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BACKGROUND: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. METHODS: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5?*?5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete. FINDINGS: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). INTERPRETATION: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. FUNDING: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

Introduction: The aim was assess the oncological and functional outcome of the watch-and-wait (W&W) approach in older patients with a clinical (near)complete response after neoadjuvant treatment for rectal cancer.Material and methods: Patients were included in a W&W-approach (2004-2019) when digital rectal examination, endoscopy and MRI showed a (near)clinical complete response. Patients underwent endoscopy and MRI every 3 months during the first year, and 6-monthly thereafter. Patients aged >= 75 and >= 2 years of follow-up (FU) were selected. Oncological outcomes were assessed with Kaplan-Meier curves. Functional outcome was assessed with colostomy-free rate, Vaizey incontinence score, low anterior resection syndrome-score and International Prostate Syndrome Score.Results: 43/304 (14%) of patients in a W&W-approach met the inclusion criteria. Median FU was 37 (24-109) months. 5/43(12%) developed a local regrowth. All were treated surgically, with one patient experiencing a pelvic failure. Distant metastases occurred in 3/43 patients and 4 patients died, 3 of whom not related to rectal cancer. The 3-year local regrowth-free rate was 88%, 3-year non-regrowth disease-free survival 91%, overall survival 97% and 3-year colostomy-free rate 93%. Overall, the bowel- and urinary dysfunction scores at 3, 12 and 24 months indicated good continence, no or minor LARS and moderate urinary problems.Conclusion: W&W for older patients with a clinical (near) complete response appears to be a safe alternative to a total mesorectal excision (TME), with a very high pelvic control rate, and few rectal cancer related deaths. Most patients can avoid major surgery and a definitive colostomy, and have a reasonable anorectal and urinary function. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Introduction: The revised Dutch colorectal cancer guideline (2014), led to an overall decrease in preoperative radiotherapy (RT) use. This study evaluates hospital variation in RT use for resectable rectal cancer and the influence of guideline revision, including the nationwide impact of changing RT application on short term outcomes.Methods: Data of surgically resected rectal cancer patients registered in the Dutch ColoRectal Audit were extracted between 2011 and 2017. Patients were divided into groups based on time of guideline revision (= 2014). Primary outcome was guideline adherence at hospital level regarding RT application, stratified for three stage groups. Secondary outcomes included positive circumferential resection (CRM+) and 30-day complicated postoperative course.Results: The groups consisted of 7364 and 12,057 patients, respectively. In total, 6772 patients did not receive RT (17.6% (= 2014), p < 0.001). The largest increase of surgery alone was observed for cT1-2N0 stage rectal cancer (35.1% vs. 91.8%, p < 0.001), with a substantial decrease in hospital variation (IQR 22.2-50.0% vs. IQR 87.6-98.0%). For cT1-3N1MRF-stage rectal cancer, a substantial amount of hospital variation in short course RT remained after guideline revision (IQR 26.8-54.1% vs. IQR 26.2-50.0%). A significant decrease in CRMthorn (5.8% vs. 4.2%, p < 0.001) and complicated course (22.5% vs. 18.5%, p < 0.001) was observed.Conclusions: Radiotherapy for early-stage rectal cancer was uniformly abandoned after guideline revision, while substantial hospital variation remained for intermediate risk resectable rectal cancer in the Netherlands. The substantial nationwide decrease in the use of RT for rectal cancer treatment did not negatively impact CRM involvement. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

an unacceptable functional result. They might even have a better QoL than patients with colorectal or coloanal anastomoses as the latter patient group often suffers from fecal incontinence due to the lack of filling capacity of the neorectum [1] . Not only medical considerations but also the cultural mindset in the heads of both patients and their doctors determine whether a stoma is constructed or not. Yamamoto et al. [2] describe in a single-center report their results of laparoscopic intersphincteric resection (ISR) for patients with distal rectal cancer. Only 29 patients were described in a study period of almost 10 years, suggesting a certain selection bias. Of these, 7 patients were excluded as matched cases could not be identified in the control group. ISR in rectal cancer is based on several facts and assumptions: through meticulous dissection it has become a feasible technique, it is safe in certain oncological stages, and it results in a superior QoL for the patients. However, the exact place of this technique, performed open or laparoscopically, is not completely clear. The surgeon’s expertise and the will of both surgeons and patients to preserve the anus certainly influences the likelihood that this technique will be used. As the authors describe, in order to make it a safe procedure a skilled surgical team and adequate postoperative care are prerequisites. With acceptable morbidity and absent mortality, the Japanese colleagues seem to have fulfilled this demand. Of course, the oncological outcome after (laparoscopic) ISR is of key importance. When a safe distal margin of 1–2 cm can be achieved most authors consider For many years rectal cancer has posed a challenge to oncologists, with locoregional recurrences of up to 30% being an important cause of debilitating death in the past. Since Miles introduced his abdominoperineal resection more than 100 years ago, techniques have been refined substantially, inflicting less trauma on the patient. Stapling techniques have made very distal anastomoses possible and meticulous dissection in the right anatomical planes has reduced the necessity of a wide distal resection margin. As such, the number of patients undergoing sphincter-saving surgery has increased. Transanal endoscopic microsurgery for early rectal cancers and the introduction of laparoscopy have further contributed in this respect. Apart from these major surgical advances, novel (neo)adjuvant treatment regimens have further increased both local control and survival. Preoperative radiotherapy has reduced the likelihood of local failure, and chemoradiotherapy may even induce a complete clinical response. Although this occurs only in a minority of patients, the impact is significant: wait-and-see protocols omitting surgery are currently being explored in several parts of the world. Parallel to these advances in rectal cancer treatment, more attention is being paid to the impact of several treatment options on quality of life (QoL). In general, a stoma is considered to have a negative impact on QoL. Nevertheless, major improvements have been made in stoma care and surgeons are increasingly aware of the necessity of creating a stoma that has optimal function. Patients with a permanent stoma do not necessarily end up with Published online: December 20, 2011

6050 Background: We previously published a statistical model for predicting an individual patient's probability for disease-specific survival for 5 and 9 years following an r0 resection for gastric cancer. This tool was based on a single institution experience involving 1039 patients treated from 1985 to 2002. The purpose of this study was to assess the validity of this prediction tool when applied to patients treated at different institutions. Methods: Between 1989 and 1993, 633 eligible patients underwent a r0 resection in the Dutch Gastric Cancer trial that was conducted in 80 Dutch hospitals and compared D1 with D2 lymph node dissection. After excluding those with missing values, 285 patients had values for all nomogram predictor variables, AJCC stage, and disease-specific follow-up. For each of these patients, the nomogram 5 and 9 year disease-specific survival probabilities were computed and compared with the AJCC stage on the basis of discrimination ability, as measured by the concordance index. Re...