Active Surveillance for Thyroid Cancer

(PMCAS Trial)

Overseen By Allen Ho, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Cedars-Sinai Medical Center

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

216 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether closely monitoring small thyroid cancers instead of immediate surgery can be a safe option. The focus is on papillary thyroid microcarcinoma, particularly nodules 2.0 cm or smaller. Participants will undergo monitoring every six months, and if the cancer remains stable for two years, then annually. This trial suits individuals with confirmed or suspected small papillary thyroid carcinoma who are comfortable with regular check-ups and can read and write English fluently for study questionnaires. Known as Active Surveillance (also referred to as Watchful Waiting or Observation), this approach offers an alternative to immediate surgery, potentially reducing unnecessary procedures while ensuring patient safety. As an unphased trial, it allows participants to contribute to research that could redefine treatment approaches for small thyroid cancers.

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 prior data suggests that active surveillance is safe for patients with papillary thyroid microcarcinoma?

Research has shown that carefully monitoring small papillary thyroid cancers (PTMC) is a safe option. Studies from Japan found that observing these small cancers instead of opting for immediate surgery is both safe and cost-effective over time. In these studies, no participants died from thyroid cancer or experienced metastasis.

Many health guidelines now recommend monitoring as a viable alternative to immediate surgery for low-risk thyroid cancers. This approach allows for regular check-ups without immediate surgery, offering patients a less invasive option with fewer risks of complications. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about active surveillance for thyroid cancer because it offers a less invasive alternative to immediate surgery. Unlike the standard approach of quickly removing the thyroid, active surveillance allows doctors to closely monitor small thyroid cancers, like papillary thyroid microcarcinoma, and intervene only if necessary. This method could reduce unnecessary surgeries, sparing patients from potential complications and preserving their quality of life. Additionally, it may help lower anxiety by avoiding immediate surgical intervention, offering patients a more relaxed monitoring plan with regular check-ups.

What evidence suggests that active surveillance is effective for papillary thyroid microcarcinoma?

Research has shown that watching and waiting, also known as active surveillance, is a safe and practical way to manage low-risk papillary thyroid microcarcinomas (PTMC). In this trial, participants in the active surveillance arm will undergo close monitoring every six months until the disease remains stable for two years, followed by annual check-ups. Studies have found that patients who choose this approach instead of immediate surgery often do well. In one study, only one out of 191 patients required surgery after long-term monitoring, and this patient did not experience cancer recurrence post-surgery. Many guidelines now recommend watching and waiting as a reasonable alternative to surgery for low-risk cases. This method involves regular check-ups to ensure the condition remains stable, offering a less invasive option for patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Allen Ho, MD

Principal Investigator

Cedars-Sinal Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Active Surveillance

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Japan for the following indications:

Approved in United States as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

Approved in European Union as Active Surveillance for:

• Papillary thyroid microcarcinoma (PTMC)

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+

Published Research Related to This Trial

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]

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 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 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 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]

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 1453 nonoperative and 54,718 surgical patients with papillary thyroid carcinoma, it was found that younger patients (ages 14-55) with tumors up to 6 cm showed no significant difference in 10-year disease-specific survival (DSS) between nonsurgical and surgical approaches, suggesting that active surveillance may be a safe option for this group.

However, older patients (over 75 years) with tumors larger than 6 cm exhibited a significant difference in DSS, indicating that surgery is crucial for this demographic, as their survival rates dropped dramatically without surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality Risk of Nonoperative Papillary Thyroid Carcinoma: A Corollary for Active Surveillance. Ho, AS., Luu, M., Zalt, C., et al.[2020]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12145405/

Global research landscape on active surveillance for papillary ... It has been proven that the active surveillance (AS) is safe and feasible for low-risk papillary thyroid microcarcinomas (PTMC).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5745193/

Active Surveillance of Papillary Thyroid Microcarcinoma Among the 191 patients who underwent a delayed operation, only one showed recurrence at 75 months of follow-up after surgery, and they concluded that delayed ...

3. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2837836

Long-Term Durability of Active Surveillance of Small, Low ... This single-center cohort study evaluates the durability of active surveillance in patients with small, low-risk papillary thyroid cancer ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02609685?cond=PAPILLARY%20THYROID%20MICROCARCINOMA&rank=4

Active Surveillance of Papillary Thyroid Microcarcinoma The purpose of this study is to better understand the outcomes of active surveillance (observation) instead of immediate surgery, which is the current standard ...

5. e-enm.org e-enm.org/journal/view.php?number=2463

Active Surveillance for Low-Risk Thyroid Cancers Many practice guidelines have adopted active surveillance as a feasible alternative to immediate surgery for low-risk thyroid cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5539410/

ACTIVE SURVEILLANCE FOR PAPILLARY THYROID ... Trials of active surveillance of asymptomatic PTMCs from Japan have revealed that nonsurgical management of PTMC is a safe and a more cost-effective long-term ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8984605/

Papillary Thyroid Microcarcinoma: Active Surveillance Against ... Active surveillance is considered a viable option for papillary thyroid microcarcinoma. Since the last decade of the 20th century, this method ...