Non-Metastatic Squamous Cell Carcinoma of the Oropharynx: Primary Surgery or (Chemo)radiotherapy?

In patients with locally advanced, non-metastatic oropharyngeal squamous cell carcinoma (OPSCC), surgery-based and nonsurgical treatment approaches have not been adequately compared in randomized Phase III clinical trials. Current clinical guidelines recommend various surgical and nonsurgical strategies across disease stages for both p16-negative and p16-positive OPSCC, without clearly favoring a single approach.

This review summarizes the available evidence relevant to clinical decision-making between primary surgical and primary nonsurgical treatment approaches in patients with non-metastatic OPSCC.

We reviewed studies evaluating tumor control across different treatment modalities, with emphasis on the highest-quality available evidence and post-treatment quality of life (QoL). Outcomes were discussed in relation to disease extent (early-stage vs. locally advanced) and treatment approaches. Emerging therapeutic strategies with the potential to improve the efficacy-to-toxicity ratio were also reviewed.

In the absence of Phase III randomized trials in non-metastatic OPSCC, the most informative comparative data derive from studies employing propensity score matching to reduce selection bias. These analyses suggest that survival outcomes are largely comparable between surgery-based and nonsurgical approaches in both p16-positive and p16-negative OPSCC. With respect to post-treatment QoL, surgery alone is generally associated with the lowest toxicity burden, whereas surgery followed by adjuvant (chemo)radiotherapy and definitive (chemo)radiotherapy demonstrate broadly comparable, albeit modality-specific, toxicity and QoL profiles. p16-positive status is consistently associated with more favorable post-treatment QoL. De-escalation strategies in p16/HPV-associated OPSCC, as well as emerging modalities such as immune checkpoint inhibitors, proton therapy, and adaptive radiotherapy, may influence future treatment paradigms.

In the absence of clear differences in oncologic efficacy between primary surgical and nonsurgical approaches, treatment selection should be guided primarily by anticipated toxicity and its impact on QoL, within the context of multidisciplinary assessment and patient preferences. The influence of treatment costs in the decision-making process varies across healthcare systems, reflecting differences in the valuation and financing of health interventions. The role of emerging treatment strategies in OPSCC will need to be defined through prospective, disease-specific clinical trials.