Active Surveillance for Thyroid Cancer

(PMCAS Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Allen Ho, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Cedars-Sinai Medical Center

Disqualifiers: High-grade PTC, Neck lymphadenopathy, Unfavorable nodule location, History of neck radiation

No Placebo Group

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to better understand the outcomes of active surveillance (observation) instead of immediate surgery, which is the current standard of care for papillary thyroid microcarcinoma (PTMC). Patients with a 1.5 cm or smaller thyroid nodule(s) with papillary thyroid carcinoma will be eligible for the study.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Active Surveillance for Thyroid Cancer?

Research shows that for younger patients with small, low-risk papillary thyroid cancers, active surveillance (monitoring the cancer closely without immediate surgery) has similar survival rates to surgery. This suggests that active surveillance can be a safe and effective option for managing certain thyroid cancers. ^{1 2 3 4 5}

Is active surveillance safe for thyroid cancer patients?

Active surveillance is generally considered a safe alternative to surgery for patients with low-risk papillary thyroid cancer, as it avoids the potential adverse events associated with surgery. ^{1 2 6 7 8}

How does active surveillance differ from other treatments for thyroid cancer?

Active surveillance for thyroid cancer involves closely monitoring the condition without immediate surgery, focusing on small, low-risk tumors. This approach is unique because it avoids the risks and recovery associated with surgery, opting instead for regular check-ups to track any changes in the cancer's status. ^{2 8 9 10 11}

Research Team

Allen Ho, MD

Principal Investigator

Cedars-Sinal Medical Center

Eligibility Criteria

This trial is for individuals with small thyroid nodules (2.0 cm or smaller) diagnosed as papillary thyroid carcinoma, who can read and write English fluently for questionnaires. It's not suitable for those with unfavorably located nodules, a history of neck radiation, aggressive cancer variants, or suspicious lymphadenopathy.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent and HIPAA Authorization form

Must be able to read and write English fluently to participate in the questionnaire portion of the study

My thyroid nodules are confirmed to be at high risk for cancer or have a BRAF mutation.

Exclusion Criteria

I have swollen lymph nodes in my neck that may indicate thyroid cancer.

My tumor is located in a risky area near important neck structures.

I have had radiation treatment to my neck.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Active Surveillance

Participants are monitored every six months until disease is stable for a two-year period and then annually thereafter

3-10 years

Biannual visits for 2 years, then annual visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Active Surveillance (Behavioural Intervention)

Trial Overview The study is examining the outcomes of monitoring patients with papillary thyroid microcarcinoma through active surveillance instead of immediate surgery to see if waiting and watching could be safe and effective.

Participant Groups

Group I: Active Surveillance Experimental Treatment 1 Intervention

Active surveillance instead of standard of care immediate surgery. Patients will be closely monitored every six months until disease is stable for a two-year period and then annually thereafter.

Group II: Immediate Surgery Active Control 1 Intervention

Patients who choose to get surgery immediately after diagnosis may choose to enroll in a questionnaire sub-study that will compare quality of life and anxiety scores to patients who enroll in the active surveillance study. This is considered "no intervention" because the protocol is not directing treatment. Surgery is the standard treatment for papillary thyroid microcarcinoma.

Active Surveillance is already approved in Canada, Japan for the following indications:

Approved in Canada as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

Approved in Japan as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

David E. Cohen

Cedars-Sinai Medical Center

Chief Medical Officer

MD and PhD in Physiology and Biophysics from Harvard University

Peter L. Slavin

Cedars-Sinai Medical Center

Chief Executive Officer

MD from Harvard Medical School, MBA from Harvard Business School

Findings from Research

A web-based decision support tool was developed to help clinicians identify patients with very low risk papillary thyroid cancer (PTC) who may be suitable for active surveillance (AS), with 52% of assessed patients meeting the criteria for AS.

In a study of 447 patients who underwent hemithyroidectomy for PTC, 83% of those selected for AS did not require further surgery or intervention during a median follow-up of over 3 years, indicating the tool's potential effectiveness in managing low-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a novel clinical support tool for active surveillance of low risk papillary thyroid cancer. White, E., Abbott, B., Schembri, G., et al.[2023]

In a review of 5 studies involving 2,097 patients, older adults (40 years and older) showed a significantly lower risk of tumor growth in low-risk papillary thyroid carcinoma compared to younger individuals, suggesting that age may be a protective factor during active surveillance.

The study found that incident metastatic disease was rare during active surveillance, indicating that this management strategy may be safe and effective for patients with small, low-risk papillary thyroid carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Patient Age With Progression of Low-risk Papillary Thyroid Carcinoma Under Active Surveillance: A Systematic Review and Meta-analysis. Koshkina, A., Fazelzad, R., Sugitani, I., et al.[2021]

In a study of 136 patients with papillary thyroid carcinoma (PTC), only 25% accepted active surveillance as an alternative to surgery, with 10% of those abandoning the approach due to anxiety.

After a median follow-up of 4.6 years, only 17% of patients experienced tumor enlargement, and those who eventually underwent surgery showed no evidence of disease after a median follow-up of 3.8 years, suggesting that active surveillance can be a safe option for managing PTC in selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active surveillance in papillary thyroid carcinoma: not easily accepted but possible in Latin America. Smulever, A., Pitoia, F.[2023]

In a study of 28,728 non-metastasized thyroid cancers, T1a and T1b tumors showed similar survival outcomes, with a very low disease-specific mortality rate of only 4.3% over a maximum follow-up of 10.9 years, indicating that many early thyroid cancers may not require aggressive treatment.

The risk of death from untreated T1a or T1b tumors was found to be 21 times lower than death from other causes, suggesting that observation and surveillance could be safely extended to these early-stage thyroid cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population-level Outcomes of Early Thyroid Cancers: A Need to Revisit Current Practice. Chaturvedi, P., Singh, A., Bhattacharjee, A., et al.[2022]

In a study of 286 patients with low-risk papillary thyroid carcinoma (PTC), those who chose active surveillance (AS) experienced fewer postoperative complications compared to those who underwent immediate surgery, suggesting AS may be a safer initial approach.

Among patients who opted for AS, only 14.6% showed tumor growth and 4.8% developed lymph-node metastases after a median follow-up of 37.5 months, indicating that AS can effectively monitor low-risk PTC without significant progression in most cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High rate incidence of post-surgical adverse events in patients with low-risk papillary thyroid cancer who did not accept active surveillance. Smulever, A., Pitoia, F.[2021]

Active surveillance for highly suspicious thyroid nodules ≤10 mm in Chinese patients shows promising oncological outcomes, with a low cumulative incidence of disease progression (6.0% at 5 years and 12.8% at 10 years) and no reported distant metastasis or deaths during a median follow-up of 28.5 months.

Younger patients (≤30 years old) experience higher levels of anxiety and worse emotional function compared to older patients, indicating a need for additional psychological support for this age group during active surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active surveillance of highly suspicious thyroid nodules cohort in China shows a worse psychological status in younger patients. Liu, C., Zhao, H., Xia, Y., et al.[2022]

In a study of 112 patients with small, highly suspicious thyroid nodules, only 3.6% showed significant growth and 1.8% developed new lymph node metastasis during an average follow-up of 4.8 years, indicating a low disease progression rate under active surveillance.

The study suggests that fine needle aspiration (FNA) may be performed less frequently in these cases, as disease progression was linked to specific growth metrics, allowing for a more conservative approach to monitoring small nodules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Undercover active surveillance of small highly suspicious thyroid nodules without fine needle aspiration. Kim, CA., Yoo, J., Oh, HS., et al.[2023]

In a study of 291 patients with low-risk papillary thyroid cancer (PTC) under active surveillance, only 3.8% showed significant tumor growth (3 mm or more) over a median follow-up of 25 months, indicating that active surveillance is a safe option for managing small PTCs.

The study found that younger age at diagnosis and specific risk categories were associated with a higher likelihood of tumor growth, and that using 3-dimensional measurements allowed for earlier detection of growth, which could help guide future treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance. Tuttle, RM., Fagin, JA., Minkowitz, G., et al.[2023]

A national Canadian study is being planned to evaluate the long-term outcomes of patients with small, low-risk papillary thyroid cancer (PTC) who opt for active surveillance instead of surgery.

This research aims to provide insights into the safety and efficacy of active surveillance as a management strategy for low-risk PTC, which could influence treatment decisions for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proceedings of the Canadian Thyroid Cancer Active Surveillance Study Group 2019 national investigator meeting. Goldstein, DP., Ghai, S., Corsten, M., et al.[2021]

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) showed similar oncological outcomes to immediate surgery (IS) in a study of 816 patients, suggesting it is a viable treatment option.

Patients undergoing IS experienced significantly higher rates of temporary vocal cord paralysis and hypoparathyroidism, along with more complaints about quality of life related to voice and scarring, indicating that AS may offer a safer alternative with fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China. Liu, C., Zhao, H., Xia, Y., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Development of a novel clinical support tool for active surveillance of low risk papillary thyroid cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Association of Patient Age With Progression of Low-risk Papillary Thyroid Carcinoma Under Active Surveillance: A Systematic Review and Meta-analysis. [2021]

3. Brazil pubmed.ncbi.nlm.nih.gov

Active surveillance in papillary thyroid carcinoma: not easily accepted but possible in Latin America. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Mortality Risk of Nonoperative Papillary Thyroid Carcinoma: A Corollary for Active Surveillance. [2020]

5. Israel pubmed.ncbi.nlm.nih.gov

Population-level Outcomes of Early Thyroid Cancers: A Need to Revisit Current Practice. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

High rate incidence of post-surgical adverse events in patients with low-risk papillary thyroid cancer who did not accept active surveillance. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Active surveillance of highly suspicious thyroid nodules cohort in China shows a worse psychological status in younger patients. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Undercover active surveillance of small highly suspicious thyroid nodules without fine needle aspiration. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Proceedings of the Canadian Thyroid Cancer Active Surveillance Study Group 2019 national investigator meeting. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Active surveillance versus immediate surgery: A comparison of clinical and quality of life outcomes among patients with highly suspicious thyroid nodules 1 cm or smaller in China. [2023]