), soluble tumor necrosis factor receptor I (sTNF RI), and sTNF RII in patients with squamous cell carcinoma of the cervix. The subjects of analysis were 138 patients with stage I-IVA according to the International Federation of Gynecology and Obstetrics (FIGO) classification. The collected research material comes from one oncology center. During the 10 years of follow-up, 56 relapses and 53 deaths were observed, and recurrent disease in early stage was confirmed in 45 % of patients. The pretreatment serum levels of SCCAg and CYFRA 21.1, and cytokines IL-6, VEGF, sTNF RI, and sTNF RII were determined in all patients. The probability of disease-free survival (DFS) and overall survival (OS) was evaluated using the log-rank test and the Cox regression model. Based on the ROC curve analysis for patients with recurrence, the largest area under the curve was demonstrated for SCCAg and IL-6 and for patients who died, for SCCAg and VEGF. Cox analysis demonstrated that independent prognostic factor for DFS was only SCCAg and for OS cytokine IL-6 and SCCAg, but in patients with early stage the prognostic value for DFS was VEGF, whereas IL-6 and CYFRA 21.1 for OS. Serum level of VEGF, CYFRA 21.1 and IL-6 before treatment in patients with early stage cervical cancer appears to be an important prognostic factor.

PAP assays in newborn screening for cystic fibrosis: a population-based cost-effectiveness study.

OBJECTIVES: To compare the cost effectiveness of adding a pancreatitis-associated protein (PAP) assay to common immunoreactive trypsinogen (IRT) and DNA cystic fibrosis (CF) newborn screening strategies. METHODS: Using data collected on 553,167 newborns, PAP cut-offs were calculated based on non-inferiority of the detection rates of classical forms of CF. Cost effectiveness was considered from the third-party payer's perspective using only direct medical costs, and the unit costs of PAP assays were assessed based on a micro-costing study. Robustness of the cost-effectiveness estimates was assessed, taking the secondary outcomes of screening (ie. detecting mild forms and CF carriers) into account. RESULTS: IRT/DNA, IRT/PAP, and IRT/PAP/DNA strategies had similar detection rates for classical forms of CF, but the strategies involving PAP assays detected smaller numbers of mild forms of CF. The IRT/PAP strategy was cost-effective in comparison with either IRT/DNA or IRT/PAP/DNA. IRT/PAP/DNA screening was cost-effective in comparison with IRT/DNA if relatively low value was assumed to be attached to the identification of CF carriers. CONCLUSIONS: IRT/PAP strategies could be strictly cost-effective, but dropping DNA would mean the test could not detect CF carriers. IRT/PAP/DNA strategies could be a viable option as they are significantly less costly than IRT/DNA, but still allow CF carrier detection.

Assessment of a Combined Panel of Six Serum Tumor Markers for Lung Cancer.

RATIONALE: We have previously identified six serum tumor markers (TMs) (carcinoembryonic antigen, carbohydrate antigen 15.3, squamous cell carcinoma-associated antigen, cytokeratin-19 fragment, neuron-specific enolase, and pro-gastrin-releasing peptide) related to the presence of lung cancer (LC). OBJECTIVES: To validate their individual performance in an independent cohort, and to explore if their combined assessment (≥1 abnormal TM value) is a more accurate marker for LC presence. METHODS: We determined these six TMs in 3,144 consecutive individuals referred to our institution by their primary care physician because of the clinical suspicion of LC. MEASUREMENTS AND MAIN RESULTS: LC was excluded in 1,316 individuals and confirmed in 1,828 patients (1,563 with non-small cell LC and 265 with small cell LC). This study validated the previously reported performance of each individual TM. We also showed that their combined assessment (≥1 abnormal TM) had a better sensitivity, specificity, negative predictive value, and positive predictive value (88.5, 82, 83.7, and 87.3%, respectively) than each TM considered individually and that it increased the diagnostic performance (area under the curve) of a clinical model that included tumor size, age, and smoking status. In patients with radiographic nodules less than 3 cm, the negative predictive value of the TM panel was 71.8%, hence providing some support for a more conservative diagnostic approach. Finally we identified two TMs (neuron-specific enolase and pro-gastrin-releasing peptide) that differentiate the risk of non-small cell LC from that of small cell LC. CONCLUSIONS: The combined assessment of a panel of six serum TMs is a more accurate marker for LC presence than these same TMs considered individually. The potential of these TMs in the diagnostic and screening settings deserves further research.

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

AIM: To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). PATIENTS AND METHODS: in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). RESULTS: The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). CONCLUSION: The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN.

Pancreatitis-associated protein has no additional value as a marker of disease activity in a real-life cohort of IBD patients.

BACKGROUND AND AIM: Monitoring of mucosal inflammation in inflammatory bowel disease (IBD) is of major importance. New noninvasive markers for intestinal inflammation are needed. Previous studies have reported that pancreatitis-associated protein (PAP) correlates with clinical activity in IBD subgroups. Our aim was to investigate the correlation of serum and fecal PAP with clinical and biochemical parameters of disease activity in a real-life IBD cohort. PATIENTS AND METHODS: Two hundred and five consecutive IBD patients were enrolled. Clinical disease activity was scored by the Harvey-Bradshaw Index or the Simple Clinical Colitis Activity Index; also, C-reactive protein (CRP), erythrocyte sedimentation rate, and fecal calprotectin were determined. As surrogate for endoscopy, a combination score of clinical indices with CRP or calprotectin was used to define active disease. Fecal and serum PAP were measured by ELISA. RESULTS: The median serum and fecal PAP did not differ in Crohn's disease (CD) or ulcerative colitis (UC) patients with active compared with inactive disease according to clinical activity indices. Defining active disease by a combination score of Harvey-Bradshaw Index of more than 4 and CRP of more than 5 mg/l or calprotectin more than 250 µg/g, serum PAP (P=0.01), but not fecal PAP (P=0.32), was significantly higher in active than inactive CD patients. Area under the curve of the corresponding receiver operating curve (ROC) was 0.64. No differences were found in serum or fecal PAP levels using the combination score for active disease in UC. CONCLUSION: Serum but not fecal PAP was higher in active compared with nonactive CD and may reflect mucosal inflammation in CD, but not in UC. However, the accuracy of serum PAP for the diagnosis of active disease was poor, and therefore, serum PAP does not seem to have additional value compared with the current noninvasive markers.

The role of biomarkers in the assessment of prostate cancer risk prior to prostate biopsy: which markers matter and how should they be used?

Prostate cancer (PCa) screening has been substantially influenced by the clinical implementation of serum prostate-specific antigen (PSA). In this context, improvement of early PCa detection and stage migration as well as reduced PCa mortality were achieved, and up-to-date PSA represents the gold standard biomarker of PCa diagnosis together with clinical findings. Nonetheless, PSA shows weakness in discriminating between malign and benign prostatic disease or indolent and aggressive cancers. As a result, the expansion of PSA screening is extensively debated with regard to overdetection and ultimately overtreatment, keeping in mind that PCa is still the third leading cause of cancer-specific mortality in the Western male population. Consequently, today's task is to increase the accuracy of PCa detection and furthermore to allow stratification for indolent PCa that might permit active surveillance and to filter out aggressive cancers necessitating treatment. Thus, novel biomarkers, especially in combination with approved clinical risk factors (e.g., age or family history of PCa), within multivariable prediction models carry the potential to improve many aspects of PCa diagnosis and to enable risk classification in clinical practice. Multivariable models lead to superior accuracy for PCa prediction instead of the use of a single risk factor. The aim of this article was to present an overview of known risk factors for PCa together with new promising blood- and urine-based biomarkers and their application within risk models that may allow risk stratification for PCa prior to prostate biopsy. Risk models may optimize PCa detection and classification with regard to improved PCa risk assessment and avoidance of unnecessary prostate biopsies.

A serum "sweet-doughnut" protein facilitates fibrosis evaluation and therapy assessment in patients with viral hepatitis.

Although liver fibrosis reflects disease severity in chronic hepatitis patients, there has been no simple and accurate system to evaluate the therapeutic effect based on fibrosis. We developed a glycan-based immunoassay, FastLec-Hepa, to fill this unmet need. FastLec-Hepa automatically detects unique fibrosis-related glyco-alteration in serum hyperglycosylated Mac-2 binding protein within 20 min. The serum FastLec-Hepa counts increased with advancing fibrosis and illustrated significant differences in medians between all fibrosis stages. FastLec-Hepa is sufficiently sensitive and quantitative to evaluate the effects of PEG-interferon-α/ribavirin therapy in a short post-therapeutic interval. The obtained fibrosis progression is equivalent to -0.30 stages/year in patients with sustained virological response, and 0.01 stages/year in relapse/nonresponders. Furthermore, long-term follow-up of the severely affected patients found hepatocellular carcinoma developed in patients after therapy whose FastLec-Hepa counts remained above a designated cutoff value. FastLec-Hepa is the only assay currently available for clinically beneficial therapy evaluation through quantitation of disease severity.

Impact of adoption of a decision algorithm including PCA3 for repeat biopsy on the costs for prostate cancer diagnosis in France.

OBJECTIVE: A recent expert study (RAND Appropriateness Method (RAM)) including a panel of 12 European urologists reported that the PCA3 score may be instrumental in taking appropriate prostate biopsy (PBx) decisions, mainly for repeat PBx. This study determined the cost/benefit balance of introducing PCA3 in the decision-making for PBx in France. METHODS: Two RAM models, without and with PCA3, were retrospectively applied to a sample of 808 French men who had PBx in 2010 (78% first, 22% repeat). Outcome measures included the proportion of PBx that could have been avoided (i.e., judged inappropriate) in the French sample according to both RAM models, and the estimated impact of application of these models on the annual number of PBx and associated costs for France (based on most recent published data). RESULTS: Complete profiles were available for 698 men. In the model without PCA3, 2% of PBx were deemed inappropriate. Knowledge of PCA3 would have avoided another 7% of PBx. Repeat PBx would have been avoided in 5% of cases without PCA3 and in 37% with PCA3. For France, application of the RAM model including PCA3 would result in 18,345 fewer repeat PBx. It would be budget-neutral in the unlikely hypothesis of no complications or no costs incurred by complications and would save €1.7 million for a mean cost for complications of €100/procedure or €5 million for a mean cost for complications of €280/procedure, calculated based on US and Canadian data. LIMITATIONS: Limitations of the study are the theoretical nature of the analysis and the fact that PCA3 distributions had to be derived from other sources. CONCLUSIONS: Adoption of RAM expert recommendations including PCA3 for repeat PBx decisions in clinical practice in France would reduce the number of repeat PBx and control costs.