Tg undetected, no need further testing

Tg < 0.1 no need for testing

"This study is helpful because it indicates that for most patients with thyroglobulin values of <0.1 ng/ml while on thyroid hormone suppression, stimulated thyroglobulin testing is unnecessary since the likelihood of identifying residual cancer is very small. These findings will cut down on the need to perform stimulated thyroglobulin testing, which is both inconvenient for patients and expensive. Long term follow up of patients with thyroid cancer, however, still requires periodic measurement of thyroglobulin, since other studies indicate that ~4% of patients with initially undetectable basal thyroglobulin levels eventually had recurrent cancer."

http://www.thyroid.org/patient-thyroid-information/ct-for-patients/vol-7-is sue-2/vol-7-issue-2-p-7-8/
When thyroglobulin is undetectable, is any further testing needed in following patients with thyroid cancer?

BACKGROUND
Thyroglobulin is a protein produced by both normal and cancerous thyroid cells. Treatment of thyroid cancer frequently involves total thyroidectomy and radioiodine therapy followed by thyroid hormone therapy to suppress serum TSH and turn off any residual normal thyroid cells. In this situation, the serum thyroglobulin level can be used as a thyroid cancer marker. Indeed, if any thyroid cancer cells are present, levels of thyroglobulin are often detectable, either on TSH suppression therapy or after stimulation with rhTSH (stimulated thyroglobulin testing). Measurement of thyroglobulin under these conditions has become standard practice in the follow up of patients with thyroid cancer. This study is an analysis of many other studies as to the usefulness of measuring serum thyroglobulin levels in managing patients with thyroid cancer.

THE FULL ARTICLE TITLE: Giovanella L et al, Unstimulated high-sensitive thyroglobulin in follow-up of differentiated thyroid cancer patients: a meta-analysis. J Clin Endocrinol Metab. 2013 Nov 27.

SUMMARY OF THE STUDY
This study is an analysis of many other studies evaluating the utility of measuring thyroglobulin levels under thyroid hormone suppression therapy and after stimulation with rhTSH in patients with thyroid cancer. The authors identified 9 studies that used the newer, more sensitive thyroglobulin assay. These studies included a total of 3178 patients. The investigators found that when the basal thyroglobulin level under thyroid hormone suppression therapy is <0.1 ng/ml, it accurately predicts that the stimulated thyroglobulin level will be <1, which indicates absence of residual cancer cells.

WHAT ARE THE IMPLICATIONS OF THIS STUDY? This study is helpful because it indicates that for most patients with thyroglobulin values of <0.1 ng/ml while on thyroid hormone suppression, stimulated thyroglobulin testing is unnecessary since the likelihood of identifying residual cancer is very small. These findings will cut down on the need to perform stimulated thyroglobulin testing, which is both inconvenient for patients and expensive. Long term follow up of patients with thyroid cancer, however, still requires periodic measurement of thyroglobulin, since other studies indicate that ~4% of patients with initially undetectable basal thyroglobulin levels eventually had recurrent cancer.

—M. Regina Castro, MD

ATA THYROID BROCHURE LINKS

Thyroid cancer: http://www.thyroid.org/cancer-of-the-thyroid-gland

Radioactive Iodine Therapy: http://www.thyroid.org/radioactive-iodine

RAI on Small Differentiated Thyroid Cancer Having Microscopic Extrathyroidal Extension

Effects of Low-Dose and High-Dose Postoperative Radioiodine Therapy on the Clinical Outcome in Patients with Small Differentiated Thyroid Cancer Having Microscopic Extrathyroidal Extension

Background: It is unclear whether differentiated thyroid cancer (DTC) patients classified as intermediate risk based on the presence of microscopic extrathyroidal extension (ETE) should be treated with low or high doses of radioiodine (RAI) after surgery. We evaluated success rates and long-term clinical outcomes of patients with DTC of small tumor size, microscopic ETE, and no cervical lymph node (LN) metastasis treated either with a low (1.1 GBq) or high RAI dose (5.5 GBq).

Methods: This is a retrospective analysis of a historical cohort from 2000 to 2010 in a tertiary referral hospital. A total of 176 patients with small (≤2 cm) DTC, microscopic ETE, and no cervical LN metastasis were included. Ninety-six patients were treated with 1.1 GBq (LO group) and 80 patients with 5.5 GBq (HI group). Successful RAI therapy was defined as (i) negative stimulated thyroglobulin (Tg) in the absence of Tg antibodies, and (ii) absence of remnant thyroid tissue and of abnormal cervical LNs on ultrasonography. Clinical recurrence was defined as the reappearance of disease after ablation, which was confirmed by cytologically or pathologically proven malignant tissue or of distant metastatic lesions.

Results: There was no significant difference in the rate of successful RAI therapy between the LO and HI group (p=0.75). In a subgroup analysis based on tumor size, success rates were not different between the LO group (34/35, 97%) and the HI group (50/56, 89%) in patients with a tumor size of 1–2 cm (p=0.24). In patients with smaller tumor size (≤1 cm), there was no significant difference in success rates between the LO (59/61, 97%) and HI group (22/24, 92%; p=0.30). No patient had clinical recurrences in either group during the median 7.2 years of follow-up.

Conclusions: Low-dose RAI therapy is sufficient to treat DTC patients classified as intermediate risk just by the presence of microscopic ETE.

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Stage III papillary thyroid cancer

Stage III is papillary carcinoma in patients older than 45 years that is larger than 4 cm and is limited to the thyroid or with minimal extrathyroid extension, or positive lymph nodes limited to the pretracheal, paratracheal, or prelaryngeal/Delphian nodes. Papillary carcinoma that has invaded adjacent cervical tissue has a worse prognosis than tumors confined to the thyroid.

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Pathology report 
 tumor #1 with focal extension into soft tissue immediately surrounding thyroid.

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any staging methods have been developed in order to predict the prognosis for a patient with differentiated thyroid cancer. These methods quantify various characteristics of the individual tumor as well as the patient. Fortunately most types of thyroid cancer have an excellent prognosis. Unlike other types of cancer, the prognosis of differentiated thyroid cancer largely depends on the age of the patient at the time it is diagnosed. Thyroid cancers which are not differentiated (medullary and anaplastic cancers), are more difficult to quantify and therefore reliable staging methods are not available. The three most commonly used methods are described below. 

It is important to note that the essence of all staging methods is that age is a major factor when determining prognosis. Young people rarely die of their disease regardless of whether the surrounding lymph nodes were affected, some of the tumor is not removed, the tumor extends into the veins or outside of the tissue which encapsulates it. However, for older patients all of these factors play a significant role in long term disease free survival. 

Another important fact to keep in mind is that as long as the cancer is completely removed (remember that up to 70% of the time the cancer can be in both lobes of the thyroid gland), it makes no difference in survival if a portion of the thyroid or the entire thyroid is removed. Furthermore, for papillary cancer, many staging methods are not concerned with the spread (metastases) of cancer in the surrounding lymph nodes. This is because, thyroid cancer that spreads to the lymph nodes of the neck does not threaten survival at all. This is a difficult concept for many patients to understand, because for many other types of cancers, such as breast, colon and lung cancers, positive lymph nodes give you a worse prognosis, but is not true for papillary thyroid cancers. 

MAICS 

The MAICS method was developed by the Mayo Clinic based on careful evaluation of a large group of patients. It is probably the most reliable staging method available and therefore most accurately predicts a patient\\\\"s outcome compared to other methods. It was developed to determine the prognosis of patients with papillary thyroid cancer. MAICS is an abbreviation for the factors taken into account to predict survival: (distant) Metastasis or spread of the cancer to areas outside the neck, Age of the patient at the time the tumor was discovered, Invasion of the cancerous tumor into surrounding areas of the neck as seen by the naked eye, (in)Completeness of surgical resection (or removal) of the tumor, and Size of the tumor. Each of these factors is mathematically scored as shown in the table below: 

FACTORS	SCORE
distant Metastasis: Did the tumor spread to other parts of the body outside of the region of the neck?	yes = 3 no = 0
Age at the time the tumor was found	less than 39 years = 3.1 over 40 = 0.08 x age
Invasion:Did the surgeon see that the tumor had extended beyond the thyroid into other regions of the neck?	yes = 1 no = 0
inComplete resection: Were there parts of the tumor that the surgeon was unable to remove (for example a part that was attached to the windpipe)?	yes = 1 no = 0
Size of tumor (measured by the pathologist)	0.3 x size in cm

Once the score for each factor is calculated, they are added up to get a total MAICS score and this total predicts the likelihood that the patient will live 20 years from the time the tumor was discovered. Fortunately most patients fall into the low risk category (MAICS score less than 6.0) and are cured of the cancer at the time of surgery.

20-year survival rate according to MAICS score
MAICS Score	< 6.0	6.0 - 6.99	7.0 - 7.99	> 8.0
20 yr Survival	99%	89%	56%	24%

TNM

The TNM method is the most universally used staging method and applies to both papillary and follicular thyroid cancers. It was introduced in 1987 by the International Union Against Cancer and adopted by the American Joint Commission on Cancer. TNM stands for:

T: Tumor size (in cm). T=1 if the tumor is less than 1cm; T = 2 if it is 1-4 cm; T=3 if it is greater than 4 cm; and T=4 if the tumor extends beyond the thyroid gland.

N: Node metastasis - presence or absence of lymph node metastases (meaning has the cancer spread to the lymph nodes in the neck). If the cancer has spread to the lymph nodes, N = 1; if none of the lymph nodes were affected, N = 0

M: distant Metastases (meaning has the cancer spread beyond the neck to other areas of the body like the lung or bone) - if there is distant metastases, M = 1, if the cancer has not spread outside of the neck region, M = 0

Based on these three categories, the cancer is assigned a Stage of 1, 2 ,3 or 4. Stage 1 is the least advanced form of cancer with the best prognosis, and Stage 4 is the most advanced category. The table below shows the likelihood of a local recurrence (or recurrence of thyroid cancer in the neck region), distant recurrence (recurrence of cancer in other areas of the body), and mortality (death) based on the stage of a given tumor. 

STAGE	AGE < 45	AGE > 45	Local Recurrence	Distant Recurrence	Mortality
I	Any T Any N M0	T1 N0 M0	5.5%	2.8%	1.8%
II	Any T Any N M1	T2 N0 M0 T3 N0 M0	7%	7%	11.6%
III	-	T4 N0 M0 Any T Any N M1	27%	13.5%	37.8%
IV	-	Any T Any N M1	10%	100%	90%

It is important to note that classifications made by a pathologist can be very subjective, particularly for tumors that have few distinctive characteristics, which is often the case with follicular cancer. For this reason, reliably staging a follicular thyroid cancer is more difficult because it is influenced by the subjective classification made by the pathologist. For example, some pathologists define a microscopic capsular invasion and a microscopic vascular invasion (minute extensions of the tumor which can only be seen under a microscope) as cancer while others may not. 

AMES

 Anther popular staging method is the AMES method, developed by the Lahey Clinic. Like the TNM method, it is applicable to both papillary and follicular thyroid cancers. This method takes into account the Age of the patient when the tumor was discovered, Metastases of the tumor to different sites other than neck lymph nodes, the Extent of primary tumor and, the Size of the tumor (if it is larger than 5 cm, or about 2 inches). Once these factors are determined, the patient is then placed into a high or low risk category, as shown in the table below:

LOW RISK 1.8% Mortality Rate	HIGH RISK 46% Mortality Rate
Men under 41 and Women under 51 without distant metastases	All patients with distant metastases
All men over 41 and women over 51 with: Intra-thyroidal papillary cancer (papillary cancer confined present only within the thyroid gland) ORfollicular cancer tumor with minor capsular involvement(the tumor slightly extends into the capsule which surrounds it) AND Primary tumor less than 5 cm in diameter AND No distant metastases	All men over 41 and women over 51 with: Extra-thyroidal papillary cancer (extends beyond the thyroid gland) OR follicular cancer tumor with major capsular involvement(the tumor extends significantly into the capsule which surrounds it) AND/OR Primary cancer is 5 cm in diameter or larger, regar

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RAI for node negative PTC with capsular invasion only

Here's a new study which found that RAI treatment doesn't affect the recurrence rate for patients with microscopic capsular invasion:

http://onlinelibrary.wiley.com/doi/10.1111/ajco.12159/abstract;jsessionid=C 8E8BD1F53EC125912D7470200CA70B0.f03t04?deniedAccessCustomisedMessage=&userI sAuthenticated=false

Keywords:

• capsular invasion;
• papillary thyroid carcinoma;
• radioactive iodine ablation;
• recurrence

Abstract

Aim

With thyroid carcinoma the decision to use radioactive iodine (RAI) ablation depends on the risk of poor outcomes. Although extrathyroid extension (ETE) is well known as a risk of poor outcomes for papillary thyroid carcinoma (PTC), the definition of minimal ETE is too broad, as it encompasses both microscopic invasion of the thyroid capsule (capsular invasion [CI]) and macroscopic invasion of the sternothyroid muscle.

Methods

We conducted a retrospective study to analyze the prognostic benefit of RAI ablation according to the presence of CI in a consecutive series of patients with PTC between October 1997 and December 2008. We studied two groups of patients, including those who received RAI (group I, n = 121) and those who did not (group II, n = 108). During follow-up, we assessed the locoregional recurrence of all patients.

Results

There were no statistically significant difference between the groups regarding locoregional recurrence at follow-up (13.2% for group I vs 9.3% for group II, P = 0.441). The association between RAI and locoregional recurrence in PTC patients with CI remained insignificant after adjusting for potential confounders, such as age, tumor size, sex, lymphatic invasion, vascular invasion and tumor multiplicity (P = 0.409, hazard ratio = 0.698, 95% confidence interval, 0.298–1.639).

Conclusions

This retrospective study suggests that RAI treatment is not associated with less locoregional recurrence in PTC patients who only demonstrate CI, although further prospective studies are required to confirm these findings.