Management in 2006 of Patients with Low-Risk Papillary Thyroid Carcinoma Management in 2006 of...

Management in 2006 of Management in 2006 of Patients with Low-Risk Patients with Low-Risk

Papillary Thyroid Papillary Thyroid CarcinomaCarcinoma

Professor Ian D. Hay MB PhD FRCPProfessor Ian D. Hay MB PhD FRCP

Mayo Clinic College of MedicineMayo Clinic College of Medicine

Differentiated Thyroid CarcinomaDifferentiated Thyroid CarcinomaManaged at Mayo Clinic 1940-2000Managed at Mayo Clinic 1940-2000

Histotype DistributionHistotype Distribution

CP1028491-8

n=3,0481940-2000n=3,048

1940-2000

8%5%5%

Papillary (2,512)82%

Medullary (246)

Medullary (246)

Follicular (155)

Follicular (155)

Hürthle cell (155)

Hürthle cell (155)

2,512 Papillary Thyroid Carcinoma Patients2,512 Papillary Thyroid Carcinoma PatientsManaged At Mayo Clinic During 1940-2000Managed At Mayo Clinic During 1940-2000

Presenting DiseasePresenting Disease

p TNM Stagesp TNM Stages MACIS ScoresMACIS Scores

I (60%)

III (18%)

II (21%)

IV (1%)IV (1%)

<6 (84%)

6+ (16%)

CP1028491-1

n=2,5121940-2000n=2,512

1940-2000

Managing Low-risk DTC in 2005Managing Low-risk DTC in 2005A Day in the Life of a Mayo PTC Specialist!A Day in the Life of a Mayo PTC Specialist!

• In an attempt, perhaps, to better define In an attempt, perhaps, to better define later a more rational approach to the later a more rational approach to the postoperative management of low-risk postoperative management of low-risk differentiated thyroid cancer, let us differentiated thyroid cancer, let us first consider, by way of introduction, first consider, by way of introduction, two cases of papillary thyroid two cases of papillary thyroid microcarcinoma (PTM) seen on a microcarcinoma (PTM) seen on a recent Mayo clinic outpatient day recent Mayo clinic outpatient day

Case 1: Node-Positive PTMCase 1: Node-Positive PTM

• 3/99: 59y/o male; 4hr op (TTx, central 3/99: 59y/o male; 4hr op (TTx, central compartment exploration, (L)MND) for compartment exploration, (L)MND) for bilateral multicentric 1 cm PTM; 20/46 bilateral multicentric 1 cm PTM; 20/46 pos nodes(Delphian, central, lat neck)pos nodes(Delphian, central, lat neck)

• 5-9/99: 30 + 100 mCi I-131 for ablation5-9/99: 30 + 100 mCi I-131 for ablation

• 3/00: rhTSH-stimulated I-123 WBS and 3/00: rhTSH-stimulated I-123 WBS and US neck negative; Tg auto-ab pos US neck negative; Tg auto-ab pos

Case 1: Node-Positive PTMCase 1: Node-Positive PTM

• 4/01-4/04: annual neck US showed 2 4/01-4/04: annual neck US showed 2 (L) bed lesions, initially 4 and 6 mm, (L) bed lesions, initially 4 and 6 mm, but growing to 6, 8mm with incr. flow, but growing to 6, 8mm with incr. flow, microcalcifications; Tg 0.3-0.6 Ab-posmicrocalcifications; Tg 0.3-0.6 Ab-pos

• 4/04: Pos USGB (L) bed led to 2 hr op, 4/04: Pos USGB (L) bed led to 2 hr op, excising 2/2 pos (L) T/E groove nodesexcising 2/2 pos (L) T/E groove nodes

• 9/05: Ab-neg Tg <0.1ng/mL; US neck 9/05: Ab-neg Tg <0.1ng/mL; US neck negative for recurrence at 78 p/op monegative for recurrence at 78 p/op mo

Case 2: Recurrent node-positive PTC Case 2: Recurrent node-positive PTC

• 4/98: 28y/o female: TTx, central NLND 4/98: 28y/o female: TTx, central NLND for multifocal PTM ; 6/7 pos nodesfor multifocal PTM ; 6/7 pos nodes

• 5/98: 175 mCi I-131 for 6.8% uptake5/98: 175 mCi I-131 for 6.8% uptake

• 1/99: re- exploration for palpable (L) 1/99: re- exploration for palpable (L) lat nodes: 1/5 nodes pos at path examlat nodes: 1/5 nodes pos at path exam

• 10/99: 200 mCi given for neck uptake10/99: 200 mCi given for neck uptake

• 4/00: rhTSH- WBS neg; Tg (USC) <1 4/00: rhTSH- WBS neg; Tg (USC) <1

Case 2: Another Uncooperative NNMCase 2: Another Uncooperative NNM

• 2001-2003: multiple neg rhTSH-WBS 2001-2003: multiple neg rhTSH-WBS but Tg rise after stim led to neg MRI but Tg rise after stim led to neg MRI of neck and whole body FDG-PET/CT of neck and whole body FDG-PET/CT

• 2/03: Pos USGB of 7X4X3mm node, 2/03: Pos USGB of 7X4X3mm node, and pt sent to MC for possible PEIand pt sent to MC for possible PEI

• 3/03: Tg 0.3(Ab-neg); 8X5X3mm (L) 3/03: Tg 0.3(Ab-neg); 8X5X3mm (L) bed node treated with US-guided PEI bed node treated with US-guided PEI

Case 2: Adequately Treated NNMCase 2: Adequately Treated NNM

• 7/03: node re-treated with 0.2cc EtOH7/03: node re-treated with 0.2cc EtOH

• 11/03- 10/04: injected node no longer 11/03- 10/04: injected node no longer identifiable on repeated US examsidentifiable on repeated US exams

• 10/05: TSH 0.1, Tg <0.1 ng/mL; neck 10/05: TSH 0.1, Tg <0.1 ng/mL; neck US negative for recurrence at 90 moUS negative for recurrence at 90 mo

What do these cases illustrate?What do these cases illustrate?

• Inadequacy of regional nodal Inadequacy of regional nodal resection at first neck explorationresection at first neck exploration

• Futility of p/op remnant ablationFutility of p/op remnant ablation

• Efficiency of PEI in nodal ablationEfficiency of PEI in nodal ablation

What clinical and research experiences What clinical and research experiences would justify such atypical views on would justify such atypical views on

postop management?postop management?

• 23 years consulting on patients with 23 years consulting on patients with thyroid malignancy at the Mayo Clinic thyroid malignancy at the Mayo Clinic

• Daily experience in managing DTC Daily experience in managing DTC patients; now >400 cases annuallypatients; now >400 cases annually

• Management approach also influenced Management approach also influenced by studying cohort of 2,512 PTC pts by studying cohort of 2,512 PTC pts treated at Mayo during 1940 to 2000treated at Mayo during 1940 to 2000

PTC Management in Five DecadesPTC Management in Five Decades

• During 1950 through 1999, mortality During 1950 through 1999, mortality and recurrence rates in 2,286 Mayo and recurrence rates in 2,286 Mayo PTC patients did PTC patients did notnot progressively progressively improve with successive decadesimprove with successive decades

• Outcome was excellent in low-risk Outcome was excellent in low-risk (MACIS <6) PTC patients treated by (MACIS <6) PTC patients treated by NTT, conservative nodal dissection, NTT, conservative nodal dissection, and and notnot improved by increasing use improved by increasing use of postoperative remnant ablationof postoperative remnant ablation

World J Surg 26: 879, 2002World J Surg 26: 879, 2002

Relevance of Epidemiology to Relevance of Epidemiology to Contemporary ManagementContemporary Management

• Presenting features (patient and tumor Presenting features (patient and tumor variables) permit outcome prediction; tumor variables) permit outcome prediction; tumor biology more powerful than therapy choicesbiology more powerful than therapy choices

• Majority (85%) of PTC patients at minimal risk Majority (85%) of PTC patients at minimal risk of recurrence or cause-specific mortalityof recurrence or cause-specific mortality

• Logically, therefore, aggressive adjunctive Logically, therefore, aggressive adjunctive treatments should be restricted to minority treatments should be restricted to minority (15%) at “high-risk,” i.e., applying the (15%) at “high-risk,” i.e., applying the principle of “letting the punishment fit the principle of “letting the punishment fit the crime.”crime.” Cady,B Am J Surg 174: 462, 1997Cady,B Am J Surg 174: 462, 1997

APPLYING “COMMON APPLYING “COMMON SENSE” TO SENSE” TO

MANAGING PATIENTS MANAGING PATIENTS WITH LOW-RISK WITH LOW-RISK

DIFFERENTIATED DIFFERENTIATED THYROID CANCERTHYROID CANCER

Five Steps in Primary Five Steps in Primary Management of LRPTCManagement of LRPTCI.I. Diagnosis: cytologic and Diagnosis: cytologic and

histopathologichistopathologicII.II. Primary surgical treatment **Primary surgical treatment **III.III. Staging and risk-group Staging and risk-group

assignment *assignment *IV.IV. Adjuvant therapy ***Adjuvant therapy ***V.V. Long-term surveillance ***Long-term surveillance ***

““Many can biopsy but few can Many can biopsy but few can interpret thyroid cytology” interpret thyroid cytology”

• If an endocrinologist or surgeon is If an endocrinologist or surgeon is to serve well patients with NTD, then to serve well patients with NTD, then he/she must identify, ideally sited he/she must identify, ideally sited conveniently, a cytopathologist conveniently, a cytopathologist whose skills are associated with whose skills are associated with acceptably low rates of both false-acceptably low rates of both false-positive and false-negative reportspositive and false-negative reports

““Common Sense” Common Sense” Approach to LRPTC Approach to LRPTC

ManagementManagementI.I. Diagnosis: cytologic and Diagnosis: cytologic and

histopathologichistopathologicII.II. Primary surgical treatmentPrimary surgical treatment

CP1028491-2

2,512 Papillary Thyroid Carcinoma Patients2,512 Papillary Thyroid Carcinoma PatientsManaged At Mayo Clinic During 1940-2000Managed At Mayo Clinic During 1940-2000

Trends in Extent of Primary SurgeryTrends in Extent of Primary Surgery

Initialthyroid

operations(%)

Initialthyroid

operations(%)

1940-1954

1940-1954

1955-1969

1955-1969

1985-2000

1985-2000

1970-1984

1970-1984

n=2,512n=2,512

Unilateral lobectomy

(293)

Unilateral lobectomy

(293)

Near-total thyroidectomy

(1,324)

Near-total thyroidectomy

(1,324)

Total thyroidectomy

(635)

Total thyroidectomy

(635)

Bilateral subtotal resection (220)

Bilateral subtotal resection (220)

Appropriate Therapy for Appropriate Therapy for Low-risk Papillary Cancer Low-risk Papillary Cancer

• ““Low-risk” PTC represents majority Low-risk” PTC represents majority of FCDC in areas of iodine sufficiency of FCDC in areas of iodine sufficiency

• Such tumors multicentric, typically Such tumors multicentric, typically bilateral, often involving neck nodesbilateral, often involving neck nodes

• Reasonable, therefore, to employ a Reasonable, therefore, to employ a bilateral approach and to determine bilateral approach and to determine nodal status on treatment day onenodal status on treatment day one

320 Papillary Thyroid Carcinoma Patients320 Papillary Thyroid Carcinoma PatientsManaged at Mayo Clinic during 1940-1954Managed at Mayo Clinic during 1940-1954

Impact of Bilateral Lobar ResectionImpact of Bilateral Lobar Resection

Cu

mu

lati

ve %

wit

h o

cc

urr

en

ceC

um

ula

tive

% w

ith

oc

cu

rre

nce

n=320P=0.35n=320P=0.35

Unilateral lobectomy(176)


Recurrence, Any SiteRecurrence, Any Site

Bilaterallobar resection

(144)


(144)

Years after initial surgeryYears after initial surgeryCP1029349-1

0 10 20 30 40


(136)


(136)

0 10 20 30 40

Mortality from PTCMortality from PTC

n=296P<0.001n=296P<0.001

Unilaterallobectomy

(160)

Unilaterallobectomy

(160)

Impact of BLR on Mortality and Recurrence inImpact of BLR on Mortality and Recurrence inLow- and High-Risk PTCLow- and High-Risk PTC

By MACIS <6 and 6+By MACIS <6 and 6+

CP1029349-2

Cu

mu

lati

ve %

wit

h o

cc

urr

en

ceC

um

ula

tive

% w

ith

oc

cu

rre

nce

Years after initial surgeryYears after initial surgery

MortalityMortality

0 5

RecurrenceRecurrence

UL (60)UL (60)

BLR (331)BLR (331)

10 15 25

1940-2000P=0.015n=280

1940-2000P=0.015n=280

UL (39)UL (39)

BLR (241)BLR (241)

20 0 5 10 15 2520

0 5 10 15 20 0 5 10 15 20

MACIS 6+P=0.007n=391

MACIS 6+P=0.007n=391

1940-54P<0.001n=256

1940-54P<0.001n=256

UL (135)UL (135)

BLR (121)BLR (121)

MACIS <6P=0.31n=296

MACIS <6P=0.31n=296 UL (160)UL (160) BLR (136)BLR (136)

Advantages of NT/TT in Advantages of NT/TT in Papillary Thyroid CancerPapillary Thyroid Cancer

• Bilateral lobar resection (BLR) Bilateral lobar resection (BLR) reduces locoregional recurrences reduces locoregional recurrences in all and reduces cause-specific in all and reduces cause-specific mortality in ‘high-risk’ PTC mortality in ‘high-risk’ PTC

• Thus: in 2006, a pre-op FNA dx of Thus: in 2006, a pre-op FNA dx of PTC should lead to BLR (NT/TT), PTC should lead to BLR (NT/TT), with safeguarding of parathyroidswith safeguarding of parathyroids

Importance of Neck Nodal Importance of Neck Nodal Status in Low-Risk PTC Status in Low-Risk PTC

• If a PTC patient has only a If a PTC patient has only a thyroidectomy and no inspection thyroidectomy and no inspection or exploration of the central or exploration of the central compartment, with sampling of compartment, with sampling of level VI nodes, then the patient level VI nodes, then the patient has been ill-served, and has has been ill-served, and has already fallen on only day one of already fallen on only day one of treatment into a “pitfall” treatment into a “pitfall”

Pre-op Ultrasound Mapping Pre-op Ultrasound Mapping and the Lateral Neckand the Lateral Neck

• Preoperative neck ultrasound, with Preoperative neck ultrasound, with identification of nodal mets, permits identification of nodal mets, permits planned appropriate nodal resection at planned appropriate nodal resection at the time of first neck explorationthe time of first neck exploration

• Discovery of a lateral neck nodal met Discovery of a lateral neck nodal met (removed at open biopsy, or positive (removed at open biopsy, or positive on USGB or at FS) should lead to on USGB or at FS) should lead to function-sparing modified neck function-sparing modified neck dissection at first neck explorationdissection at first neck exploration

Role of Preoperative StagingRole of Preoperative StagingATA 2006 GuidelinesATA 2006 Guidelines

• R21. “Preoperative neck ultrasound R21. “Preoperative neck ultrasound for the contralateral lobe and cervical for the contralateral lobe and cervical (central and bilateral) lymph nodes is (central and bilateral) lymph nodes is recommended for all patients recommended for all patients undergoing thyroidectomy for undergoing thyroidectomy for malignant cytologic findings on malignant cytologic findings on biopsy – Recommendation B biopsy – Recommendation B

The ATA Guidelines TaskforceThe ATA Guidelines Taskforce

Thyroid 16 (2): 1-33, Feb 2006.Thyroid 16 (2): 1-33, Feb 2006.

Expectations of Primary Expectations of Primary Neck Surgery in PTCNeck Surgery in PTC

• Avoidance of central compartment Avoidance of central compartment exploration no longer acceptableexploration no longer acceptable

• Iatrogenic hypoparathyroidism Iatrogenic hypoparathyroidism unwarranted and avoidable in 2006unwarranted and avoidable in 2006

• I-131 should I-131 should notnot be used as a be used as a postoperative cure-all to ‘mop up postoperative cure-all to ‘mop up leftovers’ after inadequate surgeryleftovers’ after inadequate surgery

Lymph Node Dissection in PTCLymph Node Dissection in PTCATA 2006 GuidelinesATA 2006 Guidelines

• ““R27. Routine central compartment (level VI) neck R27. Routine central compartment (level VI) neck dissection should be considered for patients with dissection should be considered for patients with PTC: Recommendation B”PTC: Recommendation B”

• ““R28. Lateral neck compartmental lymph node R28. Lateral neck compartmental lymph node dissection should be performed for patients with dissection should be performed for patients with biopsy-proven metastatic cervical biopsy-proven metastatic cervical lymphadenopathy detected clinically or by lymphadenopathy detected clinically or by imaging, especially when they are likely to fail imaging, especially when they are likely to fail RAI treatment based on lymph node size, number, RAI treatment based on lymph node size, number, or other factors, such as aggressive histology of or other factors, such as aggressive histology of the primary tumor – Recommendation B” the primary tumor – Recommendation B”


ManagementManagementI.I. Diagnosis: cytologic and Diagnosis: cytologic and

histopathologichistopathologicII.II. Primary surgical treatmentPrimary surgical treatmentIII.III. Staging and risk-group Staging and risk-group

assignmentassignment

Relevance of Post-op Assignment Relevance of Post-op Assignment to Prognostic Risk-Groupsto Prognostic Risk-Groups

•Enables post-op counseling of Enables post-op counseling of an individual DTC patientan individual DTC patient

•Helps make decisions about Helps make decisions about intensity of adjuvant therapies, intensity of adjuvant therapies, frequency of follow-up visits, frequency of follow-up visits, and allocation of resourcesand allocation of resources

Role of Postoperative Staging SystemsRole of Postoperative Staging SystemsATA 2006 Management GuidelinesATA 2006 Management Guidelines

• ““R31. Because of its utility in predicting disease R31. Because of its utility in predicting disease mortality, and its requirement for cancer mortality, and its requirement for cancer registries, AJCC/UICC staging is recommended registries, AJCC/UICC staging is recommended for all patients with differentiated thyroid cancer. for all patients with differentiated thyroid cancer. The use of postoperative clinicopathologic The use of postoperative clinicopathologic staging systems is also recommended to staging systems is also recommended to improve prognostication and to plan follow-up improve prognostication and to plan follow-up for patients with differentiated thyroid carcinoma for patients with differentiated thyroid carcinoma – Recommendation B” – Recommendation B”

Thyroid 16: 1-33, 2006.Thyroid 16: 1-33, 2006.

Utility of Staging and Prognostic ScoringUtility of Staging and Prognostic Scoring

• Clinicians caring for DTC patients Clinicians caring for DTC patients should understand and ‘try to’ use in should understand and ‘try to’ use in practice the 2002 TNM/AJCC stages!practice the 2002 TNM/AJCC stages!

• AMES or MSKCC risk-groups for FTCAMES or MSKCC risk-groups for FTC

• MACIS prognostic scoring system, MACIS prognostic scoring system, permitting PTC classification into permitting PTC classification into low-risk (scores <6) or high-risk (6+) low-risk (scores <6) or high-risk (6+) patients (Surgery 114; 1050-8, 1993), patients (Surgery 114; 1050-8, 1993), employed at Mayo for past 13 years employed at Mayo for past 13 years

0

20

40

60

80

100

0 5 10 15 20 25

Years after initial surgeryYears after initial surgeryCP1028491-11

Papillary Thyroid CarcinomaPapillary Thyroid CarcinomaManaged at Mayo Clinic 1940-2000Managed at Mayo Clinic 1940-2000

Mortality by MACISMortality by MACIS

Surviving death from

PTC (%)

Surviving death from

PTC (%) MACIS Risk Groups n=2,512 1940-2000 P<0.001

MACIS Risk Groups n=2,512 1940-2000 P<0.001

<6 (2,099)<6 (2,099)

6+ (413)6+ (413)


ManagementManagementI.I. Diagnosis: cytologic and Diagnosis: cytologic and histopathologichistopathologic

II.II. Primary surgical treatmentPrimary surgical treatmentIII.III. Staging and risk-group Staging and risk-group

assignmentassignmentIV.IV. Adjuvant therapyAdjuvant therapy

Adjuvant Therapy in Adjuvant Therapy in LRPTC PatientsLRPTC Patients

•Thyroid hormone Thyroid hormone suppressive therapy suppressive therapy

•Radioiodine remnant Radioiodine remnant ablation (RRA)ablation (RRA) ***** *****

Thyroxine Suppressive Thyroxine Suppressive Therapy in DTC ManagementTherapy in DTC Management

• Risk-group assignment can Risk-group assignment can determine a precise goal level for determine a precise goal level for suppression of serum TSHsuppression of serum TSH

• Low-risk (MACIS < 6 PTC): TSH Low-risk (MACIS < 6 PTC): TSH typically in 0.1 - 0.5 mIU/L rangetypically in 0.1 - 0.5 mIU/L range

• High-risk (MACIS 6+ PTC; FTC/HCC): High-risk (MACIS 6+ PTC; FTC/HCC): aiming for TSH of 0.1 mIU/L or less aiming for TSH of 0.1 mIU/L or less

Appropriate Degree of Initial TSH SuppressionAppropriate Degree of Initial TSH SuppressionATA 2006 DTC Management GuidelinesATA 2006 DTC Management Guidelines

• ““R40. Initial thyrotropin suppression to R40. Initial thyrotropin suppression to below 0.1 mU/L is recommended for high-below 0.1 mU/L is recommended for high-risk patients with thyroid cancer, while risk patients with thyroid cancer, while maintenance of the TSH at or slightly maintenance of the TSH at or slightly below the lower limit of normal (0.1-0.5 below the lower limit of normal (0.1-0.5 mU/L) is appropriate for low-risk patients – mU/L) is appropriate for low-risk patients – Recommendation B”Recommendation B”

Thyroid 16: 1-33, 2006.Thyroid 16: 1-33, 2006.

2,512 Papillary Thyroid Carcinoma Patients2,512 Papillary Thyroid Carcinoma PatientsManaged During 1940-2000Managed During 1940-2000

Therapeutic TrendsTherapeutic Trends

CP1028491-3

0

20

40

60

80

100

Remnant ablationn=6621940-2000

Remnant ablationn=6621940-2000

Pa

tie

nts

(%

)P

ati

en

ts (

%)

n=2,512P<0.001n=2,512P<0.001

1940-54

Bilateral lobar resection(2,179)

Bilateral lobar resection(2,179)



1955-69 1970-84 1985-2000 1940-54 1955-69 1970-84 1985-2000

46%46%

32%32%

3%3%1%1%

Radioiodine Remnant Ablation Radioiodine Remnant Ablation in MACIS <6 Low-Risk PTCin MACIS <6 Low-Risk PTC

• Recent analysis of outcome in 1,163 Recent analysis of outcome in 1,163 patients treated during 1970-2000patients treated during 1970-2000

• When patients divided into 636 node-When patients divided into 636 node-negative and 527 node-positive, negative and 527 node-positive, nono differences in outcome (mortality and differences in outcome (mortality and recurrence) were found between those recurrence) were found between those having surgery alone and those also having surgery alone and those also receiving postoperative RRAreceiving postoperative RRA

Trans ACCA 113: 241, 2002Trans ACCA 113: 241, 2002

Survival for “low risk” PTC Survival for “low risk” PTC (MACIS < 6)(MACIS < 6)

85

90

100

0 5 10 15 200

95

Sur

viva

l (ca

use-

spec

ific)

Years from diagnosis

I131 Ablation (n=498)

No Ablation (n=665)

1163 patients; total or near-total TTX; 1970 - 2000

Survival (TSurvival (TxxNN00MM00, MACIS<6), MACIS<6)

0 5 10 15 20


Sur

viva

l (%

)


No Ablation (n=441)

85

90

100

0

95

636 node negative patients; total or near-total TTX; 1970 - 2000

Survival (TSurvival (TxxNN11MM00, MACIS<6), MACIS<6)

85

90

100

0 5 10 15 200

95

Sur

viva

l (ca

use-

spec

ific)



No Ablation (n=224)

527 node positive patients; total or near-total TTX; 1970 - 2000

Recurrence in “low risk” PTCRecurrence in “low risk” PTC

0 5 10 15 2084

88

92

96

100


Rel

apse

fre

e su

rviv

al (

%)

I131 Ablation

No Ablation

1163 patients; total or near-total TTX; 1970 - 2000

Recurrence (TRecurrence (TxxNN00MM00, MACIS<6), MACIS<6)

0 5 10 15 20


I131 Ablation

No Ablation

80

90

100

636 node negative patients; total or near-total TTX; 1970 - 2000

Recurrence (TRecurrence (TxxNN11MM00, MACIS<6), MACIS<6)

5 10 15 20


I131 Ablation

No Ablation

080

90

100

527 node positive patients; total or near-total TTX; 1970 - 2000

Selective Approach to Selective Approach to Postoperative RRAPostoperative RRA

• Current Mayo practice: to restrict RRA to Current Mayo practice: to restrict RRA to patients with high-risk (MACIS 6+) PTC patients with high-risk (MACIS 6+) PTC and to patients with FTC or HCCand to patients with FTC or HCC

• Recent study of 6,841 European patients Recent study of 6,841 European patients demonstrated increased risk of both solid demonstrated increased risk of both solid tumors and leukemia after I-131 treatment tumors and leukemia after I-131 treatment and concluded that “it seems necessary to and concluded that “it seems necessary to restrict the use of I-131 to thyroid cancer restrict the use of I-131 to thyroid cancer patients in whom it may be beneficial”patients in whom it may be beneficial”

Br J Cancer 89: 1638, 2003Br J Cancer 89: 1638, 2003

Role of Postoperative RRARole of Postoperative RRAATA 2006 GuidelinesATA 2006 Guidelines

• ““R32. Radioiodine ablation is recommended for R32. Radioiodine ablation is recommended for patients with stage III and IV disease (AJCC 6patients with stage III and IV disease (AJCC 6 thth edition), all patients with stage II disease 45 edition), all patients with stage II disease 45 years or older, and selected patients with stage I years or older, and selected patients with stage I disease, especially those with multifocal disease, especially those with multifocal disease, nodal metastases, extrathyroidal or disease, nodal metastases, extrathyroidal or vascular invasion, and/or more aggressive vascular invasion, and/or more aggressive histologies – Recommendation B”.histologies – Recommendation B”.

Thyroid 16: 1-33, 2006.Thyroid 16: 1-33, 2006.

Techniques for Postoperative Techniques for Postoperative RRARRA

• Some American centers now favor “blind” Some American centers now favor “blind” administration of large (100 - 175 mCi) I-131 administration of large (100 - 175 mCi) I-131 doses without preceding diagnostic scan, doses without preceding diagnostic scan, and depend on utility of post-therapy WBSand depend on utility of post-therapy WBS

• In ‘selected’ cases, Mayo practice now is to In ‘selected’ cases, Mayo practice now is to perform uptake quantitation during I-123 scan perform uptake quantitation during I-123 scan , ‘customize’ the I-131 therapy, follow with , ‘customize’ the I-131 therapy, follow with diagnostic I-123 scans after 3-6 monthsdiagnostic I-123 scans after 3-6 months


ManagementManagementI.I. Diagnosis: cytologic and Diagnosis: cytologic and histopathologichistopathologic

II.II. Primary surgical treatmentPrimary surgical treatmentIII.III. Staging and risk-group Staging and risk-group

assignmentassignmentIV.IV. Adjuvant therapyAdjuvant therapyV.V. Long-term surveillanceLong-term surveillance

Postoperative Postoperative Surveillance in PTCSurveillance in PTC

•Thyroglobulin levelsThyroglobulin levels

•Appropriate imagingAppropriate imaging

Thyroglobulin: on or off thyroid Thyroglobulin: on or off thyroid hormone suppression therapy?hormone suppression therapy?

• Mail-in thyroid cascade (TSH-based) Mail-in thyroid cascade (TSH-based) and Tg on every returning visitand Tg on every returning visit

• Also, measure TSH and Tg, while off Also, measure TSH and Tg, while off THST, at time of I-123 body scanningTHST, at time of I-123 body scanning

• Personally, do not favor stopping T4 Personally, do not favor stopping T4 or giving rhTSH or giving rhTSH onlyonly for the purpose for the purpose of determining Tg incrementof determining Tg increment

Stimulated Tg Levels in Low-Risk PatientsStimulated Tg Levels in Low-Risk PatientsATA 2006 GuidelinesATA 2006 Guidelines

• ““R45. In low-risk patients, who have had remnant R45. In low-risk patients, who have had remnant ablation and negative cervical ultrasound and ablation and negative cervical ultrasound and TSH-suppressed Tg 6 months after treatment, TSH-suppressed Tg 6 months after treatment, serum Tg should be measured after T4 serum Tg should be measured after T4 withdrawal or rhTSH stimulation approximately withdrawal or rhTSH stimulation approximately 12 months after the ablation to verify absence of 12 months after the ablation to verify absence of disease. The timing or necessity of subsequent disease. The timing or necessity of subsequent stimulated testing is uncertain for those found to stimulated testing is uncertain for those found to be free of disease – Recommendation A.” be free of disease – Recommendation A.”

Thyroid 16: 1-33, 2006.Thyroid 16: 1-33, 2006.

rhTSH Stimulation and Presently rhTSH Stimulation and Presently Undetectable Serum Tg LevelsUndetectable Serum Tg Levels

• A recent consensus (JCEM 88:1433, 2003) A recent consensus (JCEM 88:1433, 2003) suggested that a serum Tg suggested that a serum Tg <1 ng/mL<1 ng/mL measured on THST is “misleading in a large measured on THST is “misleading in a large proportion of patients with residual DTC”proportion of patients with residual DTC”

• When Tg measured as When Tg measured as <0.1 ng/mL on THST<0.1 ng/mL on THST, , provides reassurance of a lack of relevant provides reassurance of a lack of relevant tumor recurrence in Ab-negative low-risk PTCtumor recurrence in Ab-negative low-risk PTC

• Soon, Tg assay detection limits will approach Soon, Tg assay detection limits will approach 0.01 ng/mL0.01 ng/mL ; therefore, likely making rhTSH ; therefore, likely making rhTSH stimulation a costly and unnecessary test stimulation a costly and unnecessary test

Detectable Tg and Detectable Tg and Tumor RecurrenceTumor Recurrence

• “ “I personally consider a I personally consider a ‘positive’ biopsy as proof of ‘positive’ biopsy as proof of disease rediscovery, but I disease rediscovery, but I consider a detectable Tg at consider a detectable Tg at best a possible ‘surrogate’ best a possible ‘surrogate’ for tumor recurrence”for tumor recurrence”

Postoperative Postoperative Surveillance in LRPTCSurveillance in LRPTC

•Appropriate imagingAppropriate imaging

Selective Use of Imaging Selective Use of Imaging in Postop Surveillancein Postop Surveillance

• I-131 therapy restricted to high-risk I-131 therapy restricted to high-risk patients; I-123 WBS used primarily to patients; I-123 WBS used primarily to assess adequacy of I-131 therapyassess adequacy of I-131 therapy

• CT, MRI, PET/CT CT, MRI, PET/CT notnot regularly employed regularly employed• Heavy reliance on skilled sonographers to Heavy reliance on skilled sonographers to

identify or exclude locoregional diseaseidentify or exclude locoregional disease• Real-time US used to guide biopsies of Real-time US used to guide biopsies of

possible neck recurrences, and to enable possible neck recurrences, and to enable percutaneous ethanol ablation of nodespercutaneous ethanol ablation of nodes

Treatment Alternatives for PTC in Persistent/Recurrent Neck Nodes Treatment Alternatives for PTC in Persistent/Recurrent Neck Nodes

Neck DissectionNeck Dissection RadioactiveI131 therapyRadioactiveI131 therapy External RadiationExternal Radiation

TraditionalTraditional

Alcohol AblationAlcohol AblationAlternativeAlternative

TechniqueTechnique

• 95% ethanol

• 25 g needle and Tb syringe

• 0.1-0.8 cc (mean 0.3 ml)

• Inject tiny amount until node becomes echogenic

• 95% ethanol

• 25 g needle and Tb syringe

• 0.1-0.8 cc (mean 0.3 ml)

• Inject tiny amount until node becomes echogenic

• Reinject next day in most pts• Reinject next day in most pts

Ablation of Papillary Nodal MetastasisAblation of Papillary Nodal Metastasis

Results in Stage I PTCResults in Stage I PTC

• All 60 decreased in size; 40 (67%) no longer identified

• Average decrease size = 95%

• All 60 decreased in size; 40 (67%) no longer identified

• Average decrease size = 95%

60 Nodes Treated in 35 Pts60 Nodes Treated in 35 Pts

Avg. 0.5 cmAvg. 0.5 cm33 before inj. before inj.Avg. 0.5 cmAvg. 0.5 cm33 before inj. before inj.

Avg. 0.02 cmAvg. 0.02 cm33 after inj. at 24 moafter inj. at 24 mo

Avg. 0.02 cmAvg. 0.02 cm33 after inj. at 24 moafter inj. at 24 mo

‘‘Common Sense’ Approach Common Sense’ Approach to LRPTC Managementto LRPTC ManagementI.I. Diagnosis: cytologic and Diagnosis: cytologic and

histopathologichistopathologicII.II. Primary surgical treatmentPrimary surgical treatmentIII.III. Staging and risk-group Staging and risk-group

assignmentassignmentIV.IV. Adjuvant therapyAdjuvant therapyV.V. Long-term surveillanceLong-term surveillance

Five “Golden Rules” for Five “Golden Rules” for LRDTC ManagementLRDTC Management

I.I. Carefully choose your trusted, Carefully choose your trusted, locally based, pathologistlocally based, pathologist

II.II. Know the skills and/or limitations Know the skills and/or limitations of your thyroid surgeonsof your thyroid surgeons

III.III. Use TNM stages and apply scoringUse TNM stages and apply scoringIV.IV. Try to use I-131 therapy selectivelyTry to use I-131 therapy selectivelyV.V. Revere US scanning, and permit Revere US scanning, and permit

tolerance of ‘detectable’ Tg levelstolerance of ‘detectable’ Tg levels

The endThe end

• Proceed to post testProceed to post test

• Print post testPrint post test

• Complete post testComplete post test

• Return post test to Return post test to Dr. Sandra OliverDr. Sandra Oliver 407i TAMUII407i TAMUII

Post testPost test

• List the five “Golden Rules” for List the five “Golden Rules” for LRDTC Management:LRDTC Management:

• 1.1.

• 2.2.

• 3.3.

• 4.4.

• 5.5.

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