Predictive Factors What to do before start of treatment - PowerPoint PPT Presentation

Title: Predictive Factors What to do before start of treatment


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Predictive FactorsWhat to do before start of
treatment
Dr Padraig Warde Department of Radiation
Oncology University of Toronto

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Outline

• Prognosis
• Classification of Prognostic factors
• Prognostic Models in Testis Cancer
• Pitfalls
• Need for validation
• Utility
• Ability to discriminate
• What to do before start of treatment
• Need to move into modern era

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The Basis of Prognosis

• An expert definition of outcome is based upon
• An accurate diagnosis
• Knowledge of the
• natural history of disease
• The diseases response to treatment
• Progression of the disease in in the patient in
  question

MacKillop W, The importance of prognosis in
cancer medicine UICC Prognostic Factors in
Cancer, 3rd edition 2006
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The Importance of Prognosis

• Central Role in Medical-Decision Making
• Valuable to patients in making decisions about
  all aspects of their life
• Medico-legal responsibility
• Contributes to efficiency of medical care

MacKillop W, The importance of prognosis in
cancer medicine UICC Prognostic Factors in
Cancer, 3rd edition 2006
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Classification of Prognostic Factors
Subject-Based
Tumour Related Pathology ? Grade, Pattern of
Invasion ? Morphologic classification Anatomic
Tumour Extent ? TNM, Bulk, ? sites,
Markers Tumour Biology ? Molecular markers ?
Proliferation indices
Host-Related Demographics ? Age, Race, Gender
? Education Status Comorbidity ? HIV, Cardiac
status, ? Weight, PS Compliance ? Social
reaction to illness ? Substance abuse
Environment-Related Physician ? Expertise ?
Speciality Healthcare system ? Access to
care Society ?Socioeconomic status ?Access to
transportation
Gospodarowicz, OSullivan Classification of
Prognostic Factors UICC Prognostic Factors in
Cancer, 3rd edition 2006
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Classification of Prognostic Factors- Clinical
Relevance

• Essential
• Fundamental to decisions regarding the goals and
  choice of treatment
• Additional
• These allow for finer prognostication but not an
  absolute requirement for treatment related
  decision making
• New and Promising
• May shed new light on biology or prognosis but
  incomplete evidence for an independent effect on
  outcome

Gospodarowicz, OSullivan Classification of
Prognostic Factors UICC Prognostic Factors in
Cancer, 3rd edition 2006
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Prognostic Models Testis Cancer

• IGCC Classification
• Good , Intermediate, Poor Prognosis Groups
• Extensively Validated
• Test set, independent data set
• Good discriminative ability
• Widely used
• Formal weighting of Risk Factors by Recursive
  Partitioning/Cox Regression may allow for further
  refinement

IGCCCG J Clin Oncol 15594-603. 1997 Van Dijk et
al BJC 901176-83, 2004
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Prognostic Models Testis Cancer

• Stage I Non-Seminoma
• - 30 occult disease
• MRC 1992
• Morphologic Histo-pathological factors
  Vascular, Lymphatic Invasion, Presence of
  embryonal carcinoma, absence of yolk sac elements
• 52 relapse with 3-4 factors
• Importance of Vascular invasion validated
• GTCSG 2003
• Morphologic Histo-pathological factors
• Vascular Invasion, of embryonal carcinoma
• Proliferation rate MiB-1 antibody
• 63 relapse with 3 adverse factors
• Model not validated

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Prognostic Models Testis Cancer

• Stage I Non-Seminoma
• Field moved little in 15 years
• Presence/absence of Vascular Invasion is only
  factor consistently used in clinical practice
• Risk-Adapted protocols treating patients with
  High-Risk Disease with adjuvant chemotherapy
  have been widely adopted
• Poor Discriminant ability of model has been
  ignored
• 50 of patients are over treated using this
  approach
• Adjuvant therapy for High-Risk disease precludes
  identification of prognostic factors for relapse

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Stage I Seminoma

• Management Options
• Surveillance
• Adjuvant Therapy
• Radiation Therapy or Chemotherapy
• 100 cure with all strategies
• Key issue for oncologists is
• Reduce overall Burden of Treatment while
  maintaining excellent results

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Prognostic Models Testis Cancer

• Stage I seminoma
• Pooled analysis
• 638 pts from 4 institutions
• PMH, RMH, DATECA, RLH
• Median follow-up 7 years
• 121 pts relapsed
• 5 year relapse free rate of 82.7
• Multivariate analysis
• Tumour size
• Hazard Ratio 2.0 (95 CI 1.3-3.2)
• Rete Testis invasion
• Hazard Ratio 1.7 (95 CI 1.1-2.6)

Warde et al. J Clin Oncol 204448-4452 2002
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Prognostic Models Testis Cancer
Warde et al. J Clin Oncol 204448-4452 2002
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Prognostic Models Testis Cancer

• Spanish Cooperative Group Study
• 314 patients Stage I seminoma
• 100 no adverse risk factors
• Surveillance
• 6 relapse
• 214 one/two risk factors
• 2 courses adjuvant Carboplatin
• 3.3 relapse (6 in patients with 2 factors)

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Prognostic Models Testis Cancer

• Prognostic Model
• Not validated in independent dataset
• Canadian/Danish study underway
• Low discrimination
• High-risk group still has 65 relapse-free rate
• Risk-adapted approach
• Study Protocols only

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What to do before start of treatment
Chung, Schmoll, Germ Cell Testis Tumours UICC
Prognostic Factors in Cancer, 3rd edition 2006
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What to do before start of treatment

• Tumour Related Factors
• Accurate Diagnosis
• Pathology Review
• Bloods
• CBC, Cr, electrolytes, Markers, LFTs
• Imaging
• CT Ab and pelvis, CT Chest (CXR only if
  Seminoma),
• MRI Brain, Bone scan in special circumstances

Huddart, Kataja ESMO Guidelines Working
Group Annals Oncol 19 (ii 49-54) 2008
Krege et al EGCCCG Consensus Report European Urol
53 478-496 , 2008
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What to do before start of treatment

• Host - Related Factors
• Comorbidity
• Cardiac Status, HIV Status
• Compliance
• Environment
• Expertise in managing team
• Contra-lateral testicular biopsy should be
  considered in patients
• Testicular atrophy
• Young ( ? Age lt30)

Huddart, Kataja ESMO Guidelines Working
Group Annals Oncol 19 (ii 49-54) 2008
Krege et al EGCCCG Consensus Report European Urol
53 478-496 , 2008
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What to do before start of treatment

• Need to improve Prognostic Models
• Biorepository
• Tumour Tissue
• Serum, Plasma, DNA banking
• at diagnosis
• Repeat serum, plasma banking at various time
  intervals
• Should be a prerequisite for approval of any new
  clinical trials

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Individualization of Therapy
Patients with Testis Cancer
New Biomarkers
Courtesy of Rob Bristow
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Acknowledgements PMH Testis Group

• Radiation Medicine Program
• Mary Gospodarowicz
• Charles Catton
• Andrew Bayley
• Mike Milosevic
• Betty Tew-George
• Medical Oncology
• Jeremy Sturgeon
• Malcolm Moore
• Pathology
• Diponkar Banarjee
• Joan Sweet
• Andrew Evans
• William Chapman

• Urology
• Michael Jewett
• Biostatistics
• Tony Panzarella
• Anthea Lau
• Staff - DRO TSRCC
• All referring urologists

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Thank you