Management of Low-risk (Grade I and II) DCIS
- Conditions
- DCIS
- Registration Number
- NCT02492607
- Lead Sponsor
- The Netherlands Cancer Institute
- Brief Summary
A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns slow-growing low-risk DCIS (grade I and II). This implies that many women might be unnecessarily going through intensive treatment resulting in a decrease in quality of life and an increase in health care costs, without any survival benefit.
The LORD (LOw Risk DCIS) study is a non-randomized, international, multicenter, phase III non-inferiority trial, and aims to determine whether screen-detected low-risk DCIS can safely be managed by an active surveillance strategy or that the conventional treatment, being either WLE alone, WLE + RT, or mastectomy, and possibly HT, should remain the standard of care.
- Detailed Description
Background of the study:
The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists. We hypothesize that asymptomatic, low-risk DCIS (grade I and II DCIS) can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be lowgrade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. It also may save many low-risk DCIS patients from intensive treatment.
Objective of the study:
The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years.
Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate and patient reported outcomes. To determine whether low- risk DCIS can safely (measured by ipsilateral invasive breast cancer rate at 10 years) be managed by an active surveillance strategy or if the conventional treatment, being either wide local excision (WLE) only, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy, will remain the standard of care.
Study design:
Phase III, open-label, non-inferiority, multi-center, non-randomized clinical trial. By patient's preference, women will be included into one of the following arms: active surveillance or standard treatment according to local policy, being either WLE alone, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of five years and an additional two mammograms at year seven and ten.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 2500
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Ipsilateral invasive breast cancer-free rate at 10 years 10 years from inclusion Ipsilateral invasive breast cancer-free rate at 10 years (both therapeutic policies
- Secondary Outcome Measures
Name Time Method Biopsy rate for ipsilateral breast during follow-up from inclusion to the time of death, during 10 years at minimum Biopsy rate for ipsilateral breast during follow-up (both therapeutic policies)
Time to ipsilateral grade III DCIS from inclusion to the development of a new ipsilateral DCIS of grade III, up to 10 years Time to ipsilateral grade III DCIS, both therapeutic policies
Time to failure of active surveillance strategy from inclusion to the time patients received standard treatment to the ipsilateral breast, up to 10 years Time to failure of active surveillance strategy, i.e. time to crossover to standard treatment, due to any cause
Distant metastases free interval from inclusion to the time of invasive distant metastases or death due to breast cancer, up to 10 years Distant metastases free interval,both therapeutic policies
Rate of invasive disease at the final pathology specimen (standard arm only) from inclusion till time of invasive disease during 10 years at minimum Rate of invasive disease at the final pathology specimen (standard arm only)
Rate of grade III DCIS at the final pathology specimen (standard arm only) from inclusion till time of invasive disease during 10 years at minimum Rate of grade III DCIS at the final pathology specimen (standard arm only)
Time to contralateral DCIS from inclusion to the development of a new contralateral DCIS I,II,III, up to 10 years Time to contralateral DCIS, both therapeutic policies
Cost-effectiveness 6 times from inclusion to 10 years follow-up Health economic evaluation (both therapeutic policies)
Health Related Quality of life 6 times from inclusion to 10 yrs follow-up General QoL/global health perception, specific funcionalities, pain ( both therapeutic policies
Overall survival from inclusion to the time of death, during 10 years at minimum Overall survival,both therapeutic policies
Masectomy rate for ipsilateral breast from inclusion to the time of ipsilateral breast cancer or death, during 10 years at minimum Masectomy rate for ipsilateral breast, baseline or subsequent ipsilateral DCIS or iBC (both therapeutic policies)
Time to contralateral invasive breast cancer from inclusion to the development of a contralateral invasive breast cancer, up to 10 years Time to contralateral invasive breast cancer,, both therapeutic policies
Trial Locations
- Locations (59)
Noordwest Ziekenhuisgroep- site Alkmaar
🇳🇱Alkmaar, Netherlands
Flevoziekenhuis
🇳🇱Almere, Netherlands
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Rijnstate Ziekenhuis
🇳🇱Arnhem, Netherlands
Wilhelmina Ziekenhuis Assen
🇳🇱Assen, Netherlands
Rode Kruis Ziekenhuis
🇳🇱Beverwijk, Netherlands
Alexander Monro Ziekenhuis
🇳🇱Bilthoven, Netherlands
Amphia Ziekenhuis
🇳🇱Breda, Netherlands
Reinier de Graaf Gasthuis
🇳🇱Delft, Netherlands
Scroll for more (49 remaining)Noordwest Ziekenhuisgroep- site Alkmaar🇳🇱Alkmaar, NetherlandsGea Gooiker, PhDPrincipal Investigator