Background: The optimal treatment for patients with locally recurrent rectal cancer (LRRC) is controversial. The aim of this study was to investigate different treatment strategies in two leading tertiary referral hospitals in Europe. Methods: All patients who underwent curative surgery for LRRC between January 2003 and December 2017 in Catharina Hospital, Eindhoven, the Netherlands (CHE), or Karolinska University Hospital, Stockholm, Sweden (KAR), were studied retrospectively. Available MRIs were reviewed to obtain a uniform staging for optimal comparison of both cohorts. The main outcomes studied were overall survival (OS), local re-recurrence-free survival (LRFS), and metastasis-free survival (MFS). Results: In total, 377 patients were included, of whom 126 and 251 patients came from KAR and CHE respectively. At 5 years, the LRFS rate was 62.3 per cent in KAR versus 42.3 per cent in CHE (P = 0.017), whereas OS and MFS were similar. A clear surgical resection margin (R0) was the strongest prognostic factor for survival, with a hazard ratio of 2.23 (95 per cent c.i. 1.74 to 2.86; P < 0.001), 3.96 (2.87 to 5.47; P < 0.001), and 2.00 (1.48 to 2.69; P < 0.001) for OS, LRFS, and MFS respectively. KAR performed more extensive operations, resulting in more R0 resections than in CHE (76.2 versus 61.4 per cent; P = 0.004), whereas CHE relied more on neoadjuvant treatment and intraoperative radiotherapy, to reduce the morbidity of multivisceral resections (P < 0.001). Conclusion: In radiotherapy-naive patients, neoadjuvant full-course chemoradiation confers the best oncological outcome. However, neoadjuvant therapy does not diminish the need for extended radical surgery to increase R0 resection rates.

For patients with locally recurrent rectal cancer, it is an ongoing pursuit to establish factors predicting or improving oncological outcomes. In locally advanced rectal cancer, a pCR appears to be associated with improved outcomes. The aim of this retrospective cohort study was to compare the oncological outcomes of patients with locally recurrent rectal cancer with and without a pCR. Patients who underwent neoadjuvant treatment and surgery for locally recurrent rectal cancer with curative intent between January 2004 and June 2020 at a tertiary referral hospital were analysed. Primary outcomes included overall survival, disease-free survival, metastasis-free survival, and local re-recurrence-free survival, stratified according to whether the patient had a pCR. Of a total of 345 patients, 51 (14.8 per cent) had a pCR. Median follow-up was 36 (i.q.r. 16–60) months. The 3-year overall survival rate was 77 per cent for patients with a pCR and 51.1 per cent for those without (P < 0.001). The 3-year disease-free survival rate was 56 per cent for patients with a pCR and 26.1 per cent for those without (P < 0.001). The 3-year local re-recurrence-free survival rate was 82 and 44 per cent respectively (P < 0.001). Surgical procedures (for example soft tissue, sacrum, and urogenital organ resections) and postoperative complications were comparable between patients with and without a pCR. This study showed that patients with a pCR have superior oncological outcomes to those without a pCR. It may therefore be safe to consider a watch-and-wait approach in highly selected patients, potentially improving quality of life by omitting extensive surgical procedures without compromising oncological outcomes.

Introduction: The implementation of an Enhanced Recovery After Surgery (ERAS) protocol in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) has been deemed unfeasible until now because of the heterogeneity of this disease and low caseloads. Since evidence and experience with ERAS principles in colorectal cancer care are increasing, a modified ERAS protocol for this specific group has been developed. The aim of this study is to evaluate the implementation of a tailored ERAS protocol for patients with LARC or LRRC, requiring beyond total mesorectal excision (bTME) surgery. Methods: Patients who underwent a bTME for LARC or LRRC between October 2021 and December 2022 were prospectively studied. All patients were treated in accordance with the ERAS LARRC protocol, which consisted of 39 ERAS care elements specifically developed for patients with LARC and LRRC. One of the most important adaptations of this protocol was the anaesthesia procedure, which involved the use of total intravenous anaesthesia with intravenous (iv) lidocaine, iv methadone, and iv ketamine instead of epidural anaesthesia. The outcomes showed compliance with ERAS care elements, complications, length of stay, and functional recovery. A follow-up was performed at 30 and 90 days post-surgery. Results: Seventy-two patients were selected, all of whom underwent bTME for either LARC (54.2%) or LRRC (45.8%). Total compliance with the adjusted ERAS protocol was 73.6%. Major complications were present in 12 patients (16.7%), and the median length of hospital stay was 9 days (IQR 6.0–14.0). Patients who received multimodal anaesthesia (75.0%) stayed in the hospital for a median of 7.0 days (IQR 6.8–15.5). These patients received fewer opioids on the first three postoperative days than patients who received epidural analgesia (p < 0.001). Conclusions: The implementation of the ERAS LARRC protocol seemed successful according to its compliance rate of >70%. Its complication rate was substantially reduced in comparison with the literature. Multimodal anaesthesia is feasible in beyond TME surgery with promising effects on recovery after surgery.

Patients with locally recurrent rectal cancer (LRRC) generally have poor prognosis, especially those who have (a history of) distant metastases. The aim of this study was to investigate the impact of distant metastases on oncological outcomes in LRRC patients undergoing curative treatment. Consecutive patients with surgically treated LRRC between 2005 and 2019 in two tertiary referral hospitals were retrospectively analysed. Oncological survival of patients without distant metastases were compared with outcomes of patients with synchronous distant metastases with the primary tumour, patients with distant metastases in the primary-recurrence interval, and patients with synchronous LRRC distant metastases. A total of 535 LRRC patients were analysed, of whom 398 (74%) had no (history of) metastases, 22 (4%) had synchronous metastases with the primary tumour, 44 (8%) had metachronous metastases, and 71 (13%) had synchronous LRRC metastases. Patients with synchronous LRRC metastases had worse survival compared to patients without metastases (adjusted hazard ratio: 1.56 [1.15-2.12]), whilst survival of patients with synchronous primary metastases and metachronous metastases of the primary tumour was similar as those patients who had no metastases. In LRRC patients who had metastases in primary-recurrence interval, patients with early metachronous metastases had better disease-free survival as patients with late metachronous metastases (3-year disease-free survival: 48% vs 22%, p = 0.039). LRRC patients with synchronous distant metastases undergoing curative surgery have relatively poor prognosis. However, LRRC patients with a history of distant metastases diagnosed nearby the primary tumour have comparable (oncological) survival as LRRC patients without distant metastases.

Achieving a clear surgical resection margin (R0 resection) is one of the most important prognostic factors determining survival after surgical resection of locally recurrent rectal cancer (LRRC)¹. In radiotherapy-naive patients, the most common approach to facilitating an R0 resection is to administer long-course neoadjuvant chemoradiotherapy². However, many patients with LRRC have undergone chemoradiotherapy previously for the primary tumour. The role of reirradiation in LRRC in these patients is still debated, as well as the addition of induction chemotherapy (ICT)^3,4. In previously irradiated patients, there is no consensus on whether downstaging by reirradiation in combination with ICT results in better oncological outcomes than upfront surgery. No convincing evidence exists proving the superiority of either approach⁵. In this study, outcomes of two Dutch referral centres were compared, both considering long-course chemoradiotherapy and chemoreirradiation as standard treatment for LRRC. One centre routinely treated patients with additional ICT, whereas the other did not. The aim was to evaluate long-term oncological outcomes in patients with LRRC, comparing the results from these two centres.

Target volume delineation in locally recurrent rectal cancer (LRRC) is clinically challenging. To ensure the quality of chemoradiotherapy (CRT) within the PelvEx II trial, a delineation guideline was developed and prospective quality assurance (QA) was instated for all patients. Guideline adherence, the impact of QA on target volumes, and subsequent guideline refinements are described in this paper. All PelvEx II patients, either RT naive patients (50-50.4 Gy) or reirradiation (30 Gy) patients, were eligible for QA prior to CRT. An online meeting with the treating physician and the QA team was planned for each patient prior to treatment, to peer review delineations. Adherence to each of the 7 (reirradiation) or 8 (RT naive) guideline recommendations was scored. Suggested target volume adjustments and any reasons to deviate from protocol were noted. When applicable, target volumes before and after QA were compared. Possible protocol refinements were discussed amongst the trial QA team. Prospective review of 113 cases of LRRC was performed, resulting in a high QA compliance rate of 90 %. All guideline recommendations were followed in 53 % of cases. Changes to the GTV and CTV were advised in 21 and 39 cases respectively. A median increase of GTV (+29 % (p < 0.001)) and CTV (+15 % (p < 0.001)) was seen in reirradiation patients, versus a median CTV increase of + 6 % (p = 0.002) in RT naive patients following QA. Deviations from protocol were accepted in 30 cases (27 %). Thirteen protocol refinements were agreed upon. Peer-review of LRRC target volumes leads to altered target volumes in up to 48% of cases, resulting in an updated delineation guideline.