T Sammour, BA Price, KJ Krause, GJ Chang tarik.sammour@gmail.com Non-operative management or “watch and wait” for rectal cancer with complete clinical response after neoadjuvant chemoradiotherapy – a critical appraisal. T Sammour, BA Price, KJ Krause, GJ Chang tarik.sammour@gmail.com Summary study data Follow-up (months) OS % DFS Local regrowth % Time to regrowth Salvage Surgery % Colostomy Appelt 23.9 100 23 10.4 Araujo 47.7 72 61 12 24.2 80 7 Creavin 42 90 10 19 - Dalton 25.5 . Habr-Gama 60 78 67 31 16 93 14 82 9.4 5 Lai 49.9 89 11 25 Lee 41 75 NS 50 13 Martens 41.4 94 92 14.6 Nahas 31.8 6 Renehan 33 96 88 34 26 Sanchez Loria 37.5 93.8 76 29 4 Smith JD 28 97 9 Smith RK 68.4 Vaccaro 46 17 Results In total, 15 studies met inclusion criteria including 920 patients, 575 (62.5%) who underwent NOM after cCR, and the rest forming a surgical control group. The weighted mean followup was 39.4 (12.7) months in the NOM group and 39.8 (5.1) months in the surgery group. The pooled re-growth rate in the NOM group was 21.3% at a mean of 15.6 (7.0) months. Surgical salvage was possible and undertaken in 93.2% of these patients. Overall survival in the NOM group was 91.7%, and disease free survival was 82.7%. For the comparison proctectomy group, pooled rates of local recurrence, overall survival and disease free survival were 8.4%, 92.4%, and 87.5%, respectively. Conclusion NOM may be a feasible option for surgically eligible rectal cancer patients with cCR after nCRT. Before such a strategy can be widely implemented, further prospective data is required with standardised definitions, diagnostic criteria, and management protocols, with an emphasis on shared patient-provider decision making and patient centered outcomes. Introduction There is increasing interest in non-operative management (NOM) for rectal cancer with complete clinical (cCR) response after neoadjuvant chemoradiation (nCRT). The aim of this review is to summarize the available data on NOM, with the intention of formulating standardised protocols on which to base future investigation. Methods Systematic review following PRISMA guidelines was conducted. A highly sensitive literature search identified all relevant studies published between Jan 2004 and Dec 2016. Data extraction and quality assessment was performed independently by two authors, and resolved by consensus with a third. Summary recommendations for treating patients with NOM Patient Selection Eligibility criteria cCR Active Surveillance Outcomes Inclusion Exclusion DRE Proctosigmoidoscopy Radiographic staging CT chest/abdomen/pelvis rectal cancer pelvic MRI Histologically confirmed diagnosis of rectal adenocarcimona Radiologically measurable disease cT2-T4a, N+ Nodal involvement confined to radiation field. Written informed consent for treatment and follow-up cT4b Tumor is causing symptomatic bowel obstruction (patients who have diverting ostomy are still eligible but obstructing tumor will preclude complete examination for response assessment) Any prior pelvic radiation Contraindication to fluoropyrimidine-based chemotherapy (e.g. DPD deficiency) Unwilling or unable to provide informed consent DRE: No palpable tumor when initially palpable by DRE. Endoscopy: No residual tumor AND white scar. Negative biopsies from scar are not mandatory. MRI (T2): Substantial downsizing with no residual tumor OR residual fibrosis OR residual wall thickening due to edema with fibrosis AND no suspicious lymph nodes DRE, proctoscopy, and CEA every 3 months for the first 2 years, then every 6-12 months for a total of 5 years. Scar biopsy not required unless suspicion of regrowth MRI pelvis every 6 month for 2 years and then annually CT chest/abdomen every 12 months for 5 years Prospective data collection Total number of eligible patients Rate of cCR Number of patients offered NOM Number of patients who consent Tumor regrowth and salvage rate Overall survival and disease free survival (DFS) at 1, 3, and 5 yrs. Colostomy-free rate Patient-reported outcomes (quality of life, functional outcomes).