Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ – The LORD study

Abstract

To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres.

Wherein the Authors Attempt to Minimize the Confusion Generated by Their Study “Breast Cancer Mortality after a Diagnosis of Ductal Carcinoma In Situ” by Several Commentators Who Disagree with Them and a Few Who Don’t: A Qualitative Study

“…Most articles accurately stated that the mortality rate from dcis is low (3%) and that mortality was equivalent regardless of treatment type. Nevertheless, many commentators misinterpreted the finding of low mortality to infer either that dcis is a precursor, and not a cancer [15][16][17][18] ; that dcis is overdiagnosed and does not need to be treated (that is, "watch and wait") [19][20][21][22][23][24][25][26][27][28][29] ; or that dcis is overtreated (that is, omit radiotherapy) [30][31][32][33][34] . Most troubling from our point of view was that several commentators interpreted the finding that the increased risk of death from breast cancer in dcis patients who developed an ipsilateral invasive recurrence justified efforts to prevent the invasive ipsilateral recurrence as a life-saving measure [35][36][37][38][39][40][41][42][43] .…”

Not All Ductal Carcinomas In Situ Are Created IDLE (Indolent Lesions of Epithelial Origin)

“…[15][16][17] The Low Risk DCIS (LORD; NCT02492607) trial is a phase III, noninferiority trial randomizing 1240 women older than 45 years with a core biopsy diagnosis (performed for screendetected calcifications) of low-grade DCIS to either active surveillance or standard surgery and adjuvant treatment. [15][16][17] The Low-Risk DCIS (LORIS; ISRCTN27544579) trial is a similar phase III trial randomizing 932 women older than 46 years to active surveillance or surgery, with the broader inclusion of a core biopsy (performed for screen-detected microcalcifications) diagnosis of both low-or intermediategrade DCIS. [15][16][17] The Comparison of Operative to Monitoring and Endocrine Therapy (COMET; NCT02926911) trial is randomizing women older than 40 years with a core biopsy diagnosis of low-or intermediate-grade DCIS without necrosis to either surgery or active surveillance with endocrine therapy.…”

Should local treatment of breast ductal carcinoma in situ be the same as the treatment of early invasive breast cancer

“…The basic arguments for the treatment of ductal carcinoma in situ in the same way as early invasive cancer comprise: -unknown natural history of untreated DCIS [16]; -high risk of undervaluation of the invasive component in the core-needle biopsy [10,[16][17][18]; -increase of recurrence risk with the progress of time [3,[19][20][21]; -lack of verified separators of the groups with the risk of adverse course of the disease [1,2,20]; -the results of the clinical studies confirming the justification of combined local treatment [22][23][24][25][26]; -and the proof that the clinical course of DCIS is the same as early invasive breast cancer [27,28]; -the lack of clinical studies which could justify a limitation of the treatment scope [28][29][30]. Given the fact that a large share of ductal carcinoma in situ is diagnosed as a small lesion seen only in a mammography image, and then treated with a mammotomy biopsy, a substantial part of DCIS is resected during this procedure.…”

“…One of the most essential contra-arguments against the reduction of local treatment, even in the group defined as low risk DCIS, is the lack of results of such randomised clinical studies as LORIS in Great Britain, which is a prospective study comparing surgical treatment (plus adjuvant radiotherapy or hormonotherapy) with an active observation, which was supposed to foster better understanding of the natural history of untreated DCIS [29]. In 2015 also, the LORD study was started (the third phase study EORTC-BCG 1401/BOOG 2014-04), in which in 1240 patients with a diagnosis of low risk DCIS, and with a 10 year follow-up period and active observation (watch and wait strategy) will be compared with treatment considered so far to be the standard [30].…”