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Komplettresponse nach neoadjuvanter Therapie beim Ösophaguskarzinom

Implikationen für die Chirurgie

Complete response after neoadjuvant therapy for esophageal cancer

Implications for surgery

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Zusammenfassung

Eine relevante Anzahl von Patienten mit lokal fortgeschrittenen Plattenepithel- und Adenokarzinomen des Ösophagus zeigt nach neoadjuvanter Therapie mit modernen Chemo- und Radiochemotherapieprotokollen eine lokoregionäre Komplettremission des Tumors im Operationsresektat. Aufgrund der substanziellen postoperativen Morbidität sowie der langfristigen Einschränkung der Lebensqualität nach Ösophagektomie wird der aktuelle Therapiealgorithmus mit neoadjuvanter Therapie und Ösophagektomie „en principe“ kritisch hinterfragt und ein personalisierter Therapiealgorithmus mit erweiterter Evaluation des postneoadjuvanten Remissionsstatus und Ösophagektomie „as needed“ diskutiert. Patienten mit Komplettremission nach neoadjuvanter Therapie werden in einem erweiterten Re-Staging-Protokoll identifiziert und im Falle einer klinischen Komplettremission mittels Active-Surveillance-Konzept mit Ösophagektomie „as needed“, also der Operation nur bei Nachweis eines lokalen Tumorrezidivs, behandelt. Kohortenstudien geben Hinweise, dass Active-Surveillance-Konzepte mit Ösophagektomie „as needed“ zu keiner Verschlechterung des Gesamtüberlebens des Patientenkollektivs führen. Aktuell werden in europäischen prospektiv randomisierten Nichtunterlegenheitsstudien mit onkologischem Endpunkt die Möglichkeiten organerhaltender Konzepte bei klinischer Komplettremission von Ösophaguskarzinomen evaluiert.

Abstract

A relevant number of patients with locally advanced esophageal squamous cell carcinoma and adenocarcinoma show a locoregional complete response of the tumor in the resected material after neoadjuvant therapy with modern chemotherapy and chemoradiation protocols. Due to a high rate of perioperative morbidity and decreased long-term quality of life following esophagectomy, the current treatment algorithm with neoadjuvant therapy and post-neoadjuvant esophagectomy on principle is critically questioned. An individualized treatment algorithm with extended clinical evaluation of post-neoadjuvant remission status and esophagectomy as needed is discussed. Patients with complete remission after neoadjuvant therapy are identified in an extended restaging protocol. Cases of clinical complete remission are treated with an active surveillance concept with esophagectomy as needed, i.e. surgery only when a local tumor recurrence is detected. Retrospective cohort studies have suggested that the active surveillance concept with esophagectomy as needed does not lead to a deterioration of overall survival rates in the patient collective. European prospective randomized, controlled, noninferiority studies with an oncological endpoint are currently evaluating the possibilities of organ-preserving concepts for clinical complete remission of esophageal cancer.

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Literatur

  1. Al-Batran SE, Hofheinz RD, Pauligk C et al (2016) Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol 17(12):1697–1708. https://doi.org/10.1016/S1470-2045(16)30531-9

    Article  CAS  Google Scholar 

  2. Al-Batran SE, Homann N, Pauligk C et al (2019) Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 393(10184):1948–1957. https://doi.org/10.1016/S0140-6736(18)32557-1

    Article  Google Scholar 

  3. Barbetta A, Hsu M, Tan KS et al (2018) Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by surgery for stage II to III esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 155(6):2710–2721.e3. https://doi.org/10.1016/j.jtcvs.2018.01.086

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bedenne L, Michel P, Bouché O et al (2007) Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25(10):1160–1168. https://doi.org/10.1200/JCO.2005.04.7118

    Article  CAS  PubMed  Google Scholar 

  5. Castoro C, Scarpa M, Cagol M et al (2013) Complete clinical response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic oesophagus: is surgery always necessary? J Gastrointest Surg 17(8):1375–1381. https://doi.org/10.1007/s11605-013-2269-3

    Article  PubMed  Google Scholar 

  6. Furlong H, Bass G, Breathnach O et al (2013) Targeting therapy for esophageal cancer in patients aged 70 and over. J Geriatr Oncol 4(2):107–113. https://doi.org/10.1016/j.jgo.2012.12.006

    Article  PubMed  Google Scholar 

  7. Hipp J, Nagavci B, Schmoor C et al (2021) Post-neoadjuvant surveillance and surgery as needed compared with post-neoadjuvant surgery on principle in multimodal treatment for esophageal cancer: a scoping review. Cancers (Basel) 13(3):429. https://doi.org/10.3390/cancers13030429

    Article  Google Scholar 

  8. Hoeppner J (2021) Aktuelle prä- und perioperative Konzepte in der Tumortherapie beim lokal fortgeschrittenen Ösophaguskarzinom aus chirurgischer Perspektive. Chirurg. https://doi.org/10.1007/s00104-021-01475-w

    Article  PubMed  Google Scholar 

  9. Hofheinz RD, Haag GM, Ettrich TJ, Borchert K, Kretzschmar A, Teschendorf C, Siegler GM, Ebert MP, Goekkurt E, Welslau M et al (2020) Perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2-positive resectable esophagogastric adenocarcinoma: final results of the PETRARCA multicenter randomized phase II trial of the AIO. J Clin Oncol 38:4502. https://doi.org/10.1200/JCO.2020.38.15_suppl.4502

    Article  Google Scholar 

  10. Jia R, Yin W, Li S, Li R, Yang J, Shan T, Zhou D, Wang W, Wan L, Zhou F, Gao S (2019) Chemoradiation versus oesophagectomy for locally advanced oesophageal cancer in Chinese patients: study protocol for a randomised controlled trial. Trials 20(1):206. https://doi.org/10.1186/s13063-019-3316-5

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mariette C, Markar SR, Dabakuyo-Yonli TS, Meunier B, Pezet D, Collet D, D’Journo XB, Brigand C, Perniceni T, Carrère N, Mabrut JY, Msika S, Peschaud F, Prudhomme M, Bonnetain F, Piessen G, Fédération de Recherche en Chirurgie (FRENCH), French Eso-Gastric Tumors (FREGAT) Working Group (2019) Hybrid minimally invasive esophagectomy for esophageal cancer. N Engl J Med 380(2):152–162. https://doi.org/10.1056/NEJMoa1805101

    Article  PubMed  Google Scholar 

  12. Murphy CC, Correa AM, Ajani JA, Komaki RU, Welsh JW, Swisher SG, Hofstetter WL (2013) Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma. J Gastrointest Surg 17(8):1359–1369. https://doi.org/10.1007/s11605-013-2223-4

    Article  PubMed  PubMed Central  Google Scholar 

  13. Nimptsch U, Mansky T (2017) Hospital volume and mortality for 25 types of inpatient treatment in German hospitals: observational study using complete national data from 2009 to 2014. BMJ Open 7(9):e16184. https://doi.org/10.1136/bmjopen-2017-016184

    Article  PubMed  PubMed Central  Google Scholar 

  14. Noordman BJ, de Bekker-Grob EW, Coene PPLO, van der Harst E, Lagarde SM, Shapiro J, Wijnhoven BPL, van Lanschot JJB (2018) Patients’ preferences for treatment after neoadjuvant chemoradiotherapy for oesophageal cancer. Br J Surg 105(12):1630–1638. https://doi.org/10.1002/bjs.10897

    Article  CAS  PubMed  Google Scholar 

  15. Noordman BJ, Spaander MCW, Valkema R et al (2018) Detection of residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer (preSANO): a prospective multicentre, diagnostic cohort study. Lancet Oncol 19(7):965–974. https://doi.org/10.1016/S1470-2045(18)30201-8

    Article  PubMed  Google Scholar 

  16. Noordman BJ, Wijnhoven BPL, Lagarde SM et al (2018) Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial. BMC Cancer 18(1):142. https://doi.org/10.1186/s12885-018-4034-1

    Article  PubMed  PubMed Central  Google Scholar 

  17. Park SR, Yoon DH, Kim JH et al (2019) A randomized phase III trial on the role of esophagectomy in complete responders to preoperative chemoradiotherapy for esophageal squamous cell carcinoma (ESOPRESSO). Anticancer Res 39(9):5123–5133. https://doi.org/10.21873/anticanres.13707

    Article  CAS  PubMed  Google Scholar 

  18. Porschen R (2018) S3-Leitlinie Diagnostik und Therapie der Plattenepithelkarzinome und Adenokarzinome des Ösophagus. https://www.leitlinienprogramm-onkologie.de/leitlinien/oesophaguskarzinom/ (AWMF-Registernummer: 021/023OL). Zugegriffen: 15.08.2021

  19. Rottenkolber D (2011) Discrete-Choice-Experimente zur Messung der Zahlungsbereitschaft für Gesundheitsleistungen – ein anwendungsbezogener Literaturreview. Gesundh ökon Qual manag 16(4):232–244. https://doi.org/10.1055/s-0029-1245852

    Article  Google Scholar 

  20. Stahl M, Stuschke M, Lehmann N et al (2005) Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 23(10):2310–2317. https://doi.org/10.1200/JCO.2005.00.034

    Article  PubMed  Google Scholar 

  21. Taioli E, Schwartz RM, Lieberman-Cribbin W et al (2017) Quality of life after open or minimally invasive esophagectomy in patients with esophageal cancer—a systematic review. Semin Thorac Cardiovasc Surg 29(3):377–390. https://doi.org/10.1053/j.semtcvs.2017.08.013

    Article  PubMed  Google Scholar 

  22. Taketa T, Xiao L, Sudo K et al (2013) Propensity-based matching between esophagogastric cancer patients who had surgery and who declined surgery after preoperative chemoradiation. Oncology 85(2):95–99. https://doi.org/10.1159/000351999

    Article  PubMed  Google Scholar 

  23. van der Sluis PC, van der Horst S, May AM et al (2019) Robot-assisted minimally invasive thoracolaparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer: a randomized controlled trial. Ann Surg 269(4):621–630. https://doi.org/10.1097/SLA.0000000000003031

    Article  PubMed  Google Scholar 

  24. van der Wilk BJ, Noordman BJ, Neijenhuis LKA et al (2019) Active surveillance versus immediate surgery in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal cancer: a multicenter propensity matched study. Ann Surg. https://doi.org/10.1097/SLA.0000000000003636

    Article  Google Scholar 

  25. van Hagen P, Hulshof MC, van Lanschot JJ et al (2012) Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 366(22):2074–2084. https://doi.org/10.1056/NEJMoa1112088

    Article  PubMed  Google Scholar 

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Correspondence to Jens Hoeppner.

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J. Hipp, M. Thomaschewski, R. Hummel und J. Hoeppner geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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C.T. Germer, Würzburg

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Hipp, J., Thomaschewski, M., Hummel, R. et al. Komplettresponse nach neoadjuvanter Therapie beim Ösophaguskarzinom. Chirurg 93, 132–137 (2022). https://doi.org/10.1007/s00104-021-01509-3

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