Surgery versus active surveillance in clinical complete response

Abstract

: Esophageal adenocarcinoma is an aggressive disease that is often treated with trimodality therapy for locoregionally advanced cases. However, about a quarter of these patients are found to have pathologic complete response (pCR) on resection, which raises the question of whether we can avoid esophagectomy in favor of active surveillance in patients who appear to have a complete response on clinical evaluation after neoadjuvant chemoradiation (nCRT). Two prospective trials—the SANO trial and ESOSTRATE trial—are currently ongoing in an attempt to study this question. While awaiting the results of these trials, in order to consider active surveillance as a viable alternative to upfront surgery, we must understand the accuracy of clinical tools currently used to evaluate for pCR, establish safe, efficient and reliable surveillance protocols, and finally, understand the risk of selecting either strategy. Currently available clinical tools include FDG-PET/CT, CT with IV contrast of the chest and abdomen, MRI, endoscopy with biopsy and endoscopic ultrasound. None of these modalities has been found to be reliable to independently predict pCR, and although MRI may perform better than other studies, nearly all the available data is from small scale feasibility studies. Recognizing these limits, the SANO group developed a novel technique of bite-on-bite biopsy which appears to perform better than preexisting methods (74% sensitivity and 77% specificity for residual tumor detection). However, outside of the SANO group publications, there is virtually no data regarding this technique at this time. In the meanwhile, the risk balance of either approach continues to evolve. Esophagectomy and its perioperative management continue to evolve with improved short- and long-term outcomes and improved survivorship. The objective estimation of a specific patient’s perioperative risk continues to be elusive and therefore heavily relies on subjective evaluations by clinicians. On the other hand, delayed (salvage) esophagectomy is often found to have increased morbidity, and there is no clear data establishing the safest and most effective active surveillance protocol. At this point, we find that our current ability to detect true pCR and predict outcomes after either surgery or surveillance is limited, which severely diminishes the safety of active surveillance for patients with clinical complete response. As we await the results from the aforementioned trials, any decision made in a patient with clinical complete response after nCRT must be individualized, keeping in mind the goals of care for any given patient but recognizing the limits of available data and high stakes.