Preinvasive disease: catching it earlier, understanding it better, hitting it harder

Rebecca Fitzgerald
Hutchison-MRC Research Centre, and Addenbrooke’s Hospital, Cambridge, UK

The majority of epithelial cancers have a pre-invasive stage sometimes called intraepithelial neoplasia. This pre-invasive stage generally persists over many years before it acquires the necessary genetic and epigenetic abnormalities for invasion. Since invasive disease is rapidly disseminated through the lymphovascular system most patients with clinically apparent cancer have a poor prognosis. The diagnosis of disease at a pre-invasive stage affords the opportunity for cure. However, the detection of such lesions through screening and surveillance programmes also raises questions regarding the psychosocial and economic burden of diagnosing disease which is asymptomatic and may never progress to cancer in the lifetime of the individual.

Barrett’s oesophagus is the precursor lesion to adenocarcinoma of the oesophagus and gastro-oesophageal junction that exemplifies many of the controversies and opportunities associated with the early detection of cancer. Barrett’s oesophagus is estimated to affect 1.6% of the population and 2.3% of those with heartburn symptoms, however the majority of patients are undiagnosed. The cancer conversion rate is 0.5 – 1% per annum, and once a cancer has progressed to a symptomatic stage the five year survival is an abysmal 13%. Since the oesophagus is easily accessible by endoscopy and since patients are followed up longitudinally there is an ideal opportunity to study the molecular changes in the metaplasia-dysplasia-carcinoma sequence. This has led to intense interest in developing clinically relevant biomarkers in order to risk stratify individuals. Furthermore, rapid advances in endoscopic technologies mean that it may be possible to ablate Barrett’s oesophagus without recourse to oesophagectomy. Screening might therefore be a worthwhile proposition. This lecture will discuss the current state of the Barrett’s oesophagus field and the lessons that are germane to making clinical progress in other preinvasive lesions.