Predictive medicine and esophageal cancer response to preoperative chemotherapy

Abstract

Survival rates after esophageal cancer diagnosis still remain poor despite standardization of surgery and adjuvant treatment for resectable tumors. Currently, the US cancer statistics for patients with regional or stage II/III TNM stage cancer show high mortality rates. Many patients relapse and die after complete tumor resection (R0) and multimodal adjuvant treatment with chemotherapy or chemoradiotherapy, which is associated with toxic side effects. Preoperative or neoadjuvant chemotherapy (NAC) for some cancer types, including esophageal tumor, has been associated with high response rates resulting in wider clinical use of this systemic treatment. However, how can the high relapse and death rates despite the high NAC response rates for esophageal cancer be explained? Currently, a whole-genome sequencing study provides scientific evidence that although most primary tumor cells are sensitive and are killed by initial chemotherapy, a subclone of the founding clone survives, gains additional mutations, and is expanded at relapse. DNA-damaging chemotherapy itself contributes to this treatment failure [1]. Therefore, despite tumor mass reduction in the conventional imaging technology, relapse and death occur, indicating the need for the development of robust prognostic and predictive markers [2, 3]. Considering this latest data on cancer genome and epigenome [4], can endoscopic ultrasound (EUS) be useful in the clinic for monitoring and predicting response to NAC for patients with esophageal cancer? In the February issue of Surgical Endoscopy, Misra et al. [5] evaluated whether EUS is a useful tool for assessing tumor response and staging esophageal cancers after NAC. The authors analyzed 110 patients with esophageal cancer by performing EUS before and after NAC and compared the data with the postsurgical pathologic stage (pTNM). Misra et al. [5] reported an 87 % response rate (n = 96), and among these patients, 39 % had a significant response and 61 % a partial response to NAC. In more than 50 % of the 110 patients there was an overstaging or understaging for T and N status which led the authors to conclude that EUS is an unreliable tool for staging esophageal cancer after NAC. Misra et al. [5] performed a careful study despite its retrospective nature. The data reported suggest caution in using EUS for surgical decision-making after NAC. Surgeons should critically consider the role of EUS or computerized tomography in deciding on tumor resectability and predicting R0 resection, relapse rate, and prognosis. In particular, T stage tumor that is substantially overstaged by EUS after NAC should not lead the surgeon to avoid surgery because T tumors are nonresectable or resection would be incomplete (R1/R2) because T overstaging may have resulted from a NAC-induced inflammatory effect or fibrosis. The clinical data provided by Misra et al. are in accordance with recent whole-genome, exome, transcriptome, epigenome, and functional genomic data for the heterogeneity and high complexity of esophageal and other major cancer types. Surgeons and oncologists need more effective tools than the currently used conventional clinicopathologic and imaging markers for accurately predicting therapeutic response, recurrence, and prognosis. Revolutionary technologies such as next-generation sequencing, living cells imaging using biosensors, and three-dimensional genome resolution now allow for the first time reliable systems computational biology, synthetic genomic biology, C. Hottenrott (&) Chirurgische Klinik, St. Elisabethenkrankenhaus, Ginnheimer Strase 3, 60487 Frankfurt, Germany e-mail: info@gastricbreastcancer.com