MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.

The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.

5 Background: In estrogen-receptor-positive (ER+) early breast cancer, 5 years of tamoxifen reduces breast cancer death rates by about a third throughout years 0-14. It has been uncertain how 10 years of tamoxifen compares with this. Methods: During 1991-2005, 6,953 women with ER+ (n=2755), or ER untested (4198, estimated 80% ER+ if status known) invasive breast cancer from 176 UK centres were, after 5 years of tamoxifen, randomized to stop tamoxifen or continue to year 10. Annual follow-up recorded compliance, recurrence, mortality, and hospital admissions. Results: Allocation to continue tamoxifen reduced breast cancer recurrence (580/3468 vs 672/3485, p=0.003). This reduction was time dependent: rate ratio 0.99 during years 5-6 [95%CI 0.86-1.15], 0.84 [0.73-0.95] during years 7-9, and 0.75 [0.66-0.86] later. Longer treatment also reduced breast cancer mortality (392 vs 443 deaths after recurrence, p=0.05), rate ratio 1.03 [0.84-1.27] during years 5-9 and 0.77 [0.64-0.92] later; and overall mortality (849 vs 910 deaths, p=0.1), rate ratio 1.05 [0.90-1.22] during years 5-9 and 0.86 [0.75-0.97] later. Non-breast-cancer mortality was little affected (457 vs 467 deaths, rate ratio 0.94 [0.82-1.07]). There were 102 vs 45 endometrial cancers RR=2.20 (1.31-2.34, p<0.0001) with 37 (1.1%) vs 20 (0.6%) deaths (absolute hazard 0.5%, p=0.02). Combining the similar results of aTTom and its international counterpart ATLAS (Lancet 2013) enhances statistical significance of recurrence (p<0.0001), breast cancer mortality (p=0.002) and overall survival (p=0.005) benefits. Conclusions: aTTom confirms that, in ER+ disease, continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in recurrence, from year 7 onward, and breast cancer mortality after year 10. Taken together with the reduction in breast cancer deaths seen in trials of 5 years of tamoxifen vs none, these results indicate that 10 years of adjuvant tamoxifen, compared to no tamoxifen, reduces breast cancer mortality by about one third in the first 10 years following diagnosis and by a half subsequently. Clinical trial information: ISRCTN17222211.

5 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

No abstract

This meta-analysis highlights the need for direct head-to-head randomized trials to assess the impact of adjuvant therapy on patient-rated quality of life and health economic outcomes.

Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision.Methods TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8-10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743.

IntroductionTotal mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery.Methods and analysisSTAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2.Ethics and disseminationThe medical ethical committees of all the participating countries have approved the study protocol. Results of the primary and secondary endpoints will be submitted for publication in peer-reviewed journals.Trial registration number ISRCTN14240288, 20 October 2016. NCT02945566; Pre-results, October 2016.