Current and Future Options for Treating Esophageal Cancer

Current therapy for esophageal cancer is individualized according to the stage of the patient's disease, histologic condition, and physiologic reserve. We are now seeing significant differences in the therapies offered to patients with esophageal cancer, compared with therapies of a decade or two ago. Although surgical resection has been the mainstay of treatment for potentially curable disease since the early part of the 20th century, advances in nonsurgical therapies have arisen out of a need to treat the majority of patients with esophageal cancer, who do not have a surgical option because of cancer stage or comorbid illness. Concomitantly, better staging tools, such as fluorodeoxyglucose-positron emission tomography and endoscopic ultrasonography, have shown us that there are groups of patients in whom surgery constitutes undertreatment because of more advanced disease, and still other groups in whom surgery constitutes overtreatment because of limited disease. The following is a brief description of this departure from surgery as primary therapy for esophageal cancer. The ultimate direction is toward organ-sparing options in situations where that is appropriate.

Stage

Early-stage disease, defined by high-grade dysplasia or tumor limited to the mucosa, is now recognized as having a low potential for harboring or progressing to metastatic disease. Because of the labor-intensive work done by surgical pioneers, we now recognize that the risk of concurrent lymph node metastasis ranges between 0 and 3% for disease limited to the mucosa.¹ Therefore, when patients are offered the choice between esophagectomy (with its potential for morbidity, lifestyle changes, and death) and nonsurgical intervention (with its small risk of disease progression), they most often choose to forgo esophageal resection. As a result, there has been an explosion of definitive endoscopic therapy options for high-grade dysplasia and early cancers (T0, T1aN0). These types of therapies—endoscopic mucosal resection, radiofrequency ablation, and cryotherapy—are currently delivered at centers with advanced, high-resolution endoscopic equipment; and these techniques can be mastered by surgeons and gastrointestinal specialists alike. Frequently, these therapies are combined sequentially, and the results thus far have been excellent.²

Histology

Two European clinical trials^3,4 published since 2005 have changed the way we view the treatment of locally advanced squamous cell cancer of the esophagus (SCCA). Although SCCA was once considered primarily a surgical disease, surgery alone produced mediocre-to-poor outcomes; and this prompted trials with combined multimodality therapy.⁵ Moreover, many patients underwent resection only to be told that there was no residual tumor in the resected specimen. The aforementioned European trials then asked what additional benefit, after chemoradiation (CXRT), surgery conferred in a patient population whose primary disease was SCCA. The results indicated that there was no significant difference in outcomes in patients undergoing definitive CXRT, versus CXRT plus surgery, so long as there was a favorable response to CXRT. This led to a paradigm shift in the management of locally advanced esophageal SCCA. Our current algorithm involves platinum-doublet chemotherapy delivered in a concurrent manner with 50.4 Gy of radiation (intensity-modulated radiation therapy or proton therapy), followed by re-evaluation with positron emission tomography and endoscopy. If there is evidence of incomplete treatment (in the presence of physiologic reserve), surgery is recommended; but if the response appears to have been complete, patients might consider observation. For local or regional recurrence without metastatic disease, salvage resection is considered. It is important to note that this treatment algorithm is not currently recommended for patients with adenocarcinoma.

Physiologic Reserve

Unfortunately, some patients who complete neoadjuvant chemoradiation experience a decline in performance status due to the therapy. In the past, standard trimodality therapy (chemoradiation followed by surgery) called for a resection within 5 to 8 weeks after the completion of chemoradiation. However, performing surgery on an already compromised patient can significantly increase the risk of morbidity or death associated with a major operation. In analyzing our retrospective, single-institution data, we found that waiting an additional amount of time for a patient to recover performance status and stamina did not risk advancing the tumor, nor did it inhibit our ability to resect completely.⁶ On the contrary, it facilitated recovery. In our series, surgical delays of up to 3 months were not unusual, and occasionally the wait was even longer. Furthermore, in patients who appear to have had a complete clinical response, a selective approach to surgery is supported by both retrospective and prospective data.⁷ There is always the option to observe any patient in whom the risk of surgery outweighs the potential benefit. Patients who have adequately recovered and show evidence of disease that is limited to the field of resection should be considered for a salvage resection.

In summary, there are now several more esophagus-sparing, curative options for patients to consider. However, making the appropriate choice can be complex. As with any complex disease, esophageal cancer should be evaluated at a center that specializes in the field.