Discussion
HPSCC is one of the most common head and neck malignant tumours.
Advanced HPSCC often results in death with local recurrence and distant
metastasis within five years after treatment. Despite medical advances,
the 5-year survival rate remains at approximately 40%(1). Some studies
suggested that 80% of patients with HPSCC who underwent surgery at the
initial diagnosis had pathology suggestive of neck metastases upon
examination(15, 16). The local lymph node metastasis can increase the
recurrence and mortality of HNSCC. Hence, the metastatic load of lymph
nodes is one of the most important prognostic indicators of
HNSCC(17-19).
The AJCC/ UICC tumor, node, metastasis (TNM) staging system is widely
used for HPSCC, in which pN is described for the size, location,
laterality, number, and extra-envelope invasion (ENE) of positive lymph
nodes. However, it is vulnerable to the total number of surgically
removed lymph nodes, for which we need improvement on the predictive
risk stratification model(20). LNR, the ratio of MLN to HLN, is a
surrogate mathematical marker affected by several factors, including the
extent of cervical lymphatic dissection, the surgeon’s cervical
dissection technique, and the quality of pathologic evaluation(21).
Multiple studies have validated the value of LNR in various tumors,
including HPSCC, for predicting prognosis. However, a major limitation
of LNR is that there is no corresponding discriminatory power for the
ratio of 0 and 1. The predictive value of LODDS has been validated in
various tumors (10, 11, 13, 14). LODDS distinguishes patients without
positive lymph nodes by adding 0.5 to both positive and negative lymph
nodes. Its predictive value in stage III and IV HPSCC has not been
tested yet.
Several clinical studies have verified the predictive value of LNR in
HPSCC. Yu and colleagues conducted a study involving 279 patients with
HPSCC, where the subjects received pretreatment
(radiotherapy/chemotherapy) before neck dissection. The multifactorial
analysis showed that LNR was an independent predictor of prognosis(22).
Another study of 81 patients with HPSCC suggested a better prognosis for
pN1 with LNR < 0.1 and pN2 patients(23). A meta-analysis of
stage III and IV LSCC and HPSCC suggested that LNR was a better
prognostic indicator than pN(6). Our study has selected 166 patients
with HPSCC who underwent primary lesion resection with cervical lymph
node dissection at initial diagnosis, with or without adjuvant therapy
(radiotherapy/chemotherapy) after surgery. We set a cut-off value of
0.11 for LNR based on the patient’s DFS. Patients with LNR ≥0.11 had
significantly poorer OS and DFS values (P<0.05).
Patients with LNR values of 0 and 1 can be further risk stratified by
LODDS, which has been shown to have a better predictive value for tumor
prognosis than pN and LNR in oral squamous cell carcinoma(13),
esophageal cancer(11), breast cancer(14), gastric cancer(12), bladder
cancer(10), and colorectal cancer(9). However, studies in LSCC(24) and
cervical squamous carcinoma (25) suggested LODDS was predictive of
progression but did not provide any improved predictive performance over
LNR, which is coherent with our findings. In our study, LODDS was
associated with both OS and DFS, and a LODD ≥0.91 was associated with
poorer DFS (P<0.001) but not with OS. We believe this is
caused by the dataset only having 5 patients with an LNR value of 1 and
12 patients having an LNR value of 0, which does not allow display the
true advantage of LODDS over LNR.
In our study, for the first time,
we selected patients with stage
III-IV HPSCC and verified the predictive value of LODDS. We
also evaluated the predictive
value of pN, LNR, and LODDS for advanced HPSCC and found that pN was a
stronger predictor than LNR and LODDS for OS, and LNR was stronger than
pN and LODDS for DFS. In the multivariate analysis, LNR showed a greater
predictive value for DFS than pT, pStage, surgical margins, SIRI, and
LODDS. Meanwhile, LNR, pT, and surgical margins all had independent
predictive values for OS. In contrast to other studies, our study
suggested that HLN ≥15 did not improve DFS. These contradictive findings
may be related to the fact that our research came from a single center
and was retrospective. Our study is also limited by a small clinical
sample size with potential selection and recall bias. We expect
multi-center, prospective studies to be available in the future.