DCIS Trial Adele Francis Daniel Rea Claire Gaunt

DCIS Trial Adele Francis, Daniel Rea & Claire Gaunt on behalf of the DCIS Trial Development Group ICPV Study Day, 4 th 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 Qo. L 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 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 Pu. LMi. CC 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 • 200 patient Pilot Study to examine: - reasons for accepting/declining trial, reactions to diagnosis, and patient understanding of DCIS • Regional start up meetings to provide sites with Consistent information and first approach • Inform if need for adaptation to recruitment approach • Media publicity • Trial awareness at screen attendance (poster/leaflet) • Patient Information DVD (based on experience from PROTECT trial)

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