Skip to main content

Advertisement

SpringerLink
Log in

Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10 % residual tumor

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

Neoadjuvant treatment is an accepted standard approach for treating locally advanced esophago-gastric adenocarcinomas. Despite a response of the primary tumor, a significant percentage dies from tumor recurrence. The aim of this retrospective exploratory study from two academic centers was to identify predictors of survival and recurrence in histopathologically responding patients.

Methods

Two hundred thirty one patients with adenocarcinomas (esophagus: n = 185, stomach: n = 46, cT3/4, cN0/+, cM0) treated with preoperative chemotherapy (n = 212) or chemoradiotherapy (n = 19) followed by resection achieved a histopathological response (regression 1a: no residual tumor (n = 58), and regression 1b < 10 % residual tumor (n = 173)).

Results

The estimated median overall survival was 92.4 months (5-year survival, 56.6 %) for all patients. For patients with regression 1a, median survival is not reached (5-year survival, 71.6 %) compared to patients with regression 1b with 75.3 months median (5-year survival, 52.2 %) (p = 0.031). Patients with a regression 1a had lymph node metastases in 19.0 versus 33.7 % in regression 1b. The ypT-category (p < 0.001), the M-category (p = 0.005), and the type of treatment (p = 0.04) were found to be independent prognostic factors in R0-resected patients. The recurrence rate was 31.7 % (n = 66) (local, 39.4 %; peritoneal carcinomatosis, 25.7 %; distant metastases, 50 %). Recurrence was predicted by female gender (p = 0.013), ypT-category (p = 0.007), and M-category (p = 0.003) in multivariate analysis.

Conclusion

Response of the primary tumor does not guarantee recurrence-free long-term survival, but histopathological complete responders have better prognosis compared to partial responders. Established prognostic factors strongly influence the outcome, which could, in the future, be used for stratification of adjuvant treatment approaches. Increasing the rate of histopathological complete responders is a valid endpoint for future clinical trials investigating new drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, Participants MT (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355(1):11–20

    Article  PubMed  CAS  Google Scholar 

  2. Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Geneve J, Lasser P, Rougier P (2011) Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 29(13):1715–1721.

    Article  PubMed  CAS  Google Scholar 

  3. Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, Ott K, Hoelscher A, Schneider PM, Bechstein W, Wilke H, Lutz MP, Nordlinger B, Van Cutsem E, Siewert JR, Schlag PM (2010) Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer Randomized Trial 40954. J Clin Oncol 28(35):5210–5218. doi:10.1200/JCO.2009.26.6114

    Article  PubMed  Google Scholar 

  4. Schneider PM, Baldus SE, Metzger R, Kocher M, Bongartz R, Bollschweiler E, Schaefer H, Thiele J, Dienes HP, Mueller RP, Hoelscher AH (2005) Histomorphologic tumor regression and lymph node metastases determine prognosis following neoadjuvant radiochemotherapy for esophageal cancer: implications for response classification. Ann Surg 242(5):684–692

    Article  PubMed  Google Scholar 

  5. Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, Gebski V (2011) Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 12(7):681–692. doi:10.1016/S1470-2045(11)70142-5

    Article  PubMed  Google Scholar 

  6. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366(22):2074–2084. doi:10.1056/NEJMoa1112088

    Article  PubMed  Google Scholar 

  7. Peyre CG, Hagen JA, DeMeester SR, Altorki NK, Ancona E, Griffin SM, Holscher A, Lerut T, Law S, Rice TW, Ruol A, van Lanschot JJ, Wong J, DeMeester TR (2008) The number of lymph nodes removed predicts survival in esophageal cancer: an international study on the impact of extent of surgical resection. Ann Surg 248(4):549–556. doi:10.1097/SLA.0b013e318188c474

    PubMed  Google Scholar 

  8. Lowy AM, Mansfield PF, Leach SD, Pazdur R, Dumas P, Ajani JA (1999) Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg 229(3):303–308

    Article  PubMed  CAS  Google Scholar 

  9. Ott K, Fink U, Becker K, Stahl A, Dittler HJ, Busch R, Stein H, Lordick F, Link T, Schwaiger M, Siewert JR, Weber WA (2003) Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J Clin Oncol 21(24):4604–4610. doi:10.1200/JCO.2003.06.574

    Article  PubMed  CAS  Google Scholar 

  10. Ott K, Herrmann K, Lordick F, Wieder H, Weber WA, Becker K, Buck AK, Dobritz M, Fink U, Ulm K, Schuster T, Schwaiger M, Siewert JR, Krause BJ (2008) Early metabolic response evaluation by fluorine-18 fluorodeoxyglucose positron emission tomography allows in vivo testing of chemosensitivity in gastric cancer: long-term results of a prospective study. Clin Cancer Res 14(7):2012–2018. doi:10.1158/1078-0432.CCR-07-0934

    Article  PubMed  CAS  Google Scholar 

  11. Weber WA, Ott K, Becker K, Dittler HJ, Helmberger H, Avril NE, Meisetschlager G, Busch R, Siewert JR, Schwaiger M, Fink U (2001) Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 19(12):3058–3065

    PubMed  CAS  Google Scholar 

  12. Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, Lorenzen S, Schuster T, Wieder H, Herrmann K, Bredenkamp R, Hofler H, Fink U, Peschel C, Schwaiger M, Siewert JR (2007) PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol 8(9):797–805. doi:10.1016/S1470-2045(07)70244-9

    Article  PubMed  Google Scholar 

  13. Vallbohmer D, Holscher AH, Dietlein M, Bollschweiler E, Baldus SE, Monig SP, Metzger R, Schicha H, Schmidt M (2009) 18 F]-Fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemoradiation in esophageal cancer. Ann Surg 250(6):888–894

    Article  PubMed  Google Scholar 

  14. Ott K, Herrmann K, Schuster T, Langer R, Becker K, Wieder HA, Wester HJ, Siewert JR, Buschenfelde CM, Buck AK, Wilhelm D, Ebert MP, Peschel C, Schwaiger M, Lordick F, Krause BJ (2011) Molecular imaging of proliferation and glucose utilization: utility for monitoring response and prognosis after neoadjuvant therapy in locally advanced gastric cancer. Ann Surg Oncol 18(12):3316–3323. doi:10.1245/s10434-011-1743-y

    Article  PubMed  Google Scholar 

  15. zum Buschenfelde CM, Herrmann K, Schuster T, Geinitz H, Langer R, Becker K, Ott K, Ebert M, Zimmermann F, Friess H, Schwaiger M, Peschel C, Lordick F, Krause BJ (2011) (18)F-FDG PET-guided salvage neoadjuvant radiochemotherapy of adenocarcinoma of the esophagogastric junction: the MUNICON II trial. J Nucl Med 52(8):1189–1196. doi:10.2967/jnumed.110.085803

    Article  PubMed  Google Scholar 

  16. Park JO, Lee SI, Song SY, Kim K, Kim WS, Jung CW, Park YS, Im YH, Kang WK, Lee MH, Lee KS, Park K (2003) Measuring response in solid tumors: comparison of RECIST and WHO response criteria. Jpn J Clin Oncol 33(10):533–537

    Article  PubMed  Google Scholar 

  17. Schneider PM, Metzger R, Schaefer H, Baumgarten F, Vallbohmer D, Brabender J, Wolfgarten E, Bollschweiler E, Baldus SE, Dienes HP, Hoelscher AH (2008) Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer. Ann Surg 248(6):902–908. doi:10.1097/SLA.0b013e31818f3afb

    Article  PubMed  Google Scholar 

  18. Yoshida S, Miyata Y, Ohtsu A, Boku N, Shirao K, Shimada Y (2000) Significance of and problems in adopting response evaluation criteria in solid tumor RECIST for assessing anticancer effects of advanced gastric cancer. Gastric Cancer 3(3):128–133

    Article  PubMed  Google Scholar 

  19. Langer R, Ott K, Feith M, Lordick F, Siewert JR, Becker K (2009) Prognostic significance of histopathological tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. Mod Pathol 22(12):1555–1563. doi:10.1038/modpathol.2009.123

    Article  PubMed  CAS  Google Scholar 

  20. Becker K, Langer R, Reim D, Novotny A, Meyer zum Buschenfelde C, Engel J, Friess H, Hofler H (2011) Significance of histopathological tumor regression after neoadjuvant chemotherapy in gastric adenocarcinomas: a summary of 480 cases. Ann Surg 253(5):934–939. doi:10.1097/SLA.0b013e318216f449

    Article  PubMed  Google Scholar 

  21. Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, Wieder H, Fink U, Schwaiger M, Siewert JR (2006) Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol 24(29):4692–4698. doi:10.1200/JCO.2006.06.7801

    Article  PubMed  Google Scholar 

  22. Vallbohmer D, Holscher AH, DeMeester S, DeMeester T, Salo J, Peters J, Lerut T, Swisher SG, Schroder W, Bollschweiler E, Hofstetter W (2010) A multicenter study of survival after neoadjuvant radiotherapy/chemotherapy and esophagectomy for ypT0N0M0R0 esophageal cancer. Ann Surg 252(5):744–749. doi:10.1097/SLA.0b013e3181fb8dde

    Article  PubMed  CAS  Google Scholar 

  23. Meredith KL, Weber JM, Turaga KK, Siegel EM, McLoughlin J, Hoffe S, Marcovalerio M, Shah N, Kelley S, Karl R (2010) Pathologic response after neoadjuvant therapy is the major determinant of survival in patients with esophageal cancer. Ann Surg Oncol 17(4):1159–1167. doi:10.1245/s10434-009-0862-1

    Article  PubMed  Google Scholar 

  24. Rohatgi P, Swisher SG, Correa AM, Wu TT, Liao Z, Komaki R, Walsh GL, Vaporciyan AA, Rice DC, Roth JA, Ajani JA (2005) Characterization of pathologic complete response after preoperative chemoradiotherapy in carcinoma of the esophagus and outcome after pathologic complete response. Cancer 104(11):2365–2372. doi:10.1002/cncr.21439

    Article  PubMed  Google Scholar 

  25. Rohatgi PR, Mansfield PF, Crane CH, Wu TT, Sunder PK, Ross WA, Morris JS, Pisters PW, Feig BW, Gunderson LL, Ajani JA (2006) Surgical pathology stage by American Joint Commission on Cancer criteria predicts patient survival after preoperative chemoradiation for localized gastric carcinoma. Cancer 107(7):1475–1482. doi:10.1002/cncr.22180

    Article  PubMed  Google Scholar 

  26. Fink U, Schuhmacher C, Stein HJ, Busch R, Feussner H, Dittler HJ, Helmberger A, Bottcher K, Siewert JR (1995) Preoperative chemotherapy for stage III-IV gastric carcinoma: feasibility, response and outcome after complete resection. Br J Surg 82(9):1248–1252

    Article  PubMed  CAS  Google Scholar 

  27. Ott K, Sendler A, Becker K, Dittler HJ, Helmberger H, Busch R, Kollmannsberger C, Siewert JR, Fink U (2003) Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer 6(3):159–167. doi:10.1007/s10120-003-0245-4

    Article  PubMed  CAS  Google Scholar 

  28. Blank S, Blaker H, Schaible A, Lordick F, Grenacher L, Buechler M, Ott K (2012) Impact of pretherapeutic routine clinical staging for the individualization of treatment in gastric cancer patients. Langenbecks Arch Surg 397(1):44–55. doi:10.1007/s00423-011-0805-8

    Article  Google Scholar 

  29. Bader FG, Lordick F, Fink U, Becker K, Hofler H, Busch R, Siewert JR, Ott K (2008) Paclitaxel in the neoadjuvant treatment for adeno carcinoma of the distal esophagus (AEG I) A comparison of two phase II trials with long-term follow-up. Onkologie 31(7):366–372. doi:10.1159/000135515

    Article  PubMed  CAS  Google Scholar 

  30. Reim D, Gertler R, Novotny A, Becker K, Buschenfelde CM, Ebert M, Dobritz M, Langer R, Hoefler H, Friess H, Schumacher C (2012) Adenocarcinomas of the esophagogastric junction are more likely to respond to preoperative chemotherapy than distal gastric cancer. Ann Surg Oncol 19(7):2108–2118. doi:10.1245/s10434-011-2147-8

    Article  PubMed  Google Scholar 

  31. Lorenzen S, Blank S, Lordick F, Siewert JR, Ott K (2012) Prediction of response and prognosis by a score including only pretherapeutic parameters in 410 neoadjuvant treated gastric cancer patients. Ann Surg Oncol 19(7):2119–2127. doi:doi:10.1245/s10434-012-2254-1

    Article  PubMed  Google Scholar 

  32. Fields RC, Strong VE, Gonen M, Goodman KA, Rizk NP, Kelsen DP, Ilson DH, Tang LH, Brennan MF, Coit DG, Shah MA (2011) Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer 104(12):1840–1847.

    Article  PubMed  CAS  Google Scholar 

  33. Schuhmacher CP, Fink U, Becker K, Busch R, Dittler HJ, Mueller J, Siewert JR (2001) Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up. Cancer 91(5):918–927. doi:doi:10.1002/1097-0142(20010301)91:5<918::AID-CNCR1081>3.0.CO;2-W

    Article  PubMed  CAS  Google Scholar 

  34. Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jager E (2008) Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol 19(11):1882–1887. doi:10.1093/annonc/mdn403

    Article  PubMed  Google Scholar 

  35. Overman MJ, Kazmi SM, Jhamb J, Lin E, Yao JC, Abbruzzese JL, Ho L, Ajani J, Phan A (2010) Weekly docetaxel, cisplatin, and 5-fluorouracil as initial therapy for patients with advanced gastric and esophageal cancer. Cancer 116(6):1446–1453. doi:10.1002/cncr.24925

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We thank Kathryn Hanes for revising the manuscript.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany

    Katja Ott, Susanne Blank, Leila Sisic & Markus Büchler

  2. Institute of Pathology, Technical University, Munich, Germany

    Karen Becker & Rupert Langer

  3. Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Wilko Weichert & Wilfried Roth

  4. National Center of Tumor Diseases, University of Heidelberg, Heidelberg, Germany

    Annika Stange & Dirk Jäger

  5. Directorate, University of Freiburg, Freiburg, Germany

    Jörg-Rüdiger Siewert

  6. University Cancer Center Leipzig (UCCL), University Clinic Leipzig, Leipzig, Germany

    Florian Lordick

Authors
  1. Katja Ott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susanne Blank
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karen Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rupert Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wilko Weichert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wilfried Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Leila Sisic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Annika Stange
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dirk Jäger
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Markus Büchler
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jörg-Rüdiger Siewert
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Florian Lordick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katja Ott.

Additional information

Ott Katja and Blank Susanne contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ott, K., Blank, S., Becker, K. et al. Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10 % residual tumor. Langenbecks Arch Surg 398, 239–249 (2013). https://doi.org/10.1007/s00423-012-1039-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-012-1039-0

Keywords

Search

Navigation