PSA Results Research Articles

Implications of false-positive results for future cancer screenings.

False-positive cancer screening results may affect a patient's willingness to obtain future screening. The authors conducted logistic regression analysis of 450,484 person-years of electronic medical records (2006-2015) in 92,405 individuals aged 50 to 75 years. Exposures were false-positive breast, prostate, or colorectal cancer screening test results (repeat breast imaging or negative breast biopsy ≤3 months after screening mammography, repeat prostate-specific antigen [PSA] test ≤3 months after PSA test result ≥4.0 ng/mL or negative prostate biopsy ≤3 months after any PSA result, or negative colonoscopy [without biopsy/polypectomy] ≤6 months after a positive fecal occult blood test). Outcomes were up-to-date status with breast or colorectal cancer screening. Covariates included prior screening history, clinical information (eg, family history, obesity, and smoking status), comorbidity, and demographics. Women were more likely to be up to date with breast cancer screening if they previously had false-positive mammography findings (adjusted odds ratio [AOR], 1.43 [95% confidence interval, 1.34-1.51] without breast biopsy and AOR, 2.02 [95% confidence interval, 1.56-2.62] with breast biopsy; both P<.001). The same women were more likely to be up to date with colorectal cancer screening (AOR range, 1.25-1.47 depending on breast biopsy; both P<.001). Men who previously had false-positive PSA testing were more likely to be up to date with colorectal cancer screening (AOR, 1.22 [P = .039] without prostate imaging/biopsy and AOR, 1.60 [P = .028] with imaging/biopsy). Results were stronger for individuals with more false-positive results (all P≤.005). However, women with previous false-positive colorectal cancer fecal occult blood test screening results were found to be less likely to be up to date with breast cancer screening (AOR, 0.73; P<.001). Patients who previously had a false-positive breast or prostate cancer screening test were more likely to engage in future screening. Cancer 2018;124:2390-8. © 2018 American Cancer Society.

Prospective evaluation of fluciclovine (18F) PET-CT and MRI in detection of recurrent prostate cancer in non-prostatectomy patients

PurposeTo investigate the disease detection rate, diagnostic performance and interobserver agreement of fluciclovine (18F) PET-CT and multiparametric magnetic resonance imaging (mpMR) in recurrent prostate cancer. MethodsTwenty-four patients with biochemical failure after non-prostatectomy definitive therapy, 16/24 of whom had undergone brachytherapy, underwent fluciclovine PET-CT and mpMR with interpretation by expert readers blinded to patient history, PSA and other imaging results. Reference standard was established via a multidisciplinary truth panel utilizing histology and clinical follow-up (22.9 ± 10.5 months) and emphasizing biochemical control. The truth panel was blinded to investigative imaging results. Diagnostic performance and interobserver agreement (kappa) for the prostate and extraprostatic regions were calculated for each of 2 readers for PET-CT (P1 and P2) and 2 different readers for mpMR (M1 and M2). ResultsOn a whole body basis, the detection rate for fluciclovine PET-CT was 94.7% (both readers), while it ranged from 31.6–36.8% for mpMR. Kappa for fluciclovine PET-CT was 0.90 in the prostate and 1.0 in the extraprostatic regions. For mpMR, kappa was 0.25 and 0.74, respectively.In the prostate, 22/24 patients met the reference standard with 13 malignant and 9 benign results. Sensitivity, specificity and positive predictive value (PPV) were 100.0%, 11.1% and 61.9%, respectively for both PET readers. For mpMR readers, values ranged from 15.4–38.5% for sensitivity, 55.6–77.8% for specificity and 50.0–55.6% for PPV.For extraprostatic disease determination, 18/24 patients met the reference standard. Sensitivity, specificity and PPV were 87.5%, 90.0% and 87.5%, respectively, for fluciclovine PET-CT, while for mpMR, sensitivity ranged from 50 to 75%, specificity 70–80% and PPV 57–75%. ConclusionThe disease detection rate for fluciclovine PET-CT in non-prostatectomy patients with biochemical failure was 94.7% versus 31.6–36.8% for mpMR. For extraprostatic disease detection, fluciclovine PET-CT had overall better diagnostic performance than mpMR. For the treated prostate, fluciclovine PET-CT had high sensitivity though low specificity for disease detection, while mpMR had higher specificity, though low sensitivity. Interobserver agreement was also higher with fluciclovine PET-CT compared with mpMR.

Representing Uncertainty In Economic Evaluations: Getting More From PSA Results

Representing Uncertainty In Economic Evaluations: Getting More From PSA Results

Risk mitigation strategy by Passive IN-core Cooling system for advanced nuclear reactors

After the Fukushima accident, the installation of passive safety systems for nuclear power plants becomes necessary as protection against external power failures. Recently, an innovative safety system was introduced by employing a hybrid heat-pipe concept asa Passive IN-core Cooling system (PINCs). The hybrid heat-pipe concept employs the combination of a control rod and a heat pipe to passively shutdown a reactor in an accident condition and simultaneously remove decay heat from the core. As a result, a PINCs can handle the entire accident sequence in a single system, leading to significant enhancement in nuclear reactor safety. In this study, the safety enhancement of various nuclear reactors has been quantitatively evaluated by using the probabilistic safety assessment method (PSA). PSA models of the APR1400, PGSFR, and SMART nuclear reactors developed in Korea, are developed, and a PINCs model has been applied to each reactor. The PSA model of the PINCs has been developed based on the systematic design and configuration of each reactor. In addition, postulated accident sequences where the PINCs operates have been developed in the PSA model. Finally, the consequence of each accident sequence has been quantitatively evaluated in the form of core damage frequency (CDF) and minimal cut set (MCS) for each nuclear reactor. Based on the PSA results, it is confirmed that the application of the PINCs effectively reduces the overall CDF of all nuclear reactors. In addition, the failure paths causing the core damage are restricted for APR1400 and PGSFR. In conclusion, the employment of the PINCs significantly improved the overall safety degrees of various nuclear reactors.

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga68-PSMA PET/CT in patients with recurrent PCa. A total of 109 consecutive patients (median age 71years; range 48-89years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented. In 91(83.4%) patients at least one lesion characteristic for PCa was detected by68Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640)ng/ml.There was a significant difference between 68Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67ng/ml for distinguishing between positive and negative 68Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993). 68Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68Ga-PSMA PET/CT results.

Effect of power uprate on core damage frequency in a MBLOCA with multiple operator actions

In the present study, the methodology developed by the Committee on the Safety of Nuclear Installations (CSNI) of Nuclear Energy Agency was used to quantify the changes in core damage frequency (CDF) owing to a power uprate. The Maanshan Nuclear Power Station of Taiwan Power Company was the plant selected for the analysis. The plant employs a 3-loop pressurized water reactor designed by Westinghouse. The power level was increased from 102% to 105%. The sequence analyzed corresponded to a medium-break loss-of-coolant accident with a break size of 3in. There were two operator actions in the accident mitigation. These actions were the emergency cooldown and depressurization (CND) of RCS and the lineup the high-head safety recirculation (HHSR) when RWST was empty.In the present study, the success of operator action was judged based on the results of the simulation of system thermal hydraulic code, RELAP5-3D. An uncertainty analysis of code calculation was performed. There were 20 parameters in PIRT table, and 124 sets of input data were generated using the Monte Carlo Sampling technique. The times for the operators to execute CND and HHSR were included as one of the parameter in the uncertainty analysis. The results demonstrated that, compared with the PSA results using the conventional HEP model, the CDF of MBLOCA increased by 188%. The dominant core damage sequence in MBLOCA was also changed.The simulation results showed that the CND failure probability increased by 23% after the power uprate. The sequence CDF increased by 16% after the power uprate. The results of the importance analyses indicated that the time to execute CND was not a significant factor in determining the success of CND. The uncertainty involved in the simulations of reactor coolant system thermal hydraulic responses is important in the determination of human error probability.

A comparison of 3 on-line nomograms with the detection of primary circulating prostate cells to predict prostate cancer at initial biopsy

IntroductionThe use of nomograms which include the PSA may improve the predictive power of obtaining a prostate biopsy (PB) positive for cancer. We compare the use of three on-line nomagrams with the detection of primary malignant circulating prostate cells (CPCs) to predict the results of an initial PB in men with suspicion of prostate cancer. Methods and patientsConsecutive men with suspicion of prostate cancer underwent a 12 core TRUS prostate biopsy; age, total serum PSA, percent free PSA, family history, ethnic origin and prostate ultrasound results were used for risk assessment using the online nomograms.Mononuclear cells were obtained by differential gel centrifugation from 8ml of blood and CPCs were identified using double immunomarcation with anti-PSA and anti-P504S. A CPC was defined as a cell expressing PSA and P504S and defined as negative/positive. Biopsies were classified as cancer/no-cancer. Areas under the curve (AUC) for each parameter were calculated and compared and diagnostic yields were calculated. Results1223 men aged >55 years participated, 467 (38.2%) had a biopsy positive for cancer of whom 114/467 (24.4%) complied with the criteria for active observation. Area under the curve analysis showed CPC detection to be superior (p<0.001), avoiding 57% of potential biopsies while missing 4% of clinically significant prostate cancers. ConclusionsThe CPC detection was superior to the nomograms in predicting the presence of prostate cancer at initial biopsy; its high negative predictive value potentially reduces the number of biopsies while missing few significant cancers, being superior to the nomograms in this aspect. Being a positive/negative test the detection of CPCs avoids defining a cutoff value which may differ between populations.

Determination of PAR configuration for PWR containment design: A hydrogen mitigation strategy

This paper deals with determination of the minimum number and identification of the best configurations of passive autocatalytic recombiners (PAR) for the effective design of the containment in a pressurized water reactor (PWR). It considers the current design of PAR in the containment of a PWR and for that tries to identify, through a large number of sensitivity analyses, the minimum required number of PARs in different compartments. In this regard, a qualified nodalization has been developed for best estimate modeling by MELCOR integrated code. The developed model includes primary and secondary systems, containment, and related safety systems. A large number of simulations including the plant specific probabilistic safety assessment and success criteria analysis are used to identify the accident scenario with the highest amount of hydrogen production and risk. We first screened postulated accidents based on the PSA results and then based on the deterministic severe accident computations. It is found that the large break loss of coolant accident (LB-LOCA) without emergency core cooling system (ECCS) actuation is the bounding case from the hydrogen hazard point of view. To find the optimal configuration with minimum number of PARs in the containment, 40 different configurations are analyzed for the selected accident for a Westinghouse type PWR. The main finding of this work is identification of the minimum required number of PARs and their best distribution among the associated compartments. The obtained configuration is equally effective for the hydrogen risk mitigation with 36% reduction in the number of PARs in comparison to the base case design. The methodology of the analysis can be used for other plants.

Comparación de 3 nomogramas en línea con la detección de las células primarias circulantes de la próstata para predecir el cáncer de próstata en la biopsia inicial

IntroductionThe use of nomograms which include the PSA may improve the predictive power of obtaining a prostate biopsy (PB) positive for cancer. We compare the use of three on-line nomagrams with the detection of primary malignant circulating prostate cells (CPCs) to predict the results of an initial PB in men with suspicion of prostate cancer. Methods and patientsConsecutive men with suspicion of prostate cancer underwent a 12 core TRUS prostate biopsy; age, total serum PSA, percent free PSA, family history, ethnic origin and prostate ultrasound results were used for risk assessment using the online nomograms.Mononuclear cells were obtained by differential gel centrifugation from 8ml of blood and CPCs were identified using double immunomarcation with anti-PSA and anti-P504S. A CPC was defined as a cell expressing PSA and P504S and defined as negative/positive. Biopsies were classified as cancer/no-cancer. Areas under the curve (AUC) for each parameter were calculated and compared and diagnostic yields were calculated. Results1,223 men aged>55 years participated, 467 (38.2%) had a biopsy positive for cancer of whom 114/467 (24.4%) complied with the criteria for active observation. Area under the curve analysis showed CPC detection to be superior (p<0.001), avoiding 57% of potential biopsies while missing 4% of clinically significant prostate cancers. ConclusionsThe CPC detection was superior to the nomograms in predicting the presence of prostate cancer at initial biopsy; its high negative predictive value potentially reduces the number of biopsies while missing few significant cancers, being superior to the nomograms in this aspect. Being a positive/negative test the detection of CPCs avoids defining a cutoff value which may differ between populations.

Clarifying the PSA grey zone: The management of patients with a borderline PSA.

Prostate specific antigen is a marker for prostate cancer and a key diagnostic tool, yet when to refer patients with a borderline PSA is currently unclear. This review describes how to assess a patient with borderline PSA and provides an algorithm for management. Current literature on reference values, factors affecting PSA, indications for referral, non-invasive investigations and the role of MRI were reviewed. Medline and EMBASE were searched using MeSH terms. The literature suggests that a PSA of over 1.5ng/mL should be used as a cut-off to consider further testing for all age groups. There is strong evidence to show that adjuncts are useful when interpreting PSA results, most notably percentage free PSA and proPSA. Considerable weighting should also be given to the ERSPC risk calculator when deciding when to refer. Multi-parametric MRI is valuable in closely examining suspicious lesions to reduce the number of negative biopsies. MRI fusion biopsy (TRUS, transrectal ultrasonography or transperineal) should be considered over standard TRUS biopsy to detect more clinically significant disease. Management of borderline PSA is not straightforward. A cut-off of 1.5ng/mL should be used in conjunction with digital rectal exam, risk calculation and PSA adjuncts. Imaging and biopsy should utilise mpMRI to achieve improved diagnosis of clinically significant prostate cancer, with fewer unnecessary investigations.

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance.

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using 11C-choline PET/CT

ObjectiveTo assess the prognostic value of the therapeutic response by 11C-choline PET/CT in prostate cancer patients with biochemical recurrence in which 11C-choline PET/CT indicated radio-guided radiotherapy. MethodsThe study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. 11C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings.One year after treatment patients underwent PSA and 11C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. Results11C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimeter in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimeter and 10 (27.0%) only less than a centimeter in size.The response by 11C-choline PET/CT was categorized one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression.The response was concordant between the PSA result and 11C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%).New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). Conclusion11C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique.The evaluation of therapeutic response by 11C-choline PET/CT has prognostic significance.

Inclusion of corrected calcium and creatinine levels in a novel nomogram for prediction of pathologically localized prostate cancer.

140 Background: The role of routine parameters in the prediction of organ-confined Prostate Cancer (oPCa) remains unclear. Methods: We conducted a retrospective study of 246 patients with PCa diagnosed on biopsy, who underwent radical prostatectomy with extended lymph node dissection. None of these patients received a neoadjuvant therapy. Gleason score (xGLS), percent of positive cores involved by PCa (pCores), results of transrectal evaluation (TRUS, DRE), prostate volume (PVol), albumin-corrected Calcium (Ca), Hemoglobin (Hb), Creatinine (Crea), PSA, and age at RPE were considered. Postoperative variables including Gleason score (pGLS), TNM stages were evaluated. These patients were divided according to disease advancement into pathologically localized (pT2) and advanced PCa (pT3/4 or pN1). A L2 penalized regression model including all preoperative parameters was evaluated to design a nomogram for oPCa prediction. Furthermore, the internal validation of the nomogram was performed using bootstrapping and cross-validations. The precision and accuracy of the novel nomogram were evaluated by using AUC, F-Score, Brier-Score and the classification accuracy (CA). Results: The lowest probability for pathologically localized PCa was found in patients having the following features: PSA &gt; 20 ng/ml, detection of PCa in all cores, high Ca [1.21 fold over upper normal limit (ULN)] and Crea levels (2.27 fold over ULN), xGls &gt; 7 and normal PVol. A nomogram for oPCa was developed including the following parameter: Crea, Ca, PSA, xGls, PVol, TRUS, pCores. The sensitivity and the specificity of the nomogram for prediction of pathologically localized PCa were 92.2% and 35.9%, respectively. AUC of 0.811, CA of 80.1%, F-Score 0.879, a precision of 84.0%. and Brier-Score of 0.2599 were calculated. The predicted probability of the novel nomogram was associated with higher accuracy for prediction of oPCa compared to those of Partin table and Kattan nomogram. Conclusions: Serum creatinine and corrected calcium are indpendent predictors of oPCa. The novel nomogram can predict oPCa with high precision and accuracy. However, an external validation of the novel nomogram is needed.

Biopsia prostática randomizada: ¿influye el número de muestras y el valor del PSA para la detección del cáncer prostático?

ObjectiveTo determine whether obtaining a larger number of core specimens, depending on the PSA value, increases the detection of prostate cancer. Materials and methodsA cross-sectional study was conducted on 994 patients with suspected prostate cancer who underwent transrectal ultrasound-guided prostate biopsy. The patients were divided into group A with a standard protocol (8 core specimens or more scheme) and group B with an extended protocol (12 core specimens or more scheme), and subdivided according to the PSA values into three groups (<3.9ng/ml, 4 to 9.9ng/ml, and >10ng/ml). The prostate cancer detection rate was evaluated in each subgroup. Clinical data was analysed using the Student t and chi-squared tests and logistic regression analysis, taking a P<0.05 as statistically significant. ResultsThe detection rate of prostate cancer in the group A was higher than group B: 43.71% vs. 34.29%; P=0.022. When analysing the results, taking into account the sub-division of PSA results, no significant statistical differences were found in the detection of malignancy in the two groups of patients evaluated. ConclusionIncreasing the number of core specimens in transrectal ultrasound-guided prostate biopsy, does not increase the overall detection rate of prostate cancer in either of the PSA sub-groups, or in either of the of prostate volume sub-groups. On the other hand, the older the patient and the higher the PSA value, the greater the detection of prostate cancer.

Impact of country-specific EQ-5D-3L tariffs on the economic value of systemic therapies used in the treatment of metastatic pancreatic cancer.

Previous Canadian cost-effectiveness analyses in cancer based on the EQ-5D-3L (EuroQoL, Rotterdam, Netherlands) have commonly used U.K. or U.S. tariffs because the Canadian equivalent only just recently became available. The implications of using non-Canadian tariffs to inform decision-making are unclear. We aimed to reevaluate an earlier cost-effectiveness analysis of therapies for metastatic pancreatic cancer (originally performed using U.S. tariffs) with tariffs from Canada and various other countries to determine the impact of using non-country-specific tariffs. We used tariffs from Canada, the United States, the United Kingdom, Denmark, France, Germany, Japan, the Netherlands, and Spain to derive EQ-5D-3L utilities for the 10 health states in the pancreatic cancer model. Quality-adjusted life years (qalys) and incremental cost-effectiveness ratios (icers) were generated, and probabilistic sensitivity analyses (psas) were performed. Canadian utilities are generally lower than the corresponding U.S. utilities and higher than those for the United Kingdom. Compared with the Canadian-valued scenarios, U.S. and U.K. estimates were statistically different for 3 and 9 scenarios respectively. Overall, 35% of the non-Canadian utilities (28 of 80) were significantly different, clinically, from the Canadian values. Canadian qalys were 6% lower than those for the United States and 6% higher than those for the United Kingdom. When comparing the qalys of each treatment with those of gemcitabine alone, the average percent change was +6.8% for a U.S. scenario and -7.5% for a U.K. scenario compared with a Canadian scenario. Consequently, Canadian icers were approximately 5.4% greater than those for the United States and 8.6% lower than those for the United Kingdom. Based on the psas and compared with the Canadian threshold value, the minimum willingness-to-pay threshold at which the combination chemotherapy regimen of gemcitabine-capecitabine is the most cost-effective is $5,239 less than in the United States and $11,986 more than in the United Kingdom. The use of non-country-specific tariffs leads to significant differences in the derived utilities, icers, and psa results. Past Canadian EQ-5D-3L-based cost-effectiveness analyses and related funding decisions might need to be re-visited using Canadian tariffs.

Severe accident mitigation strategy for the generation II PWRs in France – Some outcomes of the on-going periodic safety review of the French 1300 MWe PWR series

The 3rd Periodic Safety Review of the French 1300 MWe PWRs series includes some modifications to increase their robustness in case of a severe accident. Their review is based on both deterministic and probabilistic approaches, keeping in mind that severe accidents frequencies and radiological consequences should be as low as reasonably practicable, severe accidents management strategies should be as safe as possible and the robustness of equipment used for severe accident management should be ensured.Consequently, the IRSN level 2 probabilistic safety assessment (L2 PSA) studies for the 1300 MWe reactors have been used to re-assess the results of the utility's L2 PSA and rank them to identify the containment failure modes contributing the most to the global risk. This ranking helped the review of plant modifications.Regarding strategies for accident management, the EDF management of water in the reactor cavity during a severe accident for the 1300 MWe PWRs is presented as well as the IRSN position on this strategy: this is an example where the optimal severe accident management strategy choice is not so easy to define.Regarding the robustness of equipment used for severe accident management, the interest of a diversification or redundancy of the French emergency filtered containment venting opening is one example among many others.This paper presents the analysis conducted by IRSN during the 3rd periodic safety review of the French 1300 MWe PWRs. Future NPP upgrades to limit radioactive releases in case of containment filtered venting, to prevent containment venting and basemat melt-through are analysed in another framework (post-Fukushima and long-term operation projects).

DIAGNOSTIC CONSIDERATION OF RADIAL IMAGING METHODS IN IDENTIFYING LOCAL RECURRENCE OF PROSTATE CANCER AFTER RADICAL PROSTATECTOMY

The diagnostic consideration of the most commonly used methods of radial diagnostics in identifying local recurrence of prostate cancer after radical prostatectomy in patients with biochemical recurrence is reflected in the literature review. The identified level of PSA after radical prostatectomy can argue for both local recurrence, the presence of tumor dissemination, and a residual prostate tissue without tumor that was left on the edge of the cut. With the purpose of early diagnosis of prostate cancer recurrence, it is advisable to monitor PSA levels after 3 months after radical prostatectomy. In case of growth of PSA levels after radical prostatectomy, it is necessary to answer the question: whether the recurrence is local or metastatic. Modern imaging methods, such as transrectal ultrasound examination, bone scanning, multislice computed tomography, positron emission tomography and endorectal magnetic resonance imaging provide excluding or establishing the presence of recurrence of prostate cancer after radical prostatectomy. It should be noted that none of the methods of radiodiagnostics are not ahead of the results of PSA in the identification of local recurrence of prostate cancer after radical prostatectomy; however, in their complex application, prostate cancer recurrent after radical prostatectomy can be visualized at its earliest stages.

Patients with Persistently Elevated PSA and Negative Results of TRUS-Biopsy: Does 6-Month Treatment with Dutasteride can Indicate Candidates for Re-Biopsy. What is the Best of Saturation Schemes: Transrectal or Transperineal Approach?

To identify patients who actually need a re - biopsy, based on alterations in PSA readings after 6-month treatment with Dutasteride. We also sought to bring out the most beneficial re-biopsy scheme. We have reviewed the records of patients with persistently elevated PSA and at least one set of TRUS biopsies. Patients who were treated with alpha -blockers/Dutasteride combination were considered as the study group, while patients in control received alpha-blockers alone. Patients in both groups underwent re-biopsy 6 months later. The two protocols of re-biopsies were used at that time: 20-24 cores saturation transrectal (ST)) and ≥ 40 cores saturation transperineal template-guided (STT) biopsies. One hundred thirty-three patients were included in this study. In 86.7 % of the patients in the study group mean PSA decreased from 7.4 ± 2.69 to 4.037 ± 1.53 (p-0.001). The overall cancer detection rate was 29 % (n-39: 19 v/s 20, control and study groups, respectively). In the study group PSA decreased to 26.73 ± 11.26 % in patients with cancer, compared with 40.54 ± 13.3 % in patients without. It must be emphasized that STT-biopsies detected significantly more cancers (38.46 v/s 20.59 %, p- 0.005). Mean cores number got to 21 ± 2.45 and 45 ± 5.65 in ST and STT biopsies, respectively. Six-month treatment with Dutasteride decreases PSA readings in 86.7 % of the patients. A PSA decline of less than 40% (cutoff) should be considered as an indicator for re-biopsy. Transperineal template-guided biopsies had a higher cancer detection rate.

Variação de dados clínicos e histológicos com o Grau de Gleason na Biópsia Prostática

Introduction: In Europe, prostate cancer is the most common solid neoplasm in males. In most cases the diagnosis is made by prostate biopsy following changes in PSA or digital rectal exam (DRE). The Gleason score is a key element in addressing prostate carcinoma, with particular importance in treatment decisions and long-term prognosis.Objective: This study aims to assess the interrelationship between Gleason and DRE, age, PSA, ultrasound study and histological results in patients undergoing transrectal prostate biopsy.Materials and methods: Retrospective study of 290 transrectal ultrasound-guided prostate biopsies performed between January 2012 and December 2013. 10 cases were excluded due to lack of relevant information in the clinical file or repeated biopsy.Results: Of the 280 prostatic biopsies evaluated, 156 (55.7%) showed acinar adenocarcinoma of the prostate. The mean age of patients with carcinoma was statistically higher than those without histological evidence of adenocarcinoma (p = 0.001). The PSA ranged between 0.4 and 541ng/ml: in the subset of negative biopsy the average was 8.88 (± 4.49) ng/ml compared with 37.51 (± 73.79) ng/ml for the sub-group of Prostate Adenocarcinoma (p < 0.001). PSA also changed significantly within Gleason score: the mean PSA in patients with poorly differentiated carcinomas was superior to those with well or moderately differentiated carcinomas (p < 0.001). The DRE is described in 265 patients and suspicious in 115 (43.4%): the positive and negative predictive value was 82.6% and 64.7%, respectively, showing a higher sensitivity for diagnosis of high-grade tumors (Gleason ≥ 4+3).This study also revealed a statistically significant relationship between the degree of tumor differentiation and ultrasound study, presence of perineural invasion, number of positive fragments and maximum involvement exceeding 50% per fragment.Discussion / Conclusion: This study aims to demonstrate the differences between age, PSA, DRE, existence of hypoechoic nodules and histological data of prostate biopsy in well or moderately differentiated adenocarcinoma of the prostate (Gleason ≤ 3 +4) versus poorly differentiated (Gleason ≥ 4+3).© 2014 Associação Portuguesa de Urologia. Published by Elsevier España, S.L.U. All rights reserved.

761PD - Novel Antiandrogen Arn-509 in High-Risk Non-Metastatic (M0) Castration-Resistant Prostate Cancer (Crpc)

ABSTRACT Aim: ARN-509 selectively binds the androgen receptor and impairs its nuclear translocation and DNA binding to androgen response elements. Study ARN-509-001 evaluates ARN-509 activity in pts with high-risk M0 CRPC, chemotherapy-naive metastatic CRPC (mCRPC), and mCRPC post abiraterone acetate. We report the updated results for the M0 CRPC cohort as of February 2014. Methods: All pts had CRPC with no radiographic evidence of metastases (pelvic lymph nodes Results: M0 CRPC cohort enrolled 51 pts from Nov 2011 to Jun 2012; 4 pts had metastatic disease and were excluded from the efficacy analysis. Median age was 71 years (range 51–88). Baseline characteristics were: ECOG performance status, 0 (76%); Gleason score, ≤ 7 (57%); median PSA, 10.7 ng/mL (range 0.5-201.7); and PSADT, ≤ 10 mos (45%). All pts received prior treatment with a luteinizing hormone–releasing hormone analog with or without a first-generation antiandrogen. At median follow-up of 20.2 mos, 29 (57%) pts remain on study. Pts discontinued due to disease progression (n = 7), adverse events (AEs) (n = 7), or other reasons (n = 8). Most common treatment-emergent AEs: fatigue (57%), diarrhea (41%), nausea (29%), dysgeusia (20%), arthralgia (18%), and weight decreased (16%). No seizures were reported. Efficacy M0 CRPC N 47 PSA responsea,b, n (%) 12 wks 42/46 (91) 24 wks 40/46 (87) 36 wks 22/46 (48) Median time to PSA progression, wks (95% CI) NR (67, NR) Median MFS, wks (95% CI) NR (NR, NR) NR, not reached. a≥ 50% decline in PSA from baseline per PCWG2. b1 pt did not have postbaseline PSA results. Conclusions: ARN-509 is well tolerated in pts with high-risk M0 CRPC with robust activity based on durable PSA responses and disease control. Disclosure: M.R. Smith: has served as a consultant/advisor to and received research funding from Janssen; E.S. Antonarakis: has received honoraria and research funding from Janssen; C.J. Ryan: has received honoraria from Janssen;W. Berry: has served on a speaker bureau for Janssen;N.D. Shore: has served as a consultant/advisor to Astellas, Algeta, Bayer, Ferring, Dendreon, Janssen, Millennium, Sanofi, and BNIT;G. Liu: has received research funding from Aragon and Janssen;C. Higano: has served as a consultant/advisor to Astellas/Medivation, Bayer, Dendreon, and Johnson & Johnson, and has received research funding from Algeta, Aragon, Astellas/Medivation, Dendreon, and Sanofi;R. Bandekar, C. De Boer, M. Todd and M. Yu: is an employee of Janssen and holds stock in Johnson & Johnson;D.E. Rathkopf: has served as a consultant/advisor for Johnson & Johnson and has received research funding (uncompensated) from Celgene, Janssen/J&J, Medivation/Astellas, Millennium, and Novartis. All other authors have declared no conflicts of interest.