Editorial: Doctor's Dilemma or Patient's Choice?

Abstract

Introduction: It has been estimated that about 50% of screen-detected cases might be over-diagnosed and over-treated. In this paper we analysed the mortality of patients with screen detected cancers in the TARGIT-A trial in which patients >=45 years with an invasive duct carcinoma <=3.5 cm in size and suitable for breast conserving therapy were randomly allocated to receive either risk-adapted TARGIT IORT or conventional course of several weeks of fractionated external beam radiotherapy (EBRT). Method: This was a post-hoc subgroup analysis limited to patients whose cancers were detected by screening mammography, and we compared breast cancer mortality, non-breast cancer mortality and overall mortality between TARGIT and EBRT with Kaplan Meier plots and logrank test. The allocation of cause of death was performed by an independent clinician who was blinded to the randomisation arms of the trial. Results: A total of 3451 patients were recruited into the TARGIT-A trial. Of these, there were 2102 patients whose cancers were diagnosed by mammographic screening (61% of the total). There were 30 deaths recorded: TARGIT 10/1060vs EBRT 20/1042): 7 from breast cancer (TARGIT 4 vs. EBRT 3), 23 from other causes (TARGIT 6, EBRT 17). The overall survival with TARGIT was 2% higher than with EBRT (5-year rates: 98.03% 95%CI 95.97 – 99.04, vs 96.03% 95%CI 93.41 – 97.62, Logrank p = 0.0522), with a doubling of mortality from 2% to 4% in this population. The breast cancer-specific survival was identical between the groups (99%). The difference in overall survival was due to higher non-breast-cancer survival in the TARGIT arm (TARGIT 99.2% and EBRT 96.7%) attributable to deaths in the EBRT arm from cardiac causes and other cancers (TARGIT 3 vs. EBRT 14). Interpretation: Harm from overtreatment of patients with screen detected cancers eligible to receive TARGIT IORT (<3.5 cm ductal cancers), who form a large proportion of the eligible group, in the form of deaths due cardiac causes and other cancers could be potentially avoided if they were instead treated by receive TARGIT IORT instead of conventional external beam radiotherapy. After discussions and volunteers with personal case histories to relate and a break there was a final session to consider the ethical and legal responsibility of doctors in the new era of shared decision-making with a brief run-through of key cases by Suzanne White of Leigh Day solicitors and then a keen Q&A discussion. Should we try for a Judicial Review of the failure to provide IORT in the NHS? Should a case be brought under the Human Rights Act using crowd funding? Something must be done if the medical establishment does not put IORT into practice in the NHS round the country.