Open Access

Adjuvant Radioactive iodine 131 ablation in papillary microcarcinoma of thyroid: Saudi Arabian experience

  • Khalid Hussain AL-Qahtani1,
  • Mushabbab Al Asiri2,
  • Mutahir A. Tunio2Email author,
  • Naji J. Aljohani3,
  • Yasser Bayoumi4,
  • Hanadi Fatani5 and
  • Abdulrehman AlHadab6
Journal of Otolaryngology - Head & Neck Surgery201544:51

DOI: 10.1186/s40463-015-0108-0

Received: 1 July 2015

Accepted: 23 November 2015

Published: 1 December 2015

The Erratum to this article has been published in Journal of Otolaryngology - Head & Neck Surgery 2016 45:6

Abstract

Background

Papillary Microcarcinoma (PMC) of thyroid is a rare type of differentiated thyroid cancer (DTC), which according to the World Health Organization measures 1.0 cm or less. The gold standard of treatment of PMC is still controversy. Our aim was to contribute in resolving the debate on the therapeutic choices of the surgical and adjuvant I-131 (RAI) treatment in PMC.

Methods

From 2000 to 2012, 326 patients were found to have PMC and were retrospectively reviewed for clinicopathological characteristics, treatment outcomes and prognostic factors.

Results

Mean age of cohort was 42.6 years (range: 18–76) and the mean tumor size was 0.61 cm ± 0.24; lymph node involvement was seen in 12.9 % of cases. Median follow up period was 8.05 years (1.62–11.4). Total 23 all site recurrences (7.13 %) were observed; more observed in patients without I-131 ablation (p <0.0001). Ten year DFS rates were 89.6 %. Cox regression Model analysis revealed size, histopathologic variants, multifocality, extrathyroidal extension, lymphovascular space invasion, nodal status, and adjuvant RAI ablation the important prognostic factors affecting DFS.

Discussion

Despite excellent DFS rates, a small proportion of patients with PMC develop recurrences after treatment. Adjuvant RAI therapy improves DFS in PMC patients with aggressive histopathologic variants, multifocality, ETE, LVSI, tumor size (> 0.5 cm) and lymph node involvement. Failure of RAI ablation to decrease risk in N1a/b supports prophylactic central neck dissection during thyroidectomy, however more trials are warranted.

Conclusion

Adjuvant I-131 ablation following thyroidectomy in PMC patients, particularly with poor prognostic factors improves DFS rates.

Keywords

Papillary microcarcinoma Optimal treatment Adjuvant radioiodine ablation Disease free survival Saudi Population

Background

In Saudi Arabia, the incidence of differentiated thyroid cancers (DTC) especially papillary thyroid cancers (PTC) is increasing exponentially over the past years accounting for more than 10 % of all cancers among females [1, 2]. Higher rates for identification of PTC in recent years are attributed to the use of high resolution neck ultrasonography (USG) and USG-guided fine needle aspiration biopsy (FNAB) [3]. With the use of these high resolution transducers, papillary microcarcinoma (PMC), i.e. tumor size 1 cm or less can easily be detected [4, 5]. Patients with PMC have generally an excellent outlook with use of surgery, radioactive iodine-131 (RAI) ablation, suppression of thyroid-stimulating hormone (TSH) secretion with levothyroxine, with long term disease-free survival (DFS) of 84–97 % [6]. However, still there is much debate regarding the most appropriate treatment of PMC ranging from observation alone to over-treatment with surgery followed by adjuvant RAI ablation [710].

In the present study, we aimed to evaluate the different prognostic factors for DFS in PMC patients in our population, and also to determine the DFS in patients with PMC treated with or without adjuvant RAI ablation following thyroidectomy.

Methods

After formal approval from the institutional ethical committee, medical records of 1192 patients with confirmed papillary thyroid cancers (PTC) who were treated or followed up in two major referral hospitals of Riyadh, Saudi Arabia, during the period of July 2000 and December 2012 were reviewed using computer based departmental database system. Patients with PMC were retrieved in following manner;

Definition

PMC was defined according WHO classification system for thyroid tumors as “PTC is measuring ≤ 1 cm in greatest dimension” [5].

Demographic, clinicopathological and radiological variables

Demographic and clinical data including age at the diagnosis, gender, and symptomatology were reviewed. A detailed second review of all histopathological specimens was performed by experienced histopathologist. Different histopathological parameters, including the location of tumor, tumor size, histopathologic variants, multifocality, extrathyroidal extension (ETE), lymphovascular space invasion (LVSI), surgical margin status, and cervical lymph node status and background thyroid tissue were also recorded. Data from different imaging modalities, including neck ultrasonography, whole body I-131 scintigraphy (WBS), computed tomography (CT) scan of neck and chest, flourodeoxyglucose positron emission tomography (FDG-PET) was collected. Periodic postoperative thyroid function tests (TFTs), thyroid antibodies and stimulated thyroglobulin (TG) levels (off thyroxin or thyrotropin-Alfa injection) were also reviewed. Different treatment modalities, including hemi-thyroidectomy (removal of lobe and isthmus), total thyroidectomy (removal of entire gland), neck dissection, adjuvant RAI ablation, different doses used in millicurie (mCi) and the details of neck irradiation details (if given) were also reviewed.

The primary endpoint was the disease free survival (DFS). Secondary points were; the frequency of PMC and histologic variants, local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and overall survival (OS) according to (a) treatment with or without adjuvant I-131 ablation and (b) according to primary tumor size (≤0.5 cm vs. > 0.5 cm).

Local recurrence was defined as, clinically or radiologically detectable recurrences in the thyroid bed or in cervical lymph nodes on imaging (ultrasonography, WBS and CT-PET) after evaluating for elevated thyroglobulin (TG) levels. Distant metastasis was defined as, clinically or radiologically detectable disease outside the neck on imaging (WBS, CT imaging and CT-PET) after evaluating for elevated thyroglobulin (TG) levels. The DFS was defined as, the duration between the surgery date and the date of documented disease reappearance/relapse, death from cancer and/or last follow-up (censored). The OS was defined as, the duration between the surgery date and the date of patient death or last follow-up (censored).

Statistical analysis

Chi-square test, Student’s t test, or Fisher exact tests were used to determine the differences in various clinical variables. Multivariate logistic regression was done using Cox proportional hazards modeling. Probabilities of LRFS, DMFS, DFS and OS were shown with the Kaplan-Meier method and the comparisons for various survival curves were performed using log rank. All statistical analyses were performed using the computer program SPSS version 16.0.

Results

Demographic and clinicopathological features of cohort

Among the 1192 PTC patients in our departmental database, 377 (31.6 %) patients were found to have PMC. Fifty one (13.3 %) patients with insufficient data regarding size, treatment and follow-up period were excluded. The remaining study cohort (n = 326) consisted of 271 (83.1 %) women and 55 (16.9 %) men; the median age at diagnosis was 42.6 years ±11.6. The majority of patients had total thyroidectomy (n = 299, 91.7 %); only 27 (8.3 %) patients underwent lobectomy. The mean tumor size was 0.61 cm ± 0.24, with 12.9 % (n = 42) involvement of cervical lymph nodes (level VI in 34 patients). The predominant histopathologic variants were, classic (265 patients), follicular (41 patients), and tall cell (11 patients). Other clinicopathological features are described in Table 1.
Table 1

Patients characteristics

Variable

Whole cohort N (%)

RAI ablation N (%)

Without RAI ablation N (%)

P value*

 Total patients

326/1192 (27.4 %)

182/326 (55.8)

144/326 (44.2)

0.06

Age (years)

42.6 (18–76) SD ±11.6

43.2 (18–76) SD ± 12.4

41.8 (19–71) SD ± 10.2

 

  ≤45 years

201 (61.7)

110 (60.4)

94 (65.3)

0.81

  ≥45 years

125 (38.3)

72 (39.6)

50 (34.7)

 

Gender

  Female

271 (83.1)

146 (80.2)

125 (86.8)

0.06

  Male

55 (16.9)

36 (19.8)

19 (13.2)

 

 Female to male ratio

4.9

4.0

6.5

 

Type of surgery

 Total thyroidectomy

299 (91.7)

182 (100)

117 (81.3)

0.04

 Hemi-thyroidectomy

27 (8.3)

-

27 (18.7)

 

Lymph node surgery

 Central neck dissection

88 (27.0)

54 (29.7)

34 (23.6)

 

 Lateral neck dissection

18 (5.5)

9 (4.9)

9 (6.3)

0.9

 Sampling

55 (16.9)

25 (13.7)

30 (20.8)

 

 None

165 (50.6)

94 (51.7)

71 (49.3)

 

Mean size (cm)

0.61 (0.1–1.0) ± 0.24

0.72 (0.2–1.0) ± 0.21

0.44 (0.1–0.9) ± 0.2

 

  ≤0.5 cm

161 (49.4)

50 (27.5)

111 (77.1)

<0.0001

  ≥0.5 cm

165 (50.6)

132 (72.5)

33 (22.9)

 

Histopathologic variants

  Classic

265 (81.3)

143 (78.6)

122 (84.7)

 

  Follicular

41 (12.6)

21 (11.5)

20 (13.9)

 

  Hurthle cell

8 (2.5)

6 (3.3)

2 (1.4)

 

  Tall cell

11 (3.4)

11 (6.0)

-

0.001

  Sclerosing

1 (0.3)

1 (0.5)

-

 

Multifocal

  Yes

125 (38.3)

122 (67.1)

3 (2.1)

<0.0001

  No

201 (61.7)

60 (32.9)

141 (97.9)

 

ETE

  Yes

62 (19.0)

57 (31.3)

5 (3.5)

<0.0001

  No

264 (81.0)

125 (68.7)

139 (96.5)

 

LVSI

  Yes

55 (16.9)

49 (26.9)

6 (4.2)

<0.0001

  No

271 (83.1)

133 (73.1)

138 (95.8)

 

Surgical margins

  Positive

35 (10.7)

30 (16.5)

5 (3.5)

<0.0001

  Negative

291 (89.3)

152 (83.5)

139 (96.5)

 

Lymph node metastasis

  Yes

42 (12.9)

42 (23.1)

-

<0.0001

  N1a

34 (73.8)

34 (73.8)

  

  N1b

8 (19.2)

8 (19.2)

  

  No

284 (87.1)

140 (76.9)

144 (100)

 

Background thyroid tissue

 Normal

98 (30.1)

47 (25.8)

51 (35.4)

 

 Multi-nodular goiter

106 (32.5)

60 (32.9)

46 (31.9)

 

 Lymphocytic thyroiditis/Hashimotos’ thyroiditis

122 (37.5)

75 (41.3)

47 (32.6)

0.052

Distant Metastasis at presentation

3 (0.9)

3 (1.65)

-

<0.0001

AJCC staging

  I

217 (66.5)

73 (40.1)

139 (96.5)

 

  II

-

-

-

 

  III

96 (29.5)

96 (52.6)

5 (3.5)

<0.0001

  IVA

10 (3.1)

10 (5.6)

-

 

  IVB

-

-

-

 

  IVC

3 (0.9)

3 (1.7)

-

 

Mean postoperative TG (ng/ml)

1.39 (0.1–42890)

2.44 (0.1–42890)

0.39 (0.1–8.9)

0.62

RAI dose

  30 mCi

 

50 (27.5)

-

<0.0001

  100 mCi

 

85 (46.7)

-

 

  150-200 mCi

 

47 (25.8)

-

 

RT to Neck

2 (0.61)

2 (1.1)

-

<0.0001

Recurrences

    

 Locoregional

13 (3.9)

4 (2.2)

9 (6.2)

<0.001

 Distant

10 (3.1)

4 (2.2)

6 (4.2)

 

*P value pertaining to the variation in clinicopathological characteristics between two groups

RAI radioactive iodine 131, N number, SD standard deviation, ETE extra-thyroidal extension, LVSI lymphovascular space invasion, AJCC American joint committee on cancer, TG thyroglobulin, mCi millicurie, RT radiation therapy

Clinicopathological features and DFS Comparison in PMC patients treated with and without I-131 ablation

Among 326 patients, 182 (55.8 %) patients were given adjuvant RAI ablation as shown in Table 1. Major indications for adjuvant RAI ablation were multifocality (67.1 %), extra-thyroidal extension (ETE) in 31.3 % of cases, aggressive histopathologic variants (tall cell, sclerosing), lymph node metastasis (23.1 %) and distant metastasis at time of presentation (1.65 %). Primary tumor size was not a primary indication in our series; however the observed mean tumor size was bigger in patients treated with adjuvant RAI ablation (0.72 cm vs. 0.44 cm). RAI ablation doses were as; 30 m-curie (mCi) for tumors with multifocality and focal ETE (27.5 %); 100 mCi for tumors with multifocality, ETE, LVSI, positive surgical margins, poor histopathologic variants, and elevated postoperative stimulated TG levels (>2 ng/ml) (46.7 %); 150 mCi for positive lymph nodes (24.7 %), and 200 mCi for distant metastasis at the time of diagnosis (1.65 %). RAI ablation was tolerated well without any grade 3 or 4 side effects. Additional neck irradiation was given in two patients with adherent tumors; trachea (one patient; 0.5 %) and skeletal muscle (one patient; 0.5 %).

A median follow-up period was 8.05 years (range: 1.62–11.4). For whole cohort, the 5 and 10 years LRFS were 98.4 % and 96.8 % respectively; DMFS rates were 92.4 % at 5 years and 90 % at 10 years. Five and 10 years OS rates were 99.3 % and 98.6 % (two deaths) and the 5 and 10 years DFS rates were 94.7 % and 89.6 %.

Total 23 recurrences (7.13 %) were observed; 8/182 in patients with RAI ablation and 15/144 in patients without RAI ablation. The pattern of recurrences was as: three patients had disease in thyroid bed only, 10 had cervical nodes, and 10 failed at distant sites (9 patients in lungs and one patient in bones). Combined locoregional and distant recurrences were seen in 3 patients. The elevated TG levels were always seen with local recurrences and distant metastasis. The isolated locoregional recurrences were salvaged by surgery (lateral neck dissection; 7 patients, completion thyroidectomy; 2 patients and excision in one patient), followed by RAI ablation (12 patients) and distant failures were salvaged by RAI ablation (9 patients) and palliative irradiation for bony lesion (one patient). Time to initial local recurrence was 0.8 years and time to initial distant metastasis was 1.5 year. The 5 and 10 year DFS rates were 95.7 % vs. 90.9 % and 92.2 % vs. 84 % in patients with and without RAI ablation respectively (p = 0.04) Fig. 1a. The 5 and 10 year DFS rates according to different prognostic factors are summarized in Table 2. The overall 5 and 10 year DFS rates were significantly dropped in the presence of poor histopathologic variants (p < 0.001) and ETE. In addition to these factors, multifocality (p < 0.001) LVSI (p = 0.001) and elevated postoperative thyroglobulin levels > 2 ng/ml (p = 0.04) resulted in inferior 5 and 10 year DFS in patients treated without RAI ablation.
Fig. 1

Kaplan-Meier curves of disease free survival (a) according to treated with or without radioactive iodine 131 ablation, (b) primary size (≤0.5 cm vs. > 0.5 cm) treated with or without radioactive iodine 131 ablation, (c) lymph node status and (d) dose regimens (30 mCi vs. 100 mCi)

Table 2

Disease free survival according to different prognostic factors

Variable

RAI ablation

Without RAI ablation

 

5 years-DFS

p

10 years-DFS

p

5 years-DFS

p

10 years-DFS

p

Age

 ≤45 years

97.8 %

 

93.5 %

 

87.6 %

 

83.6 %

 

 ≥45 years

92.5 %

NS

85.3 %

NS

88.5 %

NS

84.5 %

NS

Gender

 Female

95.4 %

 

91.2 %

 

93.8 %

 

82.2 %

 

 Male

96.8 %

NS

89.4 %

NS

90.4 %

NS

82.0 %

NS

Histopathologic variants

 Classic

96.1 %

 

93.5 %

 

95.5 %

 

92.3 %

 

 Follicular

94.7 %

 

90.9 %

 

78.9 %

 

59.6 %

 

 Hurthle cell

96.1 %

 

92.7 %

 

90.0 %

0.001

78.9 %

<0.001

 Tall cell

68.2 %

 

-

  

-

  

 Sclerosing

55.0 %

0.002

-

<0.001

 

-

  

Multifocal

        

 Yes

95.2 %

 

90.9 %

 

66.7 %

 

33.3 %

 

 No

96.6 %

NS

93.4 %

NS

90.0 %

<0.001

88.3 %

<0.0001

Surgical margins

 Positive

96.6 %

 

91.5 %

 

86.3 %

 

84.0 %

 

 Negative

96.8 %

NS

95.3 %

NS

93.2 %

NS

87.9 %

NS

ETE

 Yes

89.5 %

 

85.5 %

 

40.0 %

 

0.0 %

 

 No

98.2 %

0.03

95.1 %

0.02

91.7 %

<0.0001

80.1 %

<0.0001

LVSI

 Yes

89.5 %

 

85.5 %

 

80.0 %

 

60.0 %

 

 No

92.5 %

NS

89.4 %

NS

93.2 %

0.02

84.4 %

0.001

Mean postoperative TG

 ≤2 ng/ml

96.6 %

 

93.4 %

 

93.2 %

 

91.7 %

 

 >2 ng/ml

89.5 %

NS

85.5 %

NS

87.9 %

NS

80.1 %

0.04

Surgery

 Total thyroidectomy

96.0 %

 

94.4 %

 

93.2 %

 

87.5 %

 

 Hemi-thyroidectomy

91.5 %

0.03

86.0 %

0.03

85.1 %

0.04

80.2 %

0.02

RAI radioactive iodine 131, yr year, DFS disease free survival, SD standard deviation, ETE extra-thyroidal extension, LVSI lymphovascular space invasion, TG thyroglobulin

Clinicopathological features and DFS comparison among PMC of size ≤ 0.5 cm and > 0.5 cm

With regard to the difference in DFS (locoregional and distant failure), a comparative analysis was performed according to primary tumor size (≤0.5 cm vs. > 0.5 cm) as described in the Table 3. About 161 (49.4 %) patients had tumors of size ≤ 0.5 cm and 165 (50.6 %) patients had tumors of size above 0.5 cm in greatest dimension. Significant demographic and clinicopathological differences were observed between two groups. Patients with tumor size ≤ 0.5 cm were younger (mean age 36.7 years), with higher female to male ratio (6.3), and with more aggressive histopathologic variants (tall cell, sclerosing). The cervical lymph node metastases were seen in 9.3 % of patients with tumor size ≤ 0.5 cm as compared to patients with tumor size > 0.5 cm (16.4 %) with p < 0.001. Patients with tumor size ≤ 0.5 cm had high rates of hemi-thyroidectomy (18.7 %), less adjuvant RAI ablation (31.1 %) with low recurrence rates. There was also no significant difference in 5 and 10 year DFS rates in in patients with tumor size ≤ 0.5 cm treated with or without adjuvant RAI ablation (p = 0.71) Fig. 1b. Further it was seen that adjuvant RAI ablation did better in N0 as compared to N1 neck status Fig. 1c. Also in patients treated with adjuvant RAI ablation, no significant difference was observed between two dose regimens (30 mCi vs. 100 mCi) with p = 0.62 (Fig. 1d).
Table 3

Comparative analysis of clinicopathological characteristics based on the size of primary tumors

Variable

Tumor size ≤ 0.5 cm N (%)

Tumor size > 0.5 cm N (%)

P value

 Total patients

161/326 (49.4)

165/326 (50.6)

-

Age (years)

36.7 (8–71)

47.8 (8–76)

 

 ≤45 years

107 (66.5)

94 (56.9)

0.034

 ≥45 years

54 (33.5)

71 (43.1)

 

Gender

 Female

139 (86.4)

132 (80.0)

0.08

 Male

22 (13.6)

33 (20.0)

 

Mean size (cm)

0.38 (0.1–0.5)

0.68 (0.6–1.0)

<0.001

Histopathologic variants

 Classic

126 (78.2)

139 (84.3)

 

 Follicular

26 (16.2)

14 (8.5)

 

 Hurthle cell

4 (2.5)

4 (2.4)

0.023

 Tall cell

4 (2.5)

7 (4.3)

 

 Sclerosing

1 (0.6)

-

 

Multifocal

 Yes

36 (22.4)

89 (53.9)

 

 No

125 (77.6)

76 (46.1)

<0.001

ETE

 Yes

16 (9.9)

46 (27.9)

<0.001

 No

145 (90.1)

119 (72.1)

 

LVSI

 Yes

14 (8.7)

41 (24.9)

<0.001

 No

147 (91.3)

124 (75.1)

 

Surgical margins

 Positive

5 (3.1)

30 (18.2)

 

 Negative

156 (96.9)

135 (81.8)

<0.001

Background thyroid tissue

 Normal

60 (37.3)

38 (23.0)

 

 Multi-nodular goiter

48 (29.8)

58 (35.2)

 

 Lymphocytic thyroiditis/Hashimotos’ thyroiditis

53 (32.9)

69 (41.8)

0.05

Lymph node metastasis

 Yes

15 (9.3)

27 (16.4)

 

 No

146 (90.7)

138 (83.6)

<0.001

RAI ablation

 Yes

50 (31.1)

132 (67.3)

<0.001

 No

111 (68.9)

22 (13.3)

 

Recurrences

 Locoregional

4 (2.5)

9 (5.5)

 

 Thyroid bed

1/4

2/9

 

 Lymph nodes

3/4

7/9

<0.001

 Distant

2 (1.3)

8 (4.9)

 

 Lungs

2

7/8

 

 Bone

-

1/8

 

I-131 radioactive iodine 131, N number, ETE extra-thyroidal extension, LVSI lymphovascular space invasion, RAI radioactive iodine

Prognostic factors

Cox regression Model using univariate and multivariate analysis for DFS to predict important prognostic factors Table 4. Important prognostic factors were, histopathologic variants (p < 0.0001), multifocality (p < 0.0001), ETE (p < 0.0001), LVSI (p =0.03), nodal status (p < 0.0001), and adjuvant RAI ablation (p < 0.0001).
Table 4

Cox regression model of various prognostic factors for disease specific survival

Variable

All patients

Univariate analysis

Multivariate analysis

RR (95 % CI)

p

RR (95 % CI)

p

Age

 ≤45 years

1.05 (0.7–1.3)

 

1.07 (0.8–1.3)

 

 ≥45 years

1.10 (0.8–1.4)

0.6

1.10 (0.9–1.3)

0.06

Gender

 Female

1.07 (0.9–1.4)

 

1.05 (0.7–1.3)

 

 Male

1.05 (0.7–1.3)

0.6

1.40 (1.2–1.6)

0.05

Histopathologic variants

 Classic

1.05 (0.7–1.2)

 

1.20 (0.8–1.6)

 

 Follicular

1.00 (0.6–1.8)

 

1.18 (0.7–1.5)

 

 Hurthle cell

1.30 (1.1–1.7)

 

2.00 (1.6–2.4)

 

 Tall cell

2.70 (1.6–4.5)

 

2.82 (2.4–4.6)

 

 Sclerosing

1.80 (1.6–2.9)

<0.0001

2.00 (1.6–3.0)

<0.0001

Multifocal

 Yes

3.1 (2.8–4.2)

 

2.94 (2.2–3.4)

 

 No

1.0 (0.8–1.2)

<0.0001

1.07 (0.9–1.3)

<0.0001

Surgical margins

 Positive

1.10 (0.9–1.4)

 

1.20 (0.8–1.6)

 

 Negative

1.07 (0.9–1.4)

0.7

1.17 (0.6–1.2)

0.68

ETE

 Yes

4.2 (3.5–5.1)

 

3.31 (1.7–4.2)

 

 No

1.05 (0.7–1.1)

<0.0001

1.17 (0.9–1.4)

<0.0001

LVSI

 Yes

2.0 (1.7–2.9)

 

1.81 (1.6–2.8)

 

 No

1.0 (0.8–1.2)

0.02

1.04 (0.9–1.5)

0.03

Lymph nodes

 Positive

4.45 (3.7–6.8)

 

3.74 (3.4–5.9)

 

 Negative

1.17 (0.9–1.4)

<0.0001

1.01 (0.8–1.3)

<0.0001

Mean postoperative TG

 ≤2 ng/ml

1.01 (0.7–1.2)

 

1.05 (0.7–1.2)

 

 >2 ng/ml

1.04 (0.9–1.5)

0.6

1.00 (0.6–1.8)

0.6

RAI ablation

 Yes

0.35 (0.2–0.7)

 

0.30 (0.2–0.8)

 

 No

1.09 (1.0–1.9)

<0.0001

1.00 (0.6–1.8)

<0.0001

I-131 radioactive iodine 131, RR relative risk, CI confidence interval, ETE extra-thyroidal extension, LVSI lymphovascular space invasion, TG thyroglobulin, RAI radioactive iodine

Discussion

Despite excellent DFS rates in patients with PMC, about 3–16 % of patients develop local and distant failures [11]. In present study, we were able to determine overall five and ten year DFS rates of 94.7 % and 89.6 % respectively after aggressive treatment by total thyroidectomy followed by RAI ablation in the majority of cases. These results were found in consistent with similar reported data [1215]. Several clinicopathological and treatments related prognostic factors were observed. An important prognostic factor, the age > 45 years was not found a prognosticator to predict DFS in our study, suggesting that other risk factors, such as aggressive histopathologic variants, multifocality, ETE, and LVSI are more important clinicopathological predictors than age in PMC [16]. Similarly, in contrast to other reported data, gender was also not found an important predictor of DFS [17]. Improved DFS was observed in patients who underwent total thyroidectomy. Possible explanation for this could be (a) high percentage of multifocality, and (b) more aggressive histopathological variants (tall cell and diffuse sclerosing variants) in our series, which is in agreement with few previously published studies of PMC [1820].

Recent studies regarding PMC have reported that patients with multinodular goiter (MNG) and with lymphocytic or Hashimotos’ thyroiditis are associated with better prognosis; however, we could not reproduce the same results. Reason could be (a) few cases of histopathological proven MNG (32.5 %); (b) lack of preoperative TFTs in MNG patients; and (c) few number of patients with lymphocytic/Hashimoto’s thyroiditis (37.5 %) [21].

Further, present study showed the lymph node involvement and tumor size as the most significant independent risk factors for recurrence. Although we found tumor size > 0.5 cm seem to be associated with high recurrence rates, we were not able to identify a size threshold below which there was no lymph node involvement and no risk of recurrence; as in tumor of size ≤ 0.5 cm, 9.3 % lymph node metastasis were seen along with 2.5 % local and 1.3 % distant failures. This supports the hypothesis, that lymph node involvement status is higher in PMC of size > 0.8 cm, but is independent of tumor size [22]. Patients tolerated adjuvant RAI ablation very well with minimal toxicity. Failure of RAI ablation to decrease local or distant failure risk in N1a/b as compared to N0 disease is an indicator of underlying tumor burden in neck and this supports the idea of prophylactic central neck dissection during thyroidectomy [23]. However, still there is much debate over the prophylactic central neck dissection because of potential increased risk of hypoparathyroidism associated with central neck dissection [24].

Strengths of our study were; (a) reasonable sample size of Saudi patients with PMC, and (b) long term follow up period. Limitations of our study were; (a) retrospective data; (b) no intention to treat based analysis, and (c) lack of availability of preoperative clinical data, diagnostic methods (FNAC and radiology), tumor characteristics and baseline TFTs.

Conclusions

In conclusion, among all PTC, 31.6 % of patients are diagnosed as PMC. Despite excellent DFS rates, a small proportion of patients with PMC develop recurrences after treatment. These recurrences not only badly affect physical health, but also mental and social health and overall quality of life. Based on our results we conclude that;
  • High percentage of multifocality in our population of PMC favors near total or total thyroidectomy against lobectomy, which can be an option for unifocal PMC.

  • Age > 45 years and gender were not found strong prognostic factors of DFS.

  • Adjuvant RAI therapy improves DFS in PMC patients with aggressive histopathologic variants, multifocality, ETE, LVSI, tumor size (>0.5 cm in absence of other features) and lymph node involvement (≥150 mCi). In absence of N0 neck, there is significant difference of DFS in two doses (30 mCi vs. 100 mCi).

  • Failure of RAI ablation to decrease risk in N1a/b supports prophylactic central neck dissection during thyroidectomy, however more trials are warranted.

Abbreviations

DTC: 

Differentiated thyroid cancer

DFS: 

Disease free survival

DMC: 

Distant metastasis control

ETE: 

Extrathyroid extension

PMC: 

Papillary microcarcinoma

PTC: 

Papillary thyroid cancer

FTC: 

Follicular thyroid cancer

LVSI: 

Lymphovascular invasion

LR: 

Locoregional recurrence

LRC: 

Locoregional control

mCi: 

Millicurie

OS: 

Overall survival

RAI: 

Radioactive iodine-131

TG: 

Thyroglobulin

WBS: 

Whole body scintigraphy

Declarations

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Otolaryngology-Head & Neck Surgery, College of Medicine, King Saud University
(2)
Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City
(3)
Endocrinology and thyroid Oncology, King Fahad Medical City
(4)
Radiation Oncology, NCI, Cairo University
(5)
Histopathology, King Fahad Medical City
(6)
Radiation Oncology, King AbdulAziz University

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Copyright

© AL-Qahtani et al. 2016

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