Locoregional Recurrence in p16‐Positive Oropharyngeal Squamous Cell Carcinoma After TORS

Abstract

Objective: To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC).Study Design: Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCNguideline-compliant adjuvant therapy at a single institution from 2007 to 2017.Methods: Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease-free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments.Results: Of 541 patients who completed guideline-indicated therapy, the estimated 5-year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09-0.83], P = .023), but there was no difference in DFS (P = .21) and OS (P = .86) between adjuvant therapy groups. The 5-year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P < .001). Patients who initially received adjuvant chemoradiation and those suffering local, in-field, and/or retropharyngeal node recurrences had decreased disease control after salvage therapy.Conclusion: LRR rates are low for HPV+ OPSCCs completing TORS and guideline-compliant adjuvant therapy. Patients without indication for adjuvant therapy more often suffer LRR, but these recurrences are generally controllable by salvage therapy. Improved understanding of the patterns of recurrence most amenable to salvage therapy may guide treatment decisions, counseling, and adjuvant therapy de-escalation trials.

Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma of the Tonsil versus Base of Tongue: A Systematic Review and Meta-Analysis

“…A more recent but smaller study endorsed these findings of margin status not being a predictive factor in p16 positive tumors [ 18 ]. These findings have been further confirmed by Carey et al, who could not find any pathological features associated with locoregional recurrence in p16 positive OPSCC [ 38 ]. However, a recent NCBD did endorse positive margin status as a statistically significant prognosticator for risk of death in the univariate analysis, but these findings did not persist into the multivariate analysis [ 66 ].…”

“…The recurrence of OPSCC after TORS was analyzed by subsite in 13 studies [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. There was no statistically significant difference in the odds of total recurrence between tonsillar and BOT OPSCC (1.1 [95%CI 0.8–1.5], p = 0.480) ( Figure 4 ).…”

“…Only two studies reported differences in adjuvant therapy between subsites, with Fradet et al finding no differences in the rate of adjuvant therapy, whereas Persky et al found that BOT OPSCC underwent more chemoradiation secondary to more positive margins [ 12 , 40 ]. In looking at all the subsites combined, a few studies have endorsed TORS with adjuvant therapy to be superior to TORS alone, particularly when considering locoregional control [ 16 , 38 ]. However, the literature is not consistent, with two studies showing excellent locoregional (3.0% to 3.3%) and distant control (0.0% to 8.4%) in patients with HPV-positive OPSCC undergoing single modality TORS therapy, regardless of margin status [ 78 , 79 ].…”

Human Papillomavirus-Associated Head and Neck Cancers. Where are We Now? A Systematic Review

“… T1 - 22/60 T2 - 23/60 T3 - 6/60 Tx- 9/60 Mean 30.3 ± 26.9 5-year overall survival of the total group was 77.6%, the 5-year disease-free survival rate was 85.2%, and the 5-year local recurrence-free survival rate was 90.6%. No major complications Carey et al 53 (2021) 541 with HPV-DNA positive OPSCC TORS - 89 TORS with RT - 248 TORS with CRT - 204 T0 - 9 T1 - 233 T2 - 256 T3 - 32 T4 - 9 Mean 51.7 The 5-year DFS rates: 83.4% - TORS alone 88.2% - TORS and RT 85.1% - TORS and CRT The 5-year OS rates: 92.2% - TORS alone 93.5% - TORS and RT 92.0% - TORS and CRT Moore et al 54 (2018) 314 patients, with HPV-DNA positive in the primary tumour in 286 patients TORS and ND - 75 TORS and RT - 88 TORS and CRT - 151 T1 - 130/314 T2 - 143/314 > 36 months Estimated local or regional RFS rates at 1, 3, and 5 years after surgery were 94%, 93% and 92%, respectively NR O’Hara et al 55 (2021) 107 TORS - 39 TORS and RT - 50 TORS and CRT - 31 T0 - 5 T1 - 50 T2 - 50 T3 - 2 Minimum 12 Estimated 3 –year%: OS - 88 DSS - 93 PFS - 88 NR Abbreviations : TORS, transoral robotic surgery; ND, neck dissection; IO, intraoperative; PO, postoperative; OS, overall survival; DSS, disease specific survival; DFS, disease free survival; RFS, recurrence free survival; OPSCC, oropharyngeal squamous cell carcinoma; PCF, pharyngocutaneous fistula; RT, radiotherapy; CT, chemotherapy; CRT, chemoradiation; NR, not reported. …”

Second window indocyanine green for oropharyngeal tumours: A case series and comparison of near‐infrared camera systems

“…Positive margin rates have improved with increased experience with TORS, but remain high at nearly 16% nationally 2 and 26% at low-volume centres. 3,4 The ability to obtain favourable oncologic outcomes with TORS on even locally advanced tumours has been demonstrated, 5,6 but avoidance of postoperative adjuvant therapy is dependent on ability to obtain negative margins amongst other factors. 7,8 Fluorescence molecular imaging (FMI) using near-infrared (NIR) fluorophores has been increasingly used to augment margin definition and residual tumour detection in vivo for achieving tumour-free margins.The NIR dye indocyanine green (ICG), routinely used for FMI, accumulates in areas of disrupted, permeable endothelium (i.e., neoplastic tissue) via the enhanced-permeability-and-retention effect.…”