Role of active observation Role of active observation in the management of in the management of

thyroid papillary thyroid papillary microcarcinomamicrocarcinoma

Joint Hospital Surgical Grand RoundJoint Hospital Surgical Grand Round

PYNEH, 18PYNEH, 18th th April 2015April 2015

Lam Shi, RHLam Shi, RH

DefinitionDefinition

papillary thyroid microcarcinoma (PTMC)papillary thyroid microcarcinoma (PTMC)

– papillary carcinoma ≤ 1cmpapillary carcinoma ≤ 1cm

WHO monograph on histologic typing of thyroid tumorsWHO monograph on histologic typing of thyroid tumors

Rising incidence of Rising incidence of small papillary thyroid carcinoma (PTC)small papillary thyroid carcinoma (PTC)

North America 1980 - 2008North America 1980 - 2008

PTC

PTC follicular variantFollicular carcinoma

87% PTCs < 2cm

Pellegriti et al. J Cancer Epidemiol Pellegriti et al. J Cancer Epidemiol 20132013Davies et al. JAMA 2006Davies et al. JAMA 2006

FNAC: PTC

Risk FactorsAge > 45H&N irradiationMultifocalLocal / LN invasionAggressive histologyT3 (> 4cm)

≤ 1cm

Total or Hemithyroidectomy

1-4cm

Total thyroidectomy

No

Any

Total thyroidectomy + prophylactic Lv 6 LN dissection

therapeutic MND

Thyroid scan

+/- RAI

Current management of PTMCCurrent management of PTMC

McLeod. Lancet 2013

Excellent outcomes of Excellent outcomes of surgical treatment for PTMCsurgical treatment for PTMC

Author, yearFollow-

up (Year)

No. of patients

Recurrence Mortality

Noguchi, 2011

10 867 1% 0.2%

Baudin, 1998 7.3 281 4% 0%

Ito, 2003 10 626 5% 0%

Hay, 2008 17.2 900 6% 0.3%

Chow, 2003 10 203 7% 1%

Favorable outcome of Favorable outcome of incidentalincidental vs vs non-indicentalnon-indicental PTMC PTMC

Author N

Multicentric

(%)

Bilateral(%)

Lymph nodemet (%)

Distantmet (%)

Recurrence (%)

Mortality(%)

I NI I NI I NI I NI I NI I NI

Baudin28

13

061

13

23 22 91 0 8.62.

17.6 0 0

Pellegriti

299

25

391

522 16 45 0.7 4.7 ns ns 0 0

Roti24

31

936

11

20 4 16 0 2 ns ns 0 0

Lo18

41

232 0 39 0 2.7 0 12 0 3.6

I = incidental; NI = non-incidental

““Over-treatment” of latent PTCs?Over-treatment” of latent PTCs?

Prevalence Prevalence of PTMCof PTMC == 3 3 –– 18 % 18 % Autopsy series 1966 Autopsy series 1966 –– 1990 1990 Pacini. Pacini.

20122012

Incidence Incidence Ca thyroid =Ca thyroid = 1.6 1.6 –– 6 / 100 000 6 / 100 000 Registry data 1973 Registry data 1973 –– 1977 1977 Pre-USG era Pre-USG era Kilfoy et al. 2009Kilfoy et al. 2009

Ca thyroid relatedCa thyroid related mortality mortality = 0.5 / 100 000= 0.5 / 100 000 Epidemiology database 1973 Epidemiology database 1973 –– 2002 2002 Davies et al. Davies et al.

20062006

Can PTMCs be observed without Can PTMCs be observed without immediate surgery ? immediate surgery ?

HypothesisHypothesis A significant proportion of PTMCs are indolent and may A significant proportion of PTMCs are indolent and may

not manifest in onenot manifest in one’’s lifetimes lifetime

ProposalProposal To observe newly diagnosed incidental PTMCTo observe newly diagnosed incidental PTMC Operate only when lesion showed sign of progressionOperate only when lesion showed sign of progression

QuestionQuestion Safety of delaying surgery until lesion showed evidence Safety of delaying surgery until lesion showed evidence

of progression ? of progression ?

1993 -20011993 -2001 732 patients with 732 patients with FNAC diagnosed PTMCFNAC diagnosed PTMC exclusionexclusion (570): (570):

– RLN palsyRLN palsy– tumor close to trachea / RLNtumor close to trachea / RLN– suspicious LN in lateral compartmentssuspicious LN in lateral compartments– high grade malignancyhigh grade malignancy– patientpatient’’s choices choice

162 patients for 162 patients for observationobservation USGUSG every 6 every 6 –– 12 months 12 months surgery if tumor progresses surgery if tumor progresses ≥ 10mm≥ 10mm, new suspicious , new suspicious

LN in lateral compartmentLN in lateral compartment

Ito et al. (2003) - An observation trial for PTMCIto et al. (2003) - An observation trial for PTMC

162 patients 162 patients followed-up for followed-up for 18 – 113 months (mean 18 – 113 months (mean 47)47)

Tumor sizeTumor size no change at all time points: 70 - 83%no change at all time points: 70 - 83% increase to increase to ≥≥ 10mm: 18 (11%) 10mm: 18 (11%)

Lymph node (lateral compartment)Lymph node (lateral compartment) 2 (1.2%) newly detected by USG2 (1.2%) newly detected by USG

Operation rate Operation rate 56 patients (35%) operated56 patients (35%) operated At 19 – 56 months after observationAt 19 – 56 months after observation indications: disease progression (9), ? patientindications: disease progression (9), ? patient’’s s

choice (47)choice (47)

Ito et al. (2003) - An observation trial for PTMCIto et al. (2003) - An observation trial for PTMC

% TNM staging (AJCC 6th Ed. 2002)% TNM staging (AJCC 6th Ed. 2002)

pTpT pNpN MM

00 6363 100100

1a1a 5050 3232 00

1b1b 4141 55

22 55

33 00

4a4a 33

Clinical outcomeClinical outcome local recurrence 2.6%local recurrence 2.6% distant metastasis / mortality 0%distant metastasis / mortality 0%

Ito et al. (2003) - An observation trial for PTMCIto et al. (2003) - An observation trial for PTMC

< 1cm

1 – 4 cm

> 4 cm

Extra-cap invasion

1993 -2011, 1993 -2011, n = 1235n = 1235 follow-up 1.5 – 19 years (mean 5 years)follow-up 1.5 – 19 years (mean 5 years) 58 (4.6%) with tumor enlargement; 43 (3.5%) > 12mm58 (4.6%) with tumor enlargement; 43 (3.5%) > 12mm 19 (1.5%) LN metastasis during observation19 (1.5%) LN metastasis during observation 10-year rates10-year rates

– size enlargement – 8.3% (6.8% > 12mm)size enlargement – 8.3% (6.8% > 12mm)– new LN during observation – 3.8%new LN during observation – 3.8%– Age < 40 as an independent predictorAge < 40 as an independent predictor

191 (16%) underwent operation191 (16%) underwent operation post-operative follow-up 75 monthspost-operative follow-up 75 months

– Local recurrence 0.5%Local recurrence 0.5%– Mortality 0Mortality 0

Ito et al. (2013) – Age predicts progressionIto et al. (2013) – Age predicts progression

Tumor enlargement

> 12mm

New lymph node

1993 -20011993 -2001 230 patients chose initial observation230 patients chose initial observation 300 PTMCs (multifocal in 48 pts)300 PTMCs (multifocal in 48 pts) Mean follow-up 60 monthsMean follow-up 60 months 7 patients lost to follow-up, 6 patients died of 7 patients lost to follow-up, 6 patients died of

other diseaseother disease Surgery if tumor growth towards adjacent Surgery if tumor growth towards adjacent

structures, increase in size, LN / distant structures, increase in size, LN / distant metastasis, patient’s preferencemetastasis, patient’s preference

Sugitani et al. (2010) – Observation trialSugitani et al. (2010) – Observation trial

Tumor sizeTumor size no change / decrease: 93%no change / decrease: 93% increase : 7% (22 patients)increase : 7% (22 patients)

Lymph node metastasis - Lymph node metastasis - 1%1%

Operation rate Operation rate 16 patients (7%)16 patients (7%) indications: disease progression (12), patientindications: disease progression (12), patient’’s s

choice (4)choice (4) ? 6 patient with increased size not operated? 6 patient with increased size not operated

Recurrence / mortality: Recurrence / mortality: 00

Sugitani et al. (2010) – Observation trialSugitani et al. (2010) – Observation trial

SummarySummary

Natural history – 10 years (Ito)Natural history – 10 years (Ito) 8.3% increase by > 2mm8.3% increase by > 2mm 3.8% progress to > 12mm3.8% progress to > 12mm 3.8% develop new LN in lateral compartment3.8% develop new LN in lateral compartment

Operation rate: Operation rate: 7 – 16% (Ito, Sugitani)7 – 16% (Ito, Sugitani) Total thyroidectomy 13 – 50%Total thyroidectomy 13 – 50% ““limitted” thyroidectomy 50 – 87%limitted” thyroidectomy 50 – 87% Lymph node dissectionLymph node dissection

– Therapeutic lateral ND 1% - 18% Therapeutic lateral ND 1% - 18% – Prophylatic CND 6 – 100%Prophylatic CND 6 – 100%

High incidence of microscopic lymph node (38%) and High incidence of microscopic lymph node (38%) and multifocality (69%) in the operated cohortmultifocality (69%) in the operated cohort

Outcome of delayed surgeryOutcome of delayed surgery Local recurrence: 0.5 – 2.6%; Mortality: 0%Local recurrence: 0.5 – 2.6%; Mortality: 0%

Immediate vs delayed surgery for Immediate vs delayed surgery for incidental PTMCincidental PTMC

Author NMulticentri

c(%)

Bilateral(%)

Lymph node

met (%)

Distantmet (%)

Recurrence (%)

Mortality(%)

Baudin 281 30 13 22 0 2.1 0

Pellegriti

299 25 15 16 0.7 ns 0

Roti 243 19 11 4 0 ns 0

Lo 184 12 0 0 0 0

Ito 186 69 38 0 0.5 0

LimitationLimitationStudy designStudy design Single-centered case seriesSingle-centered case series Small sample size of operated group for detection of rare Small sample size of operated group for detection of rare

eventsevents Patient’s choice to operate Patient’s choice to operate increased denominator with increased denominator with

non-progressive lesions non-progressive lesions mitigate recurrence rate mitigate recurrence rate Duration of follow-up relatively shortDuration of follow-up relatively short

Data qualityData quality Defaulted cases not explicitly describedDefaulted cases not explicitly described Some patient has tumor enlargement but not operatedSome patient has tumor enlargement but not operated

GeneralizabilityGeneralizability Dedicated USG surveillance programDedicated USG surveillance program Cultural issuesCultural issues

JSTS / JAES Guideline 2011JSTS / JAES Guideline 2011

““ observation without immediate observation without immediate surgey can be an option for surgey can be an option for patients with low-risk papillary patients with low-risk papillary microcarcinomamicrocarcinoma””

ConclusionConclusion

Role of initial observationRole of initial observation a “step” rather than “option” a “step” rather than “option” to futher risk-stratify low-risk PTMCs into to futher risk-stratify low-risk PTMCs into

progressive and non-progressive lesionsprogressive and non-progressive lesions may avoid surgery for indolent tumors in patients may avoid surgery for indolent tumors in patients

with limitted life expectancywith limitted life expectancy

Practical considerationsPractical considerations ? reliable USG surveillance programme? reliable USG surveillance programme patient anxiety / quality of lifepatient anxiety / quality of life

Thank you!Thank you!