Managing Depth of Invasion in Oral Cavity Cancer

Extranodal Extension

“The second important change in AJCC8 was the inclusion of ENE in lymph node staging for non-human papillomavirus (HPV) metastases. ENE profoundly affects prognosis, and thus it was added to the number and size of lymph nodes in the staging guidelines,” Dr. Faden said.

Extranodal extension is the extension of malignancy through an affected lymph node capsule. To classify overt, macroscopic ENE, clinical evidence of extension must be found during the examination and supported by strong radiologic and histologic evidence; the disease is staged as cN3b. The detection of microscopic ENE is significantly more challenging. In AJCC8, microscopic ENE is classified as ≤2 mm and macroscopic as >2mm.

The inclusion of DOI and ENE in AJCC8 has resulted in upstaging of OCSCC compared to the 7th edition. “Analysis of data using the 8th edition oral cavity staging system demonstrates good risk stratification using the new criteria,” Dr. Teng noted. In one study, AJCC8 led to upstaging of 35.6% (n = 235) of oral cavity cancer patients (Oral Oncol. 2018;85:82-86). The inclusion of ENE in AJCC8 results in upstaging of the neck, increasing the proportion of patients in the cN3b category by 40.3%, according to the findings of another study (Ann Surg Oncol. 2018;25:1730-1736). “Altogether, the upstaging of oral cavity cancers in the 8th edition system modestly improves predictive capacity for overall and disease-specific survival in this disease,” Dr. Teng explained.

Inclusion of ENE in AJCC 8 increased the proportion of patients in the cN3b category by 40.3% in patients with OCSCC, according to the findings of another study. Estimates of model performance revealed modest predictive capacity for OS and DSS in OCSCC (Harrell’s C of 0.66 in both) and weak predictive capacity in OCSCC (Harrell’s C of 0.58 and 0.61, respectively) (Ann Surg Oncol. 2018;25:1730-1736).

Biggest Challenges Remaining

Accurately staging OCSCC isn’t the only challenge in assessing malignancy. “Patients with oral cavity carcinoma have very different outcomes based not only on the clinical and pathologic staging of the tumor, but [also] on its biologic behavior,” Dr. Teng said. “In my opinion, the unpredictability of how certain patients do after treatment, despite their prognosis based on their stage, is the most difficult aspect of treating this patient population.”

According to Dr. Faden, the biggest challenges in oral cavity cancer have been, and continue to be, “a high rate of recurrence and death, as well as the morbidity of the cancers themselves, and our treatments, which often result in significant functional and quality of life deficits.”

For Dr. Nathan, the ability to accurately evaluate surgical margins intraoperatively is one of the biggest challenges in oral cavity cancer surgery. “Typically, CT and MRI imaging, which can be used preoperatively, cannot provide real-time guidance intraoperatively to gauge margins,” she said. “Varvares and colleagues have been investigating whether intraoperative sonography is a feasible technique for assessment of tumor thickness and depth of invasion.”