UCSF Study Finds 25% of Patients with HPV+ Oropharynx Cancer May Require Chemoradiotherapy After Robotic Surgery

In a nearly 10-year retrospective study involving 136 carefully selected patients with HPV-positive (HPV+) oropharynx cancer, UC San Francisco researchers found that one in four may meet possible indications for adjuvant chemoradiotherapy following transoral robotic surgery (TORS). 

Key points:

  • Knowing which patients are more likely to need adjuvant chemoradiotherapy after robotic surgery for HPV+ oropharynx squamous cell carcinoma (OPSCC) can help guide patient counseling and selection.
  • Extranodal extension (ENE) and positive surgical margins (PSM) are current possible indications for adjuvant cisplatin chemotherapy.
  • Radiologic assessment of lymph node ENE is limited in predictive accuracy, making ENE difficult to rule in or rule out confidently.
  • Using patient data, researchers found that about one-quarter of patients who were carefully selected for surgery with no clinically obvious signs of ENE were ultimately found to have pathologic ENE. A higher number of lymph node metastases found prior to surgery was associated with a greater likelihood of pathologic ENE.

Evaluating individual patient risk

TORS addresses some of the limitations of traditional transoral and transcervical oropharynx surgery by providing improved visualization, access and agility in the oropharynx. TORS has been shown to lead to excellent disease outcomes and better quality of life for patients with HPV+ OPSCC. In a separate multi-institutional analysis of 344 select HPV+ OPSCC patients treated with surgery alone regardless of whether adjuvant treatments were indicated, UCSF researchers found these patients had a two-year disease-free survival rate of 91% and a disease-specific survival rate of 98%.

While some patients may be able to avoid adjuvant therapy, others undergo adjuvant treatments that can cause significant short- and long-term side effects, including nausea and vomiting, kidney damage, hearing loss, mucositis, dry mouth, dental decay, taste changes, swallowing dysfunction, chronic pain, poor aesthetic outcomes and financial burden. UCSF head and neck oncologic surgeon and associate professor William Ryan, MD, FACS, led both studies. “Each form of therapy – whether it is surgery, radiation or chemotherapy – has its own consequences and risks of complications and toxicities,” he said.

Estimating the individual likelihoods of meeting indications for possible adjuvant chemoradiotherapy after surgery for HPV+ OPSCC could help improve decision-making for both patients and doctors. 

Identifying pathologic ENE and PSM

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According to current National Comprehensive Cancer Network guidelines, possible indications for adjuvant chemoradiotherapy include pathologic ENE or PSM or both. Pathologic ENE can be difficult to predict clinically given the imperfect accuracy of radiologic scans and physical exams.  To better quantify the likelihood of meeting indication for adjuvant treatment, UCSF researchers studied data on 136 patients with HPV+ OPSCC but no obvious ENE, all of whom underwent TORS with neck dissection at UCSF between 2012 and 2021.

The researchers recorded patient age, sex, race and ethnicity, tobacco and alcohol use, and tumor site and size as well as T and N categories using the seventh and eighth editions of the American Joint Committee on Cancer staging manual.

More than 80% of patients had at least one indication for potential adjuvant radiotherapy, including pT3-pT4 disease, perineural invasion (PNI), lymphovascular invasion (LVI), a single node greater than 3 centimeters or multiple positive lymph nodes. Twenty-five percent of patients had indications for possible adjuvant chemoradiotherapy. Of these, 19.9% had pathologic ENE, 7.3% had PSM and 2.2% had both.

Age, smoking, alcohol consumption and clinical T score were not associated with the presence of pathologic ENE, PSM, PNI or LVI. The proportion of pathologic ENE was greater in those with higher clinical N categories, more so in patients who had clinical N2b disease.

The study results were published in JAMA Otolaryngology – Head & Neck Surgery. The authors say that despite careful patient selection and a strong desire to limit adjuvant chemoradiotherapy, about one in four patients will likely have indications for it across all patients typically selected for surgery. 

“Even when a clinical exam and radiology seem to show resectability and no extranodal extension, there is a chance the patient will have surgical specimen-based indications for chemotherapy and radiation that are unexpected,” said Ryan, senior author of the study. “Careful training and experience in transoral surgery, neck dissection, head and neck radiation and delivery of chemotherapy are critical for optimized patient oncologic and quality-of-life outcomes.”

UCSF Medical Center is No. 5 in the nation for ear, nose and throat care and best hospital in Northern California for cancer care according to U.S. News & World Report’s 2021-2022 Best Hospitals survey.

Cancer research and treatment take place within the UCSF Helen Diller Family Comprehensive Cancer Center.

To learn more 

UCSF Head and Neck Surgery Cancer Program

Phone: (415) 885-7528 | Fax: (415) 885-7711

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