Data cast doubt on 5-mm standard, use of frozen sections
A commonly used metric for defining a close surgical margin for resected oral-cavity tumors failed to identify adequately the patients at increased risk of recurrence, a retrospective review of 432 cases showed.
The analysis showed an inverse relationship with increasing distance between invasive tumor and inked main specimen margin on the main specimen, but results of a receiver operating characteristic curve analysis identified a cutoff of < 1 mm as most appropriate for classifying patients as having a high risk of local recurrence, as opposed to the more commonly used cutoff of 5 mm.
The analysis also showed that resection of tissue beyond 1 mm on intraoperative frozen section did not improve local disease control, as reported online in JAMA Otolaryngology-Head and Neck Cancer.
“The commonly used cutoff of 5 mm for a close margin lacks an evidential basis in predicting local recurrence,” Steven M. Sperry, MD, of the University of Iowa in Iowa City, and colleagues concluded. “Invasive tumor within 1 mm of the permanent specimen margin is associated with a significantly higher local recurrence risk, though there is no significant difference for greater distances.
“This study suggests that a cutoff of less than 1 mm identifies patients at increased local recurrence risk who may benefit from additional treatment. Analysis of the tumor specimen, rather than the tumor bed, is necessary for this determination.”
The results add to a growing volume of evidence that margins <5 mm can still be curative, said Michael Burkey, MD, of the Cleveland Clinic, who was not involved in the study. The data also add to evidence that the margins calculated from the main specimen are more predictive than frozen-section margins that many head and neck surgeons have used for years.
“This doesn’t change the fact that clearly getting all the tumor out and clearing margins microscopically are still critical to curative surgery,” Burkey told MedPage Today. “The study provided good data to show that when they got positive margins, even if they subsequently treated with radiation therapy, that led to no improvement in local recurrence.”
“A second key point is that the way we determine the adequacy of surgery is changing,” he added. “We used to say 5 mm, and now it’s probably 1 to 2 mm. More and more we’re finding that the best way to look at margins is off the main specimen, not by taking frozen sections from the tumor bed.”
Despite widespread use in surgical management of head and neck cancers, interpretation of margin status and associated prognostic implications remain imprecise. A survey of head and neck surgeons showed that 83% of respondents considered carcinoma in situ as a positive margin and 17% included dysplasia in the definition. Additionally, 69% of the surgeons used a cutoff of <5 mm between invasive tumor and resection margin to a close margin, consistent with multiple reports in the literature. However, other literature suggested a smaller-distance cutoff is adequate, Sperry’s group noted.
To continue an investigation of the clinical significance and impact of surgical margins in oral-cavity cancer, the authors retrospectively reviewed results in 432 consecutive patients with primary oral-cavity squamous cell carcinoma treated at the University of Iowa from 2005 to 2014. Patients with recurrent disease were excluded from the analysis. The primary outcome was local recurrence as determined by minimum distance in millimeters between invasive tumor and inked main specimen margin.
The patients had a median age of 62, and men accounted for 58% of the study population. T-stage distribution consisted of T1 disease in 45% of patients, T2 in 21%, and T3/4 in 34%. Subsite location was tongue in 45%, alveolus in 21%, floor of the mouth in 18%, and other in 15%.
Rates of local recurrence by margin status were:
44% for microscopic positive margins
28% for margins <1 mm
17% for 1-mm margins
13% for 2-mm and 3-mm margins
14% for 4-mm margins
11% for ≥5-mm margins
“These data demonstrated an exponential inverse relationship between distance and local recurrence, with no appreciable difference in local recurrence for distances greater than 1 mm,” the authors reported.
Local recurrence also was determined on the basis of intraoperative frozen section assessment from tumor bed sampling. The analysis showed similar recurrence rates for close-margin distances between patients with involved and negative frozen sections. Among patients with a positive main specimen margin, those with an involved frozen margin had the highest local recurrence rate at 54%, as compared with 36% for patients with a negative frozen margin.
The authors analyzed the results on the basis of whether additional tissue was resected to achieve a negative margin after initial frozen section indicated cancer. The analysis incorporated collapsed margins of ≥5 mm, 1 to 5 mm, <1 mm, and positive. Success was defined as a final margin uninvolved with either invasive carcinoma or carcinoma in situ after further resection. For patients with a positive main specimen margin, successful additional resection did not improve local control.
“For patients with final margin distances grater than 0 millimeter, the local recurrence rate appeared to be the same whether a successful additional resection of the margin was performed or note,” the authors reported.
Finally, Sperry’s group analyzed local recurrence according to whether patients received adjuvant radiation therapy. For patients with a positive main specimen margin, radiotherapy did not improve local control, and the recurrence rate was the same for the other main-specimen margin categories, regardless of whether radiation therapy was administered.
Study limitations included a relatively small group of surgeons performing the majority of surgical procedures, and the inability to compare results based on different methods of intraoperative margin evaluation, such as tumor bed versus main specimen sampling, the authors noted.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
JAMA Otolaryngology-Head and Neck Surgery
Source Reference: Tasche KK, et al “Definition of ‘close margin’ in oral cancer surgery and association of margin distance with local recurrence rate” JAMA Otolaryngol Head Neck Surg 2017; DOI:10.1001/jamaoto.2017.0548.