Cryoablation Versus Lumpectomy in Early-Stage Breast Cancer (CRYSTAL)

March 16, 2026 updated by: Linda Riks, Franciscus Gasthuis & Vlietland (Hospital)

Cryoablation as Alternative for Lumpectomy in Early-Stage Breast Cancer: The CRYSTAL Trial

The goal of this randomised controlled trial is to compare ipsilateral breast cancer recurrence rates in patients with early-stage breast cancer between patients treated with breast conserving surgery and patient treated with percutaneous cryo-ablation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

938

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Women
  2. Age > 60 years
  3. Postmenopausal (no menstrual period for at least 12 months or in case of an intra-uterine device (IUD) hormone levels that indicate the menopause: follicle stimulating hormone (FSH) > 20 IE/l and estradiol < 100 pmol/l)
  4. Histopathological confirmed primary invasive ER+/HER2- type breast cancer
  5. Bloom Richardson grade 1 or 2 (low or intermediate malignancy grade)
  6. Unilateral and unifocal breast cancer
  7. A clinical T1N0M0 tumor (≤ 2cm and N0 on US and/or MRI), without distant metastases. The largest diameter measured will be used to determine eligibility.
  8. Tumor should be visible and well delineated (all borders of the tumor should be visible) on ultrasound at diagnosis and during the procedure.
  9. Sufficient knowledge of the Dutch language to complete the questionnaires
  10. To be able to give written informed consent

Exclusion Criteria:

  1. History of invasive breast cancer
  2. Breast augmentation
  3. BRCA-1 or 2 gene mutation carrier
  4. Lobular carcinoma
  5. Triple negative breast cancer
  6. Multifocality
  7. HER2-neu overexpressing tumors
  8. Lymph vascular invasion (LVI) on core needle biopsy or histopathological confirmed after lumpectomy
  9. Indication for neoadjuvant systemic therapy
  10. Intraductal component > 25% of the diameter of the invasive tumor on MRI, complete area of the primary tumor should not exceed 2cm.
  11. Allergic to local anesthetics
  12. Electrical devices and/or implants that are not compatible with MRI
  13. Current severe breast infection
  14. Uncorrectable coagulopathy
  15. Hemodynamic instability
  16. Respiratory instability
  17. Refraining from adjuvant radiotherapy
  18. Indication for oncoplastic surgery (surgical volume replacement techniques e.g. LICAP)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Patients will be treated with ultrasound-guided percutaneous cryoablation
Ultrasound-guided percutaneous cryoablation
Procedure: Percutaneous cryoablation
In this trial, the IceCure Prosense Cryoablation System will be used to execute the percutaneous cryoablation procedure.
Other Names:
  • Minimally invasive treatment
  • Thermal ablation
  • Thermoablation
Other: Breast-conserving surgery
Patients will be treated with breast-conserving surgery.
Procedure: Breast-conserving surgery
Breast-conserving surgery
Other Names:
  • Lumpectomy
  • Lumpectomie

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ipsilateral breast cancer recurrence
Time Frame: Until 5 years after the intervention
Proportion of ipsilateral breast cancer recurrences (IBTR) after 5 years in both study arms.
Until 5 years after the intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complication Rate
Time Frame: Within 30 days after the intervention
The proportion of complications within 30 days (percentage Clavien-Dindo classification).
Within 30 days after the intervention
Regional breast cancer recurrences
Time Frame: Until 5 years after the intervention
Regional breast cancer recurrences, defined as clinically, radiologically, and/or histologically confirmed recurrence in regional lymph nodes.
Until 5 years after the intervention
Disease Free Survival
Time Frame: until 15 years after the intervention
Disease free survival (DFS) is defined as the time from date of intervention to the first occurrence of recurrent disease of the same histological characteristics as the primary tumor and in the same quadrant as the primary tumor
until 15 years after the intervention
Overall Survival
Time Frame: through study completion, an average of 15 years
Overall survival (OS) is defined as the time from breast cancer diagnosis to death from any cause.
through study completion, an average of 15 years
Cosmetic Outcomes
Time Frame: at baseline, 6 months and 1 year after the intervention
o assess cosmetic outcomes following treatment with cryoablation or lumpectomy using the BCTOS-13 and BREAST-Q questionnaires at specified follow-up visits, and objective assessment using BCCT.core software. Higher scores indicate better cosmetic outcomes.
at baseline, 6 months and 1 year after the intervention
Hospital-related costs
Time Frame: Until 5 years after the intervention
Hospital-related costs, including expenses made due to additional findings on inclusion MRI
Until 5 years after the intervention
Out-of-hospital (non)-medical costs
Time Frame: Until 5 years after the intervention
To assess out-of-hospital medical and non-medical costs and productivity losses using the iMTA Medical Consumption Questionnaire (iMCQ) and iMTA Productivity Cost Questionnaire (iPCQ) questionnaires.
Until 5 years after the intervention
Generic Health-related Quality of Life
Time Frame: At baseline, 6 months after the intervention, 1 and 5 years after the intervention
To assess general health-related quality of life using the EQ-5D-5L questionnaire, with higher scores indicating better health status
At baseline, 6 months after the intervention, 1 and 5 years after the intervention
Disease-specific quality of life
Time Frame: At baseline, 6 months after the intervention, 1 and 5 years after the intervention
To assess cancer-specific quality of life using the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires. Higher scores indicate better functioning or greater symptom burden depending on the subscale.
At baseline, 6 months after the intervention, 1 and 5 years after the intervention
Complete ablation rate
Time Frame: 2 weeks after the intervention (cryoablation)
On magnetic resonance imaging
2 weeks after the intervention (cryoablation)
Predictive value of MRI
Time Frame: until 5 years after the intervention
The negative predictive-, and diagnostic value of MRI for incomplete ablation
until 5 years after the intervention
Proportion of reinterventions
Time Frame: For the duration of the study, most likely within 2 weeks after the intervention
For both study arms.
For the duration of the study, most likely within 2 weeks after the intervention
Radiation Toxicity
Time Frame: At baseline, prior to radiation, 1 year and 5 years after the intervention
The proportion of acute and long-term breast irradiation toxicity (radiation dermatitis, superficial or deep connective tissue fibrosis, chest wall pain, localized edema) using common toxicity criteria (CTCAE v5.0) and cosmetic questionnaires
At baseline, prior to radiation, 1 year and 5 years after the intervention
Incremental cost-utility ratio (ICUR)
Time Frame: Until 5 years after the intervention
To estimate the incremental cost-utility ratio (ICUR). Higher ICUR values indicate higher costs per quality-adjusted life year (QALY) gained.
Until 5 years after the intervention

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Any other parameters
Time Frame: until the end of the study, which is an average of 5 years
To explore patient- or tumor-related factors that may influence complete ablation or surgical outcomes, including breast density and other relevant parameters.
until the end of the study, which is an average of 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Franciscus Gasthuis & Vlietland (Hospital)

Investigators

  • Principal Investigator: T.M.A.L. GE Klem, MD, PhD, Franciscus Gasthuis & Vlietland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

December 31, 2035

Study Completion (Estimated)

December 31, 2038

Study Registration Dates

First Submitted

March 11, 2026

First Submitted That Met QC Criteria

March 16, 2026

First Posted (Actual)

March 19, 2026

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL-010714

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Early-Stage Breast Cancer

Clinical Trials on Breast-conserving surgery

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mozambique

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe