The evolving modality of PDT gives patients with premalignant lesions of the esophagus reason to hope. Managed care must update existing policies.
Thomas Morrow, MD
Much has been written about Barrett's esophagus and the resultant dysplastic changes that may degenerate into adenocarcinoma of the esophagus. Until now there has been little to offer patients suffering from this premalignant lesion of the esophagus besides a devastatingly difficult esophagectomy. Now, a revolutionary approach promises to shed light on this usually asymptomatic condition.
But first, let's review Barrett's. Barrett's esophagus derives its name from the British surgeon Norman Barrett. Barrett first described this condition as a "congenitally short esophagus that tethered the stomach into the mediastinum resulting in esophageal ulcers."
Later, in 1953, the presence of reflux esophagitis and its associated columnar mucosa was described. Over the next several decades the definition of Barrett's esophagus has evolved into the finding of columnar-appearing mucosa in the distal esophagus or intestinal metaplasia on biopsy through upper gastrointestinal endoscopy.
Intestinal metaplasia is the premalignant lesion that may develop into dysplasia and eventually adenocarcinoma. All of this occurs on the heel of gastroesophageal reflux disease.
Barrett's esophagus was rarely found before the widespread use of upper endoscopy. Based on a variety of studies it appears that about 1 in 60 people undergoing an endoscopy will have Barrett's esophagus. Other studies have estimated the prevalence to be about 8 percent of patients having gastroesophageal reflux disease (GERD) as the presenting symptom, with a range of 5 to 20 percent. Barrett's esophagus has long been a harbinger of bad news.
In those who develop high grade dysplasia, as many as 59 percent will develop adenocarcinoma. Alternatively, most adenocarcinomas of the esophagus arise in Barrett's epithelium. This is of great interest to managed care, as the average age of those with Barrett's esophagus is 40 years.
The reflux of bile acid and stomach acid has long been implicated in the development of Barrett's esophagus as well as adenocarcinoma. As evidenced by the considerable expense for PPIs, the decrease in pH using pharmacotherapy is a key treatment modality for physicians.
Traditional therapy for Barrett's as well as its precursor, GERD, have been acid suppression using proton pump inhibitors, physical measures such as elevation of the head of the bed to use gravity, promotility agents, repair of diaphragmatic sphincter deficiencies, repair of hiatal hernia, and antireflux surgery. Additionally, screening patients with GERD through endoscopy for the characteristic mucosal changes with biopsy verification for Barrett's is the gold standard.
But, despite all that medical therapy can offer, a significant number of people with Barrett's develop dysplasia and eventually cancer. This long road to a deadly disease has led investigators to attempt to find a way to destroy the mucosal changes characteristic of Barrett's using a variety of approaches including multipolar eletrocoagulation, plasma coagulation, and thermal laser. All of these approaches caused deeper damage to the esophagus than was desired. Recently a new approach has received FDA approval.
For more than 100 years there has been an appreciation of the interaction of light and certain chemicals, called photodynamic therapy (PDT). Using knowledge gained from other diseases and disciplines, the company Axcan Pharma studied the use of the photo-activated drug porfimer sodium, marketed under the brand name Photofrin for patients with Barrett's esophagus with high grade dysplasia. Photofrin is currently indicated for the treatment of endobronchial non-small cell lung cancer and primary or recurrent obstructing esophageal carcinoma.
Recently, the FDA granted an "approvable" letter for PDT in Barrett's with high grade dysplasia. Final approval is expected this summer and may actually be obtained as this article goes to press.
PDT consists of the infusion of porfimer sodium, with exposure 48 hours later to a laser that emits a red light tuned to 630 nanometers. The laser is not a thermal laser and has no effect on its own without the sensitizing agent. The drug is selective in its affinity for tumors, leading to selective tumor destruction.
A special endoscope equipped with a diffuser allows the light to be applied to the Barrett's mucosa. The light penetrates the tissue and reacts with the Photofrin, which then reacts with oxygen and mediates cell destruction through the development of a highly active oxygen molecule.
Necrosis is evident within two days.
Patients may need to remain in the hospital for a day or so due to pain. An optional follow-up endoscopy done three days after the procedure can detect and retreat residual abnormal mucosa. Patients can resume a normal diet a few days after the procedure. They also must be very careful about sun exposure for several weeks after the procedure due to the prolonged danger of photoactivation of the drug in the sun-exposed areas of the skin.
In the clinical trial data submitted for FDA approval, more than three-quarters of all patients had complete ablation of high grade dysplasia. Upon further biopsy during follow up, many patients exhibited evidence that previous intestinal metaplastic cells had been replaced with normal esophageal mucosa. Thus the need for esophagectomy can be reduced.
Risk of developing esophageal cancer dropped to 17 percent, 2 to 3.6 years after the procedure.
Treatment with omeprazole reduced cancer risk to 47 percent. When the two therapies are combined, the progression to cancer is even less. It is likely that further studies will move this approach to those with earlier disease such as Barrett's with lower degrees of dysplasia.
Managed care's role
As with any new therapy, managed care will be required to evaluate it. Existing policies and procedures will require updating. New contracting opportunities will exist as this procedure becomes more common.
The drug carries an average wholesale price of $2,740 per episode of care, and there will be opportunities for insurers to work with specialty pharmacies to acquire the drug directly. Office infusions, paid on a case rate basis, are one approach to save on the physician markup. Other expenses include the cost of disposable laser fiber as well as the use of the hospital and physician services.
It is also likely that more intense monitoring of patients with GERD will occur now that a therapy is available to eradicate the dysplasia. This may mean more endoscopic procedures. It is likely that there will be patient-generated demand for this procedure because, in the past, the only course of therapy for the patient was surveillance until a cancer developed. Now, patients may wish to be proactively monitored and if Barrett's develops and progresses, a comparatively noninvasive therapy is available.
PDT has the potential to shed new light, literally and figuratively, on a disease that is both common and deadly. As this technology becomes readily adopted, it will change the approach to treating Barrett's esophagus, giving patients who have high grade dysplasia another treatment option to consider. Yet again, "Tomorrow's Medicine," here today.
Thomas Morrow, MD, is president of the National Association of Managed Care Physicians and vice president and medical director of Matria Health Care. He has 19 years of managed care experience at the payer or health plan level.