In a hypertensive, nonsmoking adult with biopsy‑confirmed papillary squamous cell carcinoma of the right tonsil (6 cm) and additional left base‑of‑tongue and left tonsillar lesions but no clinically evident nodal disease, what is the recommended surgical management and should neoadjuvant concurrent chemoradiotherapy be considered before resection?

Management of Multifocal Oropharyngeal Papillary Squamous Cell Carcinoma

Primary Treatment Recommendation

For this patient with multifocal oropharyngeal papillary squamous cell carcinoma (6 cm right tonsillar mass, plus left base-of-tongue and left tonsillar lesions) without pathologically enlarged lymph nodes, definitive concurrent chemoradiotherapy is the recommended primary treatment—not upfront surgery. 1

Rationale Against Primary Surgery

• Multifocal disease involving bilateral tonsils and base of tongue makes complete surgical resection with adequate margins extremely challenging, particularly for the base-of-tongue component where positive margin rates approach 28% even with transoral robotic surgery (TORS) for unifocal disease 2
• The 6.1 cm right-sided mass with additional 3.6 cm left tonsillar and 1.4 cm base-of-tongue lesions would require extensive bilateral resection including portions of the tongue base, resulting in severe functional impairment of speech and swallowing 3
• Primary surgery for advanced multifocal oropharyngeal disease has historically shown poor functional outcomes and would likely require total glossectomy or near-total glossectomy, which is not justified when non-surgical options provide equivalent or superior survival 1, 3

Recommended Treatment Protocol

Definitive Concurrent Chemoradiotherapy (Primary Treatment)

Deliver 70 Gy in 2 Gy fractions once daily over 7 weeks using intensity-modulated radiation therapy (IMRT) to the bilateral oropharyngeal sites and bilateral neck 1, 4

Concurrent high-dose cisplatin at 100 mg/m² on days 1,22, and 43 of radiation therapy (Category 1 evidence) 1, 4

• This regimen provides superior locoregional control and overall survival compared to radiation alone for locally advanced oropharyngeal cancer 1
• The total cumulative cisplatin dose should reach 200 mg/m² for optimal benefit 1

Alternative Systemic Therapy Options

If the patient cannot tolerate high-dose cisplatin (due to renal dysfunction, hearing loss, or neuropathy), acceptable alternatives include:

• Cisplatin 100 mg/m² plus 5-fluorouracil (5-FU) 1000 mg/m²/day continuous infusion days 1-4 of weeks 1 and 4 1
• Weekly cisplatin 40 mg/m² has shown non-inferiority in some postoperative settings but remains controversial for definitive treatment 4, 5
• Cetuximab 400 mg/m² loading dose followed by 250 mg/m² weekly should only be used if the patient is completely unfit for platinum-based therapy, as it provides inferior outcomes compared to cisplatin-based regimens 1

Radiation Field Design

• Bilateral neck irradiation to levels II-IV bilaterally is mandatory given the multifocal bilateral disease 1, 5
• The right oropharyngeal mass, left tonsillar mass, and left base-of-tongue lesion all require full-dose coverage to 70 Gy 1
• Elective nodal regions should receive 54-56 Gy 1

Why Neoadjuvant Chemoradiation Before Surgery Is NOT Recommended

Neoadjuvant (induction) chemoradiotherapy followed by surgery is explicitly NOT recommended for oropharyngeal cancer 1

• The evidence shows that postoperative chemotherapy should not be delivered alone or sequentially with postoperative radiotherapy (high-quality evidence, strong recommendation) 1
• This principle extends to the neoadjuvant setting—there is no role for chemotherapy or chemoradiation before planned surgical resection in oropharyngeal cancer 1
• If surgery is performed first, adjuvant therapy follows; if chemoradiation is chosen, it is definitive (not neoadjuvant) 1

Surgical Considerations (If Definitive CRT Fails)

Surgery should be reserved for salvage treatment if there is residual or recurrent disease after definitive chemoradiotherapy 1

If Surgery Were Considered Primary (Not Recommended Here):

• Transoral robotic surgery (TORS) would be technically feasible only for well-lateralized T1-T2 tonsillar lesions without base-of-tongue involvement 1
• This patient's multifocal disease with bilateral involvement and base-of-tongue extension violates the criteria for TORS 1
• Open surgical approach would require bilateral tonsillectomy, partial glossectomy of the tongue base, and bilateral neck dissection (levels II-IV), followed by mandatory adjuvant chemoradiation given the T3 primary size 1, 4
• The functional morbidity of this extensive surgery combined with the need for adjuvant therapy makes primary surgery inferior to definitive CRT 1, 3

Critical Pitfalls to Avoid

• Do not attempt primary surgery for multifocal bilateral oropharyngeal disease involving the base of tongue—the margin positivity rate will be unacceptably high and functional outcomes devastating 2, 3
• Do not use weekly cisplatin at 30 mg/m² as it has been proven inferior to 3-weekly high-dose cisplatin 1, 4
• Do not substitute cetuximab for cisplatin unless the patient is truly platinum-ineligible, as cetuximab provides inferior survival 1
• Do not delay treatment start—definitive chemoradiation should begin promptly after staging is complete 4
• Do not use unilateral radiation fields—bilateral disease mandates bilateral neck treatment 1, 5

HPV Testing and Prognosis

• HPV testing should be performed on the biopsy specimen, as HPV-positive oropharyngeal cancer has significantly better prognosis and response to treatment 1, 6
• Papillary squamous cell carcinoma of the tonsil is frequently HPV-associated (HPV 16 most common) 6, 7
• HPV status does not change the treatment recommendation for this advanced multifocal presentation, but it provides important prognostic information 1, 6

Surveillance After Definitive CRT

• Clinical examination every 1-3 months for years 1-2, then every 3-6 months for years 3-5 4
• PET-CT at 12 weeks post-treatment completion to assess response 4
• TSH monitoring at 1,2, and 5 years post-bilateral neck irradiation due to 20-25% risk of hypothyroidism 4, 5
• Imaging (CT or MRI) only for clinically concerning findings, not routine surveillance 4