Contemporary management of lymph node metastases from an unknown primary to the neck: II. a review of therapeutic options.
Although uncommon, cancer of an unknown primary (CUP) metastatic to cervical lymph nodes poses a range of dilemmas relating to optimal treatment. The ideal resolution would be a properly designed prospective randomized trial, but it is unlikely that this will ever be conducted in this group of patients. Accordingly, knowledge gained from retrospective studies and experience from treating patients with known head and neck primary tumors form the basis of therapeutic strategies in CUP. This review provides a critical appraisal of various treatment approaches described in the literature. Emerging treatment options for CUP with metastases to cervical lymph nodes are discussed in view of recent innovations in the field of head and neck oncology and suitable therapeutic strategies for particular clinical scenarios are presented. For pN1 or cN1 disease without extracapsular extension (ECE), selective neck dissection or radiotherapy offer high rates of regional control. For more advanced neck disease, intensive combined treatment is required, either a combination of neck dissection and radiotherapy, or initial (chemo)radiotherapy followed by neck dissection if a complete response is not recorded on imaging. Each of these approaches seems to be equally effective. Use of extensive bilateral neck/mucosal irradiation must be weighed against toxicity, availability of close follow-up with elective neck imaging and guided fine-needle aspiration biopsy (FNAB) when appropriate, the human papillomavirus (HPV) status of the tumor, and particularly against the distribution pattern (oropharynx in the majority of cases) and the emergence rate of hidden primary lesions (<10% after comprehensive workup). The addition of systemic agents is expected to yield similar improvement in outcome as has been observed for known head and neck primary tumors.
Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia.
Primož
P
Strojan
Alfio
A
Ferlito
Johannes A
JA
Langendijk
June
J
Corry
Julia A
JA
Woolgar
Alessandra
A
Rinaldo
Carl E
CE
Silver
Vinidh
V
Paleri
Johannes J
JJ
Fagan
Phillip K
PK
Pellitteri
Missak
M
Haigentz
Carlos
C
Suárez
K Thomas
KT
Robbins
Juan P
JP
Rodrigo
Kerry D
KD
Olsen
Michael L
ML
Hinni
Jochen A
JA
Werner
Vanni
V
Mondin
Luiz P
LP
Kowalski
Kenneth O
KO
Devaney
Remco
R
de Bree
Robert P
RP
Takes
Gregory T
GT
Wolf
Ashok R
AR
Shaha
Eric M
EM
Genden
Leon
L
Barnes
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection / Q000379:methods; D009382:Neoplasms, Unknown Primary / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome