Nodale Metastasierung und Stellenwert der Neck Dissection bei T1/2-Oro- und Hypopharynxkarzinomen

Zusammenfassung

Hintergrund Die Indikation zur elektiven Neck Dissection (END) bei Patienten mit T1/2-Plattenepithelkarzinomen des Hypopharynx (HPSCC) und Oropharynx (OPSCC) wird nicht einheitlich gestellt. In der vorliegenden Studie erfolgte daher eine detaillierte Analyse des Metastasierungsverhaltens von HPSCC und OPSCC.

Material und Methoden Es erfolgte eine multizentrische retrospektive Analyse des nodalen Metastasierungsverhaltens und der onkologischen Parameter von 262 chirurgisch therapierten HPSCC- und OPSCC-Patienten. Zudem erfolgte eine systematische Literaturrecherche.

Ergebnisse Bei HPSCC-Patienten lag in 62,1% der Fälle eine Diskrepanz zwischen klinischem und pathologischem N-Status vor, bei OPSCC in 52,4% (p16-) bzw. 43,6% (p16+). Die okkulte Metastasierungsrate in den Primärtumorstadien T1/2 lag dabei bei 38,9% für HPSCC und bei 17,8% (p16-) und 11,1% (p16+) für OPSCC. Bei HPSCC traten in den Stadien cT1/2cN0 in 22,2% der Fälle kontralaterale Metastasen auf; die Rate bei OPSCC lag bei lediglich 9,1% (p16-) bzw. 0% (p16+). Patienten mit p16-positiven OPSCC wiesen ein besseres rezidivfreies und Gesamtüberleben auf als p16-negative OPSCC- und HPSCC-Patienten. Ein direkter Zusammenhang zwischen Patientenüberleben und Ausmaß der chirurgischen Therapie des Halses ließ sich nicht nachweisen.

Schlussfolgerung Patienten mit HPSCC weisen ab Stadium cT1/2cN0 ein hohes Risiko für okkulte Halslymphknotenmetastasen auf, welches die Durchführung einer beidseitigen END rechtfertigt. Bei Patienten mit T1/2cN0-OPSCC manifestieren sich ipsilateral in >20% der Fälle okkulte Metastasen; das Risiko für eine kontralaterale okkulte Metastasierung liegt jedoch bei <10%, sodass bei streng lateralisierten Tumoren ein Verzicht auf die kontralaterale Neck Dissection erwogen werden kann.

Abstract

Background Due to heterogeneous data, the indication for elective neck dissection (END) in patients with squamous cell carcinoma of the hypopharynx and oropharynx (HPSCC and OPSCC) in stages T1/2N0 is somewhat unclear. Therefore, in this multicenter study, we performed detailed analysis of the metastatic behavior of HPSCC and OPSCC.

Material and Methods The nodal metastatic patterns of 262 HPSCC and OPSCC patients who had undergone surgery was retrospectively investigated. In addition, recurrence-free and overall survival were recorded. Furthermore, a systematic literature review on the topic was completed.

Results In patients with HPSCC, a discrepancy between clinical and pathologic N status was recorded in 62.1% of patients vs. 52.4% for p16- OPSCC, and 43.6% for p16+ OPSCC. The occult metastasis rate in cT1/2cN0 primary tumors was 38.9% for HPSCC vs. 17.8% (p16- OPSCC) and 11.1% (p16+ OPSCC). Contralateral metastases occurred in 22.2% of cases for HPSCC at stages cT1/2cN0, compared to only 9.1% for p16- OPSCC, and 0% for p16+ OPSCC patients.

Patients with p16+ OPSCC had better recurrence-free and overall survival than p16- OPSCC and HPSCC patients. A direct association between patient survival and the extent of neck surgical therapy could not be demonstrated in our patients.

Conclusion Patients with HPSCC are at risk for bilateral neck metastases from stage cT1/2cN0, justifying bilateral END. Patients with T1/2 OPSCC present with occult metastases ipsilaterally in >20% of cases; however, the risk for contralateral occult metastasis is <10%. Hence, in strictly lateralized cT1/2CN0 tumors, omission of contralateral END may be considered.

Schlüsselwörter

Oropharynxkarzinom - Hypopharynxkarzinom - okkulte Metastasen - elektive Neck Dissection

Keywords

OPSCC - HPSCC - p16 - cT1/2 cN0 - elective neck dissection - END - early stage

Publication History

Received: 13 November 2023

Accepted after revision: 27 February 2024

Article published online:
03 June 2024

• Literatur

• 1 Buckley JG, MacLennan K. Cervical node metastases in laryngeal and hypopharyngeal cancer: a prospective analysis of prevalence and distribution. Head Neck 2000; 22: 380-385 (PMID: 10862022)
• 2 Amar A, Dedivitis RA, Rapoport A. et al. Indication of elective contralateral neck dissection in squamous cell carcinoma of the hypopharynx. Braz J Otorhinolaryngol 2009; 75: 493-496 DOI: 10.1016/s1808-8694(15)30485-7. (PMID: 19784415)
• 3 Shin YS, Kim SH, Koh YW. et al. Necessity of level IV dissection in cN0 hypopharyngeal carcinoma. Acta Otolaryngol 2011; 131: 665-669 DOI: 10.3109/00016489.2011.554437. (PMID: 21395474)
• 4 Garrel R, Poissonnet G, Temam S. et al. Review of sentinel node procedure in cN0 head and neck squamous cell carcinomas. Guidelines from the French evaluation cooperative subgroup of GETTEC. Eur Ann Otorhinolaryngol Head Neck Dis 2017; 134: 89-93 DOI: 10.1016/j.anorl.2016.10.004.
• 5 Fasunla AJ, Greene BH, Timmesfeld N. et al. A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck. Oral Oncol 2011; 47: 320-324 DOI: 10.1016/j.oraloncology.2011.03.009.
• 6 Koyfman SA, Ismaila N, Crook D. et al. Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline. J Clin Oncol 2019; 37: 1753-1774 DOI: 10.1200/jco.18.01921. (PMID: 30811281)
• 7 Walvekar RR, Li RJ, Gooding WE. et al. Role of surgery in limited (T1–2, N0–1) cancers of the oropharynx. Laryngoscope 2008; 118: 2129-2134 DOI: 10.1097/MLG.0b013e3181857950. (PMID: 18948826)
• 8 Strojan P, Ferlito A, Langendijk JA. et al. Indications for radiotherapy after neck dissection. Head Neck 2012; 34: 113-119 DOI: 10.1002/hed.21599. (PMID: 22162247)
• 9 Olzowy B, Hillebrand M, Harréus U. Frequency of bilateral cervical metastases in hypopharyngeal squamous cell carcinoma: a retrospective analysis of 203 cases after bilateral neck dissection. Eur Arch Otorhinolaryngol 2017; 274: 3965-3970 DOI: 10.1007/s00405-017-4724-3. (PMID: 28840308)
• 10 Olzowy B, Tsalemchuk Y, Schotten KJ. et al. Frequency of bilateral cervical metastases in oropharyngeal squamous cell carcinoma: a retrospective analysis of 352 cases after bilateral neck dissection. Head Neck 2011; 33: 239-243 DOI: 10.1002/hed.21436. (PMID: 20848445)
• 11 Dünne AA, Folz BJ, Kuropkat C. et al. Extent of surgical intervention in case of N0 neck in head and neck cancer patients: an analysis of data collection of 39 hospitals. Eur Arch Otorhinolaryngol 2004; 261: 295-303 DOI: 10.1007/s00405-003-0680-1. (PMID: 13680262)
• 12 Psychogios G, Mantsopoulos K, Kuenzel J. et al. Primary surgical treatment of T2 oropharyngeal carcinoma. J Surg Oncol 2012; 105: 719-723 DOI: 10.1002/jso.23026. (PMID: 22213267)
• 13 Shin HA, Lim YC, Jeong HM. et al. Role of primary surgery for early-stage (T1–2N0) squamous cell carcinoma of the oropharynx. Oral Oncol 2009; 45: 1063-1066 DOI: 10.1016/j.oraloncology.2009.07.017. (PMID: 19717331)
• 14 Liao LJ, Lo WC, Hsu WL. et al. Detection of cervical lymph node metastasis in head and neck cancer patients with clinically N0 neck-a meta-analysis comparing different imaging modalities. BMC Cancer 2012; 12: 236 DOI: 10.1186/1471-2407-12-236.
• 15 Lechner M, Liu J, Masterson L. et al. HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol 2022; 19: 306-327 DOI: 10.1038/s41571-022-00603-7. (PMID: 35105976)
• 16 Guo T, Qualliotine JR, Ha PK. et al. Surgical salvage improves overall survival for patients with HPV-positive and HPV-negative recurrent locoregional and distant metastatic oropharyngeal cancer. Cancer 2015; 121: 1977-1984 DOI: 10.1002/cncr.29323.
• 17 Lin TY, Lee TL, Hsu YB. et al. Survival analyses of different treatment modalities and clinical stage for hypopharyngeal carcinoma. Front Oncol 2023; 13: 1109417 DOI: 10.3389/fonc.2023.1109417. (PMID: 36937435)
• 18 Finegersh A, Moss WJ, Saddawi-Konefka R. et al. Meta-analysis of risk of occult lymph node metastasis in the irradiated, clinically N0 neck. Head Neck 2020; 42: 2355-2363 DOI: 10.1002/hed.26248. (PMID: 32432819)
• 19 Koo BS, Lim YC, Lee JS. et al. Management of contralateral N0 neck in pyriform sinus carcinoma. Laryngoscope 2006; 116: 1268-1272 DOI: 10.1097/01.mlg.0000225936.88411.71. (PMID: 16826073)
• 20 Spector JG, Sessions DG, Haughey BH. et al. Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx. Laryngoscope 2001; 111: 1079-1087 DOI: 10.1097/00005537-200106000-00028. (PMID: 11404625)
• 21 Rivière D, Mancini J, Santini L. et al. Lymph-node metastasis following total laryngectomy and total pharyngolaryngectomy for laryngeal and hypopharyngeal squamous cell carcinoma: Frequency, distribution and risk factors. Eur Ann Otorhinolaryngol Head Neck Dis 2018; 135: 163-166 DOI: 10.1016/j.anorl.2017.11.008. (PMID: 29277379)
• 22 Hosal AS, Carrau RL, Johnson JT. et al. Selective neck dissection in the management of the clinically node-negative neck. Laryngoscope 2000; 110: 2037-2040 DOI: 10.1097/00005537-200012000-00011. (PMID: 11129016)
• 23 Böscke R, Cakir BD, Hoffmann AS. et al. Outcome after elective neck dissection and observation for the treatment of the clinically node-negative neck (cN0) in squamous cell carcinoma of the oropharynx. Eur Arch Otorhinolaryngol 2014; 271: 567-574 DOI: 10.1007/s00405-013-2545-6. (PMID: 23661061)
• 24 Candela FC, Kothari K, Shah JP. Patterns of cervical node metastases from squamous carcinoma of the oropharynx and hypopharynx. Head Neck 1990; 12: 197-203 DOI: 10.1002/hed.2880120302. (PMID: 2358329)
• 25 Ferlito A, Shaha AR, Rinaldo A. The incidence of lymph node micrometastases in patients pathologically staged N0 in cancer of oral cavity and oropharynx. Oral Oncol 2002; 38: 3-5 DOI: 10.1016/s1368-8375(01)00037-9. (PMID: 11755814)
• 26 Gross BC, Olsen SM, Lewis JE. et al. Level IIB lymph node metastasis in oropharyngeal squamous cell carcinoma. Laryngoscope 2013; 123: 2700-2705 DOI: 10.1002/lary.24129. (PMID: 23686577)
• 27 Layland MK, Sessions DG, Lenox J. The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+. Laryngoscope 2005; 115: 629-639 DOI: 10.1097/01.mlg.0000161338.54515.b1. (PMID: 15805872)
• 28 Lee SY, Lim YC, Song MH. et al. Level IIb lymph node metastasis in elective neck dissection of oropharyngeal squamous cell carcinoma. Oral Oncol 2006; 42: 1017-1021 DOI: 10.1016/j.oraloncology.2005.12.023. (PMID: 16757201)
• 29 Psychogios G, Mantsopoulos K, Agaimy A. et al. Prognostic factors in limited (T1–2, N0–1) oropharyngeal carcinoma treated with surgery ± adjuvant therapy. Head Neck 2013; 35: 1752-1758 DOI: 10.1002/hed.23229.
• 30 Bauwens L, Baltres A, Fiani DJ. et al. Prevalence and distribution of cervical lymph node metastases in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma. Radiother Oncol 2021; 157: 122-129 DOI: 10.1016/j.radonc.2021.01.028. (PMID: 33545255)
• 31 Hussain T, Thangavelu K, Kürten C. et al. The accuracy of clinical neck staging for p16-positive and negative oropharyngeal cancer and its therapeutic implications. Eur Arch Otorhinolaryngol 2022; 279: 5339-5345 DOI: 10.1007/s00405-022-07430-7. (PMID: 35781741)
• 32 Stanford-Moore GB, Ochoa E, Larson A. et al. Patterns of Nodal Metastases and Predictors of Occult Disease in HPV-Associated Oropharynx Cancer. Otolaryngol Head Neck Surg 2021; 164: 624-630 DOI: 10.1177/0194599820951473. (PMID: 32894979)
• 33 O’Sullivan B, Warde P, Grice B. et al. The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the tonsillar region. Int J Radiat Oncol Biol Phys 2001; 51: 332-343 DOI: 10.1016/s0360-3016(01)01613-3. (PMID: 11567806)
• 34 Tritter AG, Mehta V, Samuelson M. et al. Incidence of contralateral-bilateral nodes in the human papillomavirus era. Laryngoscope 2017; 127: 1328-1333 DOI: 10.1002/lary.26439. (PMID: 27905120)
• 35 Amsbaugh MJ, Yusuf M, Cash E. et al. Distribution of Cervical Lymph Node Metastases From Squamous Cell Carcinoma of the Oropharynx in the Era of Risk Stratification Using Human Papillomavirus and Smoking Status. Int J Radiat Oncol Biol Phys 2016; 96: 349-353 DOI: 10.1016/j.ijrobp.2016.06.2450. (PMID: 27598805)
• 36 Lim YC, Koo BS, Lee JS. et al. Distributions of cervical lymph node metastases in oropharyngeal carcinoma: therapeutic implications for the N0 neck. Laryngoscope 2006; 116: 1148-1152 DOI: 10.1097/01.mlg.0000217543.40027.1d. (PMID: 16826050)
• 37 McMullen CP, Garneau J, Weimar E. et al. Occult contralateral nodal disease in oropharyngeal squamous cell carcinoma patients undergoing primary TORS with bilateral neck dissection. Oral Oncol 2019; 93: 96-100 DOI: 10.1016/j.oraloncology.2019.04.017.
• 38 Plonowska KA, Strohl MP, Wang SJ. et al. Human Papillomavirus-Associated Oropharyngeal Cancer: Patterns of Nodal Disease. Otolaryngol Head Neck Surg 2019; 160: 502-509 DOI: 10.1177/0194599818801907. (PMID: 30274544)
• 39 Shah JP. Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am J Surg 1990; 160: 405-409 DOI: 10.1016/s0002-9610(05)80554-9. (PMID: 2221244)
• 40 Thompson CF, St John MA, Lawson G. et al. Diagnostic value of sentinel lymph node biopsy in head and neck cancer: a meta-analysis. Eur Arch Otorhinolaryngol 2013; 270: 2115-2122 DOI: 10.1007/s00405-012-2320-0.
• 41 Yamauchi K, Kogashiwa Y, Nakamura T. et al. Diagnostic evaluation of sentinel lymph node biopsy in early head and neck squamous cell carcinoma: a meta-analysis. Head Neck 2015; 37: 127-133 DOI: 10.1002/hed.23526. (PMID: 24478151)
• 42 Duvvuri U, Simental AA, D’Angelo G. et al. Elective neck dissection and survival in patients with squamous cell carcinoma of the oral cavity and oropharynx. Laryngoscope 2004; 114: 2228-2234 DOI: 10.1097/01.mlg.0000149464.73080.20.
• 43 Lörincz BB, Busch CJ, Möckelmann N. et al. Feasibility and safety of transoral robotic surgery (TORS) for early hypopharyngeal cancer: a subset analysis of the Hamburg University TORS-trial. Eur Arch Otorhinolaryngol 2015; 272: 2993-2998 DOI: 10.1007/s00405-014-3259-0. (PMID: 25217079)
• 44 Ye LL, Rao J, Fan XW. et al. The prognostic value of tumor depth for cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas. Head Neck 2019; 41: 2116-2122 DOI: 10.1002/hed.25667. (PMID: 30689266)
• 45 Jouhi L, Atula T, Mäkitie A. et al. Management of clinically N0 neck in oropharyngeal carcinoma. Eur Arch Otorhinolaryngol 2019; 276: 1205-1210 DOI: 10.1007/s00405-019-05314-x. (PMID: 30729294)
• 46 Knopf A, Jacob S, Bier H. et al. Bilateral versus ipsilateral neck dissection in oral and oropharyngeal cancer with contralateral cN0 neck. Eur Arch Otorhinolaryngol 2020; 277: 3161-3168 DOI: 10.1007/s00405-020-06043-2. (PMID: 32449025)
• 47 Psychogios G, Mantsopoulos K, Bohr C. et al. Incidence of occult cervical metastasis in head and neck carcinomas: development over time. J Surg Oncol 2013; 107: 384-387 DOI: 10.1002/jso.23221. (PMID: 22833224)