DCIS Trial
Adele Francis, Daniel Rea & Claire
Gaunt on behalf of the
DCIS Trial Development Group
ICPV Study Day, 4th March 2011
What cancers?
Over diagnosis
• Over diagnosis refers to the detection of
abnormalities that will never cause symptoms or
death during a patients life time.
• Over diagnosis of cancer occurs when the cancer
grows so slowly that the patient dies of other causes
before it produces symptoms or when the cancer
remains dormant (or regresses)
Over diagnosis and Mammography screening
• The question is no longer whether, but how
often, it occurs
H Gilbert Walsh Editorial BMJ July 2009
Overtreatment of DCIS
• 21,683 women
diagnosed with breast
cancer in 2006
equivalent to 7000
unnecessary breast
cancer diagnoses per
year in UK
• 2000 women
screened 3 yearly over
20 years 17.6- 11.4
lives saved, 8.6 - 2.3
over diagnosed
The original version
• ‘I will prescribe regimens for the good of my
patients according to my ability and my
judgment and never do harm to anyone.’
Modern Version:
• ‘I will apply, for the benefit of the sick, all
measures that are required, avoiding those
twin traps of overtreatment and therapeutic
nihilism’
Issues a Trial must address
• Is surgery necessary for all DCIS
• Which DCIS diagnoses don’t require surgery
• Can we predict by biopsy which DCIS requires
surgery (is life threatening)
• Can we quantify these risks better to give
‘patients’ an informed choice
Trial Flow Diagram
Patient is diagnosed with low/intermediate grade
DCIS
Obtain written informed consent
REGISTRATION
Central pathology review confirms low risk
DCIS
Patient completes Baseline Questionnaires
RANDOMISATION
STANDARD TREATMENT
ACTIVE MONITORING
Proceed to Surgery +/- radiotherapy
Annual mammograms for 5 years
Follow-up as per local practice
All patients to complete QoL Questionnaires until 5 years post-randomisation
All patients to be followed-up for 10 years
STUDY COMPLETION
Cancer Stages: In Situ
Basement Membrane
• Cancer cells localized
• Did not spread
Abnormal
cells
Cancer Stages: Invasive
Basement Membrane
• Cancer cells break through basement
membrane
• Invade surrounding tissue
Abnormal
cells
Team Expertise
• Collaboration with SLOANE* and West Midlands Cancer
Intelligence Unit (Gill Lawrence)
• Run through CR UK Clinical Trials Unit, Birmingham
 Radiologists: Matthew Wallis* and Andy Evans*,
 Pathologists: Jeremy Thomas* Sarah Pinder* & Andy
Hanby
 Patient Reported Outcomes: Lesley Fallowfield & Alison
Broome
 Translational Science: John Bartlett
 Oncologists: David Dodwell* & Dan Rea
 Surgeons: Adele Francis, Hugh Bishop*, Martin Lee*, Mike
Hallissey & Malcolm Reed
 Health Economist: Tracy Roberts
Trial End Points
• Diagnosis of invasive breast cancer in the same breast
• Patient reported outcomes
•
•
•
•
Overall survival
Translational predictors of progression to invasive disease
Time to surgery/mastectomy/mastectomy rate
Health Economics
Annual DCIS Case Load UK
• Low Grade – 500
• Intermediate Grade - 3000
• High Grade - 7000
Patient Information &
Quality of Life
Enhancing Patient Uptake
• There may be debate about the DCIS trial design comparing
Active Monitoring +/- treatment
• Difficulties recruiting both clinical teams to join trial and
patients are acknowledged
• Patients/advocates have been involved at an early stage of
trial development. Focus groups held with representative
sample of patients
• Importantly, a Patient Information DVD providing an evenhanded and consistent message about rationale and logic will
be made
• Will be made by LF’s group who have lots of experience
e.g. Patient Information DVD for
PuLMiCC Trial
• Contains relevant cartoons
and graphics
• Permits patients to take their
time, replay parts and make
informed unbiased decisions
Professor Tom Treasure
describes the lung surgery
Oncologist Dr
Pauline Leonard,
explains trial
rationale
Hayley Tapping, research nurse
discussing the trial tests
Recruitment Strategy
• Patient involvement
• Focus Day for potential user
group
• Scoping Day with relevant Health
Care Practitioners
• Regional start up meetings to
provide sites with Consistent
information and first approach
• Patient Information DVD (based
on experience from PROTECT
trial)
• 200 patient Pilot Study to
examine:- reasons for
accepting/declining trial,
reactions to diagnosis, and
patient understanding of DCIS
• Inform if need for adaptation to
recruitment approach
• Media publicity
• Trial awareness at screen
attendance (poster/leaflet)
Why we need the trial?
• There are no randomised data demonstrating
survival advantages following treatment for
low/intermediate grade DCIS
• There are no systematically collected Quality of Life
data using validated patient reported outcome
measures demonstrating harms/benefits of current
practice
• Very little Health Economic evidence
• Probably unacceptable to continue as we are
Name?
• DCIST (DCIS TRIAL)
• FANTASTIC