Well Differendated Thyroid Microcarcinoma

Well Differen*ated Thyroid Microcarcinoma Robert A. Levine, MD, FACE, ECNU Thyroid Center of New Hampshire Geisel School of Medicine at Dartmouth Objec*ves (1) •  Review epidemiology of thyroid microcarcinoma. •  Consider the changes in thyroid cancer detec*on and management over the past decade. •  Review recent changes to thyroid nodule and thyroid cancer guidelines, par*cularly regarding micronodules and microcarcinoma. •  Compare and contrast thyroid microcarcinoma and low risk thyroid cancer. •  Review prognosis of treated thyroid microcarcinoma and low risk thyroid cancer. Objec*ves (2) •  Review exis*ng (Japanese) studies concerning observa*on of thyroid microcarcinoma without surgery. •  Consider whether exis*ng studies regarding observa*on can be applied to prac*ce in the United States. •  Provide recommenda*ons regarding observa*on of sub-­‐cen*meter nodules and cancer. Davies L, Welch HG 2014 JAMA otolaryngology-­‐-­‐ head & neck surgery: Current thyroid cancer trends in the United States. Rising incidence and stable mortality Davies L, Welch HG 2014 JAMA otolaryngology-­‐-­‐ head & neck surgery: Current thyroid cancer trends in the United States. 39% < 1cm Davies L, Welch HG 2014 JAMA otolaryngology-­‐-­‐ head & neck surgery: Current thyroid cancer trends in the United States. Ahn HS, Kim HJ, Welch HG. 2014 NEJM 371(19): Korea’s Thyroid-­‐Cancer “Epidemic” – Screening and Overdiagnosis. Ahn HS, Kim HJ, Welch HG. 2014 NEJM 371(19): Korea’s Thyroid-­‐Cancer “Epidemic” – Screening and Overdiagnosis. Geographical varia*on in diagnosis of thyroid cancer Brito JP, Hay ID, Morris JC 2014 BMJ (Clinical research ed.): Low risk papillary thyroid cancer. United States Ito Y, Nikiforov YE, Schlumberger M, Vigneri R 2013 Nature reviews. Endocrinology 9(3): Increasing incidence of thyroid cancer: controversies explored. What do the DRAFT guidelines proposed by the ATA recommend for nodules and cancers smaller than 1 cm? DRAFT Guidelines regarding decision to perform biopsy. DRAFT Guidelines regarding decision to NOT perform biopsy in HIGH SUSPICION sub-­‐cen*meter nodules. DRAFT Guidelines regarding decision to observe without biopsy. DRAFT Guidelines regarding decision to observe without biopsy. DRAFT Guidelines regarding decision to perform ac*ve surveillance rather than surgery for papillary microcarcinoma Thyroid Microcarcinoma is not the same as Low Risk Thyroid Carcinoma How is Low Risk Thyroid Cancer Defined? Criteria Include: Age: 40 – 45 year old cut off Invasiveness or extra-­‐thyroidal extension Distant metastases or loco-­‐regional metastases Completeness of resec*on Size: 4-­‐5 cm or con*nuous variable Not 1 cm cut-­‐off Brito JP, Hay ID, Morris JC 2014 BMJ (Clinical research ed.): Low risk papillary thyroid cancer. Sugitani I, Fujimoto Y 2010 Surgery today: Management of low-­‐risk papillary thyroid carcinoma: unique conven*onal policy in Japan and our efforts to improve the level of evidence. Sugitani I, Fujimoto Y 2010 Surgery today: Management of low-­‐risk papillary thyroid carcinoma: unique conven*onal policy in Japan and our efforts to improve the level of evidence. What is the outcome of treated low risk thyroid cancer? Survival in low-­‐risk and high-­‐risk PTC Sugitani I, Fujimoto Y 2010 Surgery today: Management of low-­‐risk papillary thyroid carcinoma: unique conven*onal policy in Japan and our efforts to improve the level of evidence. Mortality and recurrence in low-­‐risk and high-­‐risk PTC Sugitani I, Fujimoto Y 2010 Surgery today: Management of low-­‐risk papillary thyroid carcinoma: unique conven*onal policy in Japan and our efforts to improve the level of evidence. Risk factors for poor outcome in pa*ents presen*ng with clinically evident nodes, or RLN palsy Sugitani I, Fujimoto Y 2010 Surgery today: Management of low-­‐risk papillary thyroid carcinoma: unique conven*onal policy in Japan and our efforts to improve the level of evidence. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH 2003 Cancer: 98(1) July 2003 Papillary microcarcinoma of the thyroid-­‐Prognos*c significance of lymph node metastasis and mul*focality. Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH 2003 Cancer: 98(1) July 2003 Papillary microcarcinoma of the thyroid-­‐Prognos*c significance of lymph node metastasis and mul*focality. Hay ID, Hutchinson ME, Gonzalez-­‐Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goe 2008 Surgery: Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-­‐year period. Hay ID, Hutchinson ME, Gonzalez-­‐Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goe 2008 Surgery: Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-­‐year period. Hay ID, Hutchinson ME, Gonzalez-­‐Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goe 2008 Surgery: Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-­‐year period. Hay ID, Hutchinson ME, Gonzalez-­‐Losada T, McIver B, Reinalda ME, Grant CS, Thompson GB, Sebo TJ, Goe 2008 Surgery: Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-­‐year period. Disease specific mortality 49/18,445 = 0.26% Yu XM, Wan Y, Sippel RS, Chen H 2011 Annals of surgery: Should all papillary thyroid microcarcinomas be aggressively treated? An analysis of 18,445 cases. Studies of Ac*ve Surveillance of Papillary Microcarcinoma. Ito Y, Miyauchi A, Kobayashi K, Miya A 2014 Endocrine journal: Prognosis and growth ac*vity depend on pa*ent age in clinical and subclinical papillary thyroid carcinoma. Ito – 2010 340 Observa*on 1055 Surgical treatment Enlargement of 3mm or more: 6.4% at 5 years and 15.9% at 10 years Novel Nodal Metastasis: 1.4% at 5 years and 3.4% at 10 years 109/340 (32%) underwent surgical treatment Ito Y, Miyauchi A, Inoue H et al 2010, World J Surg: An observa*onal trial for papillary micro carcinoma in Japanese pa*ents. Ito Y, Miyauchi A, Inoue H et al 2010, World J Surg: An observa*onal trial for papillary micro carcinoma in Japaneses pa*ents. Ito Y, Miyauchi A, Inoue H et al 2010, World J Surg: An observa*onal trial for papillary micro carcinoma in Japaneses pa*ents. Ito Y, Miyauchi A, Inoue H et al 2010, World J Surg: An observa*onal trial for papillary micro carcinoma in Japaneses pa*ents. Ito – 2014 1235 Observa*on Enlargement of 3mm or more: 58/1235 (4.6%) Novel Nodal Metastasis: 19/1235 (1.5%) 191/1235 (19%) underwent surgical treatment Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Thyroid : official journal of the American Thyroid Associa*on: Pa*ent age is significantly related to the progression of papillary microcarcinoma of the thyroid under observa*on. Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Thyroid : official journal of the American Thyroid Associa*on: Pa*ent age is significantly related to the progression of papillary microcarcinoma of the thyroid under observa*on. 43/1235 (3.5%) (Nodes or size >12 mm)
Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Thyroid : official journal of the American Thyroid Associa*on: Pa*ent age is significantly related to the progression of papillary microcarcinoma of the thyroid under observa*on. Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Thyroid : official journal of the American Thyroid Associa*on: Pa*ent age is significantly related to the progression of papillary microcarcinoma of the thyroid under observa*on. Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M, Fujimoto Y 2010 World journal of surgery: Three dis*nctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. Sugitani I, Fujimoto Y, Yamada K 2013 World journal of surgery: Associa*on between serum thyrotropin concentra*on and growth of asymptoma*c papillary thyroid microcarcinoma. Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Thyroid : official journal of the American Thyroid Associa*on: Pa*ent age is significantly related to the progression of papillary microcarcinoma of the thyroid under observa*on. Why the discrepancy between growth, (nodal) recurrence, and death? Ito Y, Miyauchi A, Kobayashi K, Miya A 2014 Endocrine journal: Prognosis and growth ac*vity depend on pa*ent age in clinical and subclinical papillary thyroid carcinoma. Applicability of Japanese studies to American popula*on Sugitani I, Fujimoto Y 2010 Surgery today: Management of low-­‐risk papillary thyroid carcinoma: unique conven*onal policy in Japan and our efforts to improve the level of evidence. Likely differences in Observa*on trials in United States and Japan 1.  Pa*ent acceptance may not be equivalent. 2.  Ultrasound in Japanese study performed by single surgeon at single center. 3.  Pa*ent adherence to follow up may have large cultural discrepancy 4.  Possible disease specific differences. Sugitani I, Fujimoto Y 2010 Surgery today: Management of low-­‐risk papillary thyroid carcinoma: unique conven*onal policy in Japan and our efforts to improve the level of evidence. Ac*ve Surveillance of Micro-­‐carcinoma •  “Ac3ve” Surveillance –  “Delayed versus Immediate Surgery” (Turle) •  Absolute need for LOW RISK micro-­‐carcinoma –  No Lymph node metastases –  No Extra-­‐thyroidal extension –  Not Mul*focal –  Favorable Loca*on •  Not adjacent to trachea or RLN Ultrasound factors in ac*ve surveillance •  Requires advanced ultrasound skills –  Lymph node involvement –  Extrathyroidal extension is difficult to detect1 –  High risk loca*ons. •  Ultrasound in exis*ng studies performed by single inves*gator at single site. 1Michigishi T, Yokoyama K, Kobayashi E, et al., Poster 80, 84th annual mee*ng of the ATA. October 2014 Extra-­‐thyroidal extension is difficult to detect1 •  4365 women underwent ultrasound screening for thyroid cancer. •  99 cancers detected (2.3%) –  90% <1cm •  80 underwent surgery •  32/70 (46%) papillary micro-­‐cancer showed extra-­‐
thyroidal extension. –  pEx1 -­‐ pT3 Michigishi T, Yokoyama K, Kobayashi E, et al., Poster 80, 84 annual mee*ng of the ATA. October 2014 1
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Selec*on of Pa*ents for Observa*on •  Lesion factors –  Nodes, ETE, loca*on (Adjacent to RLN or trachea) –  Signs or symptoms of invasion of RLN or trachea –  FNAB findings of high grade malignancy •  Pa*ent factors –  Familial cancer, radia*on, consent, reliability for follow-­‐up (and understanding that will be >>20 yr f/u) •  Ins*tu*on factors –  Ultrasound skill (lymph nodes and ETE) –  Follow up rate – approach to lost to follow-­‐up –  Portability – mobility of pa*ents Unanswered Ques*ons •  Will trend in progressive development of clinical disease con*nue? •  Will late recurrences have a different degree of aggressiveness? •  What is the cost effec*veness of delayed versus immediate surgery? •  What is appropriate follow up? –  Frequency of US •  Addi*onal predic*ve factors. –  Molecular, Sonographic, Clinical •  Clear need for comprehensive ongoing clinical trials prior to universal acceptance DRAFT Guidelines unanswered ques*ons regarding ac*ve surveillance. Should Ac*ve Surveillance be considered Accepted Clinical Prac*ce or Clinical Research? •  Need for informed consent? •  Approval by an IRB? •  Clear need for data collec*on and analysis. –  Ins*tu*onal studies v. Clinical prac*ces –  Poten*al role of the Thyroid Cancer Care Collabora*ve (TCCC) for centers not performing clinical study. What is the TCCC? •  HIPAA compliant internet based program with centralized data on all aspects of a thyroid cancer pa*ent’s care. •  Sponsored by the Thyroid Head and Neck Cancer Founda*on. • 
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Resource for pa*ent educa*on. Resource for disease management decision making. Invaluable resource for clinical research. Endorsed by the AACE Thyroid Scien*fic Commiree Approved by Western IRB Informed Consent for Ac*ve Surveillance What should discussed? •  Explana*on of low risk micro-­‐carcinoma –  Varie*es of thyroid cancer and the prognosis of papillary cancer –  Incidence of PMC in autopsy studies and popula*on screening compared with clinical disease prevalence. •  Current standard of care is surgery. •  Pros and cons of both Surgery and Ac*ve Surveillance. •  Pa*ents need to be informed that current understanding is based on small numbers followed for rela*vely short intervals. –  (<600 followed >5 years and < 200 followed > 10 years) •  Clear explana*on of need for follow-­‐up for >> 20 years. Conclusions •  The rise in incidence of PTMC may reflect screening and suggests a role for ac*ve surveillance. –  ATA guidelines suggest ac*ve surveillance may be appropriate for unifocal low risk tumors with no evidence of ETE, lymph node metastasis, or high grade aggressive subtypes. •  Selec*on of candidates for ac*ve surveillance requires advanced ultrasound skills and the ability to assess nodes and ETE to exclude high risk. –  Other predic*ve factors need to be determined. –  Delay in surgery has not been associated with adverse outcome, but the numbers of pa*ents, and the dura*on of follow-­‐up are limited. •  Ac*ve surveillance will require long term observa*on and the cost analysis remains unclear. •  Observa*on of suspicious nodules <1 cm without biopsy carries many of the same considera*ons as observa*on of PTMC. –  Me*culous evalua*on for evidence of ETE, lymph node metastasis, and loca*on of the nodule, along with considera*on of clinical risks is essen*al if planning to not biopsy a suspicious sub-­‐cen*meter nodule. –  The pa*ent must be informed of the suspicious nature of the lesion and join in the decision making process. •  It is essen*al that pa*ents enrolled in ac*ve surveillance be tracked for clinical status and long term data analysis.