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.