Effects of patient selection on the applicability of results from a randomised clinical trial (EORTC 10853) investigating breast-conserving therapy for DCIS

Abstract

Selection of patients for randomised clinical trials may have a large impact on the applicability of the study results to the general population presenting the same disorder. However, clinical characteristics and outcome data on non-entered patients are usually not available. The effects of patient selection for the EORTC 10853 trial investigating the role of radiotherapy in breast conserving therapy for ductal carcinoma in situ have been studied, in an analysis of all patients treated for ductal carcinoma in situ in five participating institutes. The reasons for not entering patients were evaluated and treatment results of the randomised patients were compared to those not entered. A total of 910 patients were treated for ductal carcinoma in situ. Of these, 477 (52%) were ineligible, with the size of the lesion being the main reason for ineligibility (30% of all ductal carcinoma in situ). Of the 433 eligible patients, 278 (64%) were randomised into the trial. The main reasons for non-entry of eligible patients were either physicians' preference for one of the treatment arms (26%) or patients' refusal (9%). These percentages showed significant variation among the institutes. At 4 years follow-up, those patients not entered in the trial and treated with local excision and radiotherapy, had higher local recurrence rates than the patients randomised in the trial and treated with the same approach, (17 vs 2%, P=0.03). The patients treated with local excision alone had equal local recurrence rates (11% in both groups). Selection of patients may explain the differences in outcome of the randomised patients, and those not-entered. Thus, the results of this trial may not be applicable to all patients with ductal carcinoma in situ.

Local Recurrences After Conservative Treatment of Ductal Carcinoma-In-Situ of the Breast Without Radiotherapy: The Effect of Age

“…19 However, a comparison of a subgroup of patients treated with lumpectomy followed by radiotherapy outside and inside the trial showed significantly worse 4-year local recurrence-free rates: 83% outside the trial versus 98% inside the trial (P = .03). 21 For eligible patients treated with breast-conserving surgery only outside the trial, the 4-year recurrence-free rate was 93%, compared with 89% for randomized patients (P = .45). 21 Neither the NSABP nor EORTC trial revealed a beneficial effect of radiotherapy on either distant recurrences or breast cancer-related mortality.…”

“…21 For eligible patients treated with breast-conserving surgery only outside the trial, the 4-year recurrence-free rate was 93%, compared with 89% for randomized patients (P = .45). 21 Neither the NSABP nor EORTC trial revealed a beneficial effect of radiotherapy on either distant recurrences or breast cancer-related mortality.…”

“…Two large-scale randomized studies have been performed to compare conservative treatment of DCIS by breast-conserving surgery only with excision followed by radiotherapy in reducing local recurrences. [16][17][18][19][20][21] The National Surgical Adjuvant Breast and Bowel Project (NSABP) B17 trial, published in 1998, revealed after 90 months of follow-up that 27% of patients treated with breast-conserving surgery alone developed local recurrence, compared with 12% when surgery was followed by radiotherapy. 17 The EORTC 10853 trial, which included patients with DCIS lesions up to 5 cm and excluded patients ‡70 years, revealed a 4-year local recurrence rate of 16% in the surgery-only group, compared with 9% in patients treated by postoperative radiotherapy.…”

“…[13][14][15] Recently, two large-scale randomized studies revealed that radiotherapy after breast-conserving surgery for DCIS decreased the incidence of local recurrences. [16][17][18][19][20][21] However, it has also been shown that radiotherapy cannot compensate for an inadequate excision in reducing the risk of local recurrence. [22][23][24] Therefore, a microscopically complete excision remains the cornerstone in treatment of DCIS.…”

“…Whether all patients with DCIS should receive radiotherapy after breast-conserving surgery remains a topic of active debate. 11,21 The aim of this population-based study was to assess the outcome of conservative surgical treatment of patients with DCIS without radiotherapy and to identify subgroups of patients at increased risk for local recurrence.…”