0021-972X/90/7102-0414$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1990 by The Endocrine Society
Vol. 71, No. 2 Printed in U.S.A.
Natural History, Treatment, and Course of Papillary Thyroid Carcinoma* LESLIE J. D E G R O O T , EDWIN L. KAPLAN, MAUREEN McCORMICK, AND FRANCIS H. STRAUS Thyroid Study Unit, Department of Medicine, University of Chicago, Chicago, Illinois 60637
ABSTRACT. We have analyzed the course of papillary thyroid
rences, but not increased deaths. Extrathyroidal invasion carried
carcinoma in 269 patients managed at the University of Chicago,
an increased risk of 5.8-fold for death, and distant metastases
with an average follow-up period of 12 yr from the time of diagnosis. Patients were categorized by clinical class; I, with intrathyroidal disease; II, with cervical nodal metastases; III, with extrathyroidal invasion; and IV, with distant metastases. Half of the patients had a history of thyroid enlargement known, on the average, for over 3 yr. In 15% of patients given thyroid hormone, the mass decreased in size. The peak incidence of cancer was when subjects were between 20-40 yr of age. Tumors averaged 2.4 cm in size; 21.6% had tumor capsule invasion, and 46% of patients had multifocal tumors. Sixty-six percent of the patients had near-total or total thyroidectomy. The overall incidence of postoperative hypoparathyroidism was 8.4%, but the incidence was zero in 83 near-total or total thyroidectomies carried out by 1 surgeon. Twenty-five percent of the patients had continuing or recurrent disease, and 8.2% died from cancer. Deaths occurred largely in patients with class III or IV disease. Cervical lymph nodes were associated with increased recur-
increased this risk 47-fold. Age over 45 yr at diagnosis increased the risk of death 32-fold. Tumor size over 3 cm increased the risk of death 5.8-fold. Surgical treatment combining lobectomy plus at least contralateral subtotal thyroidectomy was associated, by Cox proportional hazard analysis, with decreased risk of death in patients with tumors larger than 1 cm and decreased risk of recurrence among all patients, including patients in classes I and II, compared to patients who underwent unilateral thyroid surgery or bilateral subtotal resections. By x2 analysis, 131 I ablation of residual thyroid tissue after operation was associated with decreased risk of recurrence in tumors larger than 1 cm and decreased risk of death in patients in classes I and II with tumors more than 1 cm in size. The data strongly support the use of more extensive initial surgery in class I and II patients with tumors more than 1 cm in size as well as postoperative radioactive 131I ablation of thyroid remnant tissue. (J Clin Endocrinol Metab 7 1 : 414-424, 1990)
T
HE PROPER management of thyroid cancer remains of interest and concern. Treatment of this disease interacts with the management of thyroid nodules, which are common in the general population. Management of thyroid malignancy remains largely in the hands of internists, endocrinologists, and surgeons and has not yet become the province of oncologists. It is a disease with a relatively good prognosis, with a large proportion of patients who are at low risk of death. In this situation it is crucial to balance the possible sideeffects of treatment against possible benefits gained by more conservative or more aggressive treatment. We have analyzed the data obtained from carefully following a group of patients with papillary thyroid cancer over an average of 12 yr. Our analysis specifically addresses the important therapeutic question of the proper extent of
surgery in patients with a good prognosis, those who have intrathyroidal disease, or those who have only neck metastases. Our data indicate that a thyroid lobectomy on the side of the initial lesion combined with a contralateral subtotal and followed by 131I thyroid remnant ablation, offers the best prognosis and can be carried out with a low incidence of complications.
Materials and Methods Patient selection
Received February 5, 1990. Address all correspondence and requests for reprints to: Leslie J. DeGroot, M.D., Thyroid Study Unit, Box 138, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637. * This work was supported by USPHS Grants DK-13377 and DK27384, March of Dimes Grant 1-1166, The Boots Co., the David Wiener Research Fund, and the Nathan and Frances Goldblatt Society for Cancer Research.
The study population consisted of individuals with papillary thyroid carcinoma whose care was supervised by the first author during the interval 1968-1988. The usual plan of management for patients initially treated at this institution was 1) neartotal thyroidectomy, followed by 2) low dose (30 mCi) outpatient radioactive iodide (131I) ablation of residual thyroid tissue 6-12 weeks after operation (1), if focal 131I uptake was detected in the thyroid bed on a 72-h 2 mCi 131I scintiscan, 3) whole body iodide scanning within 1 yr, 4) reablation with 131I if uptake persisted, 5) yearly follow-up, and 6) periodic whole body 131I scans. Patients with unifocal cancers under 1 cm in size and less than 25 yr of age usually were not given 131I unless there was a history of prior x-ray treatment (2). Patients with
414
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 10 May 2015. at 10:56 For personal use only. No other uses without permission. . All rights reserved.
PAPILLARY THYROID CARCINOMA known or presumed invasive disease or known metastatic disease were treated with sequential doses of 131I of 75-200 mCi at intervals of 6-12 months until 131I uptake was absent. Patients with tumors less than 1 cm in size and less than 25 yr of age received partial thyroidectomy in some instances, and reoperation was not performed if such tumors were found incidentally in thyroid specimens removed for other reasons (e.g. thyroid adenoma). If patients were operated on in this institution before 1968 or in other institutions, data are included if these allowed classification of the operative pathology and disease characteristics with certainty. All patients were given replacement therapy with thyroid hormone, usually L-T4, in an amount adequate to suppress TSH to a low or normal level, depending upon the patient's disease status. The study group consisted of 269 patients, 181 females and 88 males, indicating the usual predominance of females over males in thyroid carcinoma. Duration of follow-up was, on the average, 12 yr, but varied from less than 1 to 38 yr. (Some individuals were initially operated on before 1968, some individuals have been lost to follow-up, and some have been operated on recently.) The information on all patients is included in Cox and Kaplan-Meier analyses for the interval during which their condition could be ascertained. At their last follow-up, 223 patients were alive and disease free, 11 alive with evidence of continuing disease, and 35 had died, including 22 who died of thyroid carcinoma. Overall, 8.2% of the patients died of thyroid carcinoma, and 25.3% had some recurrence or continued disease. Patients were classified for extent of disease at diagnosis as follows. Class I includes patients with intrathyroidal disease. Class II includes patients with positive cervical nodes. Class III patients had tumor invasion outside the thyroid or fixed lymph nodes that were believed, on the basis of surgical and pathological examination, to be incompletely resected. Class IV patients had distant metastasis. The extent of disease observed within 6 months of first diagnosis was used in this classification, including data from any reoperation within this period and from 131I whole body scans. Data analysis Data were initially assembled using a microcomputer in DBase files (Ashton-Tate, Culver City, CA), and some analyses were performed in this format. For most analyses, data were transferred to program STATA (Computing Resource Center, Los Angeles, CA). Time-dependent variables were analyzed by the Cox proportional hazard model and the Kaplan-Meier product limit estimates of survival curves. Many variables were also analyzed by the x2 test. The relative risks of two conditions were calculated from the Cox models. Observed differences are assumed statistically significant if the probability of chance occurrence is P < 0.05.
415
before diagnosis. Thirty-nine individuals had a trial of thyroid hormone suppression therapy preoperatively. Fifteen percent of these patients had an apparent decrease in the size of the thyroid mass recorded, while 41% had an increase in size during thyroid hormone suppression; 36.4% of patients had a history of prior radiation exposure to the head or neck, an incidence which may be higher than that in other series, since this group includes individuals who sought our attention because of our known interest in radiation-associated thyroid disease (3). Graves' disease had been previously diagnosed in 4.8% of the patients, and 1.9% had known Hashimoto's thyroiditis. The 4.8% incidence of Graves' disease in this group reflects in part the discovery of unsuspected cases in patients given primary surgical therapy of hyperthyroidism. All patients had a detectable thyroid abnormality on physical examination; 55.7% were felt to have a single nodule on physical examination, and 27% had a cold nodule on scintiscan. Frequency of diagnosis peaked in the third and fourth decades of age. Younger patients predominate in clinical classes I and II. As shown in Fig. 1, a greater relative frequency of class IV tumors occurred in the older age decades. Pathological characteristics of tumor (Table 1) One hundred and twenty-eight patients had class I, 89 class II, 29 class III, and 20 class IV disease. (Three could not be classified from the information available.) The average size of tumor at pathological examination overall was 2.4 cm, and increased from an average size of 1.6 cm in class I patients to 2.9 in class IV patients (Table 1). Invasion of tumor capsule was found microscopically in 21.6% of the patients, and gross invasion of tumor capsule was present in 10.8% (Table 1). The frequency of tumor capsule invasion was greater in class III disease than in other classes (P < 0.005). Multifocality was found class 1
class 2
755025-
Total
0-
7550-
class 3
class 4
75-
25-
o-
50-
i so
eoeJ
25-
Results
00
Historical antecedents to thyroid tumor Fifty-three percent of the patients had a history of thyroid enlargement known, on the average, for 3.1 yr
2040
0
2 0 4 0 6 0 BO
AGE OF DIAGNOSIS FIG. 1. Age decade at diagnosis is shown for patients in each clinical class and for the total group.
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DEGROOT ET AL.
416 TABLE 1. Pathological characteristics of tumor, by class Class No. of patients % of group Average size of tumor (cm) Invasion of tumor capsule None Microscopic Gross Multifocality (%)
128 48.1 1.6
96 28 4 40
89 33.5 2.2
59 21 9 49
Total group IV
III 29 10.9 3.2
20 7.5 2.9
0 6 15 69
266 2.4
171 (63.6)° 58 (21.6)a 29 (10.8)° 46
16 3 1 40
" Percentage is in parentheses. TABLE 2. Primary treatment Total
Class I Total patients 128 % of group 48.1 Surgical thyroidectomy procedure A) Lobectomy (or partial lobectomy) B) Bilateral subtotal C) Lobectomy + contralateral subtotal D) Bilateral, near or total 83 Total procedures classified 127 Modified or radical neck 3 dissection % of group 2.3 Postoperative 131I Ablation 59 % of group
47
II
III
IV
89 29 20 33.5 10.9 7.5
group classified 266
J C E & M • 1990 Vol 71 • No 2
ical neck dissections at the time of thyroidectomy or within 6 months of diagnosis. Most of these were performed in patients with class II or III disease. Fortyseven percent of class II patients had associated neck dissection. Postoperative 131/ thyroid remnant ablation (Table 3) Patients were considered to have received 131I ablation if they were given 28-75 mCi 131I with the intent to ablate residual functioning, presumably normal, thyroid tissue in the thyroid bed, within 12 months of diagnosis of disease. Most patients received 30 mCi 131I, given as an out-patient procedure. Some patients received similar doses more than 1 yr from the time of diagnosis but are excluded from this classification. Individuals with stage III and IV disease, given 131I within 1 yr of diagnosis, with the intention to ablate residual thyroid tissue and/ or treat other disease, are included in the category of patients receiving ablative therapy. Some patients had no 131I uptake on postsurgical scans. In our strict definition, these patients were not considered ablated. Using
32 (11.9%) TABLE 3. Recurrence, continued disease, and death 2 16
18 (7%) 32 (11.8%)
1 1
60 86 42
22 29 13
12 19 4
177 (65.8%) 259 62
47 47
45 23
20 11
23 140
53
79
55
52
in 46% of the patients and did not vary with disease class. Primary therapy The primary therapy was surgical resection, if possible (Table 2). The majority (65.8%) of patients had neartotal or total thyroidectomy; 11.8% had lobectomy plus contralateral subtotal thyroidectomy, and 7% had bilateral subtotal resection. Only 11.9% had lobectomy or more limited procedures, and over half of these patients had class I disease. Bilateral near- or total thyroidectomies predominated in class III and IV patients. Only 9.4% of patients had a unilateral operation for class II, III, or IV disease. In our classification, the combined results of two operations, if performed within 6 months of diagnosis, are grouped together to indicate the extent of surgical thyroidectomy when these procedures constituted the intended initial surgical intervention. Sixty-two patients (23%) had modified radical or rad-
Class
II Type None A) NeckRAIU0 B) Necknode(s) C) Recurrent or continuing neck mass D) Recurrent or continuing distant metastasis Recurrence, C + D Any recurrences, no. (%) Deaths from cancer Deaths from cancer Approximate Survival from cancer at 15 yr (%) Approximate survival from cancer at 30 yr (%) Average age at diagnosis (yr) Average yr follow-up Age at diagnosis, cancer death (yr) Age at death, cancer death (yr) 1
116 2 4 3
68 7 1 4
3
9
4.7 12 (9.3) 1/128 0.8
Total group
III 12 2
IV
2
2 0 1 0
198 11 9 9
10
17
39
3
10.6
41.4 85
17.8
21 (23.6) 3/89 3.37
17 18 (89.5) (90) 4/29 14/20 13.8 70
68 (25.3) 22 8.2
100
100
87
35
90
99
96
86
30
85
36
33
35
47
35.9
10.5 43
13.3 31
15.2 58
10.8 59
63
60
64
66
Radioactive iodine uptake.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 10 May 2015. at 10:56 For personal use only. No other uses without permission. . All rights reserved.
PAPILLARY THYROID CARCINOMA
these criteria, 47-79% of the patients received postoperative radioactive 131I ablation. This included approximately half of the patients with class I and II disease. Complications of therapy The incidence of hypoparathyroidism overall was 16 of 269 patients, or 5.9%. Among the 178 patients who underwent near-total or total thyroidectomy, 3 had vocal cord paralysis, and 15 developed hypoparathyroidism. Ten of these were class I or II patients. This overall 8.4% incidence of hypoparathyroidism after near-total or total thyroidectomy, including a 7.6% incidence in class I and II patients who had this procedure, is clearly unsatisfactory. However, we note that the incidence of postoperative hypoparathyroidism varied dramatically, depending upon the surgeon. In 83 near-total or total thyroidectomies carried out by 1 surgeon, no instances of permanent hypoparathyroidism were recorded. In patients operated on at other institutions, 10 of 75 (13.3%) patients with the same operation developed hypoparathyroidism. Among 40 patients who underwent less extensive procedures (lobectomy or bilateral subtotal thyroidectomy), 1 patient developed hypoparathyroidism, an incidence of 2.5%. Recurrences, continued disease, and deaths from cancer (Table 3) Cancer recurrence was classified as new evidence of disease occurring more than 12 months after diagnosis. Cancer was classified as continuing if the initial problem, such as evidence of residual invasive or metastatic disease, persisted despite therapeutic interventions more than 12 months after initial diagnosis. Cancer deaths are those directly and reasonable ascribed to the malignancy itself. Recurrence of radioactive iodide uptake in the neck or a positive neck node that could be resected has lesser significance than the occurrence of a neck mass or distant metastases. We have, therefore, analyzed most data in relation to 1) any evidence of recurrence and 2) recurrence of neck mass or distant metastases. Eighteen percent of the patients had serious recurrences or continued disease (Table 3) during the follow-up period, and 25.3% of the group had some evidence of recurrence or continued disease. The incidence of recurrences and continued disease was, not suprisingly, much higher in patients with class II, class III, and especially class IV disease. Overall, 8.2% of the patients died from carcinoma, including one patient in class I and three (3.4%) in class II, 13.7% of patients in class III, and 70% with class IV disease. Among all classes of patients, deaths tended to occur in the older age groups, especially in age decades 6 and 7
417
(Fig. 2). The Kaplan-Meier plots of probability of survival from cancer and recurrence-free survival for the entire group of patients are shown in Fig. 3. Cancer survival and recurrence-free survival in relation to disease clinical class are shown in Figs. 4 and 5. Deaths and recurrences are significantly greater among class III and class IV patients (P < 0.001). Survival did not differ between classes I and II. Cancer deaths were more frequent among individuals diagnosed when they were over 40 yr of age (Fig. 6), and recurrences were more common in patients over 60 yr of age (data not shown). Deaths were excessive class
class 1
class 4
class. 3
i zb
Vol. 71, No. 2 Printed in U.S.A.
Natural History, Treatment, and Course of Papillary Thyroid Carcinoma* LESLIE J. D E G R O O T , EDWIN L. KAPLAN, MAUREEN McCORMICK, AND FRANCIS H. STRAUS Thyroid Study Unit, Department of Medicine, University of Chicago, Chicago, Illinois 60637
ABSTRACT. We have analyzed the course of papillary thyroid
rences, but not increased deaths. Extrathyroidal invasion carried
carcinoma in 269 patients managed at the University of Chicago,
an increased risk of 5.8-fold for death, and distant metastases
with an average follow-up period of 12 yr from the time of diagnosis. Patients were categorized by clinical class; I, with intrathyroidal disease; II, with cervical nodal metastases; III, with extrathyroidal invasion; and IV, with distant metastases. Half of the patients had a history of thyroid enlargement known, on the average, for over 3 yr. In 15% of patients given thyroid hormone, the mass decreased in size. The peak incidence of cancer was when subjects were between 20-40 yr of age. Tumors averaged 2.4 cm in size; 21.6% had tumor capsule invasion, and 46% of patients had multifocal tumors. Sixty-six percent of the patients had near-total or total thyroidectomy. The overall incidence of postoperative hypoparathyroidism was 8.4%, but the incidence was zero in 83 near-total or total thyroidectomies carried out by 1 surgeon. Twenty-five percent of the patients had continuing or recurrent disease, and 8.2% died from cancer. Deaths occurred largely in patients with class III or IV disease. Cervical lymph nodes were associated with increased recur-
increased this risk 47-fold. Age over 45 yr at diagnosis increased the risk of death 32-fold. Tumor size over 3 cm increased the risk of death 5.8-fold. Surgical treatment combining lobectomy plus at least contralateral subtotal thyroidectomy was associated, by Cox proportional hazard analysis, with decreased risk of death in patients with tumors larger than 1 cm and decreased risk of recurrence among all patients, including patients in classes I and II, compared to patients who underwent unilateral thyroid surgery or bilateral subtotal resections. By x2 analysis, 131 I ablation of residual thyroid tissue after operation was associated with decreased risk of recurrence in tumors larger than 1 cm and decreased risk of death in patients in classes I and II with tumors more than 1 cm in size. The data strongly support the use of more extensive initial surgery in class I and II patients with tumors more than 1 cm in size as well as postoperative radioactive 131I ablation of thyroid remnant tissue. (J Clin Endocrinol Metab 7 1 : 414-424, 1990)
T
HE PROPER management of thyroid cancer remains of interest and concern. Treatment of this disease interacts with the management of thyroid nodules, which are common in the general population. Management of thyroid malignancy remains largely in the hands of internists, endocrinologists, and surgeons and has not yet become the province of oncologists. It is a disease with a relatively good prognosis, with a large proportion of patients who are at low risk of death. In this situation it is crucial to balance the possible sideeffects of treatment against possible benefits gained by more conservative or more aggressive treatment. We have analyzed the data obtained from carefully following a group of patients with papillary thyroid cancer over an average of 12 yr. Our analysis specifically addresses the important therapeutic question of the proper extent of
surgery in patients with a good prognosis, those who have intrathyroidal disease, or those who have only neck metastases. Our data indicate that a thyroid lobectomy on the side of the initial lesion combined with a contralateral subtotal and followed by 131I thyroid remnant ablation, offers the best prognosis and can be carried out with a low incidence of complications.
Materials and Methods Patient selection
Received February 5, 1990. Address all correspondence and requests for reprints to: Leslie J. DeGroot, M.D., Thyroid Study Unit, Box 138, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637. * This work was supported by USPHS Grants DK-13377 and DK27384, March of Dimes Grant 1-1166, The Boots Co., the David Wiener Research Fund, and the Nathan and Frances Goldblatt Society for Cancer Research.
The study population consisted of individuals with papillary thyroid carcinoma whose care was supervised by the first author during the interval 1968-1988. The usual plan of management for patients initially treated at this institution was 1) neartotal thyroidectomy, followed by 2) low dose (30 mCi) outpatient radioactive iodide (131I) ablation of residual thyroid tissue 6-12 weeks after operation (1), if focal 131I uptake was detected in the thyroid bed on a 72-h 2 mCi 131I scintiscan, 3) whole body iodide scanning within 1 yr, 4) reablation with 131I if uptake persisted, 5) yearly follow-up, and 6) periodic whole body 131I scans. Patients with unifocal cancers under 1 cm in size and less than 25 yr of age usually were not given 131I unless there was a history of prior x-ray treatment (2). Patients with
414
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 10 May 2015. at 10:56 For personal use only. No other uses without permission. . All rights reserved.
PAPILLARY THYROID CARCINOMA known or presumed invasive disease or known metastatic disease were treated with sequential doses of 131I of 75-200 mCi at intervals of 6-12 months until 131I uptake was absent. Patients with tumors less than 1 cm in size and less than 25 yr of age received partial thyroidectomy in some instances, and reoperation was not performed if such tumors were found incidentally in thyroid specimens removed for other reasons (e.g. thyroid adenoma). If patients were operated on in this institution before 1968 or in other institutions, data are included if these allowed classification of the operative pathology and disease characteristics with certainty. All patients were given replacement therapy with thyroid hormone, usually L-T4, in an amount adequate to suppress TSH to a low or normal level, depending upon the patient's disease status. The study group consisted of 269 patients, 181 females and 88 males, indicating the usual predominance of females over males in thyroid carcinoma. Duration of follow-up was, on the average, 12 yr, but varied from less than 1 to 38 yr. (Some individuals were initially operated on before 1968, some individuals have been lost to follow-up, and some have been operated on recently.) The information on all patients is included in Cox and Kaplan-Meier analyses for the interval during which their condition could be ascertained. At their last follow-up, 223 patients were alive and disease free, 11 alive with evidence of continuing disease, and 35 had died, including 22 who died of thyroid carcinoma. Overall, 8.2% of the patients died of thyroid carcinoma, and 25.3% had some recurrence or continued disease. Patients were classified for extent of disease at diagnosis as follows. Class I includes patients with intrathyroidal disease. Class II includes patients with positive cervical nodes. Class III patients had tumor invasion outside the thyroid or fixed lymph nodes that were believed, on the basis of surgical and pathological examination, to be incompletely resected. Class IV patients had distant metastasis. The extent of disease observed within 6 months of first diagnosis was used in this classification, including data from any reoperation within this period and from 131I whole body scans. Data analysis Data were initially assembled using a microcomputer in DBase files (Ashton-Tate, Culver City, CA), and some analyses were performed in this format. For most analyses, data were transferred to program STATA (Computing Resource Center, Los Angeles, CA). Time-dependent variables were analyzed by the Cox proportional hazard model and the Kaplan-Meier product limit estimates of survival curves. Many variables were also analyzed by the x2 test. The relative risks of two conditions were calculated from the Cox models. Observed differences are assumed statistically significant if the probability of chance occurrence is P < 0.05.
415
before diagnosis. Thirty-nine individuals had a trial of thyroid hormone suppression therapy preoperatively. Fifteen percent of these patients had an apparent decrease in the size of the thyroid mass recorded, while 41% had an increase in size during thyroid hormone suppression; 36.4% of patients had a history of prior radiation exposure to the head or neck, an incidence which may be higher than that in other series, since this group includes individuals who sought our attention because of our known interest in radiation-associated thyroid disease (3). Graves' disease had been previously diagnosed in 4.8% of the patients, and 1.9% had known Hashimoto's thyroiditis. The 4.8% incidence of Graves' disease in this group reflects in part the discovery of unsuspected cases in patients given primary surgical therapy of hyperthyroidism. All patients had a detectable thyroid abnormality on physical examination; 55.7% were felt to have a single nodule on physical examination, and 27% had a cold nodule on scintiscan. Frequency of diagnosis peaked in the third and fourth decades of age. Younger patients predominate in clinical classes I and II. As shown in Fig. 1, a greater relative frequency of class IV tumors occurred in the older age decades. Pathological characteristics of tumor (Table 1) One hundred and twenty-eight patients had class I, 89 class II, 29 class III, and 20 class IV disease. (Three could not be classified from the information available.) The average size of tumor at pathological examination overall was 2.4 cm, and increased from an average size of 1.6 cm in class I patients to 2.9 in class IV patients (Table 1). Invasion of tumor capsule was found microscopically in 21.6% of the patients, and gross invasion of tumor capsule was present in 10.8% (Table 1). The frequency of tumor capsule invasion was greater in class III disease than in other classes (P < 0.005). Multifocality was found class 1
class 2
755025-
Total
0-
7550-
class 3
class 4
75-
25-
o-
50-
i so
eoeJ
25-
Results
00
Historical antecedents to thyroid tumor Fifty-three percent of the patients had a history of thyroid enlargement known, on the average, for 3.1 yr
2040
0
2 0 4 0 6 0 BO
AGE OF DIAGNOSIS FIG. 1. Age decade at diagnosis is shown for patients in each clinical class and for the total group.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 10 May 2015. at 10:56 For personal use only. No other uses without permission. . All rights reserved.
DEGROOT ET AL.
416 TABLE 1. Pathological characteristics of tumor, by class Class No. of patients % of group Average size of tumor (cm) Invasion of tumor capsule None Microscopic Gross Multifocality (%)
128 48.1 1.6
96 28 4 40
89 33.5 2.2
59 21 9 49
Total group IV
III 29 10.9 3.2
20 7.5 2.9
0 6 15 69
266 2.4
171 (63.6)° 58 (21.6)a 29 (10.8)° 46
16 3 1 40
" Percentage is in parentheses. TABLE 2. Primary treatment Total
Class I Total patients 128 % of group 48.1 Surgical thyroidectomy procedure A) Lobectomy (or partial lobectomy) B) Bilateral subtotal C) Lobectomy + contralateral subtotal D) Bilateral, near or total 83 Total procedures classified 127 Modified or radical neck 3 dissection % of group 2.3 Postoperative 131I Ablation 59 % of group
47
II
III
IV
89 29 20 33.5 10.9 7.5
group classified 266
J C E & M • 1990 Vol 71 • No 2
ical neck dissections at the time of thyroidectomy or within 6 months of diagnosis. Most of these were performed in patients with class II or III disease. Fortyseven percent of class II patients had associated neck dissection. Postoperative 131/ thyroid remnant ablation (Table 3) Patients were considered to have received 131I ablation if they were given 28-75 mCi 131I with the intent to ablate residual functioning, presumably normal, thyroid tissue in the thyroid bed, within 12 months of diagnosis of disease. Most patients received 30 mCi 131I, given as an out-patient procedure. Some patients received similar doses more than 1 yr from the time of diagnosis but are excluded from this classification. Individuals with stage III and IV disease, given 131I within 1 yr of diagnosis, with the intention to ablate residual thyroid tissue and/ or treat other disease, are included in the category of patients receiving ablative therapy. Some patients had no 131I uptake on postsurgical scans. In our strict definition, these patients were not considered ablated. Using
32 (11.9%) TABLE 3. Recurrence, continued disease, and death 2 16
18 (7%) 32 (11.8%)
1 1
60 86 42
22 29 13
12 19 4
177 (65.8%) 259 62
47 47
45 23
20 11
23 140
53
79
55
52
in 46% of the patients and did not vary with disease class. Primary therapy The primary therapy was surgical resection, if possible (Table 2). The majority (65.8%) of patients had neartotal or total thyroidectomy; 11.8% had lobectomy plus contralateral subtotal thyroidectomy, and 7% had bilateral subtotal resection. Only 11.9% had lobectomy or more limited procedures, and over half of these patients had class I disease. Bilateral near- or total thyroidectomies predominated in class III and IV patients. Only 9.4% of patients had a unilateral operation for class II, III, or IV disease. In our classification, the combined results of two operations, if performed within 6 months of diagnosis, are grouped together to indicate the extent of surgical thyroidectomy when these procedures constituted the intended initial surgical intervention. Sixty-two patients (23%) had modified radical or rad-
Class
II Type None A) NeckRAIU0 B) Necknode(s) C) Recurrent or continuing neck mass D) Recurrent or continuing distant metastasis Recurrence, C + D Any recurrences, no. (%) Deaths from cancer Deaths from cancer Approximate Survival from cancer at 15 yr (%) Approximate survival from cancer at 30 yr (%) Average age at diagnosis (yr) Average yr follow-up Age at diagnosis, cancer death (yr) Age at death, cancer death (yr) 1
116 2 4 3
68 7 1 4
3
9
4.7 12 (9.3) 1/128 0.8
Total group
III 12 2
IV
2
2 0 1 0
198 11 9 9
10
17
39
3
10.6
41.4 85
17.8
21 (23.6) 3/89 3.37
17 18 (89.5) (90) 4/29 14/20 13.8 70
68 (25.3) 22 8.2
100
100
87
35
90
99
96
86
30
85
36
33
35
47
35.9
10.5 43
13.3 31
15.2 58
10.8 59
63
60
64
66
Radioactive iodine uptake.
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PAPILLARY THYROID CARCINOMA
these criteria, 47-79% of the patients received postoperative radioactive 131I ablation. This included approximately half of the patients with class I and II disease. Complications of therapy The incidence of hypoparathyroidism overall was 16 of 269 patients, or 5.9%. Among the 178 patients who underwent near-total or total thyroidectomy, 3 had vocal cord paralysis, and 15 developed hypoparathyroidism. Ten of these were class I or II patients. This overall 8.4% incidence of hypoparathyroidism after near-total or total thyroidectomy, including a 7.6% incidence in class I and II patients who had this procedure, is clearly unsatisfactory. However, we note that the incidence of postoperative hypoparathyroidism varied dramatically, depending upon the surgeon. In 83 near-total or total thyroidectomies carried out by 1 surgeon, no instances of permanent hypoparathyroidism were recorded. In patients operated on at other institutions, 10 of 75 (13.3%) patients with the same operation developed hypoparathyroidism. Among 40 patients who underwent less extensive procedures (lobectomy or bilateral subtotal thyroidectomy), 1 patient developed hypoparathyroidism, an incidence of 2.5%. Recurrences, continued disease, and deaths from cancer (Table 3) Cancer recurrence was classified as new evidence of disease occurring more than 12 months after diagnosis. Cancer was classified as continuing if the initial problem, such as evidence of residual invasive or metastatic disease, persisted despite therapeutic interventions more than 12 months after initial diagnosis. Cancer deaths are those directly and reasonable ascribed to the malignancy itself. Recurrence of radioactive iodide uptake in the neck or a positive neck node that could be resected has lesser significance than the occurrence of a neck mass or distant metastases. We have, therefore, analyzed most data in relation to 1) any evidence of recurrence and 2) recurrence of neck mass or distant metastases. Eighteen percent of the patients had serious recurrences or continued disease (Table 3) during the follow-up period, and 25.3% of the group had some evidence of recurrence or continued disease. The incidence of recurrences and continued disease was, not suprisingly, much higher in patients with class II, class III, and especially class IV disease. Overall, 8.2% of the patients died from carcinoma, including one patient in class I and three (3.4%) in class II, 13.7% of patients in class III, and 70% with class IV disease. Among all classes of patients, deaths tended to occur in the older age groups, especially in age decades 6 and 7
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(Fig. 2). The Kaplan-Meier plots of probability of survival from cancer and recurrence-free survival for the entire group of patients are shown in Fig. 3. Cancer survival and recurrence-free survival in relation to disease clinical class are shown in Figs. 4 and 5. Deaths and recurrences are significantly greater among class III and class IV patients (P < 0.001). Survival did not differ between classes I and II. Cancer deaths were more frequent among individuals diagnosed when they were over 40 yr of age (Fig. 6), and recurrences were more common in patients over 60 yr of age (data not shown). Deaths were excessive class
class 1
class 4
class. 3
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