1. Latest Oncologic Strategies for
Well-Differentiated Thyroid
Carcinoma
April 2008
Michael W. Yeh, MD
Program Director, Endocrine Surgery
Assistant Professor of Surgery and Medicine
David Geffen School of Medicine at UCLA
www.endocrinesurgery.ucla.edu

2. Case #1
• 22 yo F biology student
• 2.5 cm right thyroid nodule
• Euthyroid
• FNA: “Sheets of follicular cells forming papillary
structures, abundant nuclear grooves and intranuclear
inclusions”
• Further workup necessary?
• What is the most appropriate operation?

3. Surgeon-performed ultrasound

6. New plan?
• Total thyroidectomy
• Central (bilateral level 6) lymph node dissection
• Right modified radical neck dissection

9. Learning objectives
• Focus on papillary thyroid carcinoma
• Extent of initial surgery for PTC
• Is there a role for initial “prophylactic” lymph node
dissection?
• Importance of ultrasound in initial staging
• Limitations of radioiodine therapy
• Impact of initial surgery on outcome and subsequent
surveillance
• Surgeon’s role in management of PTC recurrences

10. Thyroid cancer incidence is driven by PTC
Davies L, Increasing incidence of thyroid cancer in the United States, 1973-2002, JAMA
2006.

11. Survival and Recurrence in PTC
Bilimoria K, Extent of surgery affects survival for papillary thyroid cancer, Ann Surg 2007

12. Timing of Recurrences in PTC
Mazzaferri E, Current approaches to primary therapy for papillary and follicular thyroid
cancer, J Clin Endo Metab 2001

13. Prevalence of lymph node mets in PTC
Ito Y, Clinical significance of lymph node metastasis of thyroid papillary carcinoma located in
one lobe, World J Surg, 2006

14. Prevalence of lymph node mets in PTC
30%
Gimm O, Pattern
of lymph node
metastases in
papillary thyroid
carcinoma, Br J
4% 45% Surg 1998

15. • Up to 39% of re-operations for
thyroid cancer are a direct result
of incomplete initial surgery
Kouvaraki, Preventable reoperations for
persistent and recurrent papillary thyroid
carcinoma, Surgery 2004

16. What we know thus far
• PTC is increasingly common
• Survival remains excellent
• PTC <1 cm is not associated with cause-specific death
• Recurrences are common (30%)
• Most recurrences occur within 10 yrs of initial dx
• These are generally locoregional lymph node mets
• “Recurrences” may actually represent persistent disease
• Microscopic lymph node metastases of PTC are the rule
• Only a small fraction (1/4-1/3) of these go on to become
clinically significant
• Most micrometastases remain quiescent!

17. What is the impact of PTC nodal mets?
• Conventional wisdom: No clinical impact (survival)
• Swedish study examining 5123 cases of DTC
Cady B, Papillary carcinoma of the thyroid gland: Treatment based on risk group definition;
Surg Oncol Clin N Am, 1998
Lundgren C, Clinically significant prognostic factors in differentiated thyroid carcinoma, Cancer
2005

18. What is the impact of PTC nodal mets?
“We found a 4-fold risk of recurrence and a 2.5-fold risk of
cancer-specific death in patients with regional lymph node
metastases.”
Loh K,
Pathological
tumor-node-
metastasis
staging for
papillary and
follicular thyroid
carcinomas: A
retrospective
analysis of 700
patients, J Clin
Endo Metab
1997

19. Surgeon’s role in optimizing PTC care
• Management over the life span
• Prevent recurrences: survival impact, cost, risk of re-
operation, emotional toll
• Make a personal investment in long term outcome
• Partner with the endocrinologist, esp. in high risk patients

20. Surgeon’s role in optimizing PTC care
• For PTC >1 cm
• Total thyroidectomy: multifocality, give RAI, follow Tg
• Clear all palpable adenopathy at initial surgery
• Clear all sonographically detectable adenopathy at initial
surgery
• Surgeon’s responsibility to obtain high-quality pre-op US
node survey for all FNA+ PTC and have a working
knowledge of the “lay of the land”
• “Prophylactic” initial lymph node dissection??
• Concept of compartment-oriented lymph node dissection

22. 2006 ATA guidelines
R27. Routine central-compartment (level VI) neck
dissection should be considered for patients with
papillary thyroid carcinoma and suspected Hürthle
carcinoma. Near-total or total thyroidectomy without
central node dissection may be appropriate for follicular
cancer, and when followed by radioactive iodine
therapy, may provide an alternative approach for
papillary and Hürthle cell cancers—Recommendation B
The American Thyroid Association Guidelines Taskforce, Management guidelines for patients
with thyroid nodules and differentiated thyroid cancer, Thyroid 2006

23. Support for initial CND in PTC
• Goteborg study: 195 PTC patients studied prospectively
• Mean f/u 13 yrs
• Routine, meticulous bilateral central neck clearance
• RAI used sparingly
• Much lower CSM compared to controls
Tissell L, Improved survival of patients with papillary thyroid cancer after surgical
microdissection, World J Surg 1996
REVIEWED IN: White M, Central lymph node dissection in differentiated thyroid cancer, World
J Surg 2007

24. • Hannnover study: 342 pts, mean f/u 11.8 yrs
• Central compartment microdissection reduces CSM and
recurrence
Scheumann G, Prognostic significance and surgical management of locoregional lymph node
metastases in papillary thyroid cancer, World J Surg 1994

25. • Sydney study: 447 pts with PTC >1 cm and clinically
negative nodes
• 56 underwent ipsilateral CND (2002 and beyond)
• Mean post-op, post-RAI serum Tg lower in CND group
• Post-op, post-RAI serum Tg more likely to be
undetectable in CND group
Sywak M, Routine ipsilateral level 6 lymphadenectomy reduces postoperative thyroglobulin
levels in papillary thyroid cancer, Surgery 2006

26. CND: Technique

29. CND: Technique and complications
• Territory bounded by hyoid and thoracic inlet, both jugular
veins
• Majority of yield is in triangular space bounded by midline,
RLN, innominate vessels
• Routine auto-transplantation of inferior parathyroid
• Ipsilateral CND is generally sufficient – no additional
benefit to bilateral in terms of post-op Tg
• Permanent hypoparathyroidism 1.4-14.3% (3.1%)
• Permanent RLN paresis 0-4.2% (0.5%)
• Temporary RLN dysfunction may be higher
• No difference in long-term complication rate when
performed by expert/high-volume surgeons

30. Radio-iodine: Myth and reality
• Conventional wisdom: “Mops up” residual disease after
surgery
• Truth: Ineffective in treatment of macroscopic (incl.
sonographically detectable) remnants and nodal disease
• Post-op RAI is given only for ablation of residual normal
thyroid tissue (set Tg to zero)
• Even this is likely unnecessary after true TTx
• RAI is no substitute for excellent surgery
Hay I, Managing patients with papillary thyroid carcinoma: Insights gained from the Mayo
Clinic’s experience of treated 2,512 consecutive patients during 1940 through 2000, Trans Am
Clin Climatol Assoc, 2002

31. Radioiodine and lymph node mets of PTC
• Primary tumors have reduced ability to take up RAI
compared to normal thyroid
• 25% of WDTC are initially resistant to RAI
• Many nodal mets of PTC do not express NIS
• RAI has no effect on nodal mets >1 cm in diameter
• Likely has no effect on nodal mets of any size
Clark O, Textbook of endocrine surgery, Elsevier Saunders 2005

32. Case: Radioiodine misuse
• 22F Dx 2.0 cm right PTC
• Total thyroidectomy in 2004
• Post-op RAI 50 mCi
• 2005 surveillance scan shows uptake in low central neck
• Treatment dose given, 150 mCi RAI
• 2006 surveillance scan shows uptake in low central neck
• Treatment dose given, 200 mCi RAI
• Tg 10.3 ng/mL after thyroxine withdrawal
• Next step?

34. Case: Radioiodine misuse
• FNA right level 3 lymph node + metastatic PTC
• Undergoes right modified radical neck dissection (levels
2, 3, 4) and right central neck dissection (level 6)
• Path: Right levels 2, 3, 4 – 1/11 lymph nodes positive
Right level 6 – 1/1 lymph node positive
• No further RAI treatment
• Post-op US negative
• Post-op Tg undetectable
• No effect of cumulative dose 400 mCi RAI on two
subcentimeter lymph nodes!

35. Surgery vs Radioiodine
• Most PTC patients are low risk (MACIS score <6)
• For patients undergoing complete initial surgical
clearance, RAI confers no additional benefit
• For patients who do not have complete initial surgical
clearance, no amount of post-op RAI will improve the
situation – these patients need further surgery
• RAI benefits a small subset of high-risk PTC patients
• Works reasonably well for pulmonary metastases
• No impact on lymph node disease

36. Hay I, Managing patients with papillary thyroid carcinoma: Insights gained from the Mayo
Clinic’s experience of treated 2,512 consecutive patients during 1940 through 2000, Trans Am
Clin Climatol Assoc, 2002

37. Case: Piecework
• 34F Dx 2.5 cm right PTC in 1998
• Op #1: Open bx right neck lymph node
• Op #2: Total thyroidectomy, lymph node sampling (+)
• Op #3: Take back for bleeding. Disease recurs.
• Permanent hypoparathyroidism
• Op #4: Right neck dissection. Disease recurs.
• Op #5: Re-do right neck dissection. Disease recurs.
• 2001-2006: Tg elevated (144.6 ng/mL stimulated),
multiple CTs, PET scans, MRIs all inconclusive
• Tg was never satisfactorily low
• May 2006 pt seeks care at UCLA

40. Case: Piecework
• Op #6: Re-do right level 2 clearance
• Op #7: Re-do right level 6 clearance
• Path: 3 of 9 nodes positive in level 2, and 3 of 4 nodes
positive in level 6
• Post-op Tg 2.0 ng/mL
• 7 operations over 10 years
• Countless labs, scans, procedures
• Acute on chronic disability
• Cost RE lost productivity, health care $$?
• QOL?
• Importance of compartment-oriented surgery

41. Case: Missing ultrasound
• 71M with 1.5 cm right thyroid mass
• FNA: Follicular neoplasm
• Plan right thyroid lobectomy
• Pt in OR under anesthetic

48. Ultrasound
• Essential for all surgeons interested in treating thyroid
cancer
• Competent ≠ FLUENT
• Certification courses available through ACS: basic, head
& neck, instructors course
• Make it a part of your daily practice: clinic & OR
• Many available platforms: Sonosite, GE, Terason
• Probes: 9-14 MHz linear array

49. Summary points
• Ultrasound is essential: EVERY cancer case
• Clear the neck of disease
• Do it right the first time around
• When you enter a nodal compartment, commit to clearing
it completely
• No role for “node picking”
• Consider routine initial “prophylactic” ipsilateral central
(level 6) lymph node dissection for FNA positive PTC >1
cm in diameter
• Have appropriately low expectations for what RAI can do
• Be vigilant for recurrences: surveillance US and Tg