New ASCO Guideline Addresses Head/Neck Squamous Cell Carcinoma of Unknown Primary

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ASCO has released a new clinical guideline titled, “Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline.”1 The guideline, promulgated by an international expert panel, is intended to “provide evidence-based recommendations to practicing physicians and other health-care providers on the diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck.”

Ellie Maghami, MD, FACS

Ellie Maghami, MD, FACS

Jimmy Caudell, MD, PhD

Jimmy Caudell, MD, PhD

Based on a review of literature from 2008 through 2019, the guideline is the result of collaboration over a period of 2 years by the diverse members of the expert panel, said Panel Co-Chair Ellie Maghami, MD, FACS, of City of Hope, in an interview with the ASCO Daily News. Dr. Maghami and Co-Chair Jimmy Caudell, MD, PhD, of the Moffitt Cancer Center, were joined on the panel by representatives from subspecialties including medical oncology, surgery, radiation oncology, radiology, and pathology, as well as a patient advocacy expert. The panel used evidence identified in a literature review and an informal consensus process to develop the guideline recommendations.

“We feel the project was definitely worthwhile,” Dr. Maghami said. “We believe it makes a major contribution to the field of oncology, as this is a nuanced area of practice where there is no absolute clarity derived from clinical trials, and there are different approaches [that can be used] as acceptable standards of care.”

Clinical Questions Addressed

THE GUIDELINE was informed by 100 relevant studies identified in the literature search. The panel then addressed four main clinical questions, along with some subquestions, regarding the proper selection and implementation of 1) preoperative evaluations; 2) surgical diagnostic and therapeutic procedures; 3) appropriate surgical techniques and considerations in management of the neck; and 4) radiotherapy and chemotherapy for patients with squamous cell carcinoma of unknown primary.

“Sometimes, clinical decisions in head and neck oncology are clear-cut,” Dr. Maghami said. “However, the management of squamous cell carcinoma of unknown primary, depending upon which institution you go to and whom you speak with, may be very different. ASCO recognized this and thought it would be appropriate to gather together a multidisciplinary panel of experts to offer guidelines to help practitioners navigate these nuanced scenarios in day-to-day practice.”

In 2019, ASCO published management guidelines for metastatic carcinoma of the neck from a known oral cavity or oropharyngeal primary site.2 This subsequent guideline is intended to provide management recommendations when the location of the primary tumor is unknown, and it concentrates on, “the most common histology of this presentation,” which is squamous cell carcinoma, Dr. Maghami said.

“Where possible, the recommendations are based on retrospective series at expert centers and peer-reviewed publications.”
— Ellie Maghami, MD, FACS

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The target audience for the guideline is extensive, but it is of particular interest to community oncologists—clinicians who are “outside of cancer centers and large academic institutions,” Dr. Maghami said.

“This is the kind of health-care professional who is hopefully going to reference and benefit from these guidelines. That was why it was important to have a community practice medical oncologist on the panel—to help us make sure that what we put together is usable, practical, and of value to the community practitioner.”

Focus of Recommendations

IN SUMMARY, the guideline is built around the following four questions:

1) What is the appropriate preoperative evaluation for patients with a neck mass suspicious for malignancy?

2) What are the appropriate surgical diagnostic and therapeutic procedures for squamous cell carcinoma of unknown primary?

3) What are the treatment considerations and appropriate techniques for surgical management of the neck?

4) What are the treatment considerations for radiation and systemic therapy in squamous cell carcinoma of unknown primary?

For each of the questions, the guideline provides several recommendations, each of which concludes with a note about how the panel arrived at that recommendation, the quality of the evidence supporting it, and the strength of the recommendation. Complementing the text are two diagrammatic flowcharts presenting algorithms for patient management.

“What is proposed in this guideline is within the best standards of care based on the current level of evidence and the experience of individuals at high-volume centers with clinical expertise in treating this entity,” Dr. Maghami said. “Although we don’t have randomized controlled trials comparing different approaches to support many of these recommendations, where possible, the recommendations are based on retrospective series at expert centers and peer-reviewed publications.” 

DISCLOSURE: For full disclosures of the panel members, visit


1. Maghami E, Ismaila N, Alvarez A, et al: Diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck: ASCO Guideline. J Clin Oncol. April 23, 2020 (early release online).

2. Koyfman SA, Ismaila N, Crook D, et al: Management of the neck in squamous cell carcinoma of the oral cavity and oropharynx: ASCO clinical practice guideline. J Clin Oncol 37:1753-1774, 2019.

Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, April 24, 2020. All rights reserved.