Ingrid Potyka

Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial

BACKGROUND The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. METHODS TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2·5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. FINDINGS Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15·2% [239 of 1571] of patients who received TARGIT (21·6% prepathology, 3·6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3·3% (95% CI 2·1-5·1) for TARGIT versus 1·3% (0·7-2·5) for EBRT (p=0·042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2·1% (1·1-4·2) versus 1·1% (0·5-2·5; p=0·31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2·5% (TARGIT 5·4% [3·0-9·7] vs EBRT 1·7% [0·6-4·9]; p=0·069). Overall, breast cancer mortality was much the same between groups (2·6% [1·5-4·3] for TARGIT vs 1·9% [1·1-3·2] for EBRT; p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8-2·5] vs 3·5% [2·3-5·2]; p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3·9% (2·7-5·8) for TARGIT versus 5·3% (3·9-7·3) for EBRT (p=0·099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0·029). INTERPRETATION TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. FUNDING University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research.

MP33-20 THE SMARTTARGET BIOPSY TRIAL: A PROSPECTIVE PAIRED BLINDED TRIAL WITH RANDOMISATION TO COMPARE VISUAL-ESTIMATION AND IMAGE-FUSION TARGETED PROSTATE BIOPSIES

Multi-parametric MRI targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the diagnosis of clinically insignificant cancers. There is debate whether visual estimated targeting is sufficient or whether image-fusion software is required. We conducted an ethics committee approved, prospective, blinded, paired validating clinical trial of visual estimated targeted biopsies compared to non-rigid MR/US image-fusion using an academically developed fusion system (SmartTarget®).

Multidomain Quantitative Recovery Following Radical Cystectomy for Patients Within the Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion Versus Open Radical Cystectomy Randomised Controlled Trial: The First 30 Patients

Many patients develop complications after radical cystectomy (RC) [1]. Reductions in morbidity have occurred through centralisation and technical improvements [2], and perhaps through robot-assisted RC (RARC). Whilst RARC is gaining popularity, there are concerns about oncological safety [3] and extracorporeal reconstruction [4], and randomised controlled trials (RCTs) find little difference [5]. We are conducting a prospective RCT comparing open RC and RARC with mandated intracorporeal reconstruction (Robot-assisted Radical Cystectomy with intracorporeal urinary diversion versus Open Radical Cystectomy [iROC] trial) [6].

MP70-15 INTRA-PROSTATIC PRX302 FOCAL THERAPY IN TREATING CLINICALLY SIGNIFICANT LOW-INTERMEDIATE PROSTATE CANCER: AN OPEN LABEL, PROOF-OF-CONCEPT STUDY

INTRODUCTION AND OBJECTIVES: Our objective is to report local disease control after primary whole gland cryoablation when used to treat Gleason 7 localized prostate cancers at our institution. METHODS: We analyzed 134 prostate cryoablation patients who had a Gleason score of 7 who underwent primary whole gland cryoablation. Progression free survival (PFS) was defined according to Phoenix definition of PSA nadir +2 ng/ml. Among the biochemical failure (BF) patients, we assessed local disease control by postoperative prostate biopsy, pelvic MRI or CT. BS was used to assess metastatic disease. We defined local treatment failure by a positive post cryoablation prostate biopsy and/or MRI/CT scan findings suggesting local recurrence within the prostate. RESULTS: PFS was noted in 101 patients (75%) with median follow up time of 31.5 months. Among the 33 patients who showed BF, 3 patients did not have a metastatic workup. Of the remaining 30 patients, 15 (11.2% of treated patients) showed only local treatment failure as indicated by positive post cryoablation prostate biopsy and/or MRI/ CT scan findings suggesting local recurrence within the prostatic gland. The other 15 patients (11.2%) showed metastatic disease with no evidence of local treatment failure. (Table 1) CONCLUSIONS: Cryoablation is a successful primary treatment option for patients with intermediate/high grade prostate cancer. Up to half of patients who showed biochemical failure had good local disease control but had distant failure as evident by post cryoablation prostate biopsy and/or MRI/CT scans; this suggests patient selection failing to identify micro metastasis present at the time of treatment rather than local treatment failure.