In the treatment of esophageal squamous cell cancer, should we perform chemoradiation alone or chemoradiation plus surgery?

Earlier this year Michael G. Haddock, MD, and David H. Ilson, MD, PhD, debated for and against the addition of surgery after chemoradiation for patients with squamous cell carcinoma of the esophagus at Great Debates and Updates in GI Malignancies in New York. HemOnc Today spoke with Haddock and Ilson about their assigned position for the meeting and whether or not that position conforms to their own view.

Haddock argued in favor of including surgery, though in his own practice he does not believe trimodality is appropriate for all patients with squamous cell carcinoma. Ilson argued in favor of the standard treatment, which does not include surgery — a position he agrees with.

Surgery after chemoradiation

My conclusion in the debate was that surgical resection should be offered to patients with squamous cell carcinoma of the esophagus following chemoradiation. It’s a fairly complicated topic. You can look at studies and conclude that surgery shouldn’t routinely be offered to everyone, but the key is patient selection.

If you do chemoradiotherapy up front, then restage with a PET scan and do endoscopy and find there is still residual local disease, but no metastatic disease, there is probably a general agreement that surgery would be appropriate if the patient is medically a good candidate. Some of the patients with persistent local disease may have delayed complete response with further observation.

It becomes complicated when you restage and the PET scan is normal and you don’t find any cancer on endoscopy. You know that some of those patients are cured and some are going to have local relapse.

My own view is that you probably need to individualize treatment at that point. There will be some patients who may be at a lower risk for surgery based on performance status, age and comorbidities. It may be very reasonable to do surgery in those patients. However, in other patients lung function or cardiac status may be compromised, and you should probably not perform surgery. There doesn’t seem to be a single right answer on whether to operate or when to do so.

Michael G. Haddock

Currently at Mayo Clinic [in Rochester, Minn.], patients are usually seen by a surgeon and surgery is considered. Of the overall group of squamous cell patients, about half have surgery compared with about 80% of patients with adenocarcinomas. Patients with squamous cell do not undergo surgery for a variety of reasons. Sometimes it’s location, sometimes it’s stage and sometimes it’s just performance status or comorbidities.

Unfortunately, there is no good way to select patients for surgery. We’d like to be able to predict after the chemoradiation who is going to have a local relapse in the future and operate on those patients before that happens, but as of yet, we don’t have that predictive factor. Determining some factor that would predict higher risk for local relapse is a viable avenue for future research. We could operate on those patients with higher risk for local relapse and just observe those patients with a lower risk.

Some researchers are looking at functional imaging early in treatment to determine whether a patient is an early responder. That would just need to be correlated with the eventual local relapse rate. In addition, people are researching tumor-related factors or factors related to response, but there are not any good predictive assays as of right now.

You can estimate how someone might do with surgery — surgeons do that all the time — but in the group of patients who have been staged and had a clinical complete response, we do not have a good tool to say who is going to have a local relapse and who is cured.

Trimodality isn’t best for all patients, but we are not sure right now which patients should get trimodality and which should just get chemoradiation. Medicine is very poor at predicting the future.

Michael G. Haddock, MD, is a Consultant in the Department of Radiation Oncology at the Mayo Clinic in Rochester, Minn.

Treat with combined chemotherapy and radiation

For patients with adenocarcinoma, surgery is usually recommended because the rate of pathologic complete response is relatively low and most centers would argue there is a role for surgery after chemoradiation.

However, squamous cell carcinoma tends to be more responsive to chemotherapy and radiation than adenocarcinoma. Common practice to treat locally advanced squamous cell cancers is to give a combination of chemotherapy and radiation.

The difference is anatomy. Squamous cell carcinomas are often in the mid- or upper part of the chest. There’s often close proximity to the airway and major blood vessels, so the surgical management tends to be more complicated for these proximal tumors compared with tumors lower down in the distal esophagus or gastroesophageal junction where surgery is probably fraught with fewer complications.

David H. Ilson

In 2009, for patients with squamous cell carcinomas, for T3 or node-positive esophagus cancer, few would argue to send any of these patients to immediate surgery. For locally advanced cancers, there is increasing evidence that adding some other treatment, either chemotherapy or chemoradiation followed by surgery improves outcome.

To address squamous cell cancers specifically, there have been trials done evaluating primary chemotherapy and radiation by itself or chemotherapy and radiation followed by surgery. Two European trials failed to show any survival benefit in patients getting surgery after chemoradiation — there were equivalent survival outcomes. When we factor in a surgical mortality of 5% to 10%, it’s hard to justify mandating surgery in all patients with squamous cell getting primary chemotherapy and radiation.

In general for squamous cell patients, we give chemotherapy and radiation first. One could make an argument that if the patient responds and appears to have endoscopic negative findings after treatment, that patient should not undergo surgery; they should be observed. I would reserve surgery for patients who have biopsy-proven residual disease.

For adenocarcinoma, it’s a different story because these are more distal tumors and pathologic complete response rates are lower, so if you don’t operate you’ll have a higher rate of local persistence or recurrence. For patients who are medically fit, we’re more likely to advocate for surgery after chemotherapy and radiation.

In a squamous cell, there’s a stronger justification to reserve surgery only for biopsy-persistent disease. The other issue in the squamous cell patients, at least in the United States, is that these are patients who have alcohol- and tobacco-use histories, they tend to be older patients with significant medical comorbidities and they’re often not good surgical candidates.

The debate comes down to primary chemoradiation being an acceptable treatment and really applying surgery selectively in patients who have biopsy-persistent disease or you have a strong suspicion that there’s still persistent disease locally. One could also argue to recommend surgery more in younger, fitter patients with squamous cancer who could tolerate all the modalities of treatment.

David H. Ilson, MD, PhD, is an Attending Physician at Memorial Sloan-Kettering Cancer Center in New York and a HemOnc Today Editorial Board Member.