NEWS & VIEWS SURGERY
Papillary thyroid cancer—how aggressive should surgery be? Sarah E. Tevis and Herbert Chen
Papillary thyroid cancer (PTC) is the most rapidly growing cancer in the USA and in many other countries throughout the world. Historically, the management of PTC has been controversial and treatment recom mendations continue to evolve as new lit erature becomes available. Previous and ongoing studies seek to clarify the appro priate extent of resection for patients with PTC along a spectrum that ranges from observation to total thyroidectomy with prophylactic central compartment lymph node dissection (pCCND). A study in patients with PTC tumours ≥1 cm in diam eter showed that total thyroidectomy was associated with increased survival and lower recurrence rates than lobectomy, which led to the conclusion that more aggressive sur gical management was preferred in these patients.1 Other researchers have argued that patients with PTC are overtreated and observation is probably safe for patients with papillary thyroid microcarcinoma.2 Within the current debate about best management of PTC, the role of pCCND is controversial. A new study by Viola and colleagues addresses this important issue.3 Patients with PTC present with loco regional lymph node metastases in 22–90% of cases. 4 Although dissection of lymph nodes in the central neck compartment is recommended in cases of overt lymph node metastases, the value of pCCND in patients with PTC without lymph node metastases (stage N0) is unresolved. The current American Thyroid Association guidelines recommend pCCND in addition
to total thyroidectomy only in patients with advanced (stages T3 or T4) PTC.5 The effect of pCCND on postoperative complication rates and patient outcomes is unknown and, therefore, routine pCCND in patients with PTC remains controversial. In a landmark study, Viola and colleagues performed the first prospective randomized controlled trial assessing the role of pCCND in patients with PTC without clinical evidence of lymph node metastases.3 The study included 181 patients with PTC enrolled within a 2‑year period at a single institution (University of Pisa) and sought to compare long-term outcomes and postoperative complications between patients who underwent total thyroidectomy and pCCND and those who underwent total thyroidectomy but not pCCND.
‘‘
…the value of pCCND in patients with PTC without lymph node metastases (stage N0) is unresolved
’’
Proponents of pCCND argue that nodal involvement is common in patients with PTC, with micrometastases present in up to 90% of patients.6 The presence of regional lymph node metastases has been associ ated with increased rates of persistence and regional recurrence of disease. Patients with microscopic disease are more likely to require reoperation; however, the effect of lymph node resection on mortality is debated. The study by Viola et al.3 failed to
NATURE REVIEWS | ENDOCRINOLOGY
M
A prospective randomized controlled trial in patients with papillary thyroid cancer without lymph node metastases demonstrated similar oncologic outcomes in patients who underwent total thyroidectomy with prophylactic central compartment lymph node dissection (pCCND) and in those who underwent total thyroidectomy without pCCND. However, pCCND was associated with an increased rate of complications.
Th ink sto ck
Refers to Viola, D. et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J. Clin. Endocrinol. Metab. doi:10.1210/jc.2014‑3825
k ar
k/ oc iSt / r e i oz Str
show a difference in persistence of disease (assessed by structural or biochemical cri teria) postoperatively between patients who underwent total thyroidectomy alone and those who underwent total thyroid ectomy and pCCND (the rates of persistent disease were 8% and 7.5%, respectively, P = 0.9). This result is consistent with pre viously published studies, 7 although the study by Viola et al.3 is the first randomized controlled trial to address this question. Advocates for treating patients with stage N0 PTC with total thyroidectomy alone contend that mortality is rare in this patient population and recurrent disease can be safely treated with reoperation. 8 Additionally, performing a central neck dissection prophylactically is not without risk, especially with regard to parathyroid function.9 The study by Viola et al.3 identi fied a significant difference in the rate of postoperative permanent hypopara thyroidism between study groups. Patients who underwent total thyroidectomy alone were significantly less likely to suffer per manent hypoparathyroidism than patients who underwent total thyroidectomy and pCCND (8.0% versus 19.4%, P = 0.02). The rate of recurrent laryngeal nerve palsy was also lower in patients in the total thyroid ectomy group (4.3%) than in patients in the total thyroidectomy plus pCCND group (8.0%); however, this difference did not reach statistical significance (P = 0.3). ADVANCE ONLINE PUBLICATION | 1
© 2015 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS
‘‘
…patients who underwent pCCND were found to have higher rates of postoperative complications…
’’
The results of the work by Viola and col leagues 3 suggest that patients with PTC and clinically negative nodal disease do not benefit from routine pCCND. Furthermore, pCCND conferred a significantly increased risk of postoperative complications in a group of patients who were all treated by expert surgeons. Patients treated by thyroid surgeons who perform a high volume of procedures have been demonstrated to have lower incidence of postoperative complica tions, including recurrent laryngeal nerve injury and hypocalcaemia, and lower mortality, than patients treated by non expert surgeons.10 As most thyroid surgery in the world is not performed by expert surgeons, the postoperative complication rate after pCCND would probably be even higher if this approach were performed routinely by surgeons who conduct a low volume of thyroid interventions. Strengths of the study by Viola and col leagues3 include the prospective, random ized nature of the study, as well as the long-term follow-up of 5 years after sur gery. The work is, however, limited by a small sample size and because it was per formed at a single institution. Addition ally, the authors were unable to capture
postoperative complications other than impaired parathyroid function and nerve injury. The study compared bilateral central lymph node dissection to no lymph node dissection; therefore, whether unilateral central lymph node dissection would be beneficial and decrease the risk of post operative complications in patients with PTC remains an open question. Ongoing prospective randomized studies will hope fully clarify the role of unilateral pCCND in this patient population. In conclusion, the study by Viola and colleagues demonstrated no difference in clinical oncologic outcomes when pCCND was performed in addition to total thyroid ectomy in patients with PTC without pre operative or intraoperative evidence of lymph node metastases (stage N0 PTC).3 However, patients who underwent pCCND were found to have higher rates of post operative complications than patients who underwent total thyroidectomy alone. These findings suggest that routine pCCND is not beneficial in patients with clinically negative nodal disease, and that perhaps a less aggressive approach should be adopted in the treatment of PTC. Department of Surgery, University of Wisconsin, K3‑705, 600 Highland Avenue, Madison, WI 53792, USA (S.E.T., H.C.). Correspondence to: H.C. [email protected]
Bilimoria, K. Y. et al. Extent of surgery affects survival for papillary thyroid cancer. Ann. Surg. 246, 375–381 (2007). 2. Ito, Y. et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 13, 381–387 (2003). 3. Viola, D. et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J. Clin. Endocrinol. Metab. http://dx.doi.org/10.1210/jc.2014–3825. 4. Mazeh, H. & Chen, H. Advances in surgical therapy for thyroid cancer. Nat. Rev. Endocrinol. 7, 581–588 (2011). 5. Puxeddu, E. & Filetti, S. The 2009 American Thyroid Association Guidelines for management of thyroid nodules and differentiated thyroid cancer: progress on the road from consensusto evidence-based practice. Thyroid 19, 1145–1177 (2009). 6. Mazzaferri, E. L., Doherty, G. M. & Steward, D. L. The pros and cons of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma. Thyroid 19, 683–689 (2009). 7. Zetoune, T. et al. Prophylactic central neck dissection and local recurrence in papillary thyroid cancer: a meta-analysis. Ann. Surg. Oncol. 17, 3287–3293 (2010). 8. Rosenbaum, M. A. & McHenry, C. R. Central neck dissection for papillary thyroid cancer. Arch. Otolaryngol. Head Neck Surg. 135, 1092–1097 (2009). 9. Bozec, A. et al. Clinical impact of cervical lymph node involvement and central neck dissection in patients with papillary thyroid carcinoma: a retrospective analysis of 368 cases. Eur. Arch. Otorhinolaryngol. 268, 1205–1512 (2011). 10. Loyo, M., Tufano, R. P. & Gourin, C. G. National trends in thyroid surgery and the effect of volume on short-term outcomes. Laryngoscope 123, 2056–2063 (2013).
Competing interests The authors declare no competing interests.
Published online 17 February 2015; doi:10.1038/nrendo.2015.13
2 | ADVANCE ONLINE PUBLICATION
1.
www.nature.com/nrendo © 2015 Macmillan Publishers Limited. All rights reserved
Papillary thyroid cancer—how aggressive should surgery be? Sarah E. Tevis and Herbert Chen
Papillary thyroid cancer (PTC) is the most rapidly growing cancer in the USA and in many other countries throughout the world. Historically, the management of PTC has been controversial and treatment recom mendations continue to evolve as new lit erature becomes available. Previous and ongoing studies seek to clarify the appro priate extent of resection for patients with PTC along a spectrum that ranges from observation to total thyroidectomy with prophylactic central compartment lymph node dissection (pCCND). A study in patients with PTC tumours ≥1 cm in diam eter showed that total thyroidectomy was associated with increased survival and lower recurrence rates than lobectomy, which led to the conclusion that more aggressive sur gical management was preferred in these patients.1 Other researchers have argued that patients with PTC are overtreated and observation is probably safe for patients with papillary thyroid microcarcinoma.2 Within the current debate about best management of PTC, the role of pCCND is controversial. A new study by Viola and colleagues addresses this important issue.3 Patients with PTC present with loco regional lymph node metastases in 22–90% of cases. 4 Although dissection of lymph nodes in the central neck compartment is recommended in cases of overt lymph node metastases, the value of pCCND in patients with PTC without lymph node metastases (stage N0) is unresolved. The current American Thyroid Association guidelines recommend pCCND in addition
to total thyroidectomy only in patients with advanced (stages T3 or T4) PTC.5 The effect of pCCND on postoperative complication rates and patient outcomes is unknown and, therefore, routine pCCND in patients with PTC remains controversial. In a landmark study, Viola and colleagues performed the first prospective randomized controlled trial assessing the role of pCCND in patients with PTC without clinical evidence of lymph node metastases.3 The study included 181 patients with PTC enrolled within a 2‑year period at a single institution (University of Pisa) and sought to compare long-term outcomes and postoperative complications between patients who underwent total thyroidectomy and pCCND and those who underwent total thyroidectomy but not pCCND.
‘‘
…the value of pCCND in patients with PTC without lymph node metastases (stage N0) is unresolved
’’
Proponents of pCCND argue that nodal involvement is common in patients with PTC, with micrometastases present in up to 90% of patients.6 The presence of regional lymph node metastases has been associ ated with increased rates of persistence and regional recurrence of disease. Patients with microscopic disease are more likely to require reoperation; however, the effect of lymph node resection on mortality is debated. The study by Viola et al.3 failed to
NATURE REVIEWS | ENDOCRINOLOGY
M
A prospective randomized controlled trial in patients with papillary thyroid cancer without lymph node metastases demonstrated similar oncologic outcomes in patients who underwent total thyroidectomy with prophylactic central compartment lymph node dissection (pCCND) and in those who underwent total thyroidectomy without pCCND. However, pCCND was associated with an increased rate of complications.
Th ink sto ck
Refers to Viola, D. et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J. Clin. Endocrinol. Metab. doi:10.1210/jc.2014‑3825
k ar
k/ oc iSt / r e i oz Str
show a difference in persistence of disease (assessed by structural or biochemical cri teria) postoperatively between patients who underwent total thyroidectomy alone and those who underwent total thyroid ectomy and pCCND (the rates of persistent disease were 8% and 7.5%, respectively, P = 0.9). This result is consistent with pre viously published studies, 7 although the study by Viola et al.3 is the first randomized controlled trial to address this question. Advocates for treating patients with stage N0 PTC with total thyroidectomy alone contend that mortality is rare in this patient population and recurrent disease can be safely treated with reoperation. 8 Additionally, performing a central neck dissection prophylactically is not without risk, especially with regard to parathyroid function.9 The study by Viola et al.3 identi fied a significant difference in the rate of postoperative permanent hypopara thyroidism between study groups. Patients who underwent total thyroidectomy alone were significantly less likely to suffer per manent hypoparathyroidism than patients who underwent total thyroidectomy and pCCND (8.0% versus 19.4%, P = 0.02). The rate of recurrent laryngeal nerve palsy was also lower in patients in the total thyroid ectomy group (4.3%) than in patients in the total thyroidectomy plus pCCND group (8.0%); however, this difference did not reach statistical significance (P = 0.3). ADVANCE ONLINE PUBLICATION | 1
© 2015 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS
‘‘
…patients who underwent pCCND were found to have higher rates of postoperative complications…
’’
The results of the work by Viola and col leagues 3 suggest that patients with PTC and clinically negative nodal disease do not benefit from routine pCCND. Furthermore, pCCND conferred a significantly increased risk of postoperative complications in a group of patients who were all treated by expert surgeons. Patients treated by thyroid surgeons who perform a high volume of procedures have been demonstrated to have lower incidence of postoperative complica tions, including recurrent laryngeal nerve injury and hypocalcaemia, and lower mortality, than patients treated by non expert surgeons.10 As most thyroid surgery in the world is not performed by expert surgeons, the postoperative complication rate after pCCND would probably be even higher if this approach were performed routinely by surgeons who conduct a low volume of thyroid interventions. Strengths of the study by Viola and col leagues3 include the prospective, random ized nature of the study, as well as the long-term follow-up of 5 years after sur gery. The work is, however, limited by a small sample size and because it was per formed at a single institution. Addition ally, the authors were unable to capture
postoperative complications other than impaired parathyroid function and nerve injury. The study compared bilateral central lymph node dissection to no lymph node dissection; therefore, whether unilateral central lymph node dissection would be beneficial and decrease the risk of post operative complications in patients with PTC remains an open question. Ongoing prospective randomized studies will hope fully clarify the role of unilateral pCCND in this patient population. In conclusion, the study by Viola and colleagues demonstrated no difference in clinical oncologic outcomes when pCCND was performed in addition to total thyroid ectomy in patients with PTC without pre operative or intraoperative evidence of lymph node metastases (stage N0 PTC).3 However, patients who underwent pCCND were found to have higher rates of post operative complications than patients who underwent total thyroidectomy alone. These findings suggest that routine pCCND is not beneficial in patients with clinically negative nodal disease, and that perhaps a less aggressive approach should be adopted in the treatment of PTC. Department of Surgery, University of Wisconsin, K3‑705, 600 Highland Avenue, Madison, WI 53792, USA (S.E.T., H.C.). Correspondence to: H.C. [email protected]
Bilimoria, K. Y. et al. Extent of surgery affects survival for papillary thyroid cancer. Ann. Surg. 246, 375–381 (2007). 2. Ito, Y. et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 13, 381–387 (2003). 3. Viola, D. et al. Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J. Clin. Endocrinol. Metab. http://dx.doi.org/10.1210/jc.2014–3825. 4. Mazeh, H. & Chen, H. Advances in surgical therapy for thyroid cancer. Nat. Rev. Endocrinol. 7, 581–588 (2011). 5. Puxeddu, E. & Filetti, S. The 2009 American Thyroid Association Guidelines for management of thyroid nodules and differentiated thyroid cancer: progress on the road from consensusto evidence-based practice. Thyroid 19, 1145–1177 (2009). 6. Mazzaferri, E. L., Doherty, G. M. & Steward, D. L. The pros and cons of prophylactic central compartment lymph node dissection for papillary thyroid carcinoma. Thyroid 19, 683–689 (2009). 7. Zetoune, T. et al. Prophylactic central neck dissection and local recurrence in papillary thyroid cancer: a meta-analysis. Ann. Surg. Oncol. 17, 3287–3293 (2010). 8. Rosenbaum, M. A. & McHenry, C. R. Central neck dissection for papillary thyroid cancer. Arch. Otolaryngol. Head Neck Surg. 135, 1092–1097 (2009). 9. Bozec, A. et al. Clinical impact of cervical lymph node involvement and central neck dissection in patients with papillary thyroid carcinoma: a retrospective analysis of 368 cases. Eur. Arch. Otorhinolaryngol. 268, 1205–1512 (2011). 10. Loyo, M., Tufano, R. P. & Gourin, C. G. National trends in thyroid surgery and the effect of volume on short-term outcomes. Laryngoscope 123, 2056–2063 (2013).
Competing interests The authors declare no competing interests.
Published online 17 February 2015; doi:10.1038/nrendo.2015.13
2 | ADVANCE ONLINE PUBLICATION
1.
www.nature.com/nrendo © 2015 Macmillan Publishers Limited. All rights reserved
