Surveillance and Long-Term Monitoring

SURVEILLANCE AND LONG-TERM MONITORING

Despite our best initial therapeutic efforts, the majority of patients with ATC will have disease progression within a few months' time. When calculated using a weighted average approach to the data provided in Table 7, 65.8% of patients develop distant metastases at some point during follow-up (33.5% of patients having distant metastases identifiable at diagnosis and 32.3% developing newly identified distant metastases usually within the first 6–12 months of follow-up; see Table 7) (15,58,59,113,156,161,162,167,168,176,231–233). Distant metastases are most frequently detected in the lungs (80%–85%), followed by the bones (5%–10%), and the brain (5%–10%) (15,58,59,101,167,233).

TABLE 7. PERCENT OF ANAPLASTIC PATIENTS WITH DISTANT METASTASES

Reference N Metastatic disease identified at diagnosis (%) New metastatic disease identified during follow-up (%) Metastatic disease at any time (%)
McIver et al., 2001 (58) 134 46 22 68
Wang et al., 2006 (168) 47 17 34 51
Swaak-Kragten et al., 2009 (156) 75 40 35 75
Rodriguez et al., 2000 (231) 14 21 27 48
Lam et al., 2000 (59) 38 47
Schlumberger et al., 1991 (162) 20 45 20 65
Kim and Leeper, 1987 (232) 19 32 47 79
Levendag et al., 1993 (167) 51 43 32 75
Busnardo et al., 2000 (176) 29 76 21 97
De Crevoisier et al., 2004 (161) 30 20 43 63
Venkatesh et al., 1990 (15) 121 11 42 53
Hadar et al., 1993 (233) 55 42
Demeter et al., 1991 (113) 7 57

 

Respiratory insufficiency (pulmonary metastases, pneumonia, or pulmonary fibrosis) was the most common, identifiable cause of death in patients with fatal ATC (234). At the time of death from ATC, 34% had locoregional disease without distant metastases, while 24% had distant metastases alone, and 40% had both locoregional and distant disease (234).

Furthermore, failure of locoregional control is seen in 17%–41% of patients by 3 months, 35%–83% by 6 months, and 92% by 8 months of follow-up (58,167,168,235). Even in patients that have gross resection of the anaplastic primary, 38% of the R0 resections and 36% of the R1 resections have local disease progression at a median of 2.5 months follow-up (58). In this series, external beam irradiation was associated with a slight, but not statistically significant delay in time to locoregional failure from 3 to 5 months (p=0.08) (58).

These data indicate that cross-sectional imaging at frequent, early intervals is required to determine the response to additional therapy and to identify new sites of disease that may necessitate a change in the management plan. The frequency and intensity of follow-up studies is guided by both the stage at diagnosis and an assessment of individual response to initial therapy.

Surveillance after clinical remission

After initial staging and completion of initial therapy, if the patient has no clinical evidence of disease, cross-sectional imaging of the brain, neck, chest, abdomen, and pelvis should be considered every 1–3 months for the first 6–12 months, then every 4–6 months for 1 additional year in patients desiring ongoing aggressive management. Additional imaging studies should be ordered based on specific symptoms that develop during follow-up. Alternatively, patients can be followed without extensive cross-sectional imaging if the patient is not interested in aggressive therapy for asymptomatic recurrent disease. If there is no evidence of recurrence on cross-sectional imaging during the first 2 years of follow-up, cross-sectional imaging can then be done less frequently, at 6- to 12-month intervals for an additional 2–3 years. For patients with persistent structural disease (either locoregional disease or distant metastases), cross-sectional imaging of brain, neck, chest, abdomen, pelvis, and known sites of disease should be obtained as clinically indicated (usually every 2–3 months) to judge response to systemic and/or local therapy.

In addition to its role in initial staging, 18FDG PET scanning is also a valuable tool in the follow-up of patients with ATC. 18FDG PET/CT scanning has a higher sensitivity for detection of metastatic lesions than CT alone (99.6% vs. 62% in identifying 265 individual lesions in 18 patients, p<0.002) (98). It is important that the CT be done with the PET scan because very small volume pulmonary metastases can be seen with the CT that are below the limit of resolution of the PET scan (98). Furthermore, 18FDG PET scan findings alter management recommendations in 25%–50% of patients (95,98). When used in the follow-up of previously treated patients, the PET/CT findings were discordant from the CT findings in 45% of the cases (5/11). In each discordant case, the 18FDG PET findings were more informative than response to therapy as determined by change in size described by the CT scan (98).

Therefore, 18FDG PET scanning should be considered approximately 3–6 months after initial therapy in patients with no clinical evidence of disease to rule out small foci of disease that would lead to additional therapy recommendations. 18FDG PET scanning may also be of value in the follow-up of patients with known persistent structural disease as a guide to response to systemic or local therapies and to identify new sites of disease that may require a modification of the treatment plan.

While serum Tg and RAI scanning and therapy can be valuable tools in the management of well-differentiated thyroid cancer, the failure of ATCs to either produce Tg or concentrate RAI makes these tools of little help in the follow-up of patients with ATC. Therefore, serum Tg and RAI scanning are not routinely used in the management of ATC. However, consideration for RAI ablation/therapy is warranted in long-term ATC survivors if a significant component of the tumor was well differentiated since they may well have residual well-differentiated thyroid cancer metastases that could be RAI avid. Bone scintigraphy has been used in some patients in an effort to identify skeletal metastases. However, the sensitivity and specificity for detecting metastatic ATC is not well understood. 18FDG PET scanning identified the sites of disease in three ATC patients with bone metastases, while bone scintigraphy was abnormal in only one of the three patients (98). Therefore, it seems unlikely that bone scintigraphy will significantly improve staging done using 18FDG PET scanning. However, the role of bone scintigraphy and skeletal surveys as a staging or response to therapy evaluation in the absence of 18FDG PET scanning remains to be defined.

  • RECOMMENDATION 60 Following initial staging and therapy, patients without evidence for persistent structural disease desiring ongoing aggressive management should have cross-sectional imaging of the brain, neck (and/or ultrasound), chest, abdomen, and pelvis at 1- to 3-month intervals for 6–12 months, then at 4- to 6-month intervals for a minimum of one additional year.
       Strength of Recommendation: Strong
       Quality of Evidence: Low

  • RECOMMENDATION 61 18FDG PET scanning should be considered about 3–6 months after initial therapy in patients with no clinical evidence of disease to identify small volume disease that may require a change in the management plan. Furthermore, 18FDG PET scanning should also be considered at 3- to 6-month intervals in patients with persistent structural disease as a guide to the response to therapy and to identify new sites of disease that may necessitate a change in the management plan.
       Strength of Recommendation: Strong
       Quality of Evidence: Low

  • RECOMMENDATION 62 Neither serum Tg measurements nor RAI scanning or therapy are recommended in the initial management of ATC unless the anaplastic component represents a minor component of a more well-differentiated thyroid cancer.
       Strength of Recommendation: Strong
       Quality of Evidence: Low

  • RECOMMENDATION 63 After a 6- to 12-month follow-up period, patients without evidence of recurrent/progressive ATC should be considered for RAI therapy if the original tumor had well-differentiated thyroid cancer components.
       Strength of Recommendation: Strong
       Quality of Evidence: Low

Restaging of patients with persistent metastatic disease

Restaging of individual patients with persistent advanced ATC should be tailored to the pace of disease progression, the involved sites of known disease and, most especially, emerging patient symptoms. Also of critical consideration in surveillance is the particular patient's chosen approach to advanced disease. Those patients desiring continued antitumor therapy need assessments frequently enough to evaluate their response. Patients not receiving antitumor therapy may select symptom-directed rather than routine cross-sectional imaging.

  • RECOMMENDATION 64 Patients with persistent structural disease following initial staging and therapy should have frequent cross-sectional imaging (at least every 1–3 months), which may include brain, neck, chest, abdomen, pelvis, and known sites of disease as clinically indicated to guide systemic and/or local therapy.
       Strength of Recommendation: Strong
       Quality of Evidence: Low

  • RECOMMENDATION 65 Patients with persistent structural disease following initial staging and therapy who wish to minimize additional therapy may undergo symptom-directed cross-sectional imaging.
       Strength of Recommendation: Strong
       Quality of Evidence: Low