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
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?
Surgeon-performed ultrasound
New plan? Total thyroidectomy Central (bilateral level 6) lymph node dissection Right modified radical neck dissection
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
Thyroid cancer incidence is driven by PTC Davies L, Increasing incidence of thyroid cancer in the United States, 1973-2002, JAMA 2006.
Survival and Recurrence in PTC Bilimoria K, Extent of surgery affects survival for papillary thyroid cancer, Ann Surg 2007
Timing of Recurrences in PTC Mazzaferri E, Current approaches to primary therapy for papillary and follicular thyroid cancer, J Clin Endo Metab 2001
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
Prevalence of lymph node mets in PTC 30% 4% 45% Gimm O, Pattern of lymph node metastases in papillary thyroid carcinoma, Br J Surg 1998
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
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!
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
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-nodemetastasis staging for papillary and follicular thyroid carcinomas: A retrospective analysis of 700 patients, J Clin Endo Metab 1997
Surgeon s role in optimizing PTC care Management over the life span Prevent recurrences: survival impact, cost, risk of reoperation, emotional toll Make a personal investment in long term outcome Partner with the endocrinologist, esp. in high risk patients
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
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
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
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
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
CND: Technique
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
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
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
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?
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!
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
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
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
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
Case: Missing ultrasound 71M with 1.5 cm right thyroid mass FNA: Follicular neoplasm Plan right thyroid lobectomy Pt in OR under anesthetic
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
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