INTRODUCTION — Regular posttreatment follow-up is an essential part of the care of patients who are treated for squamous cell carcinoma of the head and neck.
The goals of posttreatment surveillance are the early detection of locoregional recurrences, distant metastases, or second primary malignancies, and evaluation for and management of treatment-related complications.
Posttreatment surveillance in patients with head and neck squamous cell cancer is reviewed here. An overview of the treatment of head and neck cancer is presented separately. (See "Overview of treatment for head and neck cancer".)
RATIONALE
Recurrent disease and second primary malignancies — The rationale for surveillance is that early detection of either a recurrence or a second primary tumor allows for appropriate treatment and better functional and survival outcomes. However, controlled prospective data demonstrating a survival benefit for any follow-up strategy do not exist. Therefore, retrospective data and observational studies are used to guide surveillance recommendations.
Whether early detection of recurrent disease alters outcomes is uncertain. Routine surveillance has been associated with a survival benefit in some observational studies when patients diagnosed at routine follow-up were compared with those who presented with symptoms [1,2]. However, other studies have not observed a survival benefit from detecting asymptomatic recurrences [3-6]. One explanation for the lack of a survival benefit may be the high proportion of recurrences that are symptomatic. Other studies suggest that survival in patients with recurrent disease is determined primarily by the extent of prior disease, its therapy and time to recurrence, and the location of the recurrence [7]. A randomized controlled trial of no meaningful follow-up versus surveillance after head and neck cancer treatment is impossible due to ethical considerations.
Posttreatment surveillance may be most effective in patients who initially had limited disease, thereby retaining an option for future curative therapy, such as those with early T stage (T1 and T2) tumors who received a single modality with either surgery or radiation therapy [5,8]. In one report, 87 percent of those who survived two years or longer after salvage therapy had T1 or T2 index tumors, and only 30 percent had node-positive disease [8]. Research suggests that patients who recur after treatment for early stage disease have better outcomes, especially when they are surgically salvageable and undergo adjuvant radiation or chemoradiotherapy [9].
Despite high compliance with recommended surveillance, survival remains poor for patients who were previously treated for advanced stage disease or who initially presented with regional disease [7]. Decreasing morbidity by treating recurrent tumors and, thereby, providing palliation of symptoms is also an important goal and can often be accomplished by single- or multimodality therapy [10].
Treatment-related complications — Although early detection of recurrences or second primary malignancies may not significantly improve survival, posttreatment surveillance also offers an opportunity to manage therapy-related complications (xerostomia, dental disease, hypothyroidism, osteoradionecrosis) and assess functional voice and swallowing rehabilitation, nutritional issues, ongoing alcohol and tobacco use, depression, and comorbid conditions. Furthermore, regular follow-up may provide important emotional and psychological support for patients and their families. (See "Management of late complications of head and neck cancer and its treatment" and "Speech and swallowing rehabilitation of the patient with head and neck cancer" and "Health-related quality of life in head and neck cancer".)
SURVEILLANCE — The optimal frequency and duration of follow-up and specific components of screening examinations are not well defined [11,12]. The following recommendations are consistent with guidelines from the National Comprehensive Cancer Network [13].
Frequency of follow-up — Our general approach is to see and examine patients every one to three months in the first year after treatment. In the second year, this is extended to every two to four months, in years 3 to 5, every four to six months, and after five years, every 12 months. Some practitioners stop seeing their patients at this time; however, we believe in lifelong surveillance.
In general, the intensity of follow-up is greatest in the first two to four years since approximately 80 to 90 percent of all recurrences after curative-intent treatment occur within this timeframe [3,5]. Although proven benefit from more prolonged follow-up is lacking, surveillance beyond five years is generally recommended because late recurrences are occasionally observed and because the risk of a second primary malignancy remains elevated for at least 10 years after treatment of the index tumor [14,15]. This is especially true if patients continue to smoke and abuse alcohol. (See "Second primary malignancies in patients with head and neck cancers".)
History — Patients should be educated about possible signs and symptoms of tumor recurrence, including hoarseness, pain, dysphagia, bleeding, enlarged lymph nodes and other masses, cranial nerve deficits, weight loss, and difficulty breathing. Additional points that may be elicited in the interim history include otalgia (ear pain), hemoptysis, symptoms of aspiration, facial numbness, or symptoms due to cranial nerve involvement.
Recent illnesses (eg, pneumonia) or changes in overall health (eg, weight loss, chronic fatigue) may heighten suspicion of recurrent disease. In addition, fatigue, persistent lymphedema, or cold intolerance may suggest hypothyroidism.
Tobacco and alcohol cessation — Tobacco smoking, when continued during and after therapy, decreases local control and survival, and increases the risk of second primary malignancy, in addition to its role as a major risk factor for head and neck cancer [16,17]. Patients who continue to smoke and drink alcohol have worse local control and survival. (See "Treatment of alcohol use and smoking for cancer survivors".)
Tobacco smoking during therapy has been associated with an increased risk of cancer progression and death [18]. Tobacco cessation counseling, including pharmacologic intervention, is included as a quality of care measure by the American Head and Neck Society and should be included as part of routine follow-up visits [19]. (See "Behavioral approaches to smoking cessation" and "Overview of smoking cessation management in adults" and "Screening for unhealthy use of alcohol and other drugs in primary care".)
Examination of the head and neck — The follow-up physical examination should be methodical and comprehensive. Signs of tissue asymmetry should be specifically sought and any findings carefully evaluated. Examination of the ears should note serous or acute otitis media, which can indicate eustachian tube dysfunction by an obstructing nasopharyngeal mass. The anterior nasal cavity can be evaluated with a nasal speculum, but complete evaluation of the posterior nasal cavity and nasopharynx requires rigid or fiberoptic endoscopy.
Inspection of the mouth should include careful visual examination and palpation of the mucous membranes, floor of the mouth, the anterior two-thirds of the tongue, palate, tonsillar fossae, buccal and gingival mucosa, and posterior pharyngeal wall. The dentition should be examined for signs of loose teeth, exposed bone, or osteoradionecrosis. Denture fit and any changes could also signify a malignant process. Additionally, tongue mobility and presence of trismus should be recorded. The structures within the oral cavity and oropharynx should be palpated, including the base of tongue and vallecula.
Fiberoptic nasopharyngolaryngoscopy is indicated for most patients to evaluate the primary tumor site and search for second primary cancers. This minor procedure is really an extension of the head and neck exam and should be performed by a clinician who is skilled in the conduct of a proper head and neck examination. This is a rapidly performed office procedure, with or without local anesthesia, that causes only minor discomfort. This allows for a much more thorough examination of the nasopharynx, oropharynx, hypopharynx, larynx, and subglottis than is possible with an indirect mirror examination. Aside from mucosal irregularities, other abnormalities that should be specifically searched for are impaired vocal cord mobility, pooling of secretions, asymmetries, and bleeding.
Advances in optical technology, such as high definition images and narrow band imaging, may also help to detect early or subtle precancerous lesions [20]. Some flexible endoscopes have working channels that will allow for biopsies to be taken in appropriate candidates.
Transnasal esophagoscopy can be carried out in patients with new symptoms such as dysphagia to evaluate the esophagus for carcinomas, strictures, and gastroesophageal reflux [21]. Second primary malignancies of the esophagus are significantly increased in patients with primary carcinogen-related squamous cell carcinomas of the head and neck, and these may be either synchronous or metachronous. (See "Overview of the diagnosis and staging of head and neck cancer", section on 'Initial evaluation' and "Second primary malignancies in patients with head and neck cancers".)
IMAGING — Posttreatment imaging serves two main purposes:
●"Definitive" evaluation of treatment response, which could indicate the need for additional therapy
●Screening for recurrence
The role of imaging to assess the response to treatment is well established. However, the role of screening asymptomatic individuals with various imaging procedures (eg, computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET]) is controversial. Imaging procedures to screen for recurrence have not been rigorously studied and are, therefore, not routinely recommended. Some experts advocate imaging to screen patients felt to be at high risk of recurrence during the first several years. One retrospective analysis reported that PET scans at regular intervals beginning three to four months after treatment were highly sensitive for detecting locoregional or distant recurrences [22]. Similarly, another observational study suggested that posttreatment PET/CT appears to predict outcome regardless of p16 status [23]. Since the median time to radiological recurrence was six months, some of these would be discovered with routine posttreatment imaging, and half would have been found with an additional scan.
While patients with human papillomavirus (HPV) related oropharyngeal cancer may have late or unusual sites of distant metastases, the rate remains low, and the value of detecting asymptomatic recurrences is unclear; thus, routine chest CT or PET is not recommended. (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer".)
Imaging of the head and neck
Posttreatment reevaluation — For patients treated with definitive radiation therapy or chemoradiotherapy, posttreatment reevaluation is performed by week 12 using CT, MRI, and/or PET scan. (See "Management of the neck following definitive radiotherapy with or without chemoradiotherapy in head and neck squamous cell carcinoma".)
For patients treated with curative-intent surgery, imaging of the primary tumor site and neck is indicated at least once during the first six months after treatment to establish a baseline for future reference [13]. If persistent or recurrent disease is suspected, then imaging is obtained sooner to allow for timely surgical salvage. Subsequent imaging is generally based upon the presence of signs or symptoms [24].
For patients with advanced cancer (N2 or N3 nodal disease) treated with definitive concurrent chemoradiotherapy, the role of PET-guided surveillance has been established in a randomized trial [25]. (See "Management of the neck following definitive radiotherapy with or without chemoradiotherapy in head and neck squamous cell carcinoma", section on 'Planned surgery versus PET/CT surveillance'.)
More frequent imaging may be indicated for patients felt to be at high risk for locoregional recurrence based upon tumor characteristics and/or posttreatment evaluation. For such patients, radiographic evaluation should be individualized on a case-by-case basis. One example is the patient with a residual non-mucosal-based mass that is either PET negative or PET positive but biopsy negative. In addition, residual lymph nodes not treated with lymphadenectomy should be monitored by CT or MRI of the neck. The frequency of radiographic evaluation will depend on the clinical situation but is generally every 3 to 12 months for the first two to three years.
Posttreatment surveillance — CT, MRI, PET, and ultrasonography have been used in posttreatment surveillance for locoregional recurrence [26]. Each has its own merits, and the choice of imaging modality should be based on prior imaging, available radiologic expertise, and cost.
CT and MRI are the mainstays of surveillance imaging. However, ultrasonography may be useful for directing a fine needle aspirate and has the benefit of lacking radiation exposure [27].
PET scanning has become increasingly specific and is highly sensitive. As such, PET is becoming the preferred test for posttreatment screening at many institutions and may be used to detect local, regional, and distant disease before the development of signs and symptoms [28]. However, PET scanning is quite costly and may lead to additional diagnostic evaluation for false positives [29]. The false positive rate of PET/CT may be increased for patients with higher stage primary disease [30]. For patients with oropharyngeal squamous cell carcinoma, PET/CT and CT had comparable accuracy in the evaluation of primary tumor sites; however, PET/CT showed a higher accuracy in the evaluation of cervical lymph node involvement [31]. The accuracy of posttreatment PET/CT in oropharyngeal squamous cell carcinoma does not seem to depend on p16 status [23]. (See "Overview of the diagnosis and staging of head and neck cancer", section on 'Imaging studies'.)
When planning the posttreatment surveillance strategy, care should be taken to limit the number of CT or PET scans, particularly in younger individuals, given concerns about radiation exposure and the risk for second malignancies [32,33]. (See "Radiation-related risks of imaging".)
All patients diagnosed with locoregionally recurrent disease should be evaluated for distant metastases prior to initiating retreatment. (See "Treatment of locally recurrent squamous cell carcinoma of the head and neck".)
Surveillance for smokers — Lung cancer constitutes the most frequent second primary malignancy arising in patients who have been treated for squamous cell carcinoma of the head and neck [34], with an estimated cumulative incidence of approximately 13 percent at 20 years in patients with carcinogen-related head and neck cancer [35]. In addition, the lung is the most frequent location for distant metastases in patients with head and neck cancer.
Distinguishing metastases from a second primary lung cancer, especially for a squamous cell carcinoma, can be difficult [36]. Loss of heterozygosity studies have yielded mixed results, with some studies showing the majority to be a new lung cancer primary [37], while others indicate that metastases are more common [38]. Less commonly, metastases may occur in the bone, liver, mediastinal lymph nodes, skin, and brain. (See "Second primary malignancies in patients with head and neck cancers", section on 'Incidence'.)
Routine imaging with chest radiographs has never been demonstrated to be associated with a survival benefit. However, randomized trials have demonstrated that annual low-dose helical CT improves the detection of lung cancer and results in a significant survival advantage compared with annual chest radiographs in individuals who are at high risk of developing lung cancer. Guidelines from the National Comprehensive Cancer Network classify patients who have had head and neck cancer and have a history of 20 pack years of smoking area as being at high risk and recommend annual screening with CT [13]. (See "Screening for lung cancer", section on 'Low-dose chest CT'.)
For nonsmokers, particularly those with head and neck cancers thought to be due to HPV, chest imaging may not be necessary. However, others screen patients with HPV related cancers due to evidence that some patients with oligometastatic recurrent HPV related cancers have improved survival with aggressive treatment. (See "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer".)
BIOMARKERS — There are no commercially available biomarkers that can be used as screening for recurrent head and neck cancer. While promising, the development of serum biomarkers for posttreatment surveillance continues to be an active area of investigation. Data are as follows for specific histologies:
HPV-associated tumors — For patients with human papillomavirus (HPV)-associated tumors, viral elements have been shown to be promising biomarkers [39], although additional studies are needed to standardize the use of such tests within posttreatment surveillance algorithms. As an example, in one observational study, the detection of HPV DNA in posttreatment plasma samples was found to have high positive and negative predictive values for identifying recurrence of HPV-related oropharyngeal carcinoma [40]. Further details of this study are discussed separately. (See "Treatment of human papillomavirus associated oropharyngeal cancer", section on 'Surveillance'.)
Nasopharyngeal carcinoma — In patients with Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC), there are limited data for the role of biomarkers in posttreatment surveillance, and clear management recommendations are necessary but lacking. Biomarkers of interest include posttreatment EBV DNA levels, particularly those obtained postradiotherapy [41], and circulating tumor cells. Further data on the use of such biomarkers in the posttreatment surveillance of treated NPC are discussed separately. (See "Treatment of early and locoregionally advanced nasopharyngeal carcinoma", section on 'Is there a role for EBV DNA in posttreatment surveillance?' and "Treatment of recurrent and metastatic nasopharyngeal carcinoma", section on 'Prognosis'.)
TREATMENT-RELATED COMPLICATIONS
Hypothyroidism — Patients whose head and neck cancers were originally treated with radiation therapy (with or without chemotherapy) are at risk of developing hypothyroidism if the thyroid itself or the adjacent neck was within the irradiated field. In this setting, the rate of subclinical or clinical hypothyroidism can approach 50 percent [42]. Monitoring of serum thyroid-stimulating hormone (TSH), with or without serum thyroxine (T4) level, is recommended every 6 to 12 months in patients who have undergone radiation therapy [43,44]. (See "Diagnosis of and screening for hypothyroidism in nonpregnant adults" and "Treatment of primary hypothyroidism in adults" and "Management of late complications of head and neck cancer and its treatment", section on 'Thyroid disease'.)
Dental care — Appropriate dental care is an important long-term component of the management and follow-up of patients following treatment. Special considerations surrounding posttreatment dental care are due to the adverse effects of radiation or chemoradiotherapy on the oral cavity and teeth, including xerostomia, demineralization, and hypovascularization of the maxilla and mandible, in addition to preexisting dental disease. (See "Management and prevention of complications during initial treatment of head and neck cancer", section on 'Dental issues'.)
Dental cleaning and examination must be performed at least twice yearly. Patients who have their major salivary glands within radiation treatment fields have some degree of intermediate- to long-term salivary dysfunction, which contributes to dental decay. Those with teeth are at considerably higher risk of developing devastating dental complications. Patients should be instructed to perform careful oral hygiene and to take daily fluoride treatments according to the directions of their dentist. In those planning on undergoing major dental interventions, hyperbaric oxygen may be required to prevent severe complications such as osteoradionecrosis.
Postsurgical reconstruction and dental and facial implants are discussed separately. (See "Management of acquired maxillary and hard palate defects" and "Mandibular and palatal reconstruction in patients with head and neck cancer".)
Carotid atherosclerosis — Radiation therapy may accelerate the process of carotid artery atherosclerosis, which has led to recommendations for ultrasound screening [45-47]. This practice should be individualized based on patient disease and risk. Evidence of carotid atherosclerosis may also be apparent on panoramic radiographs obtained as part of routine dental examinations [48]. (See "Cancer survivorship: Cardiovascular and respiratory issues", section on 'Atherosclerosis'.)
Obsructive sleep apnea — Obstructive sleep apnea is prevalent in head and neck cancer patients, with the incidence at least that of the general population [49,50]. The mechanism for this is not known but may be attributed to posttreatment edema, scarring/fibrosis, and surgical alterations in anatomy. Determining the cause of the sleep disturbance may be challenging as many cancer patients have difficulty with sleep. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults".)
Other complications — Regular medical follow-up care, with regard to the heart, lungs, and liver, is important since as many as 20 percent of patients with treated head and neck cancer will die in the first five years from comorbid conditions.
Patients should have periodic assessment for other treatment-related toxicity, including neck fibrosis, trismus, speech and swallowing function, and nutritional problems, and if indicated, should be referred for treatment, such as speech, hearing, and swallowing rehabilitation. Attention should also be paid to emotional and psychosocial issues.
●(See "Management of late complications of head and neck cancer and its treatment".)
●(See "Speech and swallowing rehabilitation of the patient with head and neck cancer".)
●(See "Clinical features and diagnosis of psychiatric disorders in patients with cancer: Overview".)
●(See "Management of psychiatric disorders in patients with cancer".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Head and neck cancer".)
SUMMARY AND RECOMMENDATIONS
●Regular posttreatment follow-up is an essential part of the care of patients after potentially curative treatment of head and neck cancer. Although there is no evidence documenting a survival benefit in this population, early detection of a recurrence or second primary cancer may be associated with an improved prognosis in some patients. Furthermore, close follow-up allows the detection and management of treatment-related complications and other health problems. (See 'Rationale' above.)
●The following recommendations are consistent with guidelines from the National Comprehensive Cancer Network (see 'Surveillance' above):
●History and physical examination with decreasing frequency following initial definitive therapy: every one to three months during the first year, every two to four months during the second year, every four to six months during years 3 to 5, and annually after five years. (See 'History' above and 'Examination of the head and neck' above.)
•Patient contact should include smoking cessation and alcohol counseling for those at risk. (See 'Tobacco and alcohol cessation' above.)
●Imaging of the head and neck should be carried out after initial treatment to provide a baseline for future reference. Subsequent imaging is generally based upon the presence of symptoms or findings on physical examination. (See 'Imaging of the head and neck' above and "Overview of the diagnosis and staging of head and neck cancer", section on 'Imaging studies'.)
●Annual low-dose helical computed tomography (CT) scanning of the lung is indicated for patients at high risk for the development of a second primary tumor in the lung. This includes those with a squamous cell carcinoma of the head and neck and a history of 20 or more pack years of smoking. (See 'Surveillance for smokers' above and "Screening for lung cancer", section on 'Low-dose chest CT'.)
●For patients whose initial treatment included radiation therapy to the neck, serum thyroid-stimulating hormone (TSH) should be monitored every 6 to 12 months because of the high incidence of hypothyroidism. (See 'Hypothyroidism' above and "Diagnosis of and screening for hypothyroidism in nonpregnant adults" and "Treatment of primary hypothyroidism in adults" and "Management of late complications of head and neck cancer and its treatment", section on 'Thyroid disease'.)
●Dental cleaning and examination must be performed at least twice yearly. Patients should be instructed to perform careful oral hygiene and to take daily fluoride treatments according to the directions of their dentist. (See 'Dental care' above and "Management and prevention of complications during initial treatment of head and neck cancer", section on 'Dental issues'.)
●While promising, the development of serum biomarkers for posttreatment surveillance continues to be an active area of investigation. (See 'Biomarkers' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Ted Leem, MD, MS, who contributed to an earlier version of this topic review.
