Nodal Radiographic Prognostic Factors in the New Stage I p16-Positive Oropharyngeal Cancer of the AJCC 8th Edition: Are All N1 Disease the Same?

Abstract

The AJCC 8th edition cancer staging manual consolidates all patients with p16+ oropharyngeal cancer with unilateral nodal disease no larger than 6 cm in size within the new clinical N1 group. The new classification system comprises a heterogeneous group of disease with varying radiographic findings. Our objective was to identify the radiographic characteristics which may portend a poor prognosis. We conducted a central radiological review of the staging imaging studies of patients who underwent upfront definitive concurrent chemoradiation for p16+ oropharyngeal cancer from May 2006 to September 2015. Pathology review was performed of all cases with standardized p16 reporting. All patients had at least an MRI or CT scan for review; 52% also had PET scans. Nodal stage was determined through central radiographic investigation. A total of 230 patients had AJCC 8th edition stage I (cT1-2N1) disease and were included for analysis. Image findings analyzed included the largest node size, location/level of involved node(s), overt radiographic extracapsular extension (ORECE), presence or absence of matted lymphadenopathy, and predominant appearance of involved nodes (solid, cystic, or both). Median follow-up for surviving patients was 40 [12-115] months. Median age was 61 [35-81] years. For the entire cohort, 3-year progression-free survival (PFS) and overall survival (OS) were 86% and 89%, respectively. On multivariate analysis, ORECE (HR=2.73 [1.13-6.60], P=.03), retropharyngeal (RP) involvement (HR=3.19 [1.30-7.86], P=.01), and low-neck involvement (level IV and/or Vb) (HR=4.15 [1.58-10.93], P=.004) were predictors for poorer PFS. Of note, no recurrences were observed in patients with predominantly cystic nodes (n=37). Low-neck involvement was also a poor prognostic factor for OS (HR=4.72 [1.53-14.61], P=.007), whereas RP involvement trended toward poorer OS but did not reach significance (HR=2.82 [0.98-8.13], P=.06). This analysis involving central assessment of nodal radiographic prognostic factors for stage I p16+ oropharyngeal carcinoma validates the new clinical N1 classification system by confirming no prognostic impact for size; however, additional image findings within this cohort negatively impacted outcomes. The presence of low-neck disease, RP adenopathy, and ORECE were associated with statistically significantly worse PFS. Low-neck involvement was also a statistically significant predictor for inferior OS in these patients. We believe caution is advised against de-intensification efforts in stage I patients with these factors. Interestingly, no treatment failures were observed in patients with predominantly cystic nodes; however, intercurrent disease death may have precluded a significant prognostic impact of this factor on multivariate analysis.