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DOI: 10.1055/a-2223-4083
Chirurgische Therapie des Oropharynxkarzinoms: Empfehlungen der aktuellen S3-Leitlinie – Teil I
Surgical Treatment of Oropharyngeal Cancer – Recommendations of the Current German S3 Guideline, Part IGenerell ist für das Oropharynxkarzinom in den letzten 2 Dekaden ein Trend zur transoralen Resektion + Neck Dissection + adjuvante Radio(chemo)therapie zu verzeichnen. Auf Basis der aktuell verfügbaren besten Evidenz aus Registerstudien können Empfehlungen ausgesprochen werden, wobei die aktuelle Datenlage mit gebotener Zurückhaltung bewertet werden sollte, weil bisher manche bedeutenden Parameter keinen Eingang in die Berechnung gefunden haben.
Abstract
In general, a trend towards transoral resection (as opposed to classic open approaches) + neck dissection + adjuvant radio- (chemo-) therapy has been observed for oropharyngeal carcinoma over the last 20 years. Techniques of transoral surgery (TOS), including transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) have been propagated in retrospective comparisons with conventional surgery or primary radiochemotherapy as gentle, minimally invasive procedures with good late functional results. Meta-analyses of mostly uncontrolled retrospective analyses suggest that TORS may have better disease-free survival (DFS) and a reduced risk of free flap reconstruction compared with open surgery. TORS (TOS) was associated with fewer tumor-positive resection margins (R1), a lower number of recurrences, fewer intraoperative tracheostomies, a shorter inpatient stay and a shorter duration of postoperative nasal tube feeding compared to open surgery. In principle, based on the best evidence currently available from registry studies, stage I-II oropharyngeal carcinomas can be treated either with primary surgery or radiochemotherapy with a comparable chance of survival. With comparable evidence for stage III and IVa, p16neg. oropharyngeal carcinomas, the majority of authors advocate primary surgery followed by adjuvant radiotherapy or radiochemotherapy as the treatment of first choice. For p16pos. patients the results of registry studies are inconsistent, although the largest registry study on 450 HPV-positive stage III patients shows a significant superiority of primary surgery + adjuvant radiochemotherapy. Since all registry studies did not adjust for smoking status, among other factors, the current data situation should be evaluated with the necessary caution.
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Die generellen Therapiestrategien beim Oropharynxkarzinom unterscheiden sich abhängig vom p16-Status trotz der wesentlich besseren Prognose bei HPV-/p16-positiven Tumoren nicht.
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Prinzipiell gilt auf Basis der aktuell verfügbaren besten Evidenz aus Registerstudien, dass Stadium-I- bis -II-Oropharynxkarzinome mit vergleichbarer Überlebenschance entweder primär operiert oder durch eine Radiochemotherapie behandelt werden können.
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Die Mehrzahl der Autoren spricht sich bei verfügbarer bester Evidenz aus Registerstudien bei Stadium III und IVa, p16-negativen Oropharynxkarzinomen für die primäre Chirurgie, gefolgt von adjuvanter Radio- bzw. Radiochemotherapie als Therapie der 1. Wahl aus.
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Für die p16-positiven Patienten ergeben die Registerstudien kein einheitliches Bild, obgleich die größte Registerstudie an 450 HPV-positiven Stadium-III-Patienten eine signifikante Überlegenheit der primären Chirurgie + adjuvanter Radiochemotherapie ausweist.
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Resektate für den Pathologen sollen mit topografisch eindeutigen Informationen bezüglich der anatomischen Ausrichtung und der genauen Lokalisation versehen werden.
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Zu favorisieren sind eine „En-bloc“-Übersendung und eine Schnellschnittentnahme der Resektatränder am Resektat durch den Operateur oder den Pathologen.
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Die frühere prinzipielle Ablehnung der Angabe eines R-Status nach Piecemeal-Chirurgie mancher Pathologen, die dann RX klassifizierten, sollte im Rahmen der guten Interdisziplinarität überwunden werden.
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Präferenziell erfolgt eine Portionierung der Level durch den Chirurgen, da selbst unter Anbringung von Markierungen eine exakte Ex-situ-Zuordnung in der Pathologie nur sehr eingeschränkt möglich ist.
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Die Entnahme von Schnellschnitten (Gefrierschnitten) wird generell empfohlen.
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Wenn positive chirurgische Ränder gemeldet werden, sollte bei Möglichkeit eine erneute Resektion durchgeführt werden (Nachresektion).
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Ein sauberer Resektionsrand („clear margin“) ist definiert als der Abstand von der invasiven Tumorfront, der 5mm oder mehr vom resezierten Rand entfernt ist.
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Die transorale Chirurgie erscheint im Vergleich zu den invasiveren Techniken der konventionellen Chirurgie als weniger zeitaufwendig und mit weniger Zugangsmorbidität behaftet zu sein.
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Die Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie mit der Arbeitsgemeinschaft für Onkologie warnen davor, die Ergebnisse der ORATOR-Studien (Oropharynx Radiotherapy versus Transoral Robotic Surgery) unkritisch auf die klinische Praxis zu übertragen.
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In der Gesamtbetrachtung fortgeschrittener Oropharynxkarzinome ist das primär chirurgische Vorgehen aktuell zu favorisieren, soweit eine R0-Resektion möglich und ein sinnvolles funktionelles Ergebnis zu erwarten ist.
Schlüsselwörter
Oropharynxkarzinom - p16 - HPV-16 - Kopf-Hals-Chirurgie - transorale Chirurgie - TORS - TLMKeywords
Oropharyngeal carcinoma - p16 - HPV-16 - head and neck surgery - transoral surgery - TORS - TLMPublication History
Article published online:
01 August 2024
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Literatur
- 1 S3-Leitlinie zur Diagnostik, Therapie, Prävention und Nachsorge des Oro- und Hypopharynxkarzinoms; Version 1.01; AWMF-Registernummer: 017–082OL.
- 2 El-Naggar AK, El-Naggar A. WHO classification of head and neck tumours. International Agency for Research on Cancer. 4th ed. 2017
- 3 Slootweg PJ, Grandis JR. Tumours of the hypopharynx, larynx, trachea and parapharyngeal space. In: WHO Classification of Head and Neck Tumours, 4th ed. Lyon; 2017: 77-104
- 4 Agaimy A, Hartmann A. Kopf-Hals-Tumoren: Neues aus der WHO-Klassifikation 2017. Pathologe 2018; 39: 1-2
- 5 Agaimy A, Weichert W. Grading von Tumoren der Hals-Kopf-Region. Pathologe 2016; 37 (04) 285-292
- 6 Fakhry C, Lacchetti C, Rooper LM. et al. Human Papillomavirus Testing in Head and Neck Carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline. J Clin Oncol 2018; 36 (31) 3152-3161
- 7 Lewis JS, Beadle B, Bishop JA. et al. Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists. Arch Pathol Lab Med 2018; 142: 559-597
- 8 Amin MB, Edge SB. American Joint Committee on Cancer (AJCC) cancer staging manual. 8th ed. Springer; 2017
- 9 Byers RM, El-Naggar AK, Lee YY. et al. Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue?. Head Neck 1998; 20: 138-144
- 10 Brasilino de Carvalho M. Quantitative analysis of the extent of extracapsular invasion and its prognostic significance: a prospective study of 170 cases of carcinoma of the larynx and hypopharynx. Head Neck 1998; 20: 16-21
- 11 Tankéré F, Camproux A, Barry B. et al. Prognostic value of lymph node involvement in oral cancers: a study of 137 cases. Laryngoscope 2000; 110: 2061-2065
- 12 Woolgar JA, Rogers SN, Lowe D. et al. Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread. Oral Oncol 2003; 39: 130-137
- 13 Suoglu Y, Erdamar B, Katircioglu OS. et al. Extracapsular spread in ipsilateral neck and contralateral neck metastases in laryngeal cancer. Ann Otol Rhinol Laryngol 2002; 111 (05) 447-454
- 14 Greenberg JS, Fowler R, Gomez J. et al. Extent of extracapsular spread: a critical prognosticator in oral tongue cancer. Cancer 2003; 97: 1464-1470
- 15 Esposito ED, Motta S, Cassiano B. et al. Occult lymph node metastases in supraglottic cancers of the larynx. Otolaryngol Head Neck Surg 2001; 124: 253-257
- 16 Enepekides DJ, Sultanem K, Nguyen C. et al. Occult cervical metastases: immunoperoxidase analysis of the pathologically negative neck. Otolaryngol Head Neck Surg 1999; 120: 713-717
- 17 Ferlito A, Partridge M, Brennan J. et al. Lymph node micrometastases in head and neck cancer: a review. Acta Otolaryngol 2001; 121: 660-665
- 18 Barzan L, Montomoli C, Di Carlo R. et al. Multicentre study on resection margins in carcinoma of the oral cavity, oro-hypopharynx and larynx. Acta Otorhinolaryngol Ital 2022; 42: 126-139
- 19 Looser KG, Shah JP, Strong EW. The significance of „positive“ margins in surgically resected epidermoid carcinomas. Head Neck Surg 1978; 1: 107-111
- 20 Scholl P, Byers RM, Batsakis JG. et al. Microscopic cut-through of cancer in the surgical treatment of squamous carcinoma of the tongue. Prognostic and therapeutic implications. Am J Surg 1986; 152: 354-360
- 21 Kwok P, Gleich O, Hübner G. et al. Prognostic importance of „clear versus revised margins“ in oral and pharyngeal cancer. Head Neck 2010; 32: 1479-1484
- 22 Jäckel MC, Ambrosch P, Martin A. et al. Impact of re-resection for inadequate margins on the prognosis of upper aerodigestive tract cancer treated by laser microsurgery. Laryngoscope 2007; 117: 350-356
- 23 Haughey BH, Sinha P. Prognostic factors and survival unique to surgically treated p16+ oropharyngeal cancer. Laryngoscope 2012; 122: S13-33
- 24 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Head and Neck Cancers, Version 1.2023. 2022
- 25 Cheraghlou S, Yu PK, Otremba MD. et al. Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base. Cancer 2018; 124: 717-726
- 26 Zenga J, Wilson M, Adkins DR. et al. Treatment Outcomes for T4 Oropharyngeal Squamous Cell Carcinoma. JAMA Otolaryngol Head Neck Surg 2015; 141: 1118-1127
- 27 Yeh DH, Tam S, Fung K. et al. Transoral robotic surgery vs. radiotherapy for management of oropharyngeal squamous cell carcinoma – A systematic review of the literature. Eur J Surg Oncol 2015; 41: 1603-1614
- 28 de Almeida JR, Genden EM. Robotic assisted reconstruction of the oropharynx. Curr Opin Otolaryngol Head Neck Surg 2012; 20: 237-245
- 29 Knecht R, Bussmann L, Möckelmann N. et al. Ist Radio(chemo)therapie wirklich der zukünftige Standard für die Behandlung von Oropharynxkarzinomen?. HNO 2016; 64: 221-226
- 30 Lörincz BB, Jowett N, Knecht R. Decision management in transoral robotic surgery: Indications, individual patient selection, and role in the multidisciplinary treatment for head and neck cancer from a European perspective. Head Neck 2016; 38: E2190-E2196
- 31 Weinstein GS, O’Malley BW, Snyder W. et al. Transoral robotic surgery: radical tonsillectomy. Arch Otolaryngol Head Neck Surg 2007; 133: 1220-1226
- 32 Lang S, Mattheis S, Kansy B. TORS in HPV-Positive Tumors-The New Standard?. Recent Results Cancer Res 2017; 206: 207-218
- 33 Gangwani K, Shetty L, Seshagiri R. et al. Comparison of TORS with Conventional Surgery for Oropharyngeal Carcinomas in T1-T4 Lesions. Ann Maxillofac Surg 2019; 9: 387-392
- 34 Mattheis S, Hasskamp P, Holtmann L. et al. Flex Robotic System in transoral robotic surgery: The first 40 patients. Head Neck 2017; 39: 471-475
- 35 Park YM, Byeon HK, Chung HP. et al. Comparison study of transoral robotic surgery and radical open surgery for hypopharyngeal cancer. Acta Otolaryngol 2013; 133: 641-648
- 36 Hammoudi K, Pinlong E, Kim S. et al. Transoral robotic surgery versus conventional surgery in treatment for squamous cell carcinoma of the upper aerodigestive tract. Head Neck 2015; 37: 1304-1309
- 37 Slama K, Slouka D, Slipka J. et al. Short-term postoperative distress associated with open vs. transoral robotic surgery (TORS) in patients with T1-T2 carcinomas of the tongue base and supraglottis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016; 160: 423-428
- 38 Ford SE, Brandwein-Gensler M, Carroll WR. et al. Transoral robotic versus open surgical approaches to oropharyngeal squamous cell carcinoma by human papillomavirus status. Otolaryngol Head Neck Surg 2014; 151: 606-611
- 39 Biron VL, O’Connell DA, Barber B. et al. Transoral robotic surgery with radial forearm free flap reconstruction: case control analysis. J Otolaryngol Head Neck Surg 2017; 46: 20
- 40 Richmon JD, Quon H, Gourin CG. The effect of transoral robotic surgery on short-term outcomes and cost of care after oropharyngeal cancer surgery. Laryngoscope 2014; 124: 165-171
- 41 Liu H, Wang Y, Wu C. et al. Robotic compared with open operations for cancers of the head and neck: a systematic review and meta-analysis. Br J Oral Maxillofac Surg 2019; 57: 967-976
- 42 Gangwani K, Shetty L, Seshagiri R. et al. Comparison of TORS with Conventional Surgery for Oropharyngeal Carcinomas in T1-T4 Lesions. Ann Maxillofac Surg 2019; 9: 387-392
- 43 Hutcheson KA, Holsinger FC, Kupferman ME. et al. Functional outcomes after TORS for oropharyngeal cancer: a systematic review. Eur Arch Otorhinolaryngol 2015; 272: 463-471
- 44 Nichols AC, Theurer J, Prisman E. et al. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial. Lancet Oncol 2019; 20: 1349-1359
- 45 Nichols AC, Theurer J, Prisman E. et al. Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial. J Clin Oncol 2022; 40: 866-875
- 46 Palma DA, Prisman E, Berthelet E. et al. Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial. JAMA Oncol 2022; 8: 1-7
- 47 Yom SS, Torres-Saavedra P, Caudell JJ. et al. Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002). J Clin Oncol 2021; 39: 956-965
- 48 Zech HB, Betz CS, Hoffmann TK. et al. Strahlentherapie oder Operation bei HPV-positiven Oropharynxkarzinomen? Die ORATOR2-Studie – ein Vergleich von Birnen und Äpfeln. Laryngorhinootologie 2023; 102: 169-176
- 49 Davies JC, Husain Z, Day TA. et al. Perioperative Mortality Risk in Patients Undergoing Transoral Robotic Surgery for T1-T2 Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study. Front Oncol 2021; 11: 808465
- 50 Hoffmann TK. ORATOR-Studie. Operation oder Strahlentherapie bei Oropharynxkarzinomen im HPV-Kontext?. HNO 2020; 68: 278-279
- 51 Hoffmann TK. Die „ORATOR-Studien“ – ein Update. Primäre Operation oder Strahlentherapie von Oropharynxkarzinomen im HPV-Kontext. HNO 2022; 70: 579-580
- 52 Amin JD, Kallen ME, Hatten KM. Radical Tonsillectomy and Superior Pharyngeal Constrictor Anatomy: A Cadaveric and Oncologic Specimen Assessment. J Otorhinolaryngol Relat Spec 2020; 82: 318-326
- 53 Hinni ML, Zarka MA, Hoxworth JM. Margin mapping in transoral surgery for head and neck cancer. Laryngoscope 2013; 123: 1190-1198
- 54 Stelmes JJ, Gregoire V, Poorten VV. et al. Organ Preservation and Late Functional Outcome in Oropharyngeal Carcinoma: Rationale of EORTC 1420, the „Best of“ Trial. Front Oncol 2019; 9: 999
- 55 de Almeida JR, Li R, Magnuson JS. et al. Oncologic Outcomes After Transoral Robotic Surgery: A Multi-institutional Study. JAMA Otolaryngol Head Neck Surg 2015; 141: 1043-1051
- 56 Holcomb AJ, Herberg M, Strohl M. et al. Impact of surgical margins on local control in patients undergoing single-modality transoral robotic surgery for HPV-related oropharyngeal squamous cell carcinoma. Head Neck 2021; 43: 2434-2444
- 57 Pool C, Weaver T, Zhu J. et al. Surgical Margin Determination in the Era of HPV-Positive Oropharyngeal Cancer. Laryngoscope 2021; 131: E2650-E2654
- 58 Preuss SF, Quante G, Semrau R. et al. An analysis of surgical complications, morbidity, and cost calculation in patients undergoing multimodal treatment for operable oropharyngeal carcinoma. Laryngoscope 2007; 117: 101-105
- 59 Paleri V, Simon C, Gorphe P. Caution Regarding Assessment of Toxic Effects and Survival in Treatment De-escalation With Radiotherapy vs Transoral Surgery for Human Papillomavirus-Associated Oropharyngeal Cancer. JAMA Oncol 2022; 8: 1512-1513
- 60 Simon C, Caballero C, Gregoire V. et al. Surgical quality assurance in head and neck cancer trials: an EORTC Head and Neck Cancer Group position paper based on the EORTC 1420 ‘Best of’ and 24954 ‘larynx preservation’ study. Eur J Cancer 2018; 103: 69-77
- 61 Laccourreye O, Malinvaud D, Garcia D. et al. Postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx. Ann Otol Rhinol Laryngol 2015; 124: 361-367
- 62 Salassa JR, Hinni ML, Grant DG. et al. Postoperative bleeding in transoral laser microsurgery for upper aerodigestive tract tumors. Otolaryngol Head Neck Surg 2008; 139: 453-459
- 63 Esriti A, Maurer J, Mann W. Blutungen nach CO2-laserchirurgischer Tumorentfemung im HNO-Bereich. Laryngorhinootologie 2004; 83: 102-107
- 64 Pollei TR, Hinni ML, Moore EJ. et al. Analysis of postoperative bleeding and risk factors in transoral surgery of the oropharynx. JAMA Otolaryngol Head Neck Surg 2013; 139: 1212-1218
- 65 Dietz A, Fischer M, Magill C. et al. Principles and New Approaches in Surgical Reconstruction. In: Bernier J. Head and Neck Cancer. Cham: Springer; 2016: 575-589
- 66 Remmert S. Wiederherstellung der HNO-Funktion durch plastisch-rekonstruktive Chirurgie. Expertise Plastische Chirurgie. Stuttgart: Thieme; 2018
- 67 Lang SH, Bootz F, Remmert S. Lappenplastiken und Transplantate im Kopf-Hals-Bereich. Expertise Plastische Chirurgie. Stuttgart: Thieme; 2018
- 68 Hoffmann T, Hoffmann J, Hänggi D. et al. Rekonstruktive Kopf-Hals-Chirurgie. Berlin: Springer; 2023
- 69 Amini A, Jasem J, Jones BL. et al. Predictors of overall survival in human papillomavirus-associated oropharyngeal cancer using the National Cancer Data Base. Oral Oncol 2016; 56: 1-7
- 70 Kamran SC, Qureshi MM, Jalisi S. et al. Primary surgery versus primary radiation-based treatment for locally advanced oropharyngeal cancer. Laryngoscope 2018; 128: 1353-1364
- 71 Ko HC, Chen S, Wieland AM. et al. Clinical outcomes for patients presenting with N3 head and neck squamous cell carcinoma: Analysis of the National Cancer Database. Head Neck 2017; 39: 2159-2170
- 72 Kelly JR, Park HS, An Y. et al. Upfront surgery versus definitive chemoradiotherapy in patients with human Papillomavirus-associated oropharyngeal squamous cell cancer. Oral Oncol 2018; 79: 64-70
- 73 Mahmoud O, Sung K, Civantos FJ. et al. Transoral robotic surgery for oropharyngeal squamous cell carcinoma in the era of human papillomavirus. Head Neck 2018; 40: 710-721
- 74 Patel EJ, Zhu AW, Oliver JR. et al. Treatment of Early Stage Tonsil Cancer in the Age of Human Papillomavirus-Associated Malignancies. Otolaryngol Head Neck Surg 2021; 165: 104-112
- 75 Park DA, Lee MJ, Kim SH. et al. Comparative safety and effectiveness of transoral robotic surgery versus open surgery for oropharyngeal cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2020; 46: 644-649