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Background and purpose: Combining chemoradiotherapy (CRT) with deep regional hyperthermia (HT) shows promise for enhancing clinical outcomes in selected rectal cancer patients. This study aimed to integrate the evidence and evaluate the efficacy of this combined treatment approach. Materials and methods: A systematic search of the PubMed, Scopus, and Mendeley databases was performed. This review was conducted according to the PRISMA guidelines. The quality of studies was evaluated using the Newcastle–Ottawa scale (NOS). Random-effects meta-analyses (DerSimonian and Laird) were performed. The primary outcome was pathological complete response (pCR), and secondary endpoints were overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and toxicity. Results: In total, 12 studies were included, mostly of moderate quality. Patients with locally advanced rectal cancer (LARC; n = 760) and locally recurrent rectal cancer (LRRC; n = 22) were eligible. The pooled pCR rate was 19% (95% confidence interval [CI]: 16–22%) among all 782 patients and 19% (95%CI:16–23%) among 760 LARC patients. Due to significant study heterogeneity, survival outcomes were pooled by excluding LRRC patients. The pooled 5‑year OS rate among 433 LARC patients was 87% (95%CI: 83–90%). The pooled 5‑year DFS and LRFS in LARC patients were 75% (95%CI: 70–80%) and 95% (95%CI: 92–97%), respectively. There was a lack of consistent reporting of HT treatment parameters and toxicity symptoms among the studies. Conclusion: The collective clinical evidence showed that neoadjuvant CRT combined with HT in rectal cancer patients is feasible, with a 19% pCR rate and excellent survival outcomes in long term follow-up. [ABSTRACT FROM AUTHOR]

Lateral lymph node dissection (LLND) is getting global attention as an a surgical option to reduce local recurrence in locally advanced rectal cancer. As the transanal total mesorectal excision (TaTME) is gaining popularity worldwide, a novel LLND approach was established adopting a two-team approach that combines the transabdominal and transanal approaches using the TaTME technique. This narrative review describes the advantages, anatomical landmarks, surgical techniques, and pitfalls of transanal LLND (TaLLND). The advantages of TaLLND include a magnified view and enhanced maneuverability of the laparoscopic instruments in the deep pelvis. TaLLND is also beneficial for LLND in patients with a history of pelvic surgery because surgeons can have access to the areas unaffected by previous surgery. To master the TaLLND technique, the procedure should be understood according to the following steps: S4 nerve identification, lateral space entry, lateral dissection, obturator vein, artery, and nerve identification, dissection along the external iliac vein, medial dissection, median and bottom dissection, dissection along the internal iliac artery, and dissection along the obturator nerve. TaLLND can be applied to highly advanced disease that requires combined resection of the major internal iliac vessels, pelvic nerves, or adjacent organs. In such cases, simultaneous transanal and transabdomiinal LLND utilizing a two team approach has advantages as these approaches can provide mutual complementary roles. TaLLND is expected to overcome the difficulty of transabdominal LLND and improve the quality of LLND. [ABSTRACT FROM AUTHOR]

Background: Local recurrence of rectal cancer (LRRC) previously treated with radiotherapy is associated with a poor prognosis. Historically, the integration of radiotherapy (RT) with surgery has improved the likelihood of complete resections (R0) and, consequently, enhanced survival. Unfortunately, many LRRC cases are not amenable to surgical intervention. The inclusion of chemotherapy (CHT) alongside advanced RT techniques including proton and carbon ion RT (CIRT) and stereotactic body radiation therapy (SBRT), has generated new treatment options. Therefore, there is a need for improved stratification of LRRC patients to enhance treatment outcomes. The RETRY is an integrated trial with the primary aim to explore if combining CHT with RT in all available modalities can enhance local control (LC) in LRRC patients, consequently improving survival. Methods: Experts from Italian centers specializing in rectal cancer and LRRC management collaborated to design a prospective multicenter observational study within the AIRO group for gastrointestinal malignancies. Eligible participants are adult LRRC patients who previously had pelvic RT, meet specific criteria, and are affiliated with the participating Italian centers. Specific criteria must be met for CIRT referral. A total of 88 patients will be enrolled over three years. The primary objective is to determine the 3-year LC rate. Secondary outcomes include assessing survival, quality of life, and R0 resection rates in surgery cases. A minimum dose of 40 Gy, conventional fractionation with concomitant fluoropyrimidine—with/without oxaliplatin-based CHT (CRT) is prescribed in neoadjuvant setting. Alternatively, the dose will vary from 35 to 40 Gy in 5 fractions based on clinical judgment, by SBRT. Both proton and photon therapies will be evaluated in these approaches. Surgery will be considered if deemed operable. In inoperable cases, CIRT with a dose of 40–60 Gy relative biological effectiveness (RBE) will be administered with a daily dose fraction ranging between 3 and 4.8 Gy RBE. Discussion: The RETRY trial aims to investigate the combined effects of RT and CHT and when feasible the addition of surgery, to determine whether this comprehensive approach can result in improved survival and quality of life for LRRC patients. Trial registration number ClinicalTrials.gov (No. NCT05984576). [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion The aim of this work is to report actual overall survival (AOS) at 5 and 10 years after multimodal treatment for locally recurrent rectal or sigmoid cancer (LRRC) and the importance of local re‐recurrence (reLRRC) and distant metastases for AOS.All patients resected for LRRC at a single centre between years 1990 and 2007 were included. Resections were based on images taken after neoadjuvant treatment. Patients were prospectively followed up for 5 years. After a minimum of 10 years, the records of referring hospitals were analysed.A total of 224 patients underwent resection. At 5 and 10 years 33% and 17%, respectively, had survived. Median survival was 38 months [interquartile range (IQR) 62 months]. Patients with complete resections had 5‐ and 10‐year survival of 56% and 28%, respectively, versus 22% and 11% for those with microscopic remaining tumour; none with macroscopic remains survived beyond 4 years. Median survival was 71 months (IQR 106 months), 33 months (IQR 35 months) and 15 months (IQR 17 months), respectively. With a median survival of 123 months (IQR 80 months), the 54 patients without recurrence had 5‐ and 10‐year survival of 69% and 59%, respectively. The independent predictor of survival was R‐stage. Of the 197 patients who had radical resection, 83 developed reLRRC and 108 distant metastases. ReLRRC appeared at a median of 18 months (IQR 21 months) and distant metastases at 12 months (IQR 21 months). Lung metastases were the most common form of distant disease.More than 5 years postoperatively the mortality from cancer was substantial. Most metastases appeared not to be secondary to reLRRC. Planning surgery from pretreatment images might reduce reLRRC. [ABSTRACT FROM AUTHOR]

Aim: Patients requiring a beyond total mesorectal excision (bTME) procedure for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) will probably benefit from enhanced recovery after surgery (ERAS) protocols. However, implementation of ERAS protocols in such groups of patients is considered challenging. The aims of this study were to evaluate ERAS‐related outcomes of patients with LARC or LRRC undergoing bTME and to investigate the possibility of designing a tailored ERAS protocol. Method: This study was divided into four phases. Phase one consisted of a literature study to compare functional recovery and postoperative outcomes in patients undergoing bTME. In phase two, outcomes on ERAS care elements in bTME were retrospectively evaluated. In phase three, differences in ERAS‐related outcomes and compliance of the colorectal ERAS protocol in patients who had undergone bTME were studied. In phase four, multidisciplinary team meetings were held to develop an ERAS protocol for bTME patients. Results: Seven studies reported on ERAS‐related outcomes in patients undergoing bTME. Median length of hospital stay was 9–19 days, median stay in the intensive care unit was 2–4 days and 30‐day postoperative major complication rates were 22.6%–61.3%. Seventy‐five bTME patients were included for retrospective analysis. In these patients, length of stay was 9.0 days and major postoperative complications were observed in 40.0%. The overall ERAS compliance was 44.4%. Compared with the colorectal ERAS protocol, the largest differences in management were observed in the use of epidural anaesthesia, the postoperative use of urethral catheters, oral intake and mobilization. Conclusion: Patients undergoing bTME for LARC or LRRC are substantially different from patients treated with the colorectal ERAS protocol, regarding ERAS‐related outcomes. A tailored, multimodal ERAS protocol with specific modifications was developed by an expert multidisciplinary team for patients undergoing bTME for LARC or LRRC. [ABSTRACT FROM AUTHOR]

Aim: The clinical burden of pelvic exenteration (PE) for locally advanced rectal cancer (LARC) is nationally under‐reported. The widespread use of pelvic MRI since 2005 has increased the accuracy of local staging and awareness of the need for 'beyond TME (total mesorectal excision)' surgery. The aim of this study was to assess the volume of patients undergoing PE within England, which factors affected survival outcomes and whether the use of MRI has influenced these outcomes. Method: The volume of patients undergoing PE and associated survival outcomes across England between 1995 and 2016 was evaluated from Public Health England Hospital Episode Statistics data. Results: A total of 2996 patients were recorded as undergoing PE. The 5‐year overall survival rate improved after 2005 compared with prior to 2005 (61.7% vs. 37%, p < 0.001), with no significant difference between cancer registries throughout England. After 2005, the volume of patients undergoing PE and undergoing preoperative MRI increased, as did the number of non‐T4 cancers operated on. After 2005, age, preoperative MRI and preoperative radiotherapy were the significant factors influencing 5‐year overall survival on multivariate analysis. Conclusion: This review of national data confirms that PE outcomes are under‐reported. MRI staging aids with the identification of patients suitable for perioperative treatment, surgery or palliation and facilitates treatment planning. Since 2005, MRI, likely in combination with advances in surgery and perioperative treatment, has improved survival outcomes. It is imperative that detailed information from patients with LARC undergoing PE is captured and reported in order to optimize care and future service provision. [ABSTRACT FROM AUTHOR]

Abstract Background Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. Methods From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. Results Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). Conclusions This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.

Background: Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. Methods: From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. Results: Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). Conclusions: This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE. [ABSTRACT FROM AUTHOR]

Introduction: Chronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers. Case description: In the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning. Discussion: Following successful SCS, effective pain relief was observed. Conclusion: SCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted. [ABSTRACT FROM AUTHOR]

Locally recurrent rectal cancer (LRRC) involving the lateral pelvic sidewall requires a complex approach to maximize the likelihood of R0 resection, which is the only predictor of survival. The purpose of this report is to describe a novel technique to resect a localized lateral pelvic sidewall LRRC. A 63-year-old male patient was referred for a 15-mm LRRC near the right internal iliac vessels. Endoscopic ultrasound and magnetic resonance imaging excluded any involvement of the pelvic colon or residual rectum. A combined extraperitoneal antero-lateral approach and gluteal access were used to optimize vascular control on the internal iliac vessels, to promptly identify the ureter and to achieve a better posterior exposition of the sciatic notch. This technique allowed a controlled and tailored resection of pelvic sidewall without entering into the abdominal cavity. The postoperative course was uneventful. The pathologic report confirmed clear margins (R0), with one involving obturator lymph node. At 3 months, the patient is alive and free from local re-relapse. A right lung metastasis has occurred, and it was treated by stereotactic radiotherapy. The present report proposes a novel extraperitoneal pelvic sidewall excision to resect lateral LRRC with a colorectal-sparing approach, thus minimizing the risk of exenterative surgery-related complications. A proper selection of patients is mandatory, as the proposed technique could not be generalized as the standard of care in all lateral LRRCs. [ABSTRACT FROM AUTHOR]

Carbon ion radiotherapy (CIRT) has received attention for the treatment of locally recurrent rectal cancer. When the surrounding primary organs are close to the irradiation site, a spacer is required to ensure safe irradiation. This work describes a novel technique using a bioabsorbable polyglycolic acid spacer placed laparoscopically and presents a technical report with five case studies. The short‐term surgical outcomes were as follows: mean operating time 235 min with blood loss of 38 mL. CIRT was planned, and the patients underwent irradiation within 2 months of surgery. No pelvic infections occurred, and all procedures were performed safely. Herein, were present a technical report with reference to a video of the surgical procedure. [ABSTRACT FROM AUTHOR]

Purpose: The benefit of intra-operative radiotherapy (IORT) in the treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) lie in its ability to provide high-dose of radiation to limited at-risk volume, thereby eliminating microscopic disease and decreasing toxicity. A comparative study between high-doserate (HDR) brachytherapy, named intra-operative brachytherapy (IOBT), and intra-operative electron radiotherapy (IOERT) was performed showing favorable LRFS after IOBT, possibly due to a higher surface dose that is inherent in IOBT technique. The IOERT technique in Catharina Hospital Eindhoven was adapted to increase the surface dose, aiming to improve local control. Post-operative complications due to an increased radiation dose remain the matter of concern. This retrospective study was performed to compare complication rates before and after adapted IOERT dose. Material and methods: All patients undergoing surgery with IOERT for LARC or LRRC from September 2019 until July 2023, were considered. Patients selected until August 31, 2021 were included in control cohort (n = 108), and those chosen from September 1, 2021 onwards were included in intervention cohort (n = 92). Perioperative and (major) post-operative complications were classified retrospectively, during admission, at 30 days, and at 90 days. Results: In LARC patients, a decrease in post-operative complications was observed (p = 0.009). 19% of LARC patients experienced major post-operative surgical complications, i.e., Clavien-Dindo grade 3b-5, regardless of treatment group. No difference in major 90-day complications was noted (p = 0.142). In LRRC patients, the use of induction chemotherapy decreased from 78% to 29% (p < 0.001), which complicated comparison. However, no difference in major post-operative complications was observed at 30 days (p = 0.222) or 90 days (p = 0.977) after surgery. Conclusions: Increased surface dose of IOERT does not seem to lead to an increase in post-operative complications. Further research is needed to evaluate the efficacy of dose adaptation in IOERT to improve local oncological control rates. Routine evaluation of CTCAE scores in follow-up will help uncover possible long-term radiation-induced toxicity. [ABSTRACT FROM AUTHOR]

Background and purpose: Intensity modulated proton therapy (IMPT) enables generation of conformal dose plans with organ at risk (OAR) sparing potential. However, pelvic IMPT robustness is challenged by inter-fraction motion caused by constant anatomical variations. In this study, the dosimetric impact of inter-fraction motion on target coverage and dose to OAR was quantified in the prospective phase II study ReRad-II on dose-escalated proton reirradiation for locally recurrent rectal cancer (LRRC). Materials and methods: The inter-fraction motion robustness was assessed for the initial twelve patients enrolled in the ReRad-II study. Patients with resectable LRRC were assessed for neoadjuvant IMPT (55 Gy(RBE)/44Fx) and unresectable recurrences for definitive IMPT (57.5–65 Gy(RBE)/ 46-52Fx). Target coverage and dose to OAR were assessed for robustly optimised three-field IMPT, on 12 plan computerized tomography (CT) scans (pCT) − and 47 repetitive control CT scans (cCTs) during the treatment. The target coverage and doses to OAR were re-calculated on each cCT and the mean dose ratio (pCT/cCT-ratio) and target coverage (V95%) was evaluated. Results: The target coverage was robust with a mean dose pCT/cCT-ratio of 1.00 (+/-1%). The V95% target coverage for every cCT were above the accepted worst-case scenario in the robust evaluation. Considerable variation in bladder-, bowel bag-, and bowel loop volume was observed. The OAR with the largest variation in ratio was the bladder (pCT/cCT-ratio: 1.3 (range: 0.5–4.7). Conclusions: IMPT for dose-escalated reirradiation of LRRC provided anatomically robust target coverage despite OAR changes. Inter-fraction motion resulted in OAR doses varying within clinically acceptable range.

IntroductionChronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers.Case descriptionIn the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning.DiscussionFollowing successful SCS, effective pain relief was observed.ConclusionSCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted.

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%-50%. Additionally, only approximately 40%-50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25-40 Gy/5 Fx irradiation or 15-30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery for rectal cancer involving adjacent organs (T4 primary tumors) or for locally recurrent rectal cancer requires dissection planes beyond the well-defined perimesorectal space. It is, therefore, of paramount importance to define the extent of surgery preoperatively. Magnetic resonance imaging (MRI) provides adequate guidance for the surgeon to achieve a clear resection margin. In this study, the diagnostic performance of MRI against histopathology and oncological outcomes that can be achieved with MRI-guided surgery are studied using an MRI-based division of the pelvis into seven compartments. Overall, the accuracy of MRI is good, yielding excellent results for T4 tumors and good results for locally recurrent tumors. Complete histopathologic (R0) resection is the most important determinant of outcome. Rectal cancer invading adjacent organs (T4) and locally recurrent rectal cancer (LRRC) pose a special challenge for surgical resection. We investigate the diagnostic performance of MRI and the results that can be achieved with MRI-guided surgery. All consecutive patients who underwent MRI-based multivisceral resection for T4 rectal adenocarcinoma or LRRC between 2005 and 2019 were included. Pelvic MRI findings were reviewed according to a seven-compartment staging system and correlated with histopathology. Outcomes were investigated by comparing T4 tumors and LRRC with respect to cause-specific survival in uni- and multivariate analysis. We identified 48 patients with T4 tumors and 28 patients with LRRC. Overall, 529 compartments were assessed with an accuracy of 81.7%, a sensitivity of 88.6%, and a specificity of 79.2%. Understaging was as low as 3.0%, whereas overstaging was 15.3%. The median number of resected compartments was 3 (interquartile range 3–4) for T4 tumors and 4 (interquartile range 3–5) for LRRC (p = 0.017). In 93.8% of patients with T4 tumors, a histopathologically complete (R0(local)-) resection could be achieved compared to 57.1% in LRRC (p < 0.001). Five-year overall survival for patients with T4 tumors was 53.3% vs. 32.1% for LRRC (p = 0.085). R0-resection and M0-category emerged as independent prognostic factors, whereas the number of resected compartments was not associated with prognosis in multivariate analysis. MRI predicts compartment involvement with high accuracy and especially avoids understaging. Surgery based on MRI yields excellent loco-regional results for T4 tumors and good results for LRRC. The number of resected compartments is not independently associated with prognosis, but R0-resection remains the crucial surgical factor. [ABSTRACT FROM AUTHOR]

Background: In some surgical disciplines, navigation-assisted surgery has become standard of care, but in rectal cancer, indications for navigation and the utility of different technologies remain undetermined. Methods: The NAVI-LARRC prospective study (NCT 04512937; IDEAL Stage 2a) evaluated feasibility of navigation in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC). Included patients had advanced tumours with high risk of incomplete (R1/R2) resection, and navigation was considered likely to improve the probability of complete resection (R0). Tumours were classified according to pelvic compartmental involvement, as suggested by the Royal Marsden group. The BrainlabTM navigation platform was used for preoperative segmentation of tumour and pelvic anatomy, and for intraoperative navigation with optical tracking. R0 resection rates, surgeons' experiences, and adherence to the preoperative resection plan were assessed. Results: Seventeen patients with tumours involving the posterior/lateral compartments underwent navigation-assisted procedures. Fifteen patients required abdominosacral resection, and 3 had resection of the sciatic nerve. R0 resection was obtained in 6/8 (75%) LARC and 6/9 (69%) LRRC cases. Preoperative segmentation was time-consuming (median 3.5 h), but intraoperative navigation was accurate. Surgeons reported navigation to be feasible, and adherence to the resection plan was satisfactory. Conclusions: Navigation-assisted surgery using optical tracking was feasible. The preoperative planning was time-consuming, but intraoperative navigation was accurate and resulted in acceptable R0 resection rates. Selected patients are likely to benefit from navigation-assisted surgery. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the oncological outcomes and safety of carbon ion re-irradiation with pencil beam scanning (PBS) delivery technique for previously irradiated and unresectable locally recurrent rectal cancer (LRRC). Between June 2017 and September 2021, 24 patients of unresectable LRRC with prior pelvic photon radiotherapy who underwent carbon ion re-irradiation at our institute were retrospectively analyzed. Carbon ion radiotherapy was delivered by raster scanning with a median relative biological effectiveness-weighted dose of 72 Gy in 20 fractions. Weekly CT reviews were carried out, and offline adaptive replanning was performed whenever required. The median follow-up duration was 23.8 months (range, 6.2–47.1 months). At the last follow-up, two patients had a local disease progression, and 11 patients developed distant metastases. The 1- and 2-year local control, progression-free survival and overall survival rates were 100 and 93.3%, 70.8 and 45.0% and 86.7 and 81.3%, respectively. There were no Grade 3 or higher acute toxicities observed. Three patients developed Grade 3 late toxicities, one each with gastrointestinal toxicity, skin reaction and pelvic infection. In conclusion, definitive carbon ion re-irradiation with PBS provided superior oncologic results with tolerable toxicities and may be served as a curative treatment strategy in unresectable LRRC. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to evaluate the implementation and outcomes of a tailored ERAS LARRC protocol developed for patients with locally advanced and recurrent rectal cancer who require complex surgical procedures. This study shows that the protocol is feasible with a compliance rate of 73.6% and results in a reduction in postoperative complications. Multimodal anaesthesia could potentially impact the length of stay in a beneficial way, as well as improve the recovery profile. 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to advancements in surgical techniques, patients with recurrent rectal cancer and liver or lung secondaries are being increasingly considered for aggressive surgery. Our study reports outcomes for patients within this category undergoing simultaneous surgical removal of their cancer recurrence and secondaries across four centres worldwide. Our findings show that this option is feasible in a highly motivated group of patients who are well counselled on potential outcomes, including a high risk of cancer recurrence. Introduction: Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. 'Selective' patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. Methods: A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. Results: Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/− 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/− 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5–17.5 months) and 25.9 months (IQR 6.2–39.7 months), respectively. Conclusions: Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling. [ABSTRACT FROM AUTHOR]

Simple Summary: The efficacy of carbon-ion radiotherapy (CIRT) alone vs. multimodality therapy, including surgery, chemoradiotherapy, and intraoperative radiotherapy for previously irradiated locally recurrent rectal cancer, has not been evaluated. A total of 85 patients receiving 70.4 Gy (RBE) in 16 fractions of CIRT were compared with 86 patients receiving 30 Gy in 15 fractions of chemoradiation, resection, and intraoperative electron radiotherapy. CIRT demonstrated improved two- and five-year overall survival (83.1% and 46.8% vs. 62.5% and 25.7% for CMT), with statistically equivalent local recurrence and disease progression, with reduced treatment toxicity and decreased patient cost. A prospective comparison is warranted. No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan–Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), or DP (p = 0.19). Lower acute grade ≥ 2 skin and GI/GU toxicity and lower late grade ≥ 2 GU toxicities were associated with CIRT. Higher 2-year cumulative costs were associated with CMT. Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT, and CIRT was associated with longer OS. Prospective comparative studies are needed. [ABSTRACT FROM AUTHOR]

Locally Recurrent Rectal Cancer (LRRC) remains a major clinical concern; it rapidly invades pelvic organs and nerve roots, causing severe symptoms. Curative-intent salvage therapy offers the only potential for cure but it has a higher chance of success when LRRC is diagnosed at an early stage. Imaging diagnosis of LRRC is very challenging due to fibrosis and inflammatory pelvic tissue, which can mislead even the most expert reader. This study exploited a radiomic analysis to enrich, through quantitative features, the characterization of tissue properties, thus favoring an accurate detection of LRRC by Computed Tomography (CT) and 18 F-FDG-Positron Emission Tomography/CT (PET/CT). Of 563 eligible patients undergoing radical resection (R0) of primary RC, 57 patients with suspected LRRC were included, 33 of which were histologically confirmed. After manually segmenting suspected LRRC in CT and PET/CT, 144 Radiomic Features (RFs) were generated, and RFs were investigated for univariate significant discriminations (Wilcoxon rank-sum test, p < 0.050) of LRRC from NO LRRC. Five RFs in PET/CT (p < 0.017) and two in CT (p < 0.022) enabled, individually, a clear distinction of the groups, and one RF was shared by PET/CT and CT. As well as confirming the potential role of radiomics to advance LRRC diagnosis, the aforementioned shared RF describes LRRC as tissues having high local inhomogeneity due to the evolving tissue's properties. [ABSTRACT FROM AUTHOR]

Simple Summary: Although relatively rare, locally advanced or recurrent rectal cancer (LARC and LRRC) can metastasize. Patients whose advanced rectal cancer has metastasized to the peritoneum face a very poor prognosis. In selected patients, the prognosis might be improved by undergoing very intense treatment. This multimodality treatment, consisting of intraoperative radiotherapy (IORT), cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), is aimed at attaining a microscopic radical resection of the rectal tumor and its peritoneal metastases (PM), as this is the only option for long-term survival. The present study reports on 30 consecutive patients who have undergone this multimodality treatment. The results in terms of complications and survival are comparable to the results described in the literature on IORT and CRS-HIPEC as separate treatment entities. Thus, this multimodality treatment can be considered a treatment option for highly selected patients, provided that it is performed in a tertiary referral center. Purpose: To assess the safety and long-term outcome of a multimodality treatment consisting of radical surgery, intra-operative radiotherapy (IORT), and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with locally advanced rectal cancer (LARC) or locally recurrent rectal carcinoma (LRRC) and peritoneal metastases (PM). Methods: The present study was a single-center cohort study, including all consecutive patients undergoing this treatment in a tertiary referral center for LARC, LRRC, and PM. Postoperative complications, intensive care stay (ICU stay), and re-admission rates were assessed as well as disease-free survival (DFS) and overall survival (OS). Results: A total of 14 LARC and 16 LRRC patients with PM were included in the study. The median ICU stay was 1 day, and 57% of patients developed a severe postoperative complication. No 90-day mortality was observed. Median DFS was 10.0 months (Interquartile Range 7.1–38.7), and median OS was 31.0 months (Interquartile Range 15.9–144.3). Conclusions: As postoperative complications and survival were in line with treatments that are accepted for LARC or LRRC and PM as separate procedures, we conclude that combined treatment with IORT and CRS-HIPEC should be considered as a treatment option for selected patients with LARC or LRRC and peritoneal metastases in tertiary referral centers. [ABSTRACT FROM AUTHOR]

• Delineation in LRRC is complex due to heterogeneous disease and absence of guidelines. • Inter-observer variation in LRRC is large. • Multidisciplinary target volume definition is essential. • QA data from PelvEx II trial will provide further insight in target volumes. Neoadjuvant chemoradiotherapy (nCRT) is used in locally recurrent rectal cancer (LRRC) to increase chances of a radical surgical resection. Delineation in LRRC is hampered by complex disease presentation and limited clinical exposure. Within the PelvEx II trial, evaluating the benefit of chemotherapy preceding nCRT for LRRC, a delineation guideline was developed by an expert LRRC team. Eight radiation oncologists, from Dutch and Swedish expert centres, participated in two meetings, delineating GTV and CTV in six cases. Regions at-risk for re-recurrence or irradical resection were identified by eleven expert surgeons and one expert radiologist. Target volumes were evaluated multidisciplinary. Inter-observer variation was analysed. Inter-observer variation in delineation of LRRC appeared large. Multidisciplinary evaluation per case is beneficial in determining target volumes. The following consensus regarding target volumes was reached. GTV should encompass all tumour, including extension into OAR if applicable. If the tumour is in fibrosis, GTV should encompass the entire fibrotic area. Only if tumour can clearly be distinguished from fibrosis, GTV may be reduced, as long as the entire fibrotic area is covered by the CTV. CTV is GTV with a 1 cm margin and should encompass all at-risk regions for irradical resection or re-recurrence. CTV should not be adjusted towards other organs. Multifocal recurrences should be encompassed in one CTV. Elective nodal delineation is only advised in radiotherapy-naïve patients. This study provides a first consensus-based delineation guideline for LRRC. Analyses of re-recurrences is needed to understand disease behaviour and to optimize delineation guidelines accordingly. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the suitable radial margin (RM) for favourable outcomes after pelvic exenteration (PE), focusing on the discrepancy between the concepts of circumferential resection margin (CRM) and traditional R status. Seventy-three patients with locally advanced (LARC, n = 24) or locally recurrent rectal cancer (LRRC, n = 49) who underwent PE between 2006 and 2018 were retrospectively analysed. Patients were histologically classified into the following 3 groups; wide RM (≥1 mm, n = 45), narrow RM (0–1 mm, n = 10), and exposed RM (n = 18). The analysis was performed not only in the entire cohort but also in each disease group separately. The rates of traditional R0 (RM > 0 mm) and wide RM were 75.3% and 61.6%, respectively, resulting in the discrepancy rate of 13.7% between the two concepts. Preoperative radiotherapy was given in 12.3%. In the entire cohort, the local recurrence and overall survival (OS) rates for narrow RMs were significantly worse than those for wide RMs (p < 0.001 and p = 0.002), but were similar to those for exposed RMs. In both LARC and LRRC, RM < 1 mm resulted in significantly worse local recurrence and OS rates compared to the wide RMs. Multivariate analysis showed that RM < 1 mm was an independent risk factor for local recurrence in both LARC (HR 15.850, p = 0.015) and LRRC (HR 4.874, p = 0.005). Narrow and exposed RMs had an almost equal impact on local recurrence and poor OS after PE. Preoperative radiotherapy might have a key role to ensure a wide RM. [ABSTRACT FROM AUTHOR]

Introduction: Pelvic exenteration (PE) is now the standard of care for locally advanced (LARC) and locally recurrent (LRRC) rectal cancer. Reports of the significant short-term morbidity and survival advantage conferred by R0 resection are well established. However, longer-term outcomes are rarely addressed. This systematic review focuses on long-term oncosurgical and quality of life (QoL) outcomes following PE for rectal cancer., Methods: A systematic review of the PubMed ® , Cochrane Library, MEDLINE ® and Embase ® databases was conducted, in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Studies were included if they reported long-term outcomes following PE for LARC or LRRC. Studies with fewer than 20 patients were excluded., Findings: A total of 25 papers reported outcomes for 5,489 patients. Of these, 4,744 underwent PE for LARC (57.5%) or LRRC (42.5%). R0 resection rates ranged from 23.2% to 98.4% and from 14.9% to 77.8% respectively. The overall morbidity rates were 17.8-87.0%. The median survival ranged from 12.5 to 140.0 months. None of these studies reported functional outcomes and only four studies reported QoL outcomes. Numerous different metrics and timepoints were utilised, with QoL scores frequently returning to baseline by 12 months., Conclusions: This review demonstrates that PE is safe, with a good prospect of R0 resection and acceptable mortality rates in selected patients. Morbidity rates remain high, highlighting the importance of shared decision making with patients. Longer-term oncological outcomes as well as QoL and functional outcomes need to be addressed in future studies. Development of a core outcomes set would facilitate better reporting in this complex and challenging patient group.

Purpose: To assess pain management in patients post-sacrectomy, focusing on opioid use, and to identify the factors associated with postoperative pain. Methods: Patients who underwent resection of locally recurrent rectal cancer (LRRC) with concomitant sacrectomy at one of two hospitals between 2007 and 2020 were reviewed retrospectively. We examined the use of opioids preoperatively and postoperatively. Patients were classified into high and low sacrectomy groups based on the sacral bone resection level passing through the S3 vertebra. Results: Sixty-four patients were enrolled. Opioid use was significantly higher in the high sacrectomy group than in the low sacrectomy group at all times assessed: on postoperative days 7, 14, 30, 90, 180, and 365. Opioid use 3 months after locally recurrent rectal cancer surgery was significantly higher in patients with local re-recurrence of the tumor than in those without re-recurrence (p < 0.05), and the median morphine-equivalent opioid use 3 months postoperatively was significantly higher in the high sacrectomy group (30 vs. 0 mg/day; p < 0.05). Conclusions: Opioid use after concomitant sacrectomy for LRRC was higher in the high sacrectomy group. Prolonged postoperative pain or increasing pain was associated with local recurrence. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy/(re)chemoradiation and its impact on survival in locally recurrent rectal cancer (LRRC) and to identify predictors of pCR or differences between neoadjuvant treatments. Methods: Among 394 LRRC patients treated at the National Cancer Institute of Milan (Italy), 74 (27.8%) were treated with neoadjuvant chemotherapy with or without (re)chemoradiation before surgery. The pCR rate was estimated, and its impact on 5-year survival was evaluated with the Kaplan–Meier survival method. Univariate analysis was performed to find pre-treatment predictors of pCR. Results: After surgery, in 12 (16.2%) patients, a pCR was observed. All patients who reached pCR had R0 margins after surgery; among the 62 non-pCR patients, R0 margins were obtained in 29 (46.8%) cases only (p = 0.0004). pCR patients showed a significantly higher 5-year overall survival compared to non-pCR cases (33.3% vs. 21.0%, p = 0.045) and a trend toward better 5-year re-local recurrence-free survival. On univariate analysis, no predictor of pCR was found in the present study based on pre-treatment features. Conclusion: Since pCR is significantly associated to R0 resection and 5-year overall survival, pCR could be a target for LRRC cure. However, pCR is currently unpredictable based on pre-treatment features. [ABSTRACT FROM AUTHOR]

Prognostic features in locally recurrent rectal cancer (LRRC), beyond R0 surgery, are unknown. Aim of the present study was to evaluate the prognostic role of peripheral immune estimators, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on survival outcomes in LRRC patients. 184 LRRC patients treated at the National Cancer Institute of Milan (Italy) were included. Optimal cut-off values for NLR and PLR were determined. Kaplan-Meier curves and multivariate Cox analyses were used to assess the 5-yr overall survival (OS) according to NLR and PLR, also considering margins status. NLR >3.9 (hazard ratio [HR] 3.96, P = 0.049), PLR >275 (HR 5.39, P = 0.002) and size on imaging (HR 1.36, P = 0.044) were associated to worse OS. R+ patients with NLR >3.9 showed a significantly lower 5-yr OS compared to NLR ≤3.9 (13.5% vs. 36.7%, P < 0.0001). Also PLR >275 was related with a lower 5-yr OS compared to PLR ≤275 in R+ patients (6.4% vs. 36.8%, P = 0.0003). Conversely, NLR and PLR were irrelevant in case of R0 surgery. NLR and PLR predict 5-yr OS in LRRC, also identifying a subset of R+ patients with a similar expected survival compared to R0 cases. [ABSTRACT FROM AUTHOR]

Surgery for locally recurrent rectal cancer (LRRC) presents several challenges, which is why the percentage of inadequate resections of these tumors is high. In this exploratory study, we evaluate the use of image-guided surgical navigation during resection of LRRC. Patients who were scheduled to undergo surgical resection of LRRC who were deemed by the multidisciplinary team to be at a high risk of inadequate tumor resection were selected to undergo surgical navigation. The risk of inadequate surgery was further determined by the proximity of the tumor to critical anatomical structures. Workflow characteristics of the surgical navigation procedure were evaluated, while the surgical outcome was determined by the status of the resection margin. In total, 20 patients were analyzed. For all procedures, surgical navigation was completed successfully and demonstrated to be accurate, while no complications related to the surgical navigation were discerned. Radical resection was achieved in 14 cases (70%). In five cases (25%), a tumor-positive resection margin (R1) was anticipated during surgery, as extensive radical resection was determined to be compromised. These patients all received intraoperative brachytherapy. In one case (5%), an unexpected R1 resection was performed. Surgical navigation during resection of LRRC is thus safe and feasible and enables accurate surgical guidance. [ABSTRACT FROM AUTHOR]

Locally recurrent rectal cancer is resected with clear margins in only 50% of cases, and these patients achieve a three-year survival rate of 50%. Outcomes and therapeutic strategies for nonresectable locally recurrent rectal cancer have been much less explored. The aim of the study was to assess the three-year progression-free survival and the three-year overall survival in locally recurrent rectal cancer patients treated by chemotherapy/chemoradiation only vs. chemotherapy/chemoradiation and R2 surgical debulking vs. palliative care. A total of 86 patients affected by nonresectable locally recurrent rectal cancer were included: three-year progression-free survival was 15.8% with chemotherapy/chemoradiation vs. 20.3% with R2 surgical debulking (Log-rank p=0.567), but both rates were higher than best palliative care (0.0%, Log-rank p=0.0004). Three-year overall survival rates were respectively 62.0%, 70.8% and 0.0% (Log-rank p<0.0001). Chemotherapy/chemoradiation (HR 0.33, p=0.028) and R2 surgical debulking with or without chemotherapy/chemoradiation (HR 0.23, p=0.005) were independent predictors of improved progression-free survival on multivariate analysis. In conclusion, both chemotherapy/chemoradiation alone and R2 surgery with or without chemotherapy/chemoradiation provide a survival benefit over palliative care in nonresectable locally recurrent rectal cancer. However, considering that pelvic debulking is burdened by a high rate of complications, and considering its negligible impact on progression-free survival and overall survival when associated to medical therapy, surgery should be avoided in this setting., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

• Locally recurrent rectal cancer (LRRC) is a highly complex disease. • Clinical decision making is often based on low-grade evidence and expert opinion. • Centralization of LRRC-care in expert centres should be the norm. • The Netherlands is instating a guideline for LRRC, from diagnosis to surgery. Due to improvements in treatment for primary rectal cancer, the incidence of LRRC has decreased. However, 6–12% of patients will still develop a local recurrence. Treatment of patients with LRRC can be challenging, because of complex and heterogeneous disease presentation and scarce − often low-grade − data steering clinical decisions. Previous consensus guidelines have provided some direction regarding diagnosis and treatment, but no comprehensive guidelines encompassing all aspects of the clinical management of patients with LRRC are available to date. The treatment of LRRC requires a multidisciplinary approach and overarching expertise in all domains. This broad expertise is often limited to specific expert centres, with dedicated multidisciplinary teams treating LRRC. A comprehensive, narrative literature review was performed and used to develop the Dutch National Guideline for management of LRRC, in an attempt to guide decision making for clinicians, regarding the complete clinical pathway from diagnosis to surgery. [ABSTRACT FROM AUTHOR]

In the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. Patients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. Use of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). Primary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially. • In 2016 less primary rectal cancer patients were treated with neoadjuvant (chemo)radiotherapy. • The LRRC rate remained the same between 2011 and 2016. • In 2016 LRRC patients were more often candidate for curative treatment. • In 2016 LRRC patients received full course chemoradiotherapy more often. • Survival of curatively treated LRRC patients increased significantly over time. [ABSTRACT FROM AUTHOR]

Background: Locally recurrent rectal cancer (LRRC) occurs in 5-10% of patients following previous treatment of rectal cancer. It has a significant impact on patients' overall health-related quality of life (HrQoL). Major advances in surgical treatments have led to improved survival outcomes. However, due to the lack of disease-specific, validated patient-reported outcome measure (PROM), HrQoL, is variably assessed. The aim of this study is to develop a disease-specific, psychometrically robust, and validated PROM for use in LRRC., Methods: A multicentre, three phase, mixed-methods, observational study was performed across five centres in the UK and Australia. Adult patients (>18 years old) with an existing or previously treated LRRC within the last 2 years were eligible to participate. Patients completed the proposed LRRC-QoL, EORTC QLQ-CR29, and FACT-C questionnaires. Scale structure was analysed using multi-trait scaling analysis and exploratory factor analysis, reliability was assessed using Cronbach's and the intra-class coefficient, convergent validity was assessed using Pearson's correlation, and known-groups comparison was assessed using the student t-test or ANOVA., Findings: Between 01/03/2015 and 31/12/2019, 117 patients with a diagnosis of LRRC were recruited. The final scale structure of the LRRC-QoL consisted of nine multi-item scales (healthcare services, psychological impact, pain, urostomy-related symptoms, lower limb symptoms, stoma, sexual function, sexual interest, and urinary symptoms) and three single items. Cronbach's Alpha and Intraclass correlation values of >0.7 across the majority of scales supported overall reliability. Convergent validity was demonstrated between LRRC-QoL Pain Scale and FACT-C Physical Well Being scale (r = 0.528, p < 0.001), LRRC-QoL Psychological Impact scale with EORTC QLQ CR29 Body Image (r = 0.680, p < 0.001) and the FACT-C Emotional Well Being scale (r = 0.326, p < 0.001), and LRRC-QoL Urinary Symptoms scale with EORTC QLQ-CR29 Urinary Frequency scale (r = 0.310, p < 0.001). Known-groups validity was demonstrated for gender, disease location, treatment intent, and re-recurrent disease., Interpretation: The LRRC-QoL has demonstrated robust psychometric properties and can be used in clinical and academic practice., Funding: None., Competing Interests: GV has received consulting fees from Pfizer, Eisa and Roche. She has received honoraria from Novartis, AstraZeneca and Pfizer. She sits on advisory boards for Sanofi and Seattle Genetics. The other authors have no declared conflicts of interest. NM is undertaking a PhD funded by from Bowel and Cancer Research UK., (© 2023 The Authors.)

Despite advances in rectal cancer treatments, its local recurrence rate is still 4-10 percent. And an evidence-based definition of early recurrence is lacking. Our study hopes to establish a clear threshold to distinguish early and late recurrence, and analyze risk and prognostic factors for them. Rectal cancer patients who underwent proctectomy from 2009 to 2019 were included. Patients who received neoadjuvant treatment and with incomplete records were excluded. The optimal interval was obtained using the minimum P value approach. Risk factors for early recurrence were analyzed by logistic regression models, and prognostic factors associated with additional surgery were assessed by Cox proportional hazards models. The optimal interval for the definition of early recurrence was 26 months based on the subsequent prognosis ( P < 0.001). The 5-year survival rate of early and late recurrence cohort was 32.5% and 57.1%, respectively ( P < 0.001). Adjuvant radiotherapy was the independent protective factor for early recurrence. And the presence of lymphovascular invasion, positive surgical margin, and no re-neoadjuvant radiotherapy were independent prognostic factors for the survival of LRRC patients under additional surgery., Competing Interests: None., (AJCR Copyright © 2022.)