Transoral surgery and neck dissection with deintensified risk-based post-operative management increases efficacy in oropharynx cancer

Dr Barbara Burtness - Yale School of Medicine, New Haven, USA

This year at ASCO we’re presenting the 54-month results from E3311. This was a cooperative group trial of transoral surgery followed by de-intensified risk-based post-operative therapy. Everybody had clinical T1-T2 p16-positive oropharynx cancer that was deemed resectable. They underwent transoral resection and neck dissection; they were intended not to have matted lymph nodes. The hope was that the majority of the patients would not require post-operative chemoradiation.

Based on the pathologic findings, if they had T1-T2 cancer, negative margins, either no nodes or a single node, and no extranodal extension, those patients were deemed low risk and they went on to observation. Patients who had a positive margin, extranodal extension or more than four lymph nodes involved were deemed high risk and they went on to chemoradiation, although that was slightly de-intensified by substituting weekly cisplatin as the radiation sensitiser. Then the remaining patients were deemed intermediate risk. These patients had close margins, potentially, or they had 2-4 lymph nodes or they had perineural or vascular invasion or they had extranodal extension of up to 1mm. These patients were randomised between a standard approach of 60Gy of post-operative radiation and a de-intensified approach of 50Gy.

We had previously reported from this trial the two-year progression free survival and overall survival results and now we’re coming back with long-term follow-up. For the group as a whole this strategy of transoral surgery followed by de-escalated post-operative therapy led to a 54 month progression free survival of 90% and overall survival of above 95%. So we feel that this is an extremely favourable result compared to historical experience in this patient population and strongly supports the use of transoral surgery when it’s appropriate.

The additional question of whether you could go from 60Gy to 50Gy and we’re actually seeing no statistical significance between those two groups and the progression free survival and overall survival are numerically a little bit better for the patients who got 50Gy actually. The patients who underwent surveillance, we had four recurrences in that group. If you looked at the patients who were N0 the recurrence rate was 0% but among the patients who had a single involved node the recurrence rate was 14.5%. Looking at when those recurrences happened, the first one was at 18 months but there were three of them that happened at later than 40 months. We did not see any difference in the operations for those patients, median lymph node yield was the same and the pattern of failure was similar to the other groups.

So our overall conclusion is that for a T1-T2 p16-positive oropharynx cancer if the neck nodes do not appear matted and you don’t think you’re going to end up needing chemoradiation, that it is perfectly safe to de-intensify the post-operative therapy. This can be 50Gy for patients with intermediate risk.

We are probably going to need to learn a little bit more about what are the features in a patient who has a single node that would support not giving any radiation versus whether or not some of those patients might need radiation. Since we don’t find any clinical differences there we’ll be focussing on a genomic analysis of those cases.

We also looked at smoking history, the subsite at which the tumour arose and nodal burden. So tonsil versus other oropharyngeal sites no significant difference in either progression free survival or overall survival. Those patients who were smokers versus non-smokers no difference in either progression free survival or overall survival. And those patients who had AJCC 7th edition N2a disease, that is to say a single node but bigger than 3cm, did not really do that much different from those who had more extensive nodal disease.

We had previously reported some of these tobacco findings, Dr Mehra reported them at ASCO two years ago but this extends with longer follow-up. It really raises the question, given that that’s a group of patients who don’t do as well with chemoradiation as definitive therapy, it raises the question of whether there might be a preference for transoral surgery in a patient with a smoking history. That’s something that probably bears further study.