Primary site emergence, recurrence, and distant metastasis
Despite the heterogeneity in data reporting between studies, it appears that primary emergence was consistently higher amongst patients treated with ND only. For the whole cohort of patients 66.3% of primary emergences were from non-oropharyngeal sites, and where data was available for ND only emergences, 75.0% were non-oropharyngeal. For the three studies that report on both p16 status and primary emergence (50,57,60), rates of p16 positive disease were 43.5%, 69.5% and 76.3%, with emergence rates of 7%, 1.5% and 5.3% respectively. This suggests that primary emergence rates may be lower in p16 positive disease compared to p16 negative disease where the primary site is more likely to be non-oropharyngeal and less prognostically favourable.
The 3-yr mucosal control rate for ND only was observed to be 67% in one study compared to 100% with the addition of adjuvant radiotherapy (to neck and putative primary site based on nodal basin)(61). However, this did not translate into a difference in 3-yr OS between groups (83.5% vs. 84.7%, p=0.591). Several studies additionally reported on outcomes after primary emergence. In Mizuta et al . (58) where there were six emergences after ND only (3 hypopharynx, 2 oropharynx, 1 oral cavity), three were treated with chemoradiotherapy, one with surgery and radiotherapy, and two with surgery alone. Four of the six remained disease free at the time of reporting with two of the hypopharynx cancers being alive with recurrent disease (distant metastasis). In Miller et al . (53), the sole primary emergence ND only (N2b) patient (oropharynx) was successfully treated with chemoradiotherapy 16 months after initial treatment.
The data with respect to primary emergence highlights three pertinent points. Firstly, the patterns and rates of emergence likely reflect the heterogeneity of patients included in these studies, and thus the variability in applicability and reliability of the data to contemporary practice. Secondly, the sites of emergence reported in these studies indicate a likely high incidence of p16 negative disease, conferring a poorer prognosis than p16 positive disease. Finally, consideration should be given to ‘salvageability’ when considering ND only as primary treatment, from the limited data presented, outcomes appear to be acceptable when considering the OS of ND only to the whole cohorts in these studies.
Due to the limited reporting and sample size for regional recurrence and distant metastasis it is difficult to draw any more meaningful conclusions from the data beyond what has been discussed with regards to survival and primary emergence.