Role of active observation in the management of thyroid papillary microcarcinoma

1. Role of active observation in the management of thyroid papillary microcarcinoma Lam Shi, RH Joint Hospital Surgical Grand Round PYNEH, 18th April 2015

2. Definition • papillary thyroid microcarcinoma (PTMC) • papillary carcinoma ≤ 1cm WHO monograph on histologic typing of thyroid tumors

3. Rising incidence of small papillary thyroid carcinoma (PTC) • North America 1980 - 2008 87% PTCs < 2cm PTC PTC follicular variant Follicular carcinoma Pellegriti et al. J Cancer Epidemiol 2013 Davies et al. JAMA 2006

4. Current management of PTMC FNAC: PTC Risk Factors Age > 45 H&N irradiation Multifocal Local / LN invasion Aggressive histology T3 (> 4cm) Any Total thyroidectomy + prophylactic Lv 6 LN dissection  therapeutic MND No Thyroid scan ≤ 1cm 1-4cm Total or Hemithyroidectomy Total thyroidectomy +/- RAI McLeod. Lancet 2013

5. Excellent outcomes of surgical treatment for PTMC

6. Favorable outcome of incidental vs non-indicental PTMC I = incidental; NI = non-incidental

7. “Over-treatment” of latent PTCs? Prevalence of PTMC=3 – 18 % • Autopsy series 1966 – 1990 Pacini. 2012 Incidence Ca thyroid =1.6 – 6 / 100 000 • Registry data 1973 – 1977 • Pre-USG era Kilfoy et al. 2009 Ca thyroid related mortality = 0.5 / 100 000 • Epidemiology database 1973 – 2002Davies et al. 2006

8. Can PTMCs be observed without immediate surgery ? Hypothesis • A significant proportion of PTMCs are indolent and may not manifest in one’s lifetime Proposal • To observe newly diagnosed incidental PTMC • Operate only when lesion showed sign of progression Question • Safety of delaying surgery until lesion showed evidence of progression ?

9. Ito et al. (2003) - An observation trial for PTMC • 1993 -2001 • 732 patients with FNAC diagnosed PTMC • exclusion (570): • RLN palsy • tumor close to trachea / RLN • suspicious LN in lateral compartments • high grade malignancy • patient’s choice • 162 patients for observation • USG every 6 – 12 months • surgery if tumor progresses ≥ 10mm, new suspicious LN in lateral compartment

10. Ito et al. (2003) - An observation trial for PTMC 162 patients followed-up for 18 – 113 months (mean 47) Tumor size • no change at all time points: 70 - 83% • increase to ≥ 10mm: 18 (11%) Lymph node (lateral compartment) • 2 (1.2%) newly detected by USG Operation rate • 56 patients (35%) operated • At 19 – 56 months after observation • indications: disease progression (9), ? patient’s choice (47)

11. Ito et al. (2003) - An observation trial for PTMC % TNM staging (AJCC 6th Ed. 2002) < 1cm 1 – 4 cm > 4 cm Extra-cap invasion Clinical outcome • local recurrence 2.6% • distant metastasis / mortality 0%

12. Ito et al. (2013) – Age predicts progression • 1993 -2011, n = 1235 • follow-up 1.5 – 19 years (mean 5 years) • 58 (4.6%) with tumor enlargement; 43 (3.5%) > 12mm • 19 (1.5%) LN metastasis during observation • 10-year rates • size enlargement – 8.3% (6.8% > 12mm) • new LN during observation – 3.8% • Age < 40 as an independent predictor • 191 (16%) underwent operation • post-operative follow-up 75 months • Local recurrence 0.5% • Mortality 0

13. Tumor enlargement > 12mm New lymph node

14. Sugitani et al. (2010) – Observation trial • 1993 -2001 • 230 patients chose initial observation • 300 PTMCs (multifocal in 48 pts) • Mean follow-up 60 months • 7 patients lost to follow-up, 6 patients died of other disease • Surgery if tumor growth towards adjacent structures, increase in size, LN / distant metastasis, patient’s preference

15. Sugitani et al. (2010) – Observation trial Tumor size • no change / decrease: 93% • increase : 7% (22 patients) Lymph node metastasis - 1% Operation rate • 16 patients (7%) • indications: disease progression (12), patient’s choice (4) • ? 6 patient with increased size not operated Recurrence / mortality: 0

16. Summary Natural history – 10 years (Ito) • 8.3% increase by > 2mm • 3.8% progress to > 12mm • 3.8% develop new LN in lateral compartment Operation rate: 7 – 16% (Ito, Sugitani) • Total thyroidectomy 13 – 50% • “limitted” thyroidectomy 50 – 87% • Lymph node dissection • Therapeutic lateral ND 1% - 18% • Prophylatic CND 6 – 100% • High incidence of microscopic lymph node (38%) and multifocality (69%) in the operated cohort Outcome of delayed surgery • Local recurrence: 0.5 – 2.6%; Mortality: 0%

17. Immediate vs delayed surgery for incidental PTMC

18. Limitation Study design • Single-centered case series • Small sample size of operated group for detection of rare events • Patient’s choice to operate  increased denominator with non-progressive lesions  mitigate recurrence rate • Duration of follow-up relatively short Data quality • Defaulted cases not explicitly described • Some patient has tumor enlargement but not operated Generalizability • Dedicated USG surveillance program • Cultural issues

19. JSTS / JAES Guideline 2011 “ observation without immediate surgey can be an option for patients with low-risk papillary microcarcinoma”

20. Conclusion Role of initial observation • a “step” rather than “option” • to futher risk-stratify low-risk PTMCs into progressive and non-progressive lesions • may avoid surgery for indolent tumors in patients with limitted life expectancy Practical considerations • ? reliable USG surveillance programme • patient anxiety / quality of life

21. Thank you!