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1. Comparative Evaluation of Urinary PCA3 and TMPRSS2: ERG Scores and Serum PHI in Predicting Prostate Cancer Aggressiveness

Author

Lucile Tallon, Devillier Luangphakdy, Alain Ruffion, Marc Colombel, Marian Devonec, Denis Champetier, Philippe Paparel, Myriam Decaussin-Petrucci, Paul Perrin, and Virginie Vlaeminck-Guillem

Subjects
urine biomarker, prostate cancer, PCA3, TMPRSS2-ERG gene fusion, PHI, radical prostatectomy, aggressiveness, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

It has been suggested that urinary PCA3 and TMPRSS2:ERG fusion tests and serum PHI correlate to cancer aggressiveness-related pathological criteria at prostatectomy. To evaluate and compare their ability in predicting prostate cancer aggressiveness, PHI and urinary PCA3 and TMPRSS2:ERG (T2) scores were assessed in 154 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. Univariate and multivariate analyses using logistic regression and decision curve analyses were performed. All three markers were predictors of a tumor volume ≥0.5 mL. Only PHI predicted Gleason score ≥7. T2 score and PHI were both independent predictors of extracapsular extension (≥pT3), while multifocality was only predicted by PCA3 score. Moreover, when compared to a base model (age, digital rectal examination, serum PSA, and Gleason sum at biopsy), the addition of both PCA3 score and PHI to the base model induced a significant increase (+12%) when predicting tumor volume >0.5 mL. PHI and urinary PCA3 and T2 scores can be considered as complementary predictors of cancer aggressiveness at prostatectomy.

Published
2014
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2. PCA3 and PCA3-Based Nomograms Improve Diagnostic Accuracy in Patients Undergoing First Prostate Biopsy

Author

Virginie Vlaeminck-Guillem, Paul Perrin, Philippe Paparel, Claire Rodriguez-Lafrasse, Myriam Decaussin-Petrucci, Alain Ruffion, Denis Champetier, and Marian Devonec

Subjects
urine biomarker, nomogram, initial prostate biopsy, prostate cancer, prostate cancer antigen 3, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen’s and Chun’s nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun’s and Hansen’s nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.

Published
2013
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3. Technique of Injection of Hyaluronic Acid as a Prostatic Spacer and Fiducials Before Hypofractionated External Beam Radiotherapy for Prostate Cancer

Author

A. Faix, O. Chapet, Xavier Rebillard, Corina Udrescu, Philippe Paparel, Romain Boissier, Alain Ruffion, Jean-Etienne Terrier, Marian Devonec, David Azria, Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Service d'urologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hospices Civils de Lyon (HCL), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Clinique Beau Soleil [Montpellier]

Subjects
Male, medicine.medical_specialty, Urology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Rectum, Endosonography, Injections, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Fiducial Markers, Prostate, medicine, Humans, Local anesthesia, External beam radiotherapy, Hyaluronic Acid, Radiation Injuries, ComputingMilieux_MISCELLANEOUS, Aged, Viscosupplements, medicine.diagnostic_test, business.industry, Dose fractionation, Prostatic Neoplasms, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Surgery, Radiation therapy, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Dose Fractionation, Radiation, Radiotherapy, Intensity-Modulated, Nuclear medicine, business, Radiotherapy, Image-Guided
Abstract

Objective To describe a technique combining the implantation of fiducials and a prostatic spacer (hyaluronic acid [HA]) to decrease the rectal toxicity after an image-guided external beam radiotherapy (EBRT) with hypofractionation for prostate cancer and to assess the tolerance and the learning curve of the procedure. Materials and Methods Thirty patients with prostate cancer at low or intermediate risk were included in a phase II trial: image-guided EBRT of 62 Gy in 20 fractions of 3.1 Gy with intensity-modulated radiotherapy. A transrectal implantation of 3 fiducials and transperineal injection of 10 cc of HA (NASHA gel spacer, Q-Med AB, Uppsala, Sweden) between the rectum and the prostate was performed by 1 operator. The thickness of HA was measured at 10 points on magnetic resonance imaging to establish a quality score of the injection (maximum score = 10) and determine the learning curve of the procedure. Results The quality score increased from patients 1-10, 11-20, to 21-30 with respective median scores: 7 [2-10], 5 [4-7], and 8 [3-10]. The average thicknesses of HA between the base, middle part, and apex of the prostate and the rectum were the following: 15.1 mm [6.4-29], 9.8 mm [5-21.2], and 9.9 mm [3.2-21.5]. The injection of the HA induced a median pain score of 4 [1-8] and no residual pain at mid-long term. Conclusion Creating an interface between the rectum and the prostate and the implantation of fiducials were feasible under local anesthesia with a short learning curve and could become a standard procedure before a hypofractionated EBRT for prostate cancer.

Published
2017

4. PCA3 and PCA3-Based Nomograms Improve Diagnostic Accuracy in Patients Undergoing First Prostate Biopsy

Author

Marian Devonec, Claire Rodriguez-Lafrasse, Alain Ruffion, Paul Perrin, Virginie Vlaeminck-Guillem, Myriam Decaussin-Petrucci, Philippe Paparel, and D. Champetier

Subjects
Male, PCA3, medicine.medical_specialty, Prostate biopsy, Biopsy, Urology, urologic and male genital diseases, Article, Catalysis, Inorganic Chemistry, nomogram, lcsh:Chemistry, Prostate cancer, Prostate, Humans, Medicine, Prostate Cancer Prevention Trial, urine biomarker, initial prostate biopsy, prostate cancer, prostate cancer antigen 3, Prospective Studies, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Aged, medicine.diagnostic_test, business.industry, Organic Chemistry, Prostatic Neoplasms, General Medicine, Middle Aged, Prostate-Specific Antigen, Nomogram, medicine.disease, Computer Science Applications, Prostate-specific antigen, medicine.anatomical_structure, lcsh:Biology (General), lcsh:QD1-999, business
Abstract

While now recognized as an aid to predict repeat prostate biopsy outcome, the urinary PCA3 (prostate cancer gene 3) test has also been recently advocated to predict initial biopsy results. The objective is to evaluate the performance of the PCA3 test in predicting results of initial prostate biopsies and to determine whether its incorporation into specific nomograms reinforces its diagnostic value. A prospective study included 601 consecutive patients addressed for initial prostate biopsy. The PCA3 test was performed before ≥12-core initial prostate biopsy, along with standard risk factor assessment. Diagnostic performance of the PCA3 test was evaluated. The three available nomograms (Hansen’s and Chun’s nomograms, as well as the updated Prostate Cancer Prevention Trial risk calculator; PCPT) were applied to the cohort, and their predictive accuracies were assessed in terms of biopsy outcome: the presence of any prostate cancer (PCa) and high-grade prostate cancer (HGPCa). The PCA3 score provided significant predictive accuracy. While the PCPT risk calculator appeared less accurate; both Chun’s and Hansen’s nomograms provided good calibration and high net benefit on decision curve analyses. When applying nomogram-derived PCa probability thresholds ≤30%, ≤6% of HGPCa would have been missed, while avoiding up to 48% of unnecessary biopsies. The urinary PCA3 test and PCA3-incorporating nomograms can be considered as reliable tools to aid in the initial biopsy decision.

Published
2013
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5. Down-regulation of DcR2 sensitizes androgen-dependent prostate cancer LNCaP cells to TRAIL-induced apoptosis

Author

Catherine Deschildre, David Vindrieux, Marian Devonec, Renée Grataroli, Sadok Yakoub, Jacqueline Chantepie, Marie Reveiller, Mohamed Benahmed, Alain Ruffion, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Medicine and Pathology, NYU Langone Medical Center, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), SFR Biosciences, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), This work has been funded by INSERM Contract grant sponsor: Association pour la Recherche sur les Tumeurs de la Prostate (ARTP), Fondation pour la Recherche Médicale (FRM) and Association pour la Recherche contre le Cancer (ARC), fellowship to DV. Contract grant sponsor: Ligue Contre Le Cancer: Comité de l'Ardèche & Comité de la Drôme, to RG., Grataroli, Renee, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), and BMC, Ed.

Subjects
Cancer Research, medicine.medical_specialty, Programmed cell death, medicine.drug_class, Receptor expression, TRAIL, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, urologic and male genital diseases, lcsh:RC254-282, Androgen, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, tumeur, [SDV.CAN] Life Sciences [q-bio]/Cancer, Downregulation and upregulation, Internal medicine, LNCaP, Genetics, medicine, trail, dcr2, prostate cancer, apoptosis, androgen, oncology, lcsh:QH573-671, Receptor, 030304 developmental biology, 0303 health sciences, business.industry, lcsh:Cytology, Prostate Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cancer de la prostate, Endocrinology, Oncology, 030220 oncology & carcinogenesis, Cancer research, DcR2, Primary Research, business
Abstract

Background Dysregulation of many apoptotic related genes and androgens are critical in the development, progression, and treatment of prostate cancer. The differential sensitivity of tumour cells to TRAIL-induced apoptosis can be mediated by the modulation of surface TRAIL receptor expression related to androgen concentration. Our previous results led to the hypothesis that downregulation of TRAIL-decoy receptor DcR2 expression following androgen deprivation would leave hormone sensitive normal prostate cells vulnerable to the cell death signal generated by TRAIL via its pro-apoptotic receptors. We tested this hypothesis under pathological conditions by exploring the regulation of TRAIL-induced apoptosis related to their death and decoy receptor expression, as also to hormonal concentrations in androgen-sensitive human prostate cancer, LNCaP, cells. Results In contrast to androgen-insensitive PC3 cells, decoy (DcR2) and death (DR5) receptor protein expression was correlated with hormone concentrations and TRAIL-induced apoptosis in LNCaP cells. Silencing of androgen-sensitive DcR2 protein expression by siRNA led to a significant increase in TRAIL-mediated apoptosis related to androgen concentration in LNCaP cells. Conclusions The data support the hypothesis that hormone modulation of DcR2 expression regulates TRAIL-induced apoptosis in LNCaP cells, giving insight into cell death induction in apoptosis-resistant hormone-sensitive tumour cells from prostate cancer. TRAIL action and DcR2 expression modulation are potentially of clinical value in advanced tumour treatment.

Published
2011

6. Advantages of prostate-specific antigen (PSA) clearance model over simple PSA half-life computation to describe PSA decrease after prostate adenomectomy

Author

Paul Perrin, Brigitte Tranchand, Emilie Henin, Gilles Freyer, Cécile Fournel, Benjamin Ribba, Michel Tod, Philippe Paparel, Claire Falandry, Pascal Girard, Marian Devonec, Alain Ruffion, Benoit You, Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Léon Bérard [Lyon], Université de Lyon, Numerical Medicine (NUMED), Unité de Mathématiques Pures et Appliquées (UMPA-ENSL), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Inria Grenoble - Rhône-Alpes, Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adenoma, Male, medicine.medical_specialty, Metabolic Clearance Rate, medicine.medical_treatment, Clinical Biochemistry, Population, 030232 urology & nephrology, Urology, Prostatic Hyperplasia, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Prostate, medicine, Biomarkers, Tumor, Humans, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Prostatectomy, Half-life, Prostatic Neoplasms, General Medicine, Blood Proteins, Middle Aged, Prostate-Specific Antigen, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, NONMEM, Blood Cell Count, Prostate-specific antigen, Kinetics, medicine.anatomical_structure, Standard error, 030220 oncology & carcinogenesis, Creatinine, Prostate surgery, business
Abstract

International audience; OBJECTIVES: A population kinetic approach based on PSA clearance (CL(PSA)) may be a more rational strategy to characterize prostate-specific antigen (PSA) decrease profile after prostate surgery than the commonly used method (half-life from mono/bi-exponential models). METHODS: We used 182 post-adenomectomy PSA concentrations from 56 benign prostatic hyperplasia patients to build, with NONMEM software, a multi-exponential and a CL(PSA) model for comparison. RESULTS: The best multi-exponential model was PSA(t)=4.96e(-)(0.269t)+3.10e(-)(0.16t)+0.746e(+)(0.0002t) with a stable median residual PSA at 0.64 ng/mL. The best model parametrized with clearance was CL(PSA)=0.0229()(AGE/69)(3.78). Akaike information criteria and standard errors favored the CL(PSA) model. Median peripheral zone and transitional zone productions were 0.034 ng/mL/cm(3) and 0.136 ng/mL/g. A threshold at 2 ng/mL on day 90 allowed for a diagnostic of biochemical relapse diagnostic. CONCLUSIONS: The population CL(PSA) model was superior to the multi-exponential approach for investigating individual post-adenomectomy PSA decreases.

Published
2008

7. Blood Loss During Transurethral Resection of the Prostate as Measured by the Chromium-51 Method.

Author

Aurélien Descazeaud, Abdel Rahmene Azzousi, Charles Ballereau, Frank Bruyere, Gregoire Robert, Nicolas Barry Delongchamps, Marian Devonec, Olivier Dumonceau, Marc Fourmarier, Christian Saussine, Julien Berger, Alexandre de la Taille, and Olivier Haillot

Subjects
BLOOD loss estimation, TRANSURETHRAL prostatectomy, CHROMIUM isotopes, BENIGN prostatic hyperplasia, ERYTHROCYTES, HEMATOCRIT, HEMOGLOBINS
Abstract

AbstractPurpose:To evaluate blood loss during transurethral resection of the prostate (TURP), and its predictive factors, using the chromium 51 (51Cr) labeling method.Patients and Methods:From January to June 2008, 41 patients who underwent TURP for symptomatic benign prostatic hyperplasia (BPH) at four French urology centers were included in the analysis. Red cells volume was measured by the 51Cr method 1 day before TURP, and on postoperative day 3. Overall blood loss was estimated by multiplication of red cells volume loss and preoperative venous hematocrit value.Results:Mean preoperative red cells volume was 1997 mL. Mean loss of red cells volume was 209 ml, which corresponds to an estimated blood loss of 507 mL. Mean delta of hematocrit and hemoglobin were 1.4% and 0.71 g/dL, respectively. In univariate analysis, prostate volume, weight of resected tissue, preoperative red cells volume, and resection time were significantly and directly associated with loss of red cells volume (P= 0.038, P= 0.004, P= 0.002, and P= 0.039, respectively). Bipolar and monopolar TURP did not lead to significant difference of red cells loss. In multivariate analysis, both preoperative red cells volume and weight of resected tissue were independent predictors of red cells loss (P= 0.017 and P= 0.048 respectively).Conclusion:We present the first study to measure blood loss secondary to TURP using the 51Cr method. This technique allowed evaluating blood loss not only during the surgical procedure but also during the postoperative period. We learned from this study that, on average, blood loss from the procedure until postoperative day 3 was more than 500 mL, which is larger than previously reported amounts as measured by other methods. Because significant blood loss might occur during the postoperative period, the 51Cr method should be used to measure blood loss when evaluating new emerging techniques to manage BPH. [ABSTRACT FROM AUTHOR]

Published
2010
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