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Esophageal Cancer: Improvements in Treatment, Staging, and Now Prognostic Indicators?
INVITED ARTICLE
Esophageal Cancer: Improvements in Treatment, Staging, and Now Prognostic Indicators? (Invited Editorial Commentary) Mark F. Berry, MD
COMMENTARY Esophageal cancer historically has been associated with very poor prognosis, but there have been some recent improvements in management.1 The role of induction therapy has become much better defined by several randomized trials, after years of studies showing conflicting results that prevented a consensus regarding the benefit of preoperative therapy.2 However, even beyond therapy, there have been significant improvements in the understanding of how to better stratify patients in terms of outcomes. Efforts of the Worldwide Esophageal Cancer Collaboration led to a significant revamping of esophageal staging in 2010.3-5 An important change was the development of separate staging parameters for adenocarcinoma and squamous cell carcinoma. The staging changes also recognized that both the specific number of lymph nodes involved by metastatic disease as well as the total number of lymph nodes harvested at surgery had important prognostic implications. The Worldwide Esophageal Cancer Collaboration's findings of lymph node importance were based on patients who had upfront surgery as their primary therapy.4 This current study by Philippron et al6 is a very interesting extension of studies regarding the importance of lymph node status on prognosis for patients who have had induction therapy before esophagectomy. Although lymph node biopsy during endoscopic ultrasound can provide pathologic proof of lymph node metastases before surgery, clinical staging modalities otherwise have limitations in lymph node assessment.7 Extrapolation of the importance of pathologic lymph node findings for a patient treated with induction therapy has thus been difficult. However, induction therapy reduces lymph node harvest at the time Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA Commentary on Philippron A, Bollschweiler E, Ayumi Kunikata A, Plum P, Schmidt C, Favi F, Drebber U, Hölscher AH. Prognostic relevance of histomorphologic lymph node regression after neoadjuvant chemoradiation for esophageal cancer. Semin Thorac Cardiovasc Surg. 2016 (in press). Address reprint requests to Mark F. Berry, MD, Falk Cardiovascular Research Center, 300 Pasteur Dr, Stanford, CA 94305. E-mail: [email protected]
of esophagectomy, and studies have attempted to modify the specific criteria of how lymph node data after induction therapy can be used for prognostic purposes.8,9 Mark F. Berry, MD. In this study, the authors retroCentral Message spectively examPathologic regression of lymph node metasined 403 patients tases after induction therapy affects prognosis treated with inducin esophageal cancer. tion chemoradiation followed by surgery for cT3NxM0 esophageal cancer and found that pathologic findings that suggested the presence of lymph node metastases that had been sterilized by the induction therapy had prognostic importance. Survival in the cohort of patients who both were ypN0 and had a “major” histopathologic response to induction therapy defined by less than 10% residual viable tumor was significantly better when 3 of fewer lymph nodes had pathologic findings suggestive of metastatic disease that was cleared by the induction therapy. This study has the inherent limitations of a retrospective single-institution review, and it would be very important to see these results reproduced with data from another institution or prospective analyses. Despite these limitations, the study has demonstrated important and interesting findings and may lead to further refinements in how to correlate pathologic lymph node information with clinical outcomes in patients who were treated with induction therapy before esophagectomy for locally advanced esophageal cancer. A better understanding of these topics ultimately may be able to lead to not only better predictions of prognosis after surgery, but also effect surveillance strategies and perhaps most importantly selection criteria for which patients may be benefit from additional postresection therapy.
1043-0679/$-see front matter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semtcvs.2016.08.004
1
ESOPHAGEAL CANCER positive disease. Ann Thorac Surg 92: 1. Berry MF: Esophageal cancer: staging system and 5. Rice TW, Rusch VW, Ishwaran H, et al: Cancer 491-496, 2011 of the esophagus and esophagogastric junction: guidelines for staging and treatment. J Thorac data-driven staging for the seventh edition of the 8. Issaka A, Ermerak NO, Bilgi Z, et al: Preoperative Dis (suppl 3):S289-S297, 2014 chemoradiation therapy decreases the number of American Joint Committee on Cancer/Interna2. van Hagen P, Hulshof MC, van Lanschot JJ, et al: lymph nodes resected during esophagectomy. tional Union Against Cancer Cancer Staging Preoperative chemoradiotherapy for esophageal World J Surg 39:721-726, 2015 Manuals. Cancer 116:3763-3773, 2010 or junctional cancer. N Engl J Med 366:20746. Philippron A., Bollschweiler E., Kunikata A., 9. Hanna JM, Erhunmwunsee L, Berry M, et al: The 2084, 2012 prognostic importance of the number of diset al. Prognostic relevance of lymph node regres3. Rice TW, Blackstone EH, Rusch VW: 7th edition sected lymph nodes after induction chemorasion after neoadjuvant chemoradiation for esoof the AJCC Cancer Staging Manual: esophagus diotherapy for esophageal cancer. Ann Thorac phageal cancer. Semin Thorac Cardiovasc Surg. and esophagogastric junction. Ann Surg Oncol Surg 99:265-269, 2015 2016 (in press). 17:1721-1724, 2010 4. Rice TW, Rusch VW, Apperson-Hansen C, et al: 7. Stiles BM, Mirza F, Coppolino A, et al: Clinical T2-T3N0M0 esophageal cancer: the risk of node Worldwide esophageal cancer collaboration. Dis Esophagus 22:1-8, 2009
2
Seminars in Thoracic and Cardiovascular Surgery Volume ], Number ]
Esophageal Cancer: Improvements in Treatment, Staging, and Now Prognostic Indicators? (Invited Editorial Commentary) Mark F. Berry, MD
COMMENTARY Esophageal cancer historically has been associated with very poor prognosis, but there have been some recent improvements in management.1 The role of induction therapy has become much better defined by several randomized trials, after years of studies showing conflicting results that prevented a consensus regarding the benefit of preoperative therapy.2 However, even beyond therapy, there have been significant improvements in the understanding of how to better stratify patients in terms of outcomes. Efforts of the Worldwide Esophageal Cancer Collaboration led to a significant revamping of esophageal staging in 2010.3-5 An important change was the development of separate staging parameters for adenocarcinoma and squamous cell carcinoma. The staging changes also recognized that both the specific number of lymph nodes involved by metastatic disease as well as the total number of lymph nodes harvested at surgery had important prognostic implications. The Worldwide Esophageal Cancer Collaboration's findings of lymph node importance were based on patients who had upfront surgery as their primary therapy.4 This current study by Philippron et al6 is a very interesting extension of studies regarding the importance of lymph node status on prognosis for patients who have had induction therapy before esophagectomy. Although lymph node biopsy during endoscopic ultrasound can provide pathologic proof of lymph node metastases before surgery, clinical staging modalities otherwise have limitations in lymph node assessment.7 Extrapolation of the importance of pathologic lymph node findings for a patient treated with induction therapy has thus been difficult. However, induction therapy reduces lymph node harvest at the time Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA Commentary on Philippron A, Bollschweiler E, Ayumi Kunikata A, Plum P, Schmidt C, Favi F, Drebber U, Hölscher AH. Prognostic relevance of histomorphologic lymph node regression after neoadjuvant chemoradiation for esophageal cancer. Semin Thorac Cardiovasc Surg. 2016 (in press). Address reprint requests to Mark F. Berry, MD, Falk Cardiovascular Research Center, 300 Pasteur Dr, Stanford, CA 94305. E-mail: [email protected]
of esophagectomy, and studies have attempted to modify the specific criteria of how lymph node data after induction therapy can be used for prognostic purposes.8,9 Mark F. Berry, MD. In this study, the authors retroCentral Message spectively examPathologic regression of lymph node metasined 403 patients tases after induction therapy affects prognosis treated with inducin esophageal cancer. tion chemoradiation followed by surgery for cT3NxM0 esophageal cancer and found that pathologic findings that suggested the presence of lymph node metastases that had been sterilized by the induction therapy had prognostic importance. Survival in the cohort of patients who both were ypN0 and had a “major” histopathologic response to induction therapy defined by less than 10% residual viable tumor was significantly better when 3 of fewer lymph nodes had pathologic findings suggestive of metastatic disease that was cleared by the induction therapy. This study has the inherent limitations of a retrospective single-institution review, and it would be very important to see these results reproduced with data from another institution or prospective analyses. Despite these limitations, the study has demonstrated important and interesting findings and may lead to further refinements in how to correlate pathologic lymph node information with clinical outcomes in patients who were treated with induction therapy before esophagectomy for locally advanced esophageal cancer. A better understanding of these topics ultimately may be able to lead to not only better predictions of prognosis after surgery, but also effect surveillance strategies and perhaps most importantly selection criteria for which patients may be benefit from additional postresection therapy.
1043-0679/$-see front matter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semtcvs.2016.08.004
1
ESOPHAGEAL CANCER positive disease. Ann Thorac Surg 92: 1. Berry MF: Esophageal cancer: staging system and 5. Rice TW, Rusch VW, Ishwaran H, et al: Cancer 491-496, 2011 of the esophagus and esophagogastric junction: guidelines for staging and treatment. J Thorac data-driven staging for the seventh edition of the 8. Issaka A, Ermerak NO, Bilgi Z, et al: Preoperative Dis (suppl 3):S289-S297, 2014 chemoradiation therapy decreases the number of American Joint Committee on Cancer/Interna2. van Hagen P, Hulshof MC, van Lanschot JJ, et al: lymph nodes resected during esophagectomy. tional Union Against Cancer Cancer Staging Preoperative chemoradiotherapy for esophageal World J Surg 39:721-726, 2015 Manuals. Cancer 116:3763-3773, 2010 or junctional cancer. N Engl J Med 366:20746. Philippron A., Bollschweiler E., Kunikata A., 9. Hanna JM, Erhunmwunsee L, Berry M, et al: The 2084, 2012 prognostic importance of the number of diset al. Prognostic relevance of lymph node regres3. Rice TW, Blackstone EH, Rusch VW: 7th edition sected lymph nodes after induction chemorasion after neoadjuvant chemoradiation for esoof the AJCC Cancer Staging Manual: esophagus diotherapy for esophageal cancer. Ann Thorac phageal cancer. Semin Thorac Cardiovasc Surg. and esophagogastric junction. Ann Surg Oncol Surg 99:265-269, 2015 2016 (in press). 17:1721-1724, 2010 4. Rice TW, Rusch VW, Apperson-Hansen C, et al: 7. Stiles BM, Mirza F, Coppolino A, et al: Clinical T2-T3N0M0 esophageal cancer: the risk of node Worldwide esophageal cancer collaboration. Dis Esophagus 22:1-8, 2009
2
Seminars in Thoracic and Cardiovascular Surgery Volume ], Number ]