Discovery and Validation of Prognostic Genomic Based Signatures in High Risk Bladder Cancer Following Cystectomy

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "Discovery and Validation of Prognostic Genomic Based Signatures in High Risk Bladder Cancer Following Cystectomy"

Transcription

1 Discovery and Validation of Prognostic Genomic Based Signatures in High Risk Bladder Cancer Following Cystectomy Anirban P. Mitra, M.D., Ph.D. Center for Personalized Medicine University of Southern California

2 UROTHELIAL TUMORIGENESIS AND OUTCOMES Mitra et al, JCO 2006 Mitra et al, Nat Rev Urol 2010

3 MOLECULAR ALTERATIONS Mitra et al, Curr Opin Urol 2012

4 MOLECULAR ALTERATIONS Mitra et al, Annu Rev Pathol 2009

5 PROFILING STRATEGIES PATHWAY SPECIFIC APPROACH GLOBAL APPROACH Small, finite panel Cost effective Faster clinical implementation ADVANTAGES Unbiased genomic interrogation High throughput Discovery potential Limited marker interrogation Medium to low throughput Selection based on prior studies DISADVANTAGES Larger panel size Potential for false discovery Expensive, specialized Mitra et al, Cancer Mets Rev 2009

6 PREDICTING NODAL METASTASIS Mitra et al, BMC Cancer 2006

7 PREDICTING NODAL METASTASIS Gene Usage Frequencies Predicted N+ by GP Predicted N by GP Using KDR, MAP2K6, ICAM1 Pathologically N+ Pathologically N Accuracy: 81% Sensitivity: 70% Specificity: 86% PPV: 70% NPV: 86% Mitra et al, BMC Cancer 2006

8 PREDICTING DISEASE SPECIFIC SURVIVAL Using JUN, MAP2K6, STAT3, ICAM1 External validation p < n RR (95% CI) p Favorable expression 3 of 4 genes (Reference) of 4 genes ( ) Mitra et al, JCO 2009

9 PROGNOSTIC VALUE OF PATIENT VARIABLES Categorization of smoking intensity Combination of smoking intensity and marker alterations is most prognostic Mitra et al, Cancer 2013

10 GENOMIC LANDSCAPE OF BLADDER CANCER TCGA, Nature 2014

11 WHOLE TRANSCRIPTOME PROGNOSTIC PROFILING STUDY OBJECTIVE Develop and validate a genomic signature that can predict risk of post cystectomy bladder cancer recurrence. PATIENTS AND METHODS 225 patients with pt2 T4aN0M0 or ptanyn1 3M0 urothelial carcinoma of the bladder without neoadjuvant chemotherapy. o 2 years follow up (if no recurrence) Primary tumors from cystectomy specimens as archival formalin fixed, paraffin embedded tissues. Whole transcriptome profiling by Affymetrix Human Exon 1.0 ST GeneChips. Features most predictive for recurrence identified (n=15). o Combined in a random forest machine learning algorithm to generate a signature

12 STUDY DESIGN DISCOVERY SET (n=133) Age Gender pt, pn LVI Clinical Classifier (CC) G CC VALIDATION SET (n=66) No neoadj chemo Radical cystectomy o 34 pt2n0m0 o 54 pt3 4aN0M0 o 45 ptanyn+m0 Median FU 9.3 yr 1.4x10 6 feature oligonucleotide microarray 15 feature Genomic Classifier (GC) [score 0 1] No neoadj chemo Radical cystectomy o 15 pt2n0m0 o 26 pt3 4aN0M0 o 25 ptanyn+m0 Median FU 10.8 yr G IBCNC IBCNC

13 CLASSIFIER PERFORMANCE DISCOVERY SET GC Feature Associated Gene 1. FOXO6 2. HSD17B7 3. ARID4B 4. ENAH 5. MAP4K3 6. MARCH7 7. MECOM 8. LRBA 9. MUT 10. CRCP 11. SYPL1 12. ARFGEF1 13. EHF 14. METTL7A 15. PPP1R12A Performance on Discovery Set

14 GC PERFORMANCE VALIDATION SET Locked classifier blindly applied to validation set

15 CLASSIFIER PERFORMANCE VALIDATION SET Adding GC to clinical nomograms improved their performance Risk stratification based on G CC scores p < GC+ IBCNC IBCNC: 0.73 G-IBCNC: 0.82 GC+ CC CC: 0.78 G-CC: 0.86

16 GC PERFORMANCE VALIDATION SET Multivariable associations with risk of bladder cancer recurrence Performance in LN patient subset p = RR of Recurrence HR p GC Age <70 yrs Male Gender Caucasian Race Tumor Stage pt pt pt4a Nodal Status N LVI Adj Chemo administered CC GC p = 0.004

17 GC GENES ASSOCIATED BIOLOGICAL FUNCTIONS GC genes and first degree partners extracted using interactome database Associated biological processes mapped GC components are biologically relevant

18 EXTERNAL VALIDATION OF GC Total number of patients = 341 p = p < TCGA, Nature 2014 Kim et al, Mol Cancer 2010 p < p = Als et al, Clin Cancer Res 2007 Riester et al, Clin Cancer Res 2012

19 FUTURE DIRECTIONS Non invasive bladder cancer cell sampling Urine OR Microfilter captured cells TURBT Response to neoadjuvant chemo GC Response to adjuvant chemo Birkhahn, Mitra et al, Eur J Cancer 2013 Other molecular correlates (e.g. TP53 mutations in cystectomy specimens) [SWOG 4B951]

20 CONCLUSIONS Global and pathway specific approaches may be used to profile the bladder cancer transcriptome for predictors of post cystectomy outcomes. We document the discovery and validation of a 15 marker genomic classifier (GC) comprising of biologically relevant transcripts, which was validated on external datasets. The integrated genomic clinical classifier (G CC) shows improved prognostic performance over clinical models alone. The classifier may help guide clinical decision making for adjuvant chemotherapy administration after further prospective validation.

21 ACKNOWLEDGEMENTS Prognostic Profiling Whole Transcriptome Peter C. Black, MD (UBC) Siamak Daneshmand, MD (USC) Eila C. Skinner, MD (Stanford) Timothy J. Triche, MD, PhD (USC) Elai Davicioni, PhD (GenomeDx Biosciences) Lucia L. Lam, BS (GenomeDx Biosciences) Christine Buerki, PhD, & team (GenomeDx) Funding Prognostic Profiling Other Projects Richard J. Cote, MD, FRCPath, FCAP (Univ. of Miami) Donald G. Skinner, MD (USC) Susan Groshen, PhD (USC) Victoria K. Cortessis, PhD (USC) Frederic M. Waldman, MD, PhD (UCSF) William P. Worzel, MS (Everist Genomics) TP53 Mutation Assessment MVAC Trial Seth P. Lerner, MD (Baylor) Walter M. Stadler, MD (Univ. of Chicago) Gary Steinberg, MD, FACS (Univ. of Chicago) Derek Raghavan, MD, PhD (Levine Cancer Institute) Nanotechnology Bladder Cancer Detection Yu Chong Tai, PhD (Caltech) Marc Birkhahn, MD (Urologie am Ring)

Neoadjuvant vs. Adjuvant Chemotherapy for Muscle-Invasive Bladder Cancer

Neoadjuvant vs. Adjuvant Chemotherapy for Muscle-Invasive Bladder Cancer Neoadjuvant vs. Adjuvant Chemotherapy for Muscle-Invasive Bladder Cancer Andrew J. Stephenson, MD, FRCSC, FACS Director, Urologic Oncology Associate Professor of Surgery Glickman Urological and Kidney

More information

Decipher Bladder Predicts Which Patients May Benefit from Neoadjuvant Chemotherapy Prior to Radical Cystectomy

Decipher Bladder Predicts Which Patients May Benefit from Neoadjuvant Chemotherapy Prior to Radical Cystectomy Decipher Bladder Predicts Which Patients May Benefit from Neoadjuvant Chemotherapy Prior to Cystectomy Contact the GenomeDx Customer Support Team 1.888.792.1601 (toll-free) customersupport@genomedx.com

More information

Chemotherapy and Bladder Cancer. Blayne Welk UBC Urology Grand Rounds June 4, 2008

Chemotherapy and Bladder Cancer. Blayne Welk UBC Urology Grand Rounds June 4, 2008 Chemotherapy and Bladder Cancer Blayne Welk UBC Urology Grand Rounds June 4, 2008 Outline Review of Incidence and Impact of bladder cancer Neoadjuvant chemotherapy Adjuvant chemotherapy Bladder preservation

More information

Neodjuvant chemotherapy

Neodjuvant chemotherapy Neodjuvant chemotherapy Dr Robert Huddart Senior Lecturer and Honorary Consultant in Clinical Oncology Royal Marsden Hospital and Institute of Cancer Research Why consider neo-adjuvant chemotherapy? Loco-regional

More information

FISH mcgh Karyotyping ISH RT-PCR. Expression arrays RNA. Tissue microarrays Protein arrays MS. Protein IHC

FISH mcgh Karyotyping ISH RT-PCR. Expression arrays RNA. Tissue microarrays Protein arrays MS. Protein IHC Classification of Breast Cancer in the Molecular Era Susan J. Done University Health Network, Toronto Why classify? Prognosis Prediction of response to therapy Pathogenesis Invasive breast cancer can have

More information

Providing Treatment Information for Prostate Cancer Patients

Providing Treatment Information for Prostate Cancer Patients Providing Treatment Information for Prostate Cancer Patients For all patients with localized disease on biopsy For all patients with adverse pathology after prostatectomy See what better looks like Contact

More information

PROVIDING TREATMENT INFORMATION FOR PROSTATE CANCER PATIENTS

PROVIDING TREATMENT INFORMATION FOR PROSTATE CANCER PATIENTS PROVIDING TREATMENT INFORMATION FOR PROSTATE CANCER PATIENTS For patients with localized disease on biopsy* For patients with adverse pathology after prostatectomy Contact the GenomeDx Customer Support

More information

When to Integrate Surgery for Metatstatic Urothelial Cancers

When to Integrate Surgery for Metatstatic Urothelial Cancers When to Integrate Surgery for Metatstatic Urothelial Cancers Wade J. Sexton, M.D. Senior Member and Professor Department of Genitourinary Oncology Moffitt Cancer Center Case Presentation #1 67 yo male

More information

The Predictors of Local Recurrence after Radical Cystectomy in Patients with Invasive Bladder Cancer

The Predictors of Local Recurrence after Radical Cystectomy in Patients with Invasive Bladder Cancer The Predictors of Local Recurrence after Radical Cystectomy in Patients with Invasive Bladder Cancer Hiroki Ide, Eiji Kikuchi, Akira Miyajima, Ken Nakagawa, Takashi Ohigashi, Jun Nakashima and Mototsugu

More information

Alicia K. Morgans, MD Assistant Professor of Medicine Division of Hematology/Oncology Vanderbilt University Medical Center January 24, 2015

Alicia K. Morgans, MD Assistant Professor of Medicine Division of Hematology/Oncology Vanderbilt University Medical Center January 24, 2015 Alicia K. Morgans, MD Assistant Professor of Medicine Division of Hematology/Oncology Vanderbilt University Medical Center January 24, 2015 Overview Background Perioperative chemotherapy in MIBC Neoadjuvant

More information

Urinary Bladder Cancer

Urinary Bladder Cancer Fellow GU Lecture Series, 2018 Urinary Bladder Cancer Asit Paul, MD, PhD 01/31/2018 Overview Non-muscle invasive bladder cancer Muscle invasive bladder cancer Bladder sparing chemo-radiation therapy T4b

More information

16:30-18:30 WS #67: Urology Forum - Prostate Cancer, Stones, Renal Tumours, Voiding Dysfunction (120 minutes, not repeated) -

16:30-18:30 WS #67: Urology Forum - Prostate Cancer, Stones, Renal Tumours, Voiding Dysfunction (120 minutes, not repeated) - Dr Anna Lawrence Urologist Auckland Dr Andrew Williams Urologist Auckland Madhu Koya Urologist Auckland Andrew Lienert Urologist Auckland Dr Louise Tomlinson Consultant Gynaecologist Auckland 16:30-18:30

More information

COXEN FOR PREOPERATIVE BLADDER CANCER CHEMOTHERAPY - IN DEVELOPMENT. Slide support from Dan Theodorescu

COXEN FOR PREOPERATIVE BLADDER CANCER CHEMOTHERAPY - IN DEVELOPMENT. Slide support from Dan Theodorescu COXEN FOR PREOPERATIVE BLADDER CANCER CHEMOTHERAPY - IN DEVELOPMENT Slide support from Dan Theodorescu Bladder Cancer: 0 In need of transformative change Kidney cancer: 7 newly approved drugs, more on

More information

Neoadjuvant chemotherapy for bladder cancer: fighting between evidence 1 level and real life.

Neoadjuvant chemotherapy for bladder cancer: fighting between evidence 1 level and real life. THE INTERNATIONAL CONFERENCE PROGRESS IN URO-ONCOLOGY 5th Edition September, 25th 26th 2014 CLUJ-NAPOCA Neoadjuvant chemotherapy for bladder cancer: fighting between evidence 1 level and real life. Dr.

More information

Lymph Node Positive Bladder Cancer Treated With Radical Cystectomy and Lymphadenectomy: Effect of the Level of Node Positivity

Lymph Node Positive Bladder Cancer Treated With Radical Cystectomy and Lymphadenectomy: Effect of the Level of Node Positivity EUROPEAN UROLOGY 61 (2012) 1025 1030 available at www.sciencedirect.com journal homepage: www.europeanurology.com Bladder Cancer Lymph Node Positive Bladder Cancer Treated With Radical Cystectomy and Lymphadenectomy:

More information

BCG Unresponsive Disease A Roadmap for Drug Development and Integra;on of Novel Therapies

BCG Unresponsive Disease A Roadmap for Drug Development and Integra;on of Novel Therapies BCG Unresponsive Disease A Roadmap for Drug Development and Integra;on of Novel Therapies Seth P. Lerner, MD, FACS Professor of Urology Beth and Dave Swalm Chair in Urologic Oncology Baylor College of

More information

Collection of Recorded Radiotherapy Seminars

Collection of Recorded Radiotherapy Seminars IAEA Human Health Campus Collection of Recorded Radiotherapy Seminars http://humanhealth.iaea.org Conservative Treatment of Invasive Bladder Cancer Luis Souhami, MD Professor Department of Radiation Oncology

More information

Clinical Outcomes of Patients with pt0 Bladder Cancer after Radical Cystectomy: A Single-institute Experience

Clinical Outcomes of Patients with pt0 Bladder Cancer after Radical Cystectomy: A Single-institute Experience Clinical Outcomes of Patients with pt0 Bladder Cancer after Radical Cystectomy: A Single-institute Experience Fumimasa Fukuta, Naoya Masumori *, Ichiya Honma, Masatoshi Muto, Koji Ichihara, Hiroshi Kitamura

More information

Chemo-radiotherapy in muscle invasive bladder cancer. Dr Paula Wells St Bartholomew s Hospital London

Chemo-radiotherapy in muscle invasive bladder cancer. Dr Paula Wells St Bartholomew s Hospital London Chemo-radiotherapy in muscle invasive bladder cancer Dr Paula Wells St Bartholomew s Hospital London Overview Evidence base for cystectomy vs bladder preservation Chemo-radiotherapy vs radiotherapy alone

More information

Treatment of muscle invasive bladder cancer. ie: pt2. N. Mottet

Treatment of muscle invasive bladder cancer. ie: pt2. N. Mottet Treatment of muscle invasive bladder cancer ie: pt2 N. Mottet Disclosures Astellas BMS Pierre Fabre Sanofi MIBC: really undertreated 28 691 MIBC in the US (national database). Gray Eur Urol 2013 Patients

More information

Development and external validation of nomograms predicting disease-free and cancer-specific survival after radical cystectomy

Development and external validation of nomograms predicting disease-free and cancer-specific survival after radical cystectomy Development and external validation of nomograms predicting disease-free and cancer-specific survival after radical cystectomy Giuseppe Simone, Marco Bianchi, Diana Giannarelli, Siamak Daneshmand, Rocco

More information

MammaPrint, the story of the 70-gene profile

MammaPrint, the story of the 70-gene profile MammaPrint, the story of the 70-gene profile René Bernards Professor of Molecular Carcinogenesis The Netherlands Cancer Institute Amsterdam Chief Scientific Officer Agendia Amsterdam The breast cancer

More information

Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer

Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer Kathy S. Albain, MD, FACP Professor of Medicine Dean s Scholar Loyola University Chicago Stritch School of Medicine Cardinal Bernardin

More information

Invasive Bladder Transitional Cell Carcinoma OBJECTIVES

Invasive Bladder Transitional Cell Carcinoma OBJECTIVES Invasive Bladder Transitional Cell Carcinoma UBC Urology Grand Rounds 7 September 2005 John Morrell R5 OBJECTIVES Review role of lymphadenectomy Review role of chemotherapy Review results of bimodal bladder

More information

Non Muscle Invasive Bladder Cancer. Primary and Recurrent TCC 4/10/2010. Two major consequences: Strategies: High-Risk NMI TCC

Non Muscle Invasive Bladder Cancer. Primary and Recurrent TCC 4/10/2010. Two major consequences: Strategies: High-Risk NMI TCC Intravesical Therapy 2010-When, with What, When to Stop Friday, April 9, 2010 Ralph de VereWhite, MD Director, UC Davis Cancer Center Associate Dean for Cancer Programs Professor, Department of Urolgoy

More information

PMRT for N1 breast cancer :CONS. Won Park, M.D., Ph.D Department of Radiation Oncology Samsung Medical Center

PMRT for N1 breast cancer :CONS. Won Park, M.D., Ph.D Department of Radiation Oncology Samsung Medical Center PMRT for N1 breast cancer :CONS Won Park, M.D., Ph.D Department of Radiation Oncology Samsung Medical Center DBCG 82 b & c Overgaard et al Radiot Oncol 2007 1152 pln(+), 8 or more nodes removed Systemic

More information

Case Studies on High Throughput Gene Expression Data Kun Huang, PhD Raghu Machiraju, PhD

Case Studies on High Throughput Gene Expression Data Kun Huang, PhD Raghu Machiraju, PhD Case Studies on High Throughput Gene Expression Data Kun Huang, PhD Raghu Machiraju, PhD Department of Biomedical Informatics Department of Computer Science and Engineering The Ohio State University Review

More information

Prostate Cancer Genomics When To Treat and With What? Ashley E. Ross, M.D., Ph.D. Texas Urology Specialists August 2017

Prostate Cancer Genomics When To Treat and With What? Ashley E. Ross, M.D., Ph.D. Texas Urology Specialists August 2017 Prostate Cancer Genomics When To Treat and With What? Ashley E. Ross, M.D., Ph.D. Texas Urology Specialists August 2017 Relevant Disclosures Advisory role, ownership interest, previous unrestricted grant

More information

Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer

Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer The new england journal of medicine original article Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer H. Barton Grossman, M.D., Ronald B. Natale,

More information

Bone Metastases in Muscle-Invasive Bladder Cancer

Bone Metastases in Muscle-Invasive Bladder Cancer Journal of the Egyptian Nat. Cancer Inst., Vol. 18, No. 3, September: 03-08, 006 AZZA N. TAHER, M.D.* and MAGDY H. KOTB, M.D.** The Departments of Radiation Oncology* and Nuclear Medicine**, National Cancer

More information

The Efficacy of Adjuvant Chemotherapy for Locally Advanced Upper Tract Urothelial Cell Carcinoma

The Efficacy of Adjuvant Chemotherapy for Locally Advanced Upper Tract Urothelial Cell Carcinoma Ivyspring International Publisher Research Paper 686 Journal of Cancer 2013; 4(8): 686-690. doi: 10.7150/jca.7326 The Efficacy of Adjuvant Chemotherapy for Locally Advanced Upper Tract Urothelial Cell

More information

CHEMO-RADIOTHERAPY FOR BLADDER CANCER. Dr Darren Mitchell Consultant Clinical Oncologist Northern Ireland Cancer Centre

CHEMO-RADIOTHERAPY FOR BLADDER CANCER. Dr Darren Mitchell Consultant Clinical Oncologist Northern Ireland Cancer Centre CHEMO-RADIOTHERAPY FOR BLADDER CANCER Dr Darren Mitchell Consultant Clinical Oncologist Northern Ireland Cancer Centre AIMS Muscle invasive disease Current Gold-Standard Rationale behind Chemo-Radiotherapy

More information

Impact of adjuvant chemotherapy on patients with pathological Stage T3b and/or lymph node metastatic bladder cancer after radical cystectomy

Impact of adjuvant chemotherapy on patients with pathological Stage T3b and/or lymph node metastatic bladder cancer after radical cystectomy Japanese Journal of Clinical Oncology, 2015, 45(10) 963 967 doi: 10.1093/jjco/hyv098 Advance Access Publication Date: 29 July 2015 Original Article Original Article Impact of adjuvant chemotherapy on patients

More information

Sentinel Node Biopsy. Is There Any Role for Axillary Dissection? JCCNB Nov 20, Stephen B. Edge, MD

Sentinel Node Biopsy. Is There Any Role for Axillary Dissection? JCCNB Nov 20, Stephen B. Edge, MD Sentinel Node Biopsy Is There Any Role for Axillary Dissection? JCCNB Nov 20, 2010 Tokyo, Japan Stephen B. Edge, MD Roswell Park Cancer Institute University at Buffalo Buffalo, NY USA SNB with Clinically

More information

Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle-invasive bladder cancer

Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle-invasive bladder cancer bs_bs_banner Asia-Pacific Journal of Clinical Oncology 2013; 9: 310 317 doi: 10.1111/ajco.12017 ORIGINAL ARTICLE Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for

More information

Stat3 Transgenic Mice as a Model for Human Basal Subtype of Invasive Bladder Cancer

Stat3 Transgenic Mice as a Model for Human Basal Subtype of Invasive Bladder Cancer Stat3 Transgenic Mice as a Model for Human Basal Subtype of Invasive Bladder Cancer Philip L. Ho, MD Urologic Oncology Fellow The University of Texas at MD Anderson Cancer Center Houston, TX None Disclosures

More information

Debate: Adjuvant vs. Neoadjuvant Therapy for Urothelial Cancer

Debate: Adjuvant vs. Neoadjuvant Therapy for Urothelial Cancer Debate: Adjuvant vs. Neoadjuvant Therapy for Urothelial Cancer Kala Sridhar, MD, MSc, FRCPC Medical Oncologist, Princess Margaret Hospital GU Medical Oncology Site Group Head Associate Professor, University

More information

Incidental Prostate Cancer in Patients with Bladder Urothelial Carcinoma: Comprehensive Analysis of 1,476 Radical Cystoprostatectomy Specimens

Incidental Prostate Cancer in Patients with Bladder Urothelial Carcinoma: Comprehensive Analysis of 1,476 Radical Cystoprostatectomy Specimens Incidental Prostate Cancer in Patients with Bladder Urothelial Carcinoma: Comprehensive Analysis of 1,476 Radical Cystoprostatectomy Specimens Harman Maxim Bruins,* Hooman Djaladat,* Hamed Ahmadi, Andy

More information

A Fourteen-Year Review of Radical Cystectomy for Transitional Cell Carcinoma Demonstrating the Usefulness of the Concept of Lymph Node Density

A Fourteen-Year Review of Radical Cystectomy for Transitional Cell Carcinoma Demonstrating the Usefulness of the Concept of Lymph Node Density Clinical Urology TCC of the Bladder and Lymph Node Density International Braz J Urol Vol. 32 (5): 536-549, September - October, 2006 A Fourteen-Year Review of Radical Cystectomy for Transitional Cell Carcinoma

More information

Contemporary Classification of Breast Cancer

Contemporary Classification of Breast Cancer Contemporary Classification of Breast Cancer Laura C. Collins, M.D. Vice Chair of Anatomic Pathology Professor of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA Outline

More information

Non Muscle Invasive Bladder Cancer

Non Muscle Invasive Bladder Cancer Non-Muscle-Invasive Bladder Cancer Staging, Treatment and Assessment Featuring SWOG Trials S1602 & S1605 Peter C.V. Black, M.D. S1605 Study Chair University of British Columbia Vancouver Prostate Centre

More information

Management of High Grade, T1 Bladder Cancer Douglas S. Scherr, M.D.

Management of High Grade, T1 Bladder Cancer Douglas S. Scherr, M.D. Management of High Grade, T1 Bladder Cancer Douglas S. Scherr, M.D. Assistant Professor of Urology Clinical Director, Urologic Oncology Weill Medical College-Cornell University Estimated new cancer cases.

More information

September 10, Dear Dr. Clark,

September 10, Dear Dr. Clark, September 10, 2015 Peter E. Clark, MD Chair, NCCN Bladder Cancer Guidelines (Version 2.2015) Associate Professor of Urologic Surgery Vanderbilt Ingram Cancer Center Nashville, TN 37232 Dear Dr. Clark,

More information

The changing reality of urothelial bladder cancer: should non-squamous variant. histology be managed as a distinct clinical entity?

The changing reality of urothelial bladder cancer: should non-squamous variant. histology be managed as a distinct clinical entity? The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity? 1 M. Francesca Monn MD MPH# 1, Hristos Z Kaimakliotis MD# 1, K Clint Cary

More information

Systems Pathology in Prostate Cancer. Description

Systems Pathology in Prostate Cancer. Description Section: Medicine Effective Date: July 15, 2015 Subject: Systems Pathology in Prostate Cancer Page: 1 of 8 Last Review Status/Date: June 2015 Systems Pathology in Prostate Cancer Description Systems pathology,

More information

PORT after RP. Adjuvant. Salvage

PORT after RP. Adjuvant. Salvage PORT after RP Adjuvant Or Salvage RT after RP 40-50% PSA relapse after RP in HR Definition: PSA should be undetectable within 6 weeks of RP Initial PSA is measured 6-12 weeks after RP AUA defines biochemical

More information

See Submission for References.

See Submission for References. Guideline Page and Request PROS-1 External submission from Myriad Genetic Laboratories, Inc. requesting addition of the following statement as a distinct step immediately to the right of life expectancy

More information

Systems Pathology in Prostate Cancer

Systems Pathology in Prostate Cancer Systems Pathology in Prostate Cancer Policy Number: 2.04.64 Last Review: 8/2014 Origination: 8/2010 Next Review: 8/2015 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will not provide coverage

More information

Extranodal Extension Is a Powerful Prognostic Factor in Bladder Cancer Patients with Lymph Node Metastasis

Extranodal Extension Is a Powerful Prognostic Factor in Bladder Cancer Patients with Lymph Node Metastasis EUROPEAN UROLOGY 64 (2013) 837 845 available at www.sciencedirect.com journal homepage: www.europeanurology.com Bladder Cancer Extranodal Extension Is a Powerful Prognostic Factor in Bladder Cancer Patients

More information

Management of High-Risk Non-Muscle Invasive Bladder Cancer. Seth P. Lerner, MD, FACS

Management of High-Risk Non-Muscle Invasive Bladder Cancer. Seth P. Lerner, MD, FACS Management of High-Risk Non-Muscle Invasive Bladder Cancer Seth P. Lerner, MD, FACS Professor of Urology, Beth and Dave Swalm Chair in Urologic Oncology, Scott Department of Urology, Baylor College of

More information

IDENTIFICATION OF A BIOMARKER PANEL THAT PREDICTS BLADDER CANCER OUTCOME INDEPENDENT OF ROUTINE PROGNOSTIC FACTORS AND SMOKING HISTORY

IDENTIFICATION OF A BIOMARKER PANEL THAT PREDICTS BLADDER CANCER OUTCOME INDEPENDENT OF ROUTINE PROGNOSTIC FACTORS AND SMOKING HISTORY IDENTIFICATION OF A BIOMARKER PANEL THAT PREDICTS BLADDER CANCER OUTCOME INDEPENDENT OF ROUTINE PROGNOSTIC FACTORS AND SMOKING HISTORY Anirban P. Mitra, M.D., Ph.D., Jose E. Castelao, M.D., Ph.D.*, Debra

More information

Chemotherapy Treatment Algorithms for Urology Cancer

Chemotherapy Treatment Algorithms for Urology Cancer Chemotherapy Treatment Algorithms for Urology Cancer Chemoradiation for bladder cancer; Chemotherapy algorithm for non TCC bladder cancer Squamous cell carcinoma; Chemotherapy Algorithm for Non Transitional

More information

Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era

Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era ORIGINAL RESEARCH Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era Ahva Shahabi, MPH, PhD; 1* Raj Satkunasivam, MD; 2* Inderbir S. Gill, MD; 2 Gary Lieskovsky,

More information

Implications of ACOSOG Z11 for Clinical Practice: Surgical Perspective

Implications of ACOSOG Z11 for Clinical Practice: Surgical Perspective Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10065 10th International Congress on the Future of Breast Cancer Coronado, CA 6 August 2011 Implications of ACOSOG Z11 for Clinical

More information

Guidelines for the Management of Bladder Cancer West Midlands Expert Advisory Group for Urological Cancer

Guidelines for the Management of Bladder Cancer West Midlands Expert Advisory Group for Urological Cancer Guidelines for the Management of Bladder Cancer West Midlands Expert Advisory Group for Urological Cancer West Midlands Clinical Networks and Clinical Senate Coversheet for Network Expert Advisory Group

More information

High risk stage II colon cancer

High risk stage II colon cancer High risk stage II colon cancer Joel Gingerich, MD, FRCPC Assistant Professor Medical Oncologist University of Manitoba CancerCare Manitoba Disclaimer No conflict of interests 16 October 2010 Overview

More information

Chemotherapy for Urological Cancers

Chemotherapy for Urological Cancers Chemotherapy for Urologic Cancers Matthew Rettig, MD Associate Professor Department of Medicine Division of Hematology-Oncology Department of Urology Medical Director, Prostate Cancer Program Institute

More information

Prosigna BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY

Prosigna BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY Prosigna BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY GENE EXPRESSION PROFILING WITH PROSIGNA What is Prosigna? Prosigna Breast Cancer Prognostic Gene Signature Assay is an FDA-approved assay which provides

More information

Prosigna BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY

Prosigna BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY Prosigna BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY Methodology The test is based on the reported 50-gene classifier algorithm originally named PAM50 and is performed on the ncounter Dx Analysis System

More information

Novel therapeutic strategies for NMIBC. Peter Black Vancouver Prostate Centre University of British Columbia

Novel therapeutic strategies for NMIBC. Peter Black Vancouver Prostate Centre University of British Columbia Novel therapeutic strategies for NMIBC Peter Black Vancouver Prostate Centre University of British Columbia Financial and Other Disclosures I have the following financial interests or relationships to

More information

TABLE OF CONTENTS. Executive Summary The EndoPredict Test Intended Use Population Breast Cancer Clinical Dilemma. Analytical Validity

TABLE OF CONTENTS. Executive Summary The EndoPredict Test Intended Use Population Breast Cancer Clinical Dilemma. Analytical Validity Clinical Dossier TABLE OF CONTENTS Executive Summary The EndoPredict Test Intended Use Population Breast Cancer Clinical Dilemma 1 2 3 Analytical Validity 4 Clinical Validity 4 Clinical Utility 7 Medicare

More information

Treatment of Invasive Bladder Cancer in the Elderly and Frail Pa9ent

Treatment of Invasive Bladder Cancer in the Elderly and Frail Pa9ent Treatment of Invasive Bladder Cancer in the Elderly and Frail Pa9ent Jehonathan H Pinthus MD, Ph.D, FRCSC Associate Professor Department of Surgery/Urology McMaster University Life expectancy Current age

More information

Reviewing Immunotherapy for Bladder Carcinoma In Situ

Reviewing Immunotherapy for Bladder Carcinoma In Situ Reviewing Immunotherapy for Bladder Carcinoma In Situ Samir Bidnur Dept of Urologic Sciences, Grand Rounds March 1 st, 2017 Checkpoint Inhibition and Bladder Cancer, an evolving story with immunotherapy

More information

Koji Ichihara Hiroshi Kitamura Naoya Masumori Fumimasa Fukuta Taiji Tsukamoto

Koji Ichihara Hiroshi Kitamura Naoya Masumori Fumimasa Fukuta Taiji Tsukamoto Int J Clin Oncol (2013) 18:75 80 DOI 10.1007/s10147-011-0346-8 ORIGINAL ARTICLE Transurethral prostate biopsy before radical cystectomy remains clinically relevant for decision-making on urethrectomy in

More information

Which Treatment Approach is Most Appropriate for Primary Therapy of Gastric Cancer: Neoadjuvant Chemotherapy

Which Treatment Approach is Most Appropriate for Primary Therapy of Gastric Cancer: Neoadjuvant Chemotherapy Which Treatment Approach is Most Appropriate for Primary Therapy of Gastric Cancer: Neoadjuvant Chemotherapy Joseph Chao, M.D. Assistant Clinical Professor Department of Medical Oncology & Therapeutics

More information

Multigene Testing in Prostate Cancer Risk Stratification

Multigene Testing in Prostate Cancer Risk Stratification Multigene Testing in Prostate Cancer Risk Stratification Ashley Ross, MD, PhD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Objectives Briefly review relevant molecular biology of localized

More information

Emerging Approaches for (Neo)Adjuvant Therapy for ER+ Breast Cancer

Emerging Approaches for (Neo)Adjuvant Therapy for ER+ Breast Cancer Emerging Approaches for (Neo)Adjuvant Therapy for E+ Breast Cancer Cynthia X. Ma, M.D., Ph.D. Associate Professor of Medicine Washington University in St. Louis Outline Current status of adjuvant endocrine

More information

Panel: A Case-based Approach to the Management of Bladder Cancer

Panel: A Case-based Approach to the Management of Bladder Cancer Panel: A Case-based Approach to the Management of Bladder Cancer ~ Moderator: Robert Donohue, MD Panel: David C. Beyer, MD E. David Crawford, MD Donald L. Lamm, MD Paul D. Maroni, MD TCC Cases Robert E.

More information

Influence of stage discrepancy on outcome in. in patients treated with radical cystectomy.

Influence of stage discrepancy on outcome in. in patients treated with radical cystectomy. Tumori, 96: 699-703, 2010 Influence of stage discrepancy on outcome in patients treated with radical cystectomy Ja Hyeon Ku 1, Kyung Chul Moon 2, Cheol Kwak 1, and Hyeon Hoe Kim 1 1 Department of Urology,

More information

Multifocal Lung Cancer

Multifocal Lung Cancer Multifocal Lung Cancer P. De Leyn, MD, PhD Department of Thoracic Surgery University Hospitals Leuven Belgium LEUVEN LUNG CANCER GROUP Department of Thoracic Surgery Department of Pneumology Department

More information

Quality of Pathologic Response and Surgery Correlate With Survival for Patients With Completely Resected Bladder Cancer After Neoadjuvant Chemotherapy

Quality of Pathologic Response and Surgery Correlate With Survival for Patients With Completely Resected Bladder Cancer After Neoadjuvant Chemotherapy Original Article Quality of Pathologic Response and Surgery Correlate With Survival for Patients With Completely Resected Bladder Cancer After Neoadjuvant Chemotherapy Guru Sonpavde, MD 1 ; Bryan H. Goldman,

More information

Disclosures. Outline. What IS tumor budding?? Tumor Budding in Colorectal Carcinoma: What, Why, and How. I have nothing to disclose

Disclosures. Outline. What IS tumor budding?? Tumor Budding in Colorectal Carcinoma: What, Why, and How. I have nothing to disclose Tumor Budding in Colorectal Carcinoma: What, Why, and How Disclosures I have nothing to disclose Soo-Jin Cho, MD, PhD Assistant Professor UCSF Dept of Pathology Current Issues in Anatomic Pathology 2017

More information

BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients

BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department of Urology University of Oklahoma Non-muscle Invasive Bladder Cancer Bladder

More information

Adjuvant chemotherapy in older breast cancer patients: how to decide?

Adjuvant chemotherapy in older breast cancer patients: how to decide? Adjuvant chemotherapy in older breast cancer patients: how to decide? H. Wildiers University Hospitals Leuven Belgium Wildiers H, Kunkler I, Lancet Oncol 2007 Biganzoli L, Wildiers H, Lancet Oncol. 2012

More information

The Role of Adjuvant vs Salvage Radiation Therapy after Prostatectomy. Dr. Matt Andrews Supervisor: Dr. David Bowes

The Role of Adjuvant vs Salvage Radiation Therapy after Prostatectomy. Dr. Matt Andrews Supervisor: Dr. David Bowes The Role of Adjuvant vs Salvage Radiation Therapy after Prostatectomy Dr. Matt Andrews Supervisor: Dr. David Bowes Objectives Discuss the evidence for adjuvant radiotherapy (ART) EORTC, SWOG, ARO Current

More information

CTC in clinical studies: Latest reports on GI cancers

CTC in clinical studies: Latest reports on GI cancers CTC in clinical studies: Latest reports on GI cancers François-Clément Bidard, MD PhD GI cancers are characterized by Multimodal treatment strategies Treatments are adapted to tumor burden & prognosis

More information

When PSA fails. Urology Grand Rounds Alexandra Perks. Rising PSA after Radical Prostatectomy

When PSA fails. Urology Grand Rounds Alexandra Perks. Rising PSA after Radical Prostatectomy When PSA fails Urology Grand Rounds Alexandra Perks Rising PSA after Radical Prostatectomy Issues Natural History Local vs Metastatic Treatment options 1 10 000 men / year in Canada 4000 RRP 15-year PSA

More information

ORIGINAL ARTICLE. World J Urol (2011) 29: DOI /s

ORIGINAL ARTICLE. World J Urol (2011) 29: DOI /s World J Urol (2011) 29:487 494 DOI 10.1007/s00345-011-0645-8 ORIGINAL ARTICLE Concomitant carcinoma in situ as an independent prognostic parameter for recurrence and survival in upper tract urothelial

More information

J Clin Oncol 23: by American Society of Clinical Oncology INTRODUCTION

J Clin Oncol 23: by American Society of Clinical Oncology INTRODUCTION VOLUME 23 NUMBER 21 JULY 20 2005 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine,

More information

T1HG Bladder Cancer What is the Best Therapy?

T1HG Bladder Cancer What is the Best Therapy? T1HG Bladder Cancer What is the Best Therapy? Ashish M. Kamat, MD, MBBS, FACS Professor of Urology Director, Urologic Oncology Fellowship Guidelines for T1HG Bladder Cancer AUA Recommendation: BCG induction

More information

Case presentation 04/13/2017. Genomic/morphological classification of endometrial carcinoma

Case presentation 04/13/2017. Genomic/morphological classification of endometrial carcinoma Genomic/morphological classification of endometrial carcinoma Robert A. Soslow, MD soslowr@mskcc.org architecture.about.com Case presentation 49 year old woman with vaginal bleeding Underwent endometrial

More information

Evaluation of prognostic factors after radical prostatectomy in pt3b prostate cancer patients in Japanese population

Evaluation of prognostic factors after radical prostatectomy in pt3b prostate cancer patients in Japanese population Japanese Journal of Clinical Oncology, 2015, 45(8) 780 784 doi: 10.1093/jjco/hyv077 Advance Access Publication Date: 15 May 2015 Original Article Original Article Evaluation of prognostic factors after

More information

346

346 EXTENDED LYMPHADENECTOMY IN BLADDER CANCER DURING RADICAL CYSTECTOMY: BENEFIT AND MORBIDITY Islam Mohiedden M, Diab El-Sayed M, Reda Mohamed S, Saad A M Al Qady, Department of Urology, Zagazig University,

More information

GENE EXPRESSION PROFILING AND PROTEIN BIOMARKERS FOR PROSTATE CANCER MANAGEMENT

GENE EXPRESSION PROFILING AND PROTEIN BIOMARKERS FOR PROSTATE CANCER MANAGEMENT CANCER MANAGEMENT Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs

More information

Loco-Regional Management After Neoadjuvant Chemotherapy

Loco-Regional Management After Neoadjuvant Chemotherapy 1 Loco-Regional Management After Neoadjuvant Chemotherapy Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor of Surgery,

More information

Lymphadenectomy with Cystectomy: Is It Necessary

Lymphadenectomy with Cystectomy: Is It Necessary European Urology European Urology 46 (2004) 457 461 Lymphadenectomy with Cystectomy: Is It Necessary and What Is Its Extent? Mohamed A. Ghoneim *, Hassan Abol-Enein Urology & Nephrology Center, Gomhouria

More information

Triple Negative Breast cancer New treatment options arenowhere?

Triple Negative Breast cancer New treatment options arenowhere? Triple Negative Breast cancer New treatment options arenowhere? Ofer Rotem, M.D., B.Sc. Breast Unit, Davidoff center Rabin Medical center October 2017 Case 6/2013 - M.D., 38 years old woman, healthy, no

More information

Reliable Evaluation of Prognostic & Predictive Genomic Tests

Reliable Evaluation of Prognostic & Predictive Genomic Tests Reliable Evaluation of Prognostic & Predictive Genomic Tests Richard Simon, D.Sc. Chief, Biometric Research Branch National Cancer Institute http://brb.nci.nih.gov Different Kinds of Biomarkers Prognostic

More information

Introduction. Why Do MSI/MMR Analysis?

Introduction. Why Do MSI/MMR Analysis? Clinical Significance Of MSI, KRAS, & EGFR Pathway In Colorectal Carcinoma UCSF & Stanford Current Issues In Anatomic Pathology Introduction Microsatellite instability and mismatch repair protein deficiency

More information

Surgical Considerations in Breast Cancer treated with Neoadjuvant Therapy

Surgical Considerations in Breast Cancer treated with Neoadjuvant Therapy Surgical Considerations in Breast Cancer treated with Neoadjuvant Therapy Rebecca Warburton MD Department of Surgery, University of British Columbia Mount Saint Joseph Hospital, Providence Health Care

More information

SLN Mapping in Cervical Cancer. Memorial Sloan Kettering Cancer Center New York, USA

SLN Mapping in Cervical Cancer. Memorial Sloan Kettering Cancer Center New York, USA Lead Grou p Log SLN Mapping in Cervical Cancer Nadeem R. Abu-Rustum, M.D. Memorial Sloan Kettering Cancer Center New York, USA Conflict of Interest Disclosure Nadeem R. Abu-Rustum, M.D. I have no financial

More information

Disclosures. Prostate and Bladder Cancer: Jonathan E. Rosenberg, M.D. U.S. Cancer Statistics: Prostate Cancer Known Risk Factors

Disclosures. Prostate and Bladder Cancer: Jonathan E. Rosenberg, M.D. U.S. Cancer Statistics: Prostate Cancer Known Risk Factors Prostate and Bladder Cancer: 2012 Jonathan E. Rosenberg, M.D. Associate Attending Section Head, Non-Prostate Genitourinary Oncology Service Memorial Sloan-Kettering Cancer Center Disclosures Consulting

More information

Reflex Testing Guidelines for Immunotherapy in Non-Small Cell Lung Cancer

Reflex Testing Guidelines for Immunotherapy in Non-Small Cell Lung Cancer Reflex Testing Guidelines for Immunotherapy in Non-Small Cell Lung Cancer Jimmy Ruiz, MD Assistant Professor Thoracic Oncology Program Wake Forest Comprehensive Cancer Center Disclosures I have no actual

More information

Some Seminal Studies. Chemotherapy Alone is Inadequate. Bladder Cancer Role of Radiation in Bladder Sparing. Primary Radiation for Bladder Cancer

Some Seminal Studies. Chemotherapy Alone is Inadequate. Bladder Cancer Role of Radiation in Bladder Sparing. Primary Radiation for Bladder Cancer Bladder Cancer Role of Radiation in Bladder Sparing David C. Beyer M.D., FACR, FACRO, FASTRO Arizona Oncology Services Phoenix, Arizona Primary Radiation for Bladder Cancer No modern surgery / XRT randomized

More information

Guidelines for the Management of Bladder Cancer

Guidelines for the Management of Bladder Cancer Guidelines for the Management of Bladder Cancer Date Approved by Network Governance July 2012 Date for Review July 2015 Changes Between Version 3 and 4 Sections 5.2 and 8 updated Page 1 of 9 1. Scope of

More information

Supplementary Figures

Supplementary Figures Supplementary Figures Supplementary Figure 1. Pan-cancer analysis of global and local DNA methylation variation a) Variations in global DNA methylation are shown as measured by averaging the genome-wide

More information

Case Presentation 58 year old male with recent history of hematuria, for which he underwent cystoscopy. A 1.5 cm papillary tumor was found in the left lateral wall of the bladder. Pictures of case Case

More information