1. DCIS Trial Adele Francis, Daniel Rea & Claire Gaunt on behalf of the DCIS Trial Development Group ICPV Study Day, 4 th March 2011

3. What cancers?

5. 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)

6. Over diagnosis and Mammography screening The question is no longer whether, but how often, it occurs H Gilbert Walsh Editorial BMJ July 2009

7. 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 Overtreatment of DCIS

8. 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.’

9. 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’

10. 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

11. Patient is diagnosed with low/intermediate grade DCIS Obtain written informed consent Central pathology review confirms low risk DCIS REGISTRATION All patients to complete QoL Questionnaires until 5 years post-randomisation 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 be followed-up for 10 years STUDY COMPLETION Trial Flow Diagram

12. Cancer Stages: In Situ Cancer cells localized Did not spread Basement Membrane Abnormal cells

13. Cancer Stages: Invasive Cancer cells break through basement membrane Invade surrounding tissue Basement Membrane Abnormal cells

14. 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

15. 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

16. Annual DCIS Case Load UK Low Grade – 500 Intermediate Grade - 3000 High Grade - 7000

17. Patient Information & Quality of Life

18. 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 even- handed and consistent message about rationale and logic will be made Will be made by LF’s group who have lots of experience

19. e.g. Patient Information DVD for PuLMiCC Trial Professor Tom Treasure describes the lung surgery Hayley Tapping, research nurse discussing the trial tests Oncologist Dr Pauline Leonard, explains trial rationale Contains relevant cartoons and graphics Contains relevant cartoons and graphics Permits patients to take their time, replay parts and make informed unbiased decisions Permits patients to take their time, replay parts and make informed unbiased decisions

20. 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)

21. 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

22. Name? DCIST (DCIS TRIAL) FANTASTIC