Discussion
Owing to the rarity and heterogeneity of salivary gland malignancies,
there is a paucity of high–level, large prospective studies. As a
result, little information regarding the clinicopathological factors
associated with these tumours and their long-term prognosis is
available.
The epidemiological findings of our study are relatively consistent with
those in the existing literature. The majority of our patients were male
and over the age of 50 years which is similar to previous studies(5-8){Lin, 2018 #170}. Cancers of the salivary
glands are classified broadly as arising from either one of the major
salivary or minor salivary glands. The most common site is the parotid
gland, with an incidence ten times higher than the other glands (3).
This is similar to our study, where 86% malignancies were seen in the
parotid gland.
Five-year OS in the present study was 81.7% and 5-year DFS was 71%.
This is in the context of over a third of patients presenting with stage
III or IV cancers. In comparison, a review of the National Cancer
Database (USA) reported a 5-year OS of 71%, whereas the Netherlands
Cancer Registry noted OS to be 69% (9, 10). In the
UK, Public Health England reported a 5-year survival rate of 78.7%(11).
When examining the clinicopathological variables, we found that age, pT
classification, tumour grade, TNM stage, PNI, and LVI significantly
affected DFS. This is interesting because retrospective studies of
similar size have revealed the following tumour-specific variables as
indicative of a poor prognosis: T classification, positive resection
margin status, PNI, involved lymph nodes, distant metastases, and a
fixed neck mass (6, 12, 13). Of these, PNI has been
reported to be a prognostic factor for poor survival, a finding that is
upheld by the present study. This may be linked to a greater risk of
locoregional recurrence and distant metastases (14,
15). In our study, PNI was present in almost 40% of the cohort (a
third of parotid malignancies and over half of cancers at the other
sites). Few studies have reported a high incidence (28.7-48%) of PNI,
albeit in smaller cohorts than ours (7, 13).
Higher-grade histological subtypes were strongly associated with PNI and
LVI, accounting for a poorer prognosis. In our study, contrary to others(7, 10, 11, 16), we did not find that pN
classification, or the presence of ECS, affected survival. This could
reflect the lower number of patients in these groups.
The resection margin in salivary gland cancers is often limited because
in the presence of a functioning facial nerve and the absence of
intraoperative signs of invasion the facial nerve is preserved. Sharp
dissection along the perineurium allows good macroscopic resection
though clearly often very close pathological margins. In the present
study, DFS was comparable among patients with negative and close
margins. Positive margins were associated with poorer survival, but this
was not statistically significant, implying that more functional and
less radical surgery may be acceptable, as long as it is followed by
adjuvant therapy.
A large national cancer database review of 8,580 patients has shown that
adjuvant radiotherapy improves survival regardless of TNM stage(18). To explore this further, we categorised the
patients undergoing adjuvant therapy into early- and late-stage. Nearly
half of our early-stage patients (48.6%) received adjuvant
radiotherapy. This was because of the presence of classical poor
prognostic factors such as PNI, LVI, and higher grade. Adjuvant
radiation improves survival in early and advanced stage tumours.
Patients receiving adjuvant chemoradiation had poorer survival, but this
was likely indicative of disease characteristics meriting aggressive
adjuvant therapy. The majority of these patients had high-grade tumours,
a positive margin, LVI (71.4% each) and PNI (100%). Multivariate
analysis showed worse DFS for the following factors: advanced stage (HR,
2.59), presence of PNI (HR, 1.1) and age over 50 years (HR, 1.31). None
of the factors had a statistically significant effect, but this was
expected owing to the smaller number of patients in the subgroups as
well as good survival and a low number of events.
Our study has some limitations that are associated with retrospective
studies, including some missing data. The heterogeneity of data resulted
in some analyses that were underpowered for the tumour subtypes.
Nevertheless, our study has significant merit. The follow-up period was
sufficient to capture relevant survival and recurrence-related data, the
study included a larger cohort size for salivary gland malignancies from
a single UK centre, and all patients were treated by a uniform
philosophy from a multidisciplinary team at a major teaching hospital
trust.