Perineural Invasion Predictive of Poor Survival Outcomes in Tongue Cancer

Comment: Perineural invasion (PNI) is associated with locoregional recurrence and disease progression in oral cavity squamous cell carcinoma (SCC). Previous retrospective studies have advocated elective neck dissection (END) to reduce locoregional failure and improve survival in patients with early stage oral SCC with PNI. However, this prospective RCT found no benefit of elective neck dissection in PNI-positive (+) patients, highlighting the need for more aggressive neck management in this patient population. —Samuel Selesnick, MD

What is the role of (PNI) in the regional control and survival of patients with tongue SCC?

Bottom line
PNI is an invaluable pathological parameter to independently predict cervical metastasis, local relapse, neck relapse, and poor survival outcomes, but END cannot improve benefits compared to observation for PNI (+) patients.

Background: TSCC is the most common oral cancer and is well known for its high propensity to metastasize to cervical lymph nodes. PNI is a distinct pathological feature characterized by the presence of tumor cells within the nerve sheath or perineural space. It remains unclear whether differential prognostic significance of PNI can be observed at different subsites and tumor stages of head and neck cancer.

Study design: Prospective randomized single-center trial, held from November 2008 to September 2014, with a total of 221 cT1-2N0 TSCC patients.

Setting: Department of Oral and Maxillofacial—Head and Neck Oncology, Shanghai Ninth People’s Hospital, China.

Synopsis: Oncologic outcomes including cervical lymph node (LN) metastasis, tongue local relapse, neck relapse, and distant metastasis were studied. The primary objective was to estimate whether patients with early-stage cT1-2N0 TSCC should be treated with END at the time of the primary surgery or observed with therapeutic neck dissection (TND) after neck metastasis. Between the observation and END groups, there were no significant differences in age, sex, T stage, and pathological grade; no oncologic outcome differences including LN metastasis, tongue local relapse, neck relapse, and distant metastasis; and no differences in five-year disease-free survival rate and five-year disease-specific survival rate. Of the 221 patients, 34 were presented with PNI (+). Although PNI was not associated with T stage, PNI (+) was associated with poor differentiation compared to well/moderate differentiation, and with DOI > 5 mm compared with DOI < 5 mm.

PNI presence correlated with LN metastasis, tongue local relapse, and neck relapse, but not with distant metastasis. Five-year disease-free survival rate and five-year disease-specific survival rate were significantly lower in PNI (+) patients than PNI (-) patients. PNI independently predicted LN metastasis, tongue local relapse, neck relapse and worse survival outcomes. PNI presence remained an independent predictor for LN metastasis, tongue local relapse, neck relapse, disease-free survival, and disease-specific survival after controlling for T stage and differentiation.

Limitations included a small PNI (+) subgroup sample size and the fact that pathologic parameters are not available to aid in preoperative or intraoperative decision making.

Citation: Yang X, Tian X, Wu K, et al. Prognostic impact of perineural invasion in early stage oral tongue squamous cell carcinoma: results from a prospective randomized trial. Surg Oncol. 2018;27:123–128.