Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck?

Abstract

The impact of neck involvement and occult metastasis (OM) in patients with oral squamous cell carcinoma (OSCC) favors an elective neck dissection. However, there are barely any existing data on survival for patients with OM compared with patients with positive lymph nodes detected preoperatively. This study aims to compare survival curves of patients suffering from lymph nodal metastases in a preoperatively N+ neck with those suffering from OM. In addition, clinical characteristics of the primary tumor were analyzed to predict occult nodal disease. This retrospective cohort study includes patients with an OSCC treated surgically with R0 resection with or without adjuvant chemoradiotherapy between 2010 and 2016. Minimum follow-up was 60 months. Kaplan–Meier analysis was used to compare the survival between patients with and without occult metastases and patients with N+ neck to those with occult metastases. Logistic regression was used to detect potential risk factors for occult metastases. The patient cohort consisted of 226 patients. Occult metastases occurred in 16 of 226 patients. In 53 of 226 patients, neck lymph nodes were described as suspect on CT imaging but had a pN0 neck. Higher tumor grading increased the chance of occurrence of occult metastasis 2.7-fold (OR = 2.68, 95% CI: 1.07–6.7). After 12, 24, 48 and 60 months, 82.3%, 73.8%, 69% and 67% of the N0 patients, respectively, were progression free. In the group with OM occurrence, for the same periods 66.6%, 50%, 33.3% and 33.3% of the patients, respectively, were free of disease. For the same periods, respectively, 81%, 63%, 47% and 43% of the patients in the N+ group but without OM remained disease free. The predictors for progression-free survival were a positive N status (HR = 1.44, 95% CI: 1.08–1.93) and the occurrence of OM (HR = 2.33, 95% CI: 1.17–4.64). The presence of occult metastasis could lead to decreased survival and could be a burdening factor requiring treatment escalation and a more aggressive follow-up than nodal disease detected in the preoperative diagnostic imaging.

Potential of preoperative fluorodeoxyglucose-positron emission tomography/computed tomography to diagnose contralateral lymph node metastases in patients with oral cancer

“…SUVmax of the primary tumor was found to be the most powerful parameter according to its diagnostic performance. These findings are consistent with those of previous studies reporting that the biologic and radiographic characteristics of the primary tumor are factors related to lymph node metastasis [2,[24][25][26][27]. A recent study revealed that a higher tumor grading increased the chance of metastasis by 2.7 times [2].…”

“…These findings are consistent with those of previous studies reporting that the biologic and radiographic characteristics of the primary tumor are factors related to lymph node metastasis [2,[24][25][26][27]. A recent study revealed that a higher tumor grading increased the chance of metastasis by 2.7 times [2]. Tumor grading is based on histopathological characteristics, including the degree of resemblance to normal tissues.…”

“…This means that almost half of patients with healthy contralateral lymph nodes could be wrongly detected as having CLNM and could be over-operated. Haidari et al [2] reported similar findings, where 53 of 226 patients exhibited abnormally enlarged lymph nodes on CT images, but were pathologically negative. This indicates that large lymph nodes are not necessarily metastatic; instead, they could have reactive hyperplasia [32].…”

“…The survival rate of patients correlates with lymph node metastases. It has been widely reported that tumor spread to local lymph nodes worsens the prognosis in patients with oral cancer [2][3][4]. The tendency for regional lymph node metastasis is relatively high even in small tumors [5], particularly in cases of tongue cancer due to the rich lymphatic plexus of the tongue [6].…”

BST2 regulated by the transcription factor STAT1 can promote metastasis, invasion and proliferation of oral squamous cell carcinoma via the AKT/ERK1/2 signaling pathway

“…OSCC is a malignant tumor with high morbidity and mortality and is a threat to human health (16). OSCC often involves the tongue and lips, and can easily spread to other organs, including the lungs and lymph nodes (17)(18)(19). The lack of specific detection of OSCC tumor boundaries makes it difficult to determine the extent of disease at the time of treatment and often adversely affects a patient's appearance and quality of life after surgery (20).…”