CE: ; ANNSURG-D-15-00532; Total nos of Pages: 1;
ANNSURG-D-15-00532
RESPONSE Reply to Letter: ‘‘Tumor Response and Lymph Node Status After Neoadjuvant Chemoradiotherapy for Esophageal Cancer’’ Reply: e read with some interest the correspondence of Drs Ecker and Dempsey following our recent publication of the impact of neoadjuvant chemoradiotherapy (nCRT) on lymph node status in early stage I and II esophageal cancer.1 Our published data are derived from a post hoc analysis of FFCD 9901, a multicenter randomized control trial comparing surgery alone with nCRT followed by surgery.2 The authors of this correspondence rightly observe that we found that when tumor regression grade was dichotomized as a complete/good response (TRG 1/2) or neutral/ poor response (TRG3–5) to nCRT, then no difference was found in the number of lymph nodes resected. A favorable tumor response did, however, correlate with favorable nodal response, with significantly fewer positive nodes in the resected specimen. The authors relate their experience from as yet unpublished data taken from 50 consecutive patients with stage II and III esophageal tumors—predominantly adenocarcinomas (n ¼ 46)—treated with nCRT followed by transhiatal resection and compared with patients treated with surgery alone at their own institution. In that cohort, pathological complete response (pCR) (n ¼ 7) was associated with a reduced lymph node yield (5.0 vs 15.0, P ¼ 0.02) whereas an incomplete tumoral response (n ¼ 43) was not. It seems that many differences—tumor stage, tumor histology, population size, and surgical approach—exist between their population and the randomized population on which we have reported. The authors suggest that nCRT alone decreases lymph node yield
W
TO
LETTER
after pCR. Such conclusions are difficult to make on the basis of a small population and surgery by a technique without formal 2-field lymphadenectomy and commonly associated with fewer lymph nodes being resected.3 Our experience is different. Patients in our cohort with a pCR (ypT0N0) did not have fewer lymph nodes found in the resected specimen [median number of resected nodes of 14.0 (2.0–39.0) in group nCRT ypT0N0 (n ¼ 28) vs 16.5 (0–47.0) in group nCRT non-ypT0N0 (n ¼ 52), P ¼ 0.160, data not included in the article]. Although it is still uncertain whether the number of lymph nodes resected after nCRT is of prognostic value (as it is in the absence of neoadjuvant treatment), our own data1 and those from the CROSS group4 make this increasingly unlikely. As the correspondence points out, this would be consistent with recent findings in the setting of rectal cancers.5 Even if reduced lymph node yield were to be associated only with good/complete response after nCRT and if the number of retrieved nodes after nCRT has no prognostic value, we strongly advocate that neither of these facts should change the surgical strategy. First, at present, pCR is a postoperative diagnosis with no accurate means of its prediction; second, a cooperative survival benefit seems to exist between nCRT and adequate lymphadenectomy6; and third, extended lymphadenectomy gives maximal prognostic information and avoids positive nodes being missed, with patients being erroneously classified as pN0. Finally, it must be realized that our results pertain to early-stage esophageal cancers, although we would expect our results to be amplified in more advanced disease. As our article emphasizes, positive lymph node status, and not the number of nodes resected, is the stronger prognostic indicator for patients after nCRT. It is too early to advocate a change in nodal clearance based on perceived tumor response to treatment. Extensive lymphadenectomy should be routinely performed to rule out missed nodal disease.
William B. Robb, MD Department of Digestive and Oncological Surgery University Hospital of Lille Lille, France Christophe Mariette, MD, PhD Department of Digestive and Oncological Surgery University Hospital of Lille Lille, France University of Lille–Nord de France Lille, France Inserm UMR837 Jean-Pierre Aubert Research Center Team 5 Mucins, Epithelial Differentiation and Carcinogenesis SIRIC ONCOLille Lille Cedex, France [email protected]
REFERENCES 1. Robb WB, Dahan L, Mornex F, et al. Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial. Ann Surg. 2015;261: 902–908. 2. Mariette C, Dahan L, Mornex F, et al. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of a randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014;32:2416–2422. 3. Kutup A, Nentwich MF, Bollschweiler E, et al. What should be the gold standard for the surgical component in the treatment of locally advanced esophageal cancer: transthoracic versus transhiatal esophagectomy. Ann Surg. 2014;260:1016–1022. 4. Koen Talsma A, Shapiro J, Looman CW, et al. Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival. Ann Surg. 2014;260:786–792. 5. Habr-Gama A, Perez RO, Proscurshim I, et al. Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean? Dis Colon Rectum. 2008;51:277–283. 6. Solomon N, Zhuge Y, Cheung M, et al. The roles of neoadjuvant radiotherapy and lymphadenectomy in the treatment of esophageal adenocarcinoma. Ann Surg Oncol. 2010;17:791–803.
Disclosure: The authors declare no conflicts of interest. Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0003-4932/14/26105-0821 DOI: 10.1097/SLA.0000000000001263
Annals of Surgery Volume XX, Number X, Month 2015
www.annalsofsurgery.com | 1
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
ANNSURG-D-15-00532
RESPONSE Reply to Letter: ‘‘Tumor Response and Lymph Node Status After Neoadjuvant Chemoradiotherapy for Esophageal Cancer’’ Reply: e read with some interest the correspondence of Drs Ecker and Dempsey following our recent publication of the impact of neoadjuvant chemoradiotherapy (nCRT) on lymph node status in early stage I and II esophageal cancer.1 Our published data are derived from a post hoc analysis of FFCD 9901, a multicenter randomized control trial comparing surgery alone with nCRT followed by surgery.2 The authors of this correspondence rightly observe that we found that when tumor regression grade was dichotomized as a complete/good response (TRG 1/2) or neutral/ poor response (TRG3–5) to nCRT, then no difference was found in the number of lymph nodes resected. A favorable tumor response did, however, correlate with favorable nodal response, with significantly fewer positive nodes in the resected specimen. The authors relate their experience from as yet unpublished data taken from 50 consecutive patients with stage II and III esophageal tumors—predominantly adenocarcinomas (n ¼ 46)—treated with nCRT followed by transhiatal resection and compared with patients treated with surgery alone at their own institution. In that cohort, pathological complete response (pCR) (n ¼ 7) was associated with a reduced lymph node yield (5.0 vs 15.0, P ¼ 0.02) whereas an incomplete tumoral response (n ¼ 43) was not. It seems that many differences—tumor stage, tumor histology, population size, and surgical approach—exist between their population and the randomized population on which we have reported. The authors suggest that nCRT alone decreases lymph node yield
W
TO
LETTER
after pCR. Such conclusions are difficult to make on the basis of a small population and surgery by a technique without formal 2-field lymphadenectomy and commonly associated with fewer lymph nodes being resected.3 Our experience is different. Patients in our cohort with a pCR (ypT0N0) did not have fewer lymph nodes found in the resected specimen [median number of resected nodes of 14.0 (2.0–39.0) in group nCRT ypT0N0 (n ¼ 28) vs 16.5 (0–47.0) in group nCRT non-ypT0N0 (n ¼ 52), P ¼ 0.160, data not included in the article]. Although it is still uncertain whether the number of lymph nodes resected after nCRT is of prognostic value (as it is in the absence of neoadjuvant treatment), our own data1 and those from the CROSS group4 make this increasingly unlikely. As the correspondence points out, this would be consistent with recent findings in the setting of rectal cancers.5 Even if reduced lymph node yield were to be associated only with good/complete response after nCRT and if the number of retrieved nodes after nCRT has no prognostic value, we strongly advocate that neither of these facts should change the surgical strategy. First, at present, pCR is a postoperative diagnosis with no accurate means of its prediction; second, a cooperative survival benefit seems to exist between nCRT and adequate lymphadenectomy6; and third, extended lymphadenectomy gives maximal prognostic information and avoids positive nodes being missed, with patients being erroneously classified as pN0. Finally, it must be realized that our results pertain to early-stage esophageal cancers, although we would expect our results to be amplified in more advanced disease. As our article emphasizes, positive lymph node status, and not the number of nodes resected, is the stronger prognostic indicator for patients after nCRT. It is too early to advocate a change in nodal clearance based on perceived tumor response to treatment. Extensive lymphadenectomy should be routinely performed to rule out missed nodal disease.
William B. Robb, MD Department of Digestive and Oncological Surgery University Hospital of Lille Lille, France Christophe Mariette, MD, PhD Department of Digestive and Oncological Surgery University Hospital of Lille Lille, France University of Lille–Nord de France Lille, France Inserm UMR837 Jean-Pierre Aubert Research Center Team 5 Mucins, Epithelial Differentiation and Carcinogenesis SIRIC ONCOLille Lille Cedex, France [email protected]
REFERENCES 1. Robb WB, Dahan L, Mornex F, et al. Impact of neoadjuvant chemoradiation on lymph node status in esophageal cancer: post hoc analysis of a randomized controlled trial. Ann Surg. 2015;261: 902–908. 2. Mariette C, Dahan L, Mornex F, et al. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of a randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014;32:2416–2422. 3. Kutup A, Nentwich MF, Bollschweiler E, et al. What should be the gold standard for the surgical component in the treatment of locally advanced esophageal cancer: transthoracic versus transhiatal esophagectomy. Ann Surg. 2014;260:1016–1022. 4. Koen Talsma A, Shapiro J, Looman CW, et al. Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival. Ann Surg. 2014;260:786–792. 5. Habr-Gama A, Perez RO, Proscurshim I, et al. Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean? Dis Colon Rectum. 2008;51:277–283. 6. Solomon N, Zhuge Y, Cheung M, et al. The roles of neoadjuvant radiotherapy and lymphadenectomy in the treatment of esophageal adenocarcinoma. Ann Surg Oncol. 2010;17:791–803.
Disclosure: The authors declare no conflicts of interest. Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0003-4932/14/26105-0821 DOI: 10.1097/SLA.0000000000001263
Annals of Surgery Volume XX, Number X, Month 2015
www.annalsofsurgery.com | 1
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
