Current Standards for Organ Preservation in Locoregionally Advanced Non-nasopharyngeal Head and Neck Cancer and Evolving Strategies for Favorable-Risk and Platinum-Ineligible Populations.

OPINION STATEMENT: Standard-of-care treatment for the majority of patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is either upfront surgery followed by adjuvant treatment as indicated by intraoperative or pathologic findings or concurrent chemoradiation reserving surgical salvage for non-responsive disease. An attempt at upfront complete resection should be pursued if feasible in patients with oral cavity or paranasal sinus primary tumors. Given multimodality treatment paradigms, patients with locoregionally advanced SCCHN should be managed in a multidisciplinary setting. Modern radiation therapy, whether postoperative or definitive in intent, is based on target delineation guided by high-quality imaging, using an intensity-modulated radiation technique to spare organs at risk. In select groups of low-risk patients, most notably those with HPV-associated oropharyngeal SCC (OPSCC), several treatment deintensification approaches are currently under investigation. Major experimental strategies within this non-surgical organ preservation domain include reductions in the intensity of the chemotherapy or radiation therapy components of the chemoradiation program, use of induction chemotherapy, or imaging-based selection of patients eligible for deintensified radiation-based treatment. Of note, recent efforts to substitute cetuximab for cisplatin in low-risk HPV-associated OPSCC have demonstrated the inferiority of cetuximab to cisplatin in cisplatin-eligible patients, re-confirming cisplatin as the standard systemic therapy of choice in HNSCC. In patients who are not candidates for any type of cisplatin administration, carboplatin-based therapy or cetuximab remain options, and other non-cisplatin therapies are under investigation. Altered fractionation may be considered in patients who are not candidates for any type of systemic therapy. The role of immunotherapy in the management of locoregional SCCHN remains investigational.