43 Posttreatment Surveillance
Posttreatment surveillance schedules in oral cavity cancer are multifaceted and incorporate patient demographics, stage, treatment, treatment-related sequelae, and quality of life in their construction. These schedules should be agreed upon by both patient and physician and should incorporate both clinical examination and functional outcomes. In addition to clinical examination, posttreatment locoregional imaging is essential in establishing a baseline for monitoring for recurrence, especially in advanced disease. Imaging is also important in monitoring for distant metastases. Finally, patients undergoing all forms of radiotherapy should have biannual dental evaluations and annual thyroid function testing. Each evaluation should be complete and comprehensive.
43.1 Epidemiology: Incidence, Causes, and Clinical Characteristics
Oral cavity cancer (OCC) represents a heterogenous group of malignancies with variable etiologies, histologies, and natural histories. Consistent with the Institute of Medicine definition of survivorship, the latter begins at diagnosis and continues until one expires. 1 Therefore, treatment hopefully represents the initial phase of the survivorship period and the immediate posttreatment recovery period to assess nutritional and rehabilitative goals. The remainder of survivorship entails posttreatment surveillance (PTS).
Rationale for PTS involves the identification of pathologic as well as toxicity-related issues that may arise in the survivorship period. Disease recurrence rates for OCC range from 10 to 48%. 2 – 4 Local and regional recurrences account for 90% of all treatment failures. 5 , 6 In patients with OCC that recur, 86% of all recurrences will appear within 2 years and the median time to recurrence is 7.5 to 15 months after treatment end. 4 , 7 – 10 Not unexpectedly, overall survival rates at 2 years and at 5 years in patients with recurring OCC are significantly lower than those who remain without evidence of malignancy (67.6 vs. 88.0%, 31.8 vs. 79.9%, p < 0.001). 4 Detection of recurrence is critical as early detection of locoregional recurrence can result in curative salvage and improvements in current techniques, and new therapies, such as immunotherapy, may extend survival and improve quality of life (QoL) measures for patients with distant disease. 11 – 13
Risk of recurrence is associated with a host of factors including social and demographic characteristics, and tumor histopathology. Male gender, advancing age, and non-white race have each been found to have an association with increased risk of recurrence, but the poor prognostic role is weak relative to histopathologic features of tumor or lymph node. 14 These factors include tumor differentiation, perineural invasion, lymphatic invasion, bone invasion, tumor subsite, invasion depth, and proximity of margins. 15 The presence of multiple risk factors contributes additively to increase the risk of recurrence. 15 Lymph node metastasis, extracapsular extension of disease, and positive surgical margins are the greatest risk factors for recurrence. 9 , 16 , 17
PTS is also useful to assess for second primaries. Rates of new tumors in OCC patients vary from 10 to 20% in the lungs and esophagus. 18 , 19 One study examining 72 patients with OCC over a 10-year period showed a 27.8% rate of second primaries independent of the initial tumor at a median of 32 months. 20 Seventy-five percent of second primaries discovered were in the oral cavity and 80% developed within 5 years. 20 These results mirror a larger study of 1,609 head and neck cancer (HNC) patients of which 1,153 had OCC. 21 In this subgroup, there was a second primary rate of 20%. In both studies, patients with second primaries had significantly worse survival than patients without second primaries.
Continued use of tobacco is recognized as a risk factor for recurrence. Approximately 20 to 30% of HNC patients continue to smoke after treatment. 22 Indeed, in a study that evaluated tobacco use across HNC sites, only 35.8% of OCC survivors stopped smoking, the lowest rate of all HNC sites. 23 Risk of recurrence in this population is unclear. A matched pair study of 66 never smokers, ever smokers, and current smokers showed that recurrence-free survival (p = 0.006) and disease-specific survival (p = 0.027) were significantly worse for ever smokers as compared with never smokers. 24 However, there was no difference between ever smokers, the ones who had quit at least 1 year before presentation, and current smokers. 24 Regardless, smoking increases the risk of second primaries in other organs and increases risks for other long-term health complications and therefore cessation remains advisable.
Continued alcohol use may also pose a higher risk of recurrence for OCC patients. In a study of 264 HNC patients with median follow-up of 51 months after treatment, patients who continued drinking (average of 2.3 drinks per day) had significantly increased risk of recurrence (relative risk (RR) = 2.7, 95% CI: 1.2-6.1). 25 Indeed, the patient group that drank most after diagnosis or patients who consumed more than five alcoholic drinks per day had an increased risk of mortality (RR = 4.9, 95% CI: 1.5-16.3). 25 Continued consumption of alcohol after diagnosis of HNC impacts the survival. Increased awareness of this coupled with encouragement of abstention should be incorporated into survivorship care.
Finally, sequelae of treatments and disease, both physical and mental, should be monitored. Late toxicity of OCC treatment may include osteoradionecrosis (ORN) of the mandible, pain, numbness, mucositis, dysphagia, dysgeusia, xerostomia, trismus, infection, fistula, gastric tube dependence, or even death. 26 Rates of complications are broad ranging depending on the condition of interest. For example, chronic periodontitis is observed in approximately 70% of patients post radiation therapy while ORN, a relatively rare complication, occurs in up to 5% of patients. 26 – 28 These sequelae can cause significant morbidity and decrease in QoL; this highlights the importance of prevention, when possible, and recognition of early clinical signs that must be prevented, if possible, or recognized early.
43.2 Clinical Presentation
Recurrent OCC can be much more difficult to detect. While in the primary setting symptoms and anatomy may be more clinically apparent, after-treatment symptoms may be attributed to the preceding therapy and possible distorted anatomy thus making detection more challenging. 29 In a study of 101 HNC patients with 30 recurrences, pain (Odds ratio (OR) = 16.07, 95% CI: 5.94-43.51, p < .001), odynophagia (OR = 11.20, 95% CI: 3.13-40.04, p < .001), and dysphonia (OR = 5.90, 95% CI: 1.77-17.28, p = .003) were all found to be associated with recurrence whereas dysphagia, xerostomia, and dyspnea were not. 29 Of note, 27% of patients with recurrence in this study were asymptomatic. 29 There was another study with 278 OCC patients, of which 54 had recurrent disease (21 local, 22 regional, 6 locoregional, and 6 distant) with the most common presentation of a lump (n = 35, 64%). 29 The remainder had an ulcer (n = 7, 13%) or were completely asymptomatic (n = 6, 11%). 30 These studies emphasize that recurrent symptoms may not be as recognizable to the patient as compared to primary tumors.
43.3 Diagnosis and Evaluation
Several guideline recommendations are available for OCC (▶ Table 43.1). These guidelines provide recommendations for clinical follow-up and some, but not all, provide additional recommendations for imaging, smoking cessation, swallowing rehabilitation, and for other treatment and tumor sequelae. 31 Surveillance guidelines address several issues including duration, frequency and intensity of follow-up visits, the role of imaging, symptom versus protocol-driven follow-up routine, and how to assess QoL.
43.3.1 Surveillance Schedule
In the literature, there is significant variation regarding recommendations for PTS schedule for both clinical and radiologic evaluations for OCC. The initial question of management is whether follow-up should be symptom driven or schedule driven. Some contend that regular follow-up is laborious and costly while others argue that a decrease in follow-up leads to delays in detection of recurrence. 10 , 34 – 37 In addition, patients have low compliance with follow-up appointments, with one study indicating 11% of patients followed up consistently during the first 3 years of PTS. 38 Nevertheless, a survey of 400 members of the American Head and Neck Society showed that the vast majority of surgeons recommended routine, long-term follow-up. 39 When examining surveillance for OCC, the optimal intensity, duration, and methods of surveillance should be considered.
Given that the median time to recurrence is between 7.5 and 15 months after initial treatment, 4 , 8 , 10 and events of recurrence decline after 2 years (▶ Table 43.2), 2 , 10 , 36 , 37 , 40 , 41 surveillance intensity in the National Comprehensive Cancer Network (NCCN) guidelines is highest in the initial years after treatment and tapers off after the first 2 to 3 years. In a representative study, approximately half of recurrences were detected during regularly scheduled visits (every 2-3 months for the first 2 years then every 4 months for the third year) and the other half had their recurrences detected through symptom-directed visits. 2 Presumably, earlier detection by regularly scheduled visits appears to be associated with a survival advantage. For example, among 428 patients with HNC, 154 recurrences were identified and median survival after diagnosis of recurrence for patients undergoing routine PTS was 58 months compared to 32 months for symptom-driven self-referral. 37 This suggests that increased surveillance identified asymptomatic tumors at an earlier time than symptom-driven, thus leading to improved survival.
While many guidelines recommend life-long surveillance, albeit at lower intensity than the first 2 years, the available data question its utility, especially for early-stage disease. For early-stage OCC, the risk of recurrence appears to be drastically reduced after 4 years. In a study of 102 patients with early-stage OCC with 10-year regular follow-up, no recurrences were detected after year 4. 10 However, in the same study, nine of the second primaries occurred after year 4, six of which were identified in routine follow-up. 9 While detection of recurrences drops off after 3 years, many a times second primaries are also detected in the follow-up period. 39 , 41 Therefore, routine surveillance for recurrence is necessary 3 years after completion of therapy, and thereafter long-term surveillance may be useful to monitor for second primaries in a high-risk population.
In keeping with the available literature, NCCN guidelines are broad and recommend 4 to 12 visits the first year, 2 to 6 visits the second year, and 3 to 9 visits in the following 3 years. 31 In addition, they recommend annual follow-up after 5 years. The important caveat is that patients are encouraged to schedule an appointment earlier than follow-up if they develop symptoms. In addition, visits with the multidisciplinary team are encouraged. 31
43.3.2 Clinical Surveillance
Physical examination remains the cornerstone of surveillance for OCC. 42 – 44 For local recurrence, physical examination is reliable. 45 In addition, skilled mirror examination or flexible fiberoptic endoscopy, should be utilized for a comprehensive head and neck evaluation. 46 Narrow-band imaging has also been reported as a potential aid in detection of OCC. 47 A standardized checklist during surveillance, which includes measuring functional outcomes such as weight, pain, swallowing, and voice has been proposed to ensure a comprehensive evaluation. 48 We recommend a comprehensive head and neck examination at each clinical visit with attention to the site of the primary malignancy as well as other mucosal sites at risk for second primary.