10.1245/s10434-006-9176-8
Annals of Surgical Oncology 13:1524-1528 (2006)
© 2006 Society of Surgical Oncology
Is Tumor Size the Best Predictor of Outcome for Papillary Thyroid Cancer?
Yusra Cheema, BS1,
Daniel Repplinger, BS1,
Diane Elson, MD2 and
Herbert Chen, MD, FACS1
1 Section of Endocrine Surgery, Department of Surgery, University of Wisconsin, H4/750 CSC 600 Highland Avenue, Madison, WI 53792, USA
2 Division of Endocrinology, Department of Medicine, University of Wisconsin, Madison, WI, USA
Correspondence: Address correspondence and reprint requests to: Herbert Chen, MD, FACS; E-mail: chen{at}surgery.wisc.edu
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ABSTRACT
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Background: There are many risk classification schemes that determine both treatment and outcome for patients with papillary thyroid cancer. Most of these formulas often utilize tumor size as the key predictor of outcome. Furthermore, there is no clear consensus regarding the treatment of small papillary cancers. Therefore, we reviewed our experience in order to determine which factors best predict outcome for papillary thyroid cancer. In addition, we sought to establish a tumor size threshold beyond which papillary cancers require treatment.
Methods: From May 1994 to October 2004, 174 patients underwent surgery for papillary thyroid cancer (PTC) at our institution. These patients were divided into five groups based on tumor size. The data from these groups were analyzed utilizing ANOVA, Chi-square and linear regression analysis.
Results: The mean age of the patients was 42 ± 1 years and 126 (72%) were female. Mean tumor size was 17.2 ± 1.1 mm. The overall outcome was quite good with a survival rate of 97% and a recurrence rate of 12%. On univariate analysis, there was no difference amongst the groups in regards to age or gender. However, there was a significantly higher incidence of lymph node metastasis amongst those with the largest tumors. Consequently, those patients with the largest tumors were treated more aggressively, with 75% undergoing total thyroidectomies and 85% receiving radioactive iodine therapy. However, on univariate and multivariate analysis, tumor size was not shown to correlate with higher recurrence. Rather, the only factor associated with a greater recurrence rate was the presence of lymph node metastases.
Conclusion: At our institution, the recurrence rates for PTC were similar for all sizes of tumors. Furthermore, presence of metastatic disease at the time of diagnosis, rather than tumor size, seems to be a better predictor of recurrence and outcome.
Key Words: Thyroid cancer • Thyroidectomy • Papillary • Well-differentiated
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INTRODUCTION
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In the United States, the most common endocrine malignancy is thyroid cancer.1 Of the 23,000 new cases of thyroid cancer diagnosed in 2004, 80% were classified as papillary thyroid cancer (PTC).2 For patients diagnosed with papillary thyroid cancer, the prognosis is quite good. Currently, the 10-year survival rate for PTC is over 93%.3
A multitude of factors have been used to determine outcome in patients with PTC. Age over 45, positive lymph nodes, and increasing tumor size have all shown to be predictors of poor outcome in patients with papillary thyroid cancer.4 Some authors point to increasing age at the most important indicator of poor prognosis.5 Older patients tend to have tumors with a more aggressive morphology and thus a worse prognosis.6 Others have demonstrated that increased recurrence is closely linked to lymph node metastasis.7 Still others have correlated increasing tumor size with an increased risk of extrathyroidal growth and distant metastasis.8 Therefore, we reviewed our experience in order to determine which factors best predict outcome for PTC.
Generally, tumor size is the factor most often utilized in predicting outcome for PTC patients. Larger tumors are deemed more aggressive and are treated as such. The most aggressive approach—a total thyroidectomy—is reserved for tumors measuring greater than 2 cm, while smaller tumors usually warrant a unilateral procedure. Thus, we also sought to establish a tumor size threshold beyond which papillary cancers require treatment.
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METHODS
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Between May 1994 and October 2004, 184 patients underwent surgery for PTC at the University of Wisconsin. Ten of the 184 patients were excluded as we did not have record of their tumor size. The remaining 174 patients were divided into four groups based on tumor size (see Table 1
). Data was collected from these patients including demographics, pathology results, recurrence rates, disease status, and treatment approach. This data was then analyzed retrospectively. The data collection and analysis were approved by separate protocols through the University of Wisconsin Human Subjects Institutional Review Board.
Data was recorded as mean ± SEM. Kaplan–Meier analysis was used to determine survival. SPSS software (SPSS Inc.) was used to perform statistical analysis. Statistical significance was defined as P < .05.
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RESULTS
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The mean age of patients undergoing surgery for PTC was 42 ± 1 years. There were 126 (72%) females and 48 (28%) males in our study. The mean tumor size was 17.2 ± 1.1 mm.
All 174 patients were then divided into five groups based on tumor size (see Table 1
). On univariate analysis, there was no difference in age or gender amongst any of the groups. The mean ages of patients in the groups were 45 ± 2, 39 ± 2, 42 ± 2, 40 ± 2, and 54 ± 5 years (P = NS). Obviously, there was a difference between the groups in terms of tumor size. The mean tumors sizs in the groups were 2.7 ± 0.2, 8.5 ± 0.3, 17.9 ± 0.8, 34.4 ± 1.8, and 49.4 ± 2.7 mm (P < .001). In addition, patients with the largest tumors had a significantly higher incidence of lymph node metastasis. While patients in Group 1 had only an 8% incidence of lymph node metastasis, patients in Groups 2, 3, 4, and 5 had higher incidence around 20% or higher. More than 1/3 of all patients with a tumor greater than 2 cm in size had lymph node metastases at the time of surgery.
Of the 174 patients with PTC, 127 (73%) underwent total thyroidectomy, while only 27 (16%) had a unilateral lobectomy (Table 2). In group 1 (tumors measuring less than 5 mm), 50% of patients had a total thyroidectomy. In groups 2 and 3, 89% underwent total thyroidectomy, respectively. In group 4, 89% of patients had a total thyroidectomy. In group 5, 93% of patients underwent a total thyroidectomy. This was statistically significant (P = .026). Additionally, 75% of all patients also had radioiodine ablation therapy following surgery. While only 47% of patients in group 1 underwent radioactive iodine treatment, 79% of group 2 patients, 85% of group 3 patients, 89% of group 4 patients, and 90 of group 5 patients had radioactive iodine therapy (P < .001). Patients with larger tumors tended to be treated with radioactive iodine.
There was no significant difference in survival based on tumor size (Fig. 1). Amongst those patients with tumors less than 10 mm, survival was 100%. However, even in the group with the largest tumors, there were only 3 deaths (94% survival). Of the 132 patients without lymph node metastases at the time of surgery, survival was 98% (Fig. 2). Survival amongst those positive for lymph node disease was slightly lower at 93%, but this difference was not statistically significant. When we compared patients who had total thyroidectomy with radioactive iodine to those that did not, there was not significant difference in survival (Fig. 3).
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FIG. 2. Survival in patients with papillary thyroid carcinoma based on presence/absence of lymph node metastasis.
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FIG. 3. Survival in patients with papillary thyroid carcinoma based on whether or not they underwent a total thyroidectomy.
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All four groups of tumor sizes had relatively low rates of recurrence (Fig. 4). For tumors measuring less than 10 mm, the recurrence rate was only 8%. The rate of recurrence for the mid-sized tumors was only slightly higher at 15%. Those with tumors greater than 4 cm had a recurrence rate of 21%. However, there was no statistical difference between the groups.
The presence of lymph node metastases was associated with higher recurrence rates (Fig. 5). Among the 132 patients negative for lymph node metastases, only 7% had a recurrence of disease. For those with lymph node metastases, however, the recurrence rate was almost 4 times as great at 26%. When then compare the recurrence rates in the 132 patients with positive lymph nodes between size categories. In group 1 patients, there were no recurrences. The recurrence rate in group 2, 3, 4, and 5 patients with positive lymph nodes was 25, 44, 14, and 50% (P = NS).
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FIG. 5. Rates of recurrence amongst patients with papillary thyroid carcinoma based on presence/absence of lymph node metastasis.
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We also compared recurrence rates for patients who had total thyroidectomy and radioactive iodine to those that did not. There was no significant difference between the groups (Fig. 6).
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FIG. 6. Rates of recurrence amongst patients with papillary thyroid carcinoma based on whether or not they underwent a total thyroidectomy.
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DISCUSSION
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Adequate treatment of PTC remains a topic of heated debate. Although many agree that surgery is a necessary component of treatment, there is no consensus as to the extent of surgery required. While some favor a conservative unilateral approach, others advocate more aggressive tactics. However, studies now seem to point to a definitive treatment for papillary thyroid cancer—total thyroidectomy followed by radioactive iodine 131I scanning and ablation.9 This combination has been shown to reduce recurrence and cancer-related mortality.10 Moreover, there has been no evidence of increased morbidity or mortality for unilateral versus bilateral procedures when these are performed by an experienced surgeon.9 Thus, it seems the treatment of choice for PTC is total thyroidectomy followed by radioiodine ablation.
Ultimately, treatment decisions are based on risk assessment of the situation—a poor prognosis requires an aggressive treatment approach. Current risk stratification schemes use tumor size, age, and distant metastasis as the main indicators of prognosis.11 Thus, these are the factors most often taken into account when choosing an appropriate treatment approach. Cervical lymph node disease is not as widely used to predict outcome.11 Our experience, however, indicates that lymph node metastasis does indeed predict risk of recurrence and should be used as a reliable prognostic factor. Increasing tumor size, on the other hand, did not correlate with an increased incidence of recurrence.
Other groups have reported the predictive power of cervical node disease. Survival decreases and recurrence increases amongst those patients with lymph node metastases.12 Shah et al.13 reports a 40% increase in the relative risk of death with lymph node metastasis. Lymph node metastasis seems to be an underutilized tool in assessing outcome for patients with papillary thyroid cancer. However, in these studies as well as in our current report, it is often difficult to show which factors actually are related to recurrence when there are so many confounding variables, especially in small, retrospective series.
In conclusion, our experience demonstrates similar recurrence rates for papillary thyroid tumors of all sizes, including those measuring less than 10 mm in size. In addition, it seems that the presence of lymph node metastases at the time of diagnosis is a much better predictor of outcome. Therefore, these data suggest that papillary thyroid tumors should be treated aggressively in order to reduce the incidence of local recurrence, irrespective of tumor size.
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FOOTNOTES
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Presented at the 59th annual meeting of the Society of Surgical Oncology, San Diego, CA, March 24, 2006.
Received for publication July 2, 2006.
Accepted for publication July 3, 2006.
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ABSTRACT
INTRODUCTION
