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Original Investigation |

Association of Main Specimen and Tumor Bed Margin Status With Local Recurrence and Survival in Oral Cancer Surgery ONLINE FIRST

Marisa R. Buchakjian, MD, PhD1; Kendall K. Tasche, MD1; Robert A. Robinson, MD, PhD2; Nitin A. Pagedar, MD, MPH1; Steven M. Sperry, MD1
[+] Author Affiliations
1Department of Otolaryngology–Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa
2Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
JAMA Otolaryngol Head Neck Surg. Published online July 17, 2016. doi:10.1001/jamaoto.2016.2329
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Importance  There is controversy surrounding surgical margins in oral cavity squamous cell carcinoma (OCSCC), with debate regarding the assessment and prognostic value of margins.

Objective  To analyze a large cohort of OCSCC cases for correlation between tumor specimen margins and intraoperative tumor bed frozen margins and evaluate how margin status associates with local recurrence and survival.

Design, Setting, and Participants  Retrospective cohort study of 406 patients treated with OCSCC resection between 2005 and 2014 at the University of Iowa Hospitals and Clinics. Included cases underwent margin evaluation on the tumor specimen and intraoperative frozen margin assessment from the tumor bed.

Main Outcomes and Measures  Findings of intraoperative frozen margin analysis as a test of tumor specimen margins; local recurrence and survival based on margin findings; prognosis based on clearance of positive frozen margins. To evaluate whether additional resection to “clear” positive frozen margins affected prognosis, we compared local recurrence rates for patients in 3 groups: group A included those patients with negative margins on both intraoperative and permanent specimens; group B included those with positive intraoperative margins subsequently cleared by additional resection to negative margins; and group C included those with negative intraoperative but positive permanent specimen margins.

Results  The median age of the 406 patients (234 men and 172 women) was 61 years (interquartile range, 53-72 years). When frozen margins were correlated with tumor specimen margins, frozen margin accuracy was 65%, with a 46% false-negative rate. We observed a local recurrence rate of 36% (95% CI, 24%-49%) when invasive carcinoma was present at an intraoperative frozen margin and 45% (95% CI, 34%-57%) when invasive carcinoma was found on the permanent specimen margin compared with 19% (95% CI, 14%-26%) and 13% (95% CI, 7%-22%) for completely negative frozen and permanent margin findings, respectively. There was a significant difference in local recurrence between group A (13%) and group B (27%) (absolute difference, 14%; 95% CI, 3%-26%) and between group A and group C (34%) (absolute difference, 21%; 95% CI, 8%-34%), but there was no difference between groups B and C (absolute difference, 7%; 95% CI, −8% to 22%), suggesting that additional resection to clear positive frozen margins does not improve prognosis.

Conclusions and Relevance  Intraoperative frozen margins from the tumor bed are not ideal predictors of positive margins on the main specimen. Both frozen and specimen margins are associated with local recurrence, but the specimen margin has the stronger association. Importantly, we demonstrate that clearing positive frozen margins from the tumor bed is not associated with improved outcomes.

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Observed Survival by Combined Margin Status

Kaplan-Meier plot of probability of observed survival over time from surgery, stratified by combined margin grouping. Group margin definitions: group 1 includes all patients with negative frozen and specimen margins; group 2, all patients without a positive specimen margin who are not included in group 1; group 3, those with positive specimen margins but not positive frozen margins; and group 4, those with positive frozen and specimen margins.

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