Do not de‐escalate oncology care in oropharyngeal cancer routinely

Abstract

To the Editor, With great interest, we read the article by Ilmarinen et al published recently in the Head & Neck journal. The authors retrospectively analyzed follow-up visits of 153 patients with squamous cell carcinoma of the oropharynx (OPSCC) conducted at their department in 2014. The principal finding was that tumor recurrences were rare and all of them were diagnosed in the minority of patients presenting with new symptoms. This led to the conclusion suggesting a reduction in the number of routine posttreatment visits in these patients. Of note, the investigators reported p16 positivity, a widely used surrogate marker for human papillomavirus (HPV), in about 70% of their cohort; no information was given on the smoking habits of the patients. Although we agree with the authors that unnecessary follow-up checks represent an economic burden to the health care system, we would like to point out that (a) HPV-related OPSCC exhibits a distinct pattern of dissemination occurring after a longer period of time than in HPV-negative cases etiologically linked to tobacco and alcohol exposure, (b) while locoregional recurrence is the dominant site of failure in patients with HPV-negative tumors, HPV-associated OPSCC relapses primarily at distant organs including unusual sites such as skin, brain, skeletal muscles, intra-abdominal or pericardial lymph nodes, kidney, and pancreatic tail, (c) within the group of HPV-associated locoregionally advanced OPSCC there are different risk categories, that is, those with HPV-positive OPSCC tumors with a 3-year survival expectation of over 90%, but also an HPV-positive OPSCC with a clearly less favorable outcome (3-year overall survival around 70%); in particular, patients with HPV-positive T4 tumors and N3 disease have an inadequate distant disease control, which might even ask for treatment intensification, (d) there is a trend to de-escalate treatment in HPV-associated OPSCC, and the outcome of such procedures might be quite disappointing, as we recently have noticed in two randomized trials comparing concurrent cisplatin-based chemoradiation vs cetuximab/ radiation both in lowand intermediate-risk HPV-positive OPSCC patients, De-ESCALaTE HPV and RTOG1016, pointing at the fact that such patients still benefit most from the standard treatment approach, cisplatin-based chemoradiation, and that in particular late side-effects accompanying this approach might be a threat in such patients, who are usually younger and have a longer life expectancy than HPV-negative OPSCC patients, and that some of these side effect might occur even after 5 years, (e) posttreatment surveillance takes on further roles involving early psychosocial interventions, appraisal by speech and language therapists, restoration of nutritional, swallowing, and dental status, and detection of endocrine deficiencies, all of which contribute to a holistic approach in cancer management, and (f) in the era of shared medical decision making, patient voice should also be heard and clearly not all patients favor a less intensive follow-up, especially in terms of imaging methods. For these reasons, we are not in favor of de-intensifying neither treatment nor follow-up in locoregionally advanced OPSCC, not even in the more favorable HPV-associated OPSCC group, routinely. A randomized study of a de-escalated follow-up protocol vs a standard follow-up protocol in patients who receive the standard treatment for locoregionally advanced HPV-associated OPSCC with a careful prospective evaluation of late toxicities and a careful assessment of patient preferences might have been preferable in this situation.