Recurrence patterns and management of locally recurrent rectal cancer: a retrospective cohort study

Recurrence patterns and management of locally recurrent rectal cancer: a retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Recurrence patterns and management of locally recurrent rectal cancer: a retrospective cohort study Priska Hakenberg, Georgi Kalev, Steffen Seyfried, Christoph Reißfelder, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5694880/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Apr, 2025 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted 3 You are reading this latest preprint version Abstract Purpose Treatment of locally recurrent rectal cancer (LRRC) is still challenging because of inhomogeneous patient cohorts regarding previous treatments as well as different recurrence patterns and locations. The aim of this study was to investigate the local treatments and surgical approaches tailored to them. Methods We included all patients who were treated for LRRC without distant metastasis at the University Medical Center Mannheim, Germany, between 2010 and 2022. We collected data from our electronic clinical data management system regarding the initial diagnosis and treatment as well as locations and treatment of the recurrent tumor. Results We identified a total of 666 patients who were curatively treated for rectal cancer of whom 36 patients (5.4%) developed LRRC without distant recurrence. Most patients (26/36) had a tailored therapy regimen that included surgery with or without perioperative radiation and/or chemotherapy. The most common site of local relapse was around the former colorectal anastomosis (15/36, 41.7%). The operative procedures ranged from anterior resection to multi-organ resection and exenteration. A complete resection (R0) could be achieved in 12 patients (12/22; 54.5%). The 3- and 5-year overall survival rates were 79% and 72%, respectively. Conclusion Most local recurrences happen at the anastomotic site and are mostly eligible for curative surgical therapy with good long-term survival. recurrent rectal cancer colorectal cancer abdominoperineal resection complications survival Figures Figure 1 INTRODUCTION Rectal cancer is one of the most common cancers in the world and in 2020, 12.7% of all new cancer diagnoses were colorectal cancer. Due to far-reaching advances in surgical procedures, and radio- and chemotherapy as well as improved screening and diagnostics, survival and recurrence rates could be improved over the last decades [ 1 ]. Recurrence rates ranged from about 5% to up to 30% [ 2 , 3 ], but could be improved due to above mentioned advances to 4–10% [ 3 – 6 ]. The treatment of locally recurrent rectal cancer (LRRC) is still challenging because of inhomogeneous patient cohorts regarding previous treatments as well as different recurrence patterns and locations. Therefore, LRRC is an ongoing topic of concern because of the increasing incidence of colorectal cancer especially in patients of young age with a relatively long life expectancy and thus a higher chance of local or disseminated cancer recurrence as stated in the recently published colorectal cancer statistics in the US [ 7 ] and all over the world [ 8 ]. There is no clear evidence on how to treat LRRC properly and most studies are retrospective and have a small sample size. To our knowledge, up to now there is no prospective study regarding treatment of LRRC and only one national guideline [ 9 ]. The aim of this study was to investigate local recurrence patterns of LRRC as well as the multimodal treatments and surgical approaches tailored to them. METHODS For our retrospective study, we included all patients who were treated for LRRC without distant metastasis at the University Medical Center Mannheim, Germany, between 2010 and 2022. Therefore, all patients with LRRC were included, regardless of whether the primary operation had been performed externally or at our clinic. To find all patients meeting the inclusion criteria, we searched our clinical information system for the ICD (International Statistical Classification of Diseases and Related Health Problems)-Code C20, as there is no designated code for LRRC, and then excluded all non-curative and non-operative cases as well as primary and emergency cases, manually. Patients who had developed distant metastases at the same time as the local recurrence were also excluded to be able to examine a cohort that was as homogenous as possible. We collected data regarding baseline and oncological characteristics including previous systemic and radiation treatments as well as pathological results from the time point of initial surgery, time point of first evidence of recurrent cancer, localization of recurrent tumor mass in CT or MRI scans and conducted treatment of recurrent cancer as well as survival data. As classification system for the localization of recurrence, we used the Memorial Sloan-Kettering Classification System [ 10 ]. The study was approved by the local ethics committee (ID: 2022-812-AF 11). Patients’ consent was not necessary due to the retrospective nature of the study. Descriptive statistics and survival analysis were conducted with excel 2024. RESULTS Through screening of our clinical data management system for C20, we identified a total of 699 patients with rectal cancer between January 2010 and June 2021 of which 666 were curatively treated for rectal cancer. 37 had LRRC, due to simultaneous distant tumor recurrence, we excluded one of the 37 patients with LRRC. The remaining 36 patients (36/666, 5.4%) with isolated LRRC were included into our analysis. The median age at the time of the first curative surgery was 62.5 years (IQR (interquartile range): 53–72). A complete resection, R0, could be achieved in 32 patients (32/36, 88.9%). No patient had a macroscopic incomplete resection (R2), and 2 patients (2/36, 5.6%) had a microscopically incomplete resection (R1). The R1 status occurred in patients with a T status classified as 4, and in one of those patients, a local tumor perforation had occurred. Both patients underwent a low anterior resection with a laparoscopic approach, and one patient (the patient with the tumor perforation) also received a hysterectomy and ureter reconstruction due to tumor infiltration. Twenty-four patients (24/36, 66.7%) underwent a (low) anterior resection, and most of the patients (21/36, 58.3%) had laparoscopic surgery. A total of 4 patients (4/36, 11.1%) could be treated with a local procedure such as endoscopic submucosal dissections or transanal surgery. Eight patients needed an abdominoperineal resection due to the ultra-low location and the advanced extent of their tumor. Postoperative complications occurred in 11 patients (11/36, 30.6%). Only one patient had an anastomotic leakage and needed endoscopic intervention (endoluminal vacuum therapy). Seven (7/36, 19.4%) patients had a deficiency in wound healing, and 5 (5/36, 13.9%) of those had secondary wound healing in the sacral area after abdominoperineal resection, which was the most common complication after this type of surgery. Two patients (2/36, 5.6%) developed postoperative ileus and required temporary placement of a nasogastric tube. Non-surgical complications such as pneumonia or cardiac diseases occurred in 5 patients (5/36, 13.9%). Table 1 summarizes all patient, tumor and treatment characteristics regarding the primary rectal cancer diagnosis. Table 1 Patient, procedure and tumor characteristics at the time of the primary tumor resection Characteristic Median or absolute number IQR a or percentage Time till Recurrence (months) 20.5 16.75-30 Grading G1 0 0.0% G2 9 25.0% G3 1 2.8% unknown 26 72.2% Multimodal Therapy Surgery only 7 19.4% Surgery + Chemo-/Radiotherapy 18 50.0% Chemo-/Radiotherapy only 9 25.0% Best Supportive Care 0 0.0% Unknown 2 5.6% Operative Procedure APR b 6 23.1% APR b , Sacrectomy 1 3.8% APR, b Adjacent Organ Resection 2 7.7% LAR c 4 15.4% LAR c , Adjacent Organ Resection 0 0.0% Pelvic Exenteration 3 11.5% Pelvic Exenteration, Sacrectomy 2 7.7% Palliative Surgery 4 15.4% Other 4 15.4% Intraoperative Radiotherapy : Yes 6 23.1% No 20 76.9% Not Applicable 10 27.8% R Status : R0 12 54.5% R1 9 40.9% R2 0 0.0% unknown 1 4.5% a interquartile range, b abdominoperineal resection, c low anterior resection Local recurrence patterns and outcomes after surgery for LRRC Median time until rectal cancer recurrence in our cohort was 20.5 months (IQR: 16.75–30) with a range from 2 months minimum up to 84 months. Table 2 presents tumor and treatment characteristics at the time of tumor recurrence. Table 2 Tumor and treatment characteristics at the time of tumor recurrence previous treatment (n) therapy for LRRC a (n) localisation (Memorial Sloan Kettering Classification) n % neoadjuvant adjuvant RT b /CT c RT b /CT c /Surgery surgery IORT d axial 9 25.0% 1 2 1 6 2 0 anterior 5 13.9% 4 3 1 2 2 1 posterior 4 11.1% 2 (1x only RT) 3 0 3 1 2 lateral 5 13.9% 5 (1x only RT) 2 2 2 0 1 axial + anterior 5 13.9% 2 3 0 4 1 2 axial + lateral 1 2.8% 0 1 0 0 1 0 posterior + lateral 3 8.3% 2 1 2 1 0 0 anterior + posterior 1 2.8% 1 0 0 1 0 0 unknown 3 8.3% a locally recurrent rectal cancer, b radiotherapy, c chemotherapy; d intraoperative radiotherapy In total, 26 patients (26/36, 72.2%) received a therapy regimen for their local recurrence that included surgery. Seven patients (7/36, 19.4%) were treated with surgery only, and 19 patients (19/36, 52.8%) were treated with a combination of radiotherapy, chemotherapy and surgery. Eight patients (8/36, 22.2%) received only radiotherapy and/or chemotherapy. No patient received best supportive care. For 2 patients (2/36, 5.6%), the further course of the disease is unknown as they refused any further diagnostics and treatment. The operative group covers a wide range of procedures: 9 abdominoperineal resections (9/26, 34.6%), one with sacrectomy (1/26, 3.8%), and 2 with additional organ resection (2/26, 7.7%), as well as 4 low anterior resections (4/26, 15.4%). All these patients had undergone an anterior resection or a low anterior resection in the context of their primary surgery. A complete exenteration was necessary in 5 patients (5/26, 19.2%). Most recurrences occurred around the anastomosis, with a total of 15 patients (15/36, 41.7%). Of these 15 patients, 5 patients (5/15, 66.7%) had tumor mass in the former tumor region and anterior of that with infiltration of vagina, bladder, or prostate, and one patient had tumor recurrence in the former tumor region with additional tumor mass laterally. Five patients had only anterior recurrence, and 4 only posterior tumor with infiltration of the sacrum. For 2 patients (2/36, 5.6%), the exact location of the recurrent tumor is unknown because they refused further diagnostic examinations. Only one of the 36 patients with LRRC had an anastomotic leakage after the primary operation. However, the local recurrence in this case did not occur in the area of the old anastomosis, but posteriorly and laterally, which may have corresponded anatomically to the former leakage cavity. Among the cohort of patients who underwent resection of their LRRC, an R0 resection was achieved in 12 individuals (12/22; 54.5%). Nine patients (9/36, 25.0%) had tumor recurrence only in the region of the anastomosis or at the site of the former tumor without infiltration of adjacent organs or tumor mass in any other region than the anastomotic site. Of these 9 patients, 2 had undergone an anterior resection as the original surgery, 2 had had a local resection which could be performed transanally, and the remaining 5 patients had undergone a low anterior resection as the initial surgery. 8 out of these 9 patients qualified for a second surgery for their recurrent cancer. Both patients with previous local transanal tumor resection received an abdominoperineal resection, 3 patients had again a low anterior resection, one patient with recurrent tumor mass in the region of the anastomosis had palliative stoma placement due to colon ileus and one patient had a low anterior resection with additional ileocecal resection. Table 3 shows the sites of recurrence and corresponding multimodal treatments. Table 3 Locations of tumor recurrence and corresponding multimodal treatments Procedures (n) localisation APR a APR a , sacretomy APR a , adjacent organres. LAR b LAR b + adjacent organres. pelvic exenteration pelvic exenteration + sacrectomy palliative surgery other axial 2 0 0 4 0 0 0 1 1 anterior 0 0 0 0 0 2 1 1 0 posterior 1 0 0 0 0 0 1 1 1 lateral 1 0 0 0 0 0 0 0 1 axial + anterior 1 0 2 0 0 1 0 1 0 axial + lateral 0 0 0 0 0 0 0 0 1 posterior + lateral 1 0 0 0 0 0 0 0 0 anterior + posterior 0 1 0 0 0 0 0 0 0 a abdominoperineal resection, b low anterior resection Intraoperative radiotherapy was administered in 6 patients (6/26, 23.1%). All six patients had a complex recurrence pattern of their tumor, including lateral positions and infiltration of adjacent organs. Two patients needed pelvic exenteration, and one patient needed exenteration with sacrectomy. Another patient received sacrectomy alone, and two patients underwent abdominoperineal resection. Table 4 presents the surgical approach depending on the site of recurrence. The postoperative complication rate after resection of LRRC was 57.7% (15 patients suffered at least one postoperative complication), and complications were various. One out of 3 patients (1/3, 33.3%) with low anterior resection without restoration of bowel continuity had leakage of the rectal stump which needed intervention (endoluminal vacuum therapy). 7 out of 14 patients (7/14, 50.0%) after abdominoperineal resection or pelvic exenteration had a perineal wound healing disorder. Of the 14 patients, 9 (9/14, 64.3%) had received an omentoplasty, one patient each had a VRAM (vertical rectus abdominis myocutaneous) or gluteal flap (each 7.1%), and in 3 patients (3/14, 21.4%), no omentoplasty was used and the perineal wound was closed primarily. Five of the perineal wound infections occurred after omentoplasty, one after the gluteal flap and one after primary closure of the perineal wound. Postoperative ileus occurred in 2 patients (2/26; 7.7%) and non-surgical complications including respiratory disorders or renal failure were found in one patient each (3.8% each). For survival analysis, 6 patients were lost to follow up. Thus, we could analyze the remaining 30 patients with a median follow up of 23 months (IQR: 12–30 months). The 3- and 5-year overall survival rates were 79% and 72%, respectively. Figure 1 presents the survival of the cohort over time (Kaplan-Meier curve). DISCUSSION This retrospective analysis of an almost 12-year period at a colorectal surgery center of excellence at a German university hospital revealed a local recurrence rate after curative treatment for rectal cancer of 5.4% (36/666). This is consistent with the recent literature which reports a recurrence rate of 4 to 11% [ 2 , 9 , 11 , 12 ] , . The primary and, to date, most significant surgical milestone in the development of rectal cancer surgery was the introduction of “total mesorectal excision” by Heald in the second half of the 20th century [ 13 ]. Heald was able to achieve a local recurrence rate of less than four percent, which was previously unthinkable. Most recurrent tumors have a simultaneous local and distant recurrence or only distant recurrence [ 2 , 11 , 12 , 14 ]. Jung et al. [ 2 ] who conducted a retrospective analysis regarding risk factors for local recurrence over a time period of 15 years divided their cohort in 3 groups depending on the time interval since the primary operation. The analysis showed that the recurrence rate decreased over time from up to 13% (2002–2006) down to only 5% (2012–2017). This is in concordance with our results. Jankowski et al. [ 15 ] conducted a retrospective study over a 7-year period (2001–2008) regarding the incidence of and risk factors for LRRC. In their cohort, the local recurrence rate was 7.4% (27/365). They found that the subgroup that was treated with short-term radiotherapy only, using 5x5 Gy, showed a good control regarding local recurrence with a recurrence rate of only 4.2% [ 15 ]. This treatment is not used very often nowadays and mostly applied in older patients who are not able to receive chemotherapy. At present, neoadjuvant radio-chemotherapy or total neoadjuvant therapy are the most common preoperative therapy regimes for locally advanced rectal cancer [ 16 ]. However, there a multiple potential risk factors for local recurrence after rectal cancer resection apart from the absence of neoadjuvant treatment. Jankowski et al. identified a low location in the rectum of the primary tumor as another relevant risk factor for local recurrence [ 15 ]. In our study cohort, more than one third of the patients with LRRC, (38.9% (n = 14)) had their primary tumor in the lower third of the rectum (circumferential resection margin (CRM) was involved in one of the 14 patients, whereas 10 patients had a negative CRM, one patient had a local excision, and in two cases, data one CRM were missing), whereas only 16.7% (n = 6) had their primary tumor in the upper third of the rectum (3 of the 6 patients had a negative CRM, and in the remaining 3 patients CRM was unknown). This risk factor may be due to the narrow anatomy in the pelvis with closer resection margins even with a correctly performed total mesorectal excision (TME) in the lower third of the rectum. Another retrospective single center study from Mayo Medical Center, Rochester, Minnesota, conducted by Hahnloser et al. found no correlation between the initial tumor treatment and local recurrence. They included a total of 429 patients with LRRC between 1981 and 1996 [ 17 ]. All patients had previously undergone curative surgery and received multimodal treatment for their recurrent tumor. After re-staging, 304 patients were thought to be eligible for surgery, but only 138 patients underwent curative resection (R0). 139 patients had palliative resection due to gross tumors that could not be completely resected due to technical limitations and 27 patients had microscopically residual tumor mass. Looking at these subgroups, survival was best when the tumor was completely removed (5-year survival 37%), second best with only microscopically residual tumor mass (5-year survival 22%) and poorest when larger masses of tumor had to remain (5-year survival 16%). These data are relatively old and radio-chemotherapy regimens and surgical techniques have advanced since then, but we can still conclude that the most important principle in successful treatment of LRRC is to achieve an R0 resection. This was also found by Caricato et al. in their meta-analysis regarding prognostic factors [ 18 ] after surgery for locally LRRC. They identified a total of 8 studies which confirmed that an R0 resection was a statistically significant prognostic factor and associated with better survival outcomes compared to R1 and R2 resection [ 18 ]. This is further supported by a Swedish nationwide analysis conducted by Westberg [ 19 ]. They included all patients with LRRC in the period between 1995 and 2002 and collected data in their nationwide colorectal cancer registry. They found a 5-year survival rate of 43% for patients after R0 resection and 14% for patients after R1 resection. A systematic review by Fadel et al. [ 20 ] regarding oncological outcomes after multimodal treatments and surgery in patients with LRRC found that a neoadjuvant treatment for recurrence is highly beneficial and should be done as a combination of radiation and chemotherapy whenever possible. Furthermore, Fadel at al. [ 20 ] report that neoadjuvant radio-chemotherapy was helpful in achieving an R0-resection and that patients even benefited from neoadjuvant radiation alone (followed by radical resection) compared to upfront surgery with potential adjuvant systemic treatment. Likewise, Rödel et al. found that 8% of patients with recurrent cancer that were primarily classified as nonresectable could be subjected to surgery after neoadjuvant radio-chemotherapy [ 21 ]. As Klose et al. showed in their multivariate analysis of 90 patients with LRRC, curative resection is more likely for intraluminal local recurrence compared to extraluminal recurrence and curative resection is significantly associated with prolonged survival [ 22 ]. The fact that almost half of our cohort (15 patients, 41.7%) had a recurrence at the previous anastomotic site may at least in part explain the good R0 resection rate of 54.5% (12/22), and depending on that, the good survival. Rahbari and colleagues have also shown that R0 resection of the LRRC is a decisive prognostic factor for survival, even in the presence of extrapelvic tumor recurrence: in their multivariate analysis of 107 patients with LRRC, R0 resection could be achieved in 58.7%. The R0 rate is thus comparable to the rate of 54.5% described by us. Three- and 5-year survival rates were 61% and 47%, which is lower than in our cohort. On multivariate analysis, surgical morbidity, presence of extrapelvic disease, and R1/2 resection were independent predictors of a poorer survival [ 23 ]. We found a 3-year overall survival of 79% without separating the patients in any groups due to the small sample size. Our results are in concordance with the results of Kim et al. [ 11 ] who conducted a retrospective analysis of early and late recurrent rectal cancer patients in Asia. They found a 3-year overall survival of 76% for early and 90% for the late recurrence group. Another study by Agas et al. [ 24 ] reported a relatively poor overall survival for locally recurrent rectal cancer (68%, 41%, 37% for 3-, 5-, 7-year overall survival (OS), respectively), who were eligible for surgery and had undergone intraoperative radiotherapy (IORT). Fadel et al. [ 20 ] described a lower 5-year OS in their meta-analysis compared to our and Kim’s results. They could include 14 retrospective studies and one prospective study regarding treatment and survival in locally recurrent rectal cancer patients. The patients could be divided into 4 different treatment groups and reported a 5-year OS of: 35% for the neoadjuvant radio-chemotherapy group, 30% for the surgery only group, and 29% for the neoadjuvant radiotherapy group. The poorest 5-year survival was seen in the adjuvant chemo-radiotherapy group with 21%. This is not in line with our results, which might be due to older data (the included studies included were mainly published between 1997 and 2006) and other treatments and chemotherapeutics provided in their study cohort. Our results showed that the recurrent tumor mass was mostly located at the former tumor site or anastomotic site, which is also described by Park et al. [ 25 ]. They report similar recurrence patterns as found in our study cohort. The central type of pelvic recurrence was the most common (n = 21, 33.9%) followed by the lateral (n = 14, 22.6%), posterior (n = 13, 21%), perineal (n = 8, 12.9%), and anterior types (n = 6, 9.7%). This is in accordance with our results with a rate of central recurrences of 41% (15/36), lateral recurrences of 25% (9/36), and posterior recurrences of 22% (8/36). The results differ only in regard of LRRC affecting the anterior region, where we found a much higher recurrence rate of 30% (11/36) compared to 9.7%. A large systematic review suggests that the risk of local recurrence of colorectal cancer triples after postoperative anastomotic leakage [ 26 ]. This is not fully reflected in our data: only one of the 36 patients with LRRC had had anastomotic leakage after primary surgery. Another independent risk factor for local recurrence is CRM involvement [ 27 ]. Again, our data are not entirely conclusive, partly because no data on CRM were available from the external primary surgeries: CRM was negative in 21 of 36 patients (58.3%), in 13 (36.1%) there were no data on CRM available due to external primary surgeries, and a local procedure was used in two patients. However, the R status was only not specified in 2 cases, whereas in 32 of 36 patients (88.9%), an R0 resection could be achieved, and in two patients, R1 was reported. There were no cases of R2 resection. It can therefore be concluded that most local relapses in our cohort occurred despite previous R0 resection and negative CRM. Our study has several limitations. First, selection bias cannot be excluded due to the retrospective study design. Second, despite the long observation period, the sample size is small. Nevertheless, the strengths of our study are also evident: the data summarize a period of almost 12 years of treatment of rectal cancer recurrences at a nationally recognized colorectal surgery center. This can contribute to filling the evidence gaps regarding therapeutic algorithms for local recurrences of rectal cancer. CONCLUSION LRRC remains a challenging topic, even in interdisciplinary teams and for highly educated and trained experts. With an individualized therapeutic approach, an R0 resection of the LRRC can be achieved in almost two-thirds of cases. The resulting good 5-year survival rate of 72% supports a multimodal therapeutic approach with surgical resection of the local recurrence, with acceptable postoperative morbidity. To tailor multimodal therapy even more precisely and specifically to the individual localization and tumor biology, further findings from prospective studies with large numbers of cases are required. Declarations Conflict of interest disclosure: None of the authors has a conflict of interest to declare. Ethics approval statement: This study (ID: 2022-812-AF 11) has been approved by the institutional ethics committee, the Ethikkommission II of the University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany. Funding statement: None of the authors received external financial support for preparation, conduct, or analysis of the study. Author Contribution P.H., J.H. and C.R. were involved in study conception and design. P.H. was in charge of data acquisition. P.H. and J.H. analyzed and interpreted the data, drafted the manuscript and prepared tables and figures.All authors reviewed the manuscript. 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Clin Colorectal Cancer 22:257–266. https://doi.org/10.1016/j.clcc.2023.03.002 Park J-K, Kim Y-W, Hur H et al (2009) Prognostic factors affecting oncologic outcomes in patients with locally recurrent rectal cancer: impact of patterns of pelvic recurrence on curative resection. Langenbecks Arch Surg 394:71–77. https://doi.org/10.1007/s00423-008-0391-6 Mirnezami A, Mirnezami R, Chandrakumaran K et al (2011) Increased Local Recurrence and Reduced Survival From Colorectal Cancer Following Anastomotic Leak: Systematic Review and Meta-Analysis. Ann Surg 253:890. https://doi.org/10.1097/SLA.0b013e3182128929 Kim S, Huh JW, Lee WY et al (2024) Risk factors and treatment strategies for local recurrence of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision. Eur J Surg Oncol. https://doi.org/10.1016/j.ejso.2024.108641 . 50: Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Apr, 2025 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted Editor assigned by journal 31 Dec, 2024 Submission checks completed at journal 30 Dec, 2024 First submitted to journal 22 Dec, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5694880","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":396061707,"identity":"84f524db-2c3c-4ec2-8fb7-db483e5855f6","order_by":0,"name":"Priska Hakenberg","email":"","orcid":"","institution":"University Medical Center Mannheim, Heidelberg University","correspondingAuthor":false,"prefix":"","firstName":"Priska","middleName":"","lastName":"Hakenberg","suffix":""},{"id":396061708,"identity":"7699b67e-92be-4a26-94ca-b1b723146bff","order_by":1,"name":"Georgi Kalev","email":"","orcid":"","institution":"University Medical Center Mannheim, Heidelberg University","correspondingAuthor":false,"prefix":"","firstName":"Georgi","middleName":"","lastName":"Kalev","suffix":""},{"id":396061709,"identity":"ac9070ae-2ef9-40fc-a516-7258bda93680","order_by":2,"name":"Steffen Seyfried","email":"","orcid":"","institution":"University Medical Center Mannheim, Heidelberg University","correspondingAuthor":false,"prefix":"","firstName":"Steffen","middleName":"","lastName":"Seyfried","suffix":""},{"id":396061710,"identity":"6eea6b34-c966-4938-ae2a-858052f7aae2","order_by":3,"name":"Christoph Reißfelder","email":"","orcid":"","institution":"University Medical Center Mannheim, Heidelberg University","correspondingAuthor":false,"prefix":"","firstName":"Christoph","middleName":"","lastName":"Reißfelder","suffix":""},{"id":396061711,"identity":"17dd2522-40fa-4989-967d-b7e281f256d4","order_by":4,"name":"Julia Hardt","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYBACxgbmhgMMDEDEkMD4ACx0gKAWRpiWZGYDorSANEGVJbNJEKWFeUZi44EfDHfkzdvzj1Xz5mxj4DveQMCOGYkNB3sYnhnOOfOY7TbvttsMkmcIWAPScoCH4TDjDIlkiBaDGwlE2PKH4bA9SEsxWMv9B4S1HAbakgjSwgyxBb8OBsaehw2HZQwOJ8/geWwsOXfbbR7JMwQcZtiefPjjm4rDtjPYEx9+eLvtthzf8QMEtDSASAOEAA8BZzEwyBNUMQpGwSgYBaMAAGoXTYqlEhQWAAAAAElFTkSuQmCC","orcid":"","institution":"University Medical Center Mannheim, Heidelberg University","correspondingAuthor":true,"prefix":"","firstName":"Julia","middleName":"","lastName":"Hardt","suffix":""}],"badges":[],"createdAt":"2024-12-22 17:23:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5694880/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5694880/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00423-025-03692-x","type":"published","date":"2025-04-02T15:56:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72755088,"identity":"6edbc088-be3c-48bd-a409-b9e9d2fc1a4f","added_by":"auto","created_at":"2025-01-01 16:53:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":11149,"visible":true,"origin":"","legend":"\u003cp\u003esurvival data of our cohort\u003c/p\u003e","description":"","filename":"Onlinedrawingimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5694880/v1/50e62fce1833c01b3da3f7db.png"},{"id":80081998,"identity":"4db9952e-4ce6-4b33-99c8-486f48908cea","added_by":"auto","created_at":"2025-04-07 16:05:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":734116,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5694880/v1/27532d35-9f27-4613-b80f-43a956043b33.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Recurrence patterns and management of locally recurrent rectal cancer: a retrospective cohort study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eRectal cancer is one of the most common cancers in the world and in 2020, 12.7% of all new cancer diagnoses were colorectal cancer. Due to far-reaching advances in surgical procedures, and radio- and chemotherapy as well as improved screening and diagnostics, survival and recurrence rates could be improved over the last decades [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Recurrence rates ranged from about 5% to up to 30% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], but could be improved due to above mentioned advances to 4\u0026ndash;10% [\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The treatment of locally recurrent rectal cancer (LRRC) is still challenging because of inhomogeneous patient cohorts regarding previous treatments as well as different recurrence patterns and locations. Therefore, LRRC is an ongoing topic of concern because of the increasing incidence of colorectal cancer especially in patients of young age with a relatively long life expectancy and thus a higher chance of local or disseminated cancer recurrence as stated in the recently published colorectal cancer statistics in the US [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and all over the world [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere is no clear evidence on how to treat LRRC properly and most studies are retrospective and have a small sample size. To our knowledge, up to now there is no prospective study regarding treatment of LRRC and only one national guideline [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of this study was to investigate local recurrence patterns of LRRC as well as the multimodal treatments and surgical approaches tailored to them.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eFor our retrospective study, we included all patients who were treated for LRRC without distant metastasis at the University Medical Center Mannheim, Germany, between 2010 and 2022. Therefore, all patients with LRRC were included, regardless of whether the primary operation had been performed externally or at our clinic. To find all patients meeting the inclusion criteria, we searched our clinical information system for the ICD (International Statistical Classification of Diseases and Related Health Problems)-Code C20, as there is no designated code for LRRC, and then excluded all non-curative and non-operative cases as well as primary and emergency cases, manually. Patients who had developed distant metastases at the same time as the local recurrence were also excluded to be able to examine a cohort that was as homogenous as possible.\u003c/p\u003e \u003cp\u003eWe collected data regarding baseline and oncological characteristics including previous systemic and radiation treatments as well as pathological results from the time point of initial surgery, time point of first evidence of recurrent cancer, localization of recurrent tumor mass in CT or MRI scans and conducted treatment of recurrent cancer as well as survival data.\u003c/p\u003e \u003cp\u003eAs classification system for the localization of recurrence, we used the Memorial Sloan-Kettering Classification System [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e The study was approved by the local ethics committee (ID: 2022-812-AF 11). Patients\u0026rsquo; consent was not necessary due to the retrospective nature of the study.\u003c/p\u003e \u003cp\u003eDescriptive statistics and survival analysis were conducted with excel 2024.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThrough screening of our clinical data management system for C20, we identified a total of 699 patients with rectal cancer between January 2010 and June 2021 of which 666 were curatively treated for rectal cancer. 37 had LRRC, due to simultaneous distant tumor recurrence, we excluded one of the 37 patients with LRRC. The remaining 36 patients (36/666, 5.4%) with isolated LRRC were included into our analysis.\u003c/p\u003e \u003cp\u003eThe median age at the time of the first curative surgery was 62.5 years (IQR (interquartile range): 53\u0026ndash;72). A complete resection, R0, could be achieved in 32 patients (32/36, 88.9%). No patient had a macroscopic incomplete resection (R2), and 2 patients (2/36, 5.6%) had a microscopically incomplete resection (R1). The R1 status occurred in patients with a T status classified as 4, and in one of those patients, a local tumor perforation had occurred. Both patients underwent a low anterior resection with a laparoscopic approach, and one patient (the patient with the tumor perforation) also received a hysterectomy and ureter reconstruction due to tumor infiltration.\u003c/p\u003e \u003cp\u003eTwenty-four patients (24/36, 66.7%) underwent a (low) anterior resection, and most of the patients (21/36, 58.3%) had laparoscopic surgery. A total of 4 patients (4/36, 11.1%) could be treated with a local procedure such as endoscopic submucosal dissections or transanal surgery. Eight patients needed an abdominoperineal resection due to the ultra-low location and the advanced extent of their tumor.\u003c/p\u003e \u003cp\u003ePostoperative complications occurred in 11 patients (11/36, 30.6%). Only one patient had an anastomotic leakage and needed endoscopic intervention (endoluminal vacuum therapy). Seven (7/36, 19.4%) patients had a deficiency in wound healing, and 5 (5/36, 13.9%) of those had secondary wound healing in the sacral area after abdominoperineal resection, which was the most common complication after this type of surgery. Two patients (2/36, 5.6%) developed postoperative ileus and required temporary placement of a nasogastric tube. Non-surgical complications such as pneumonia or cardiac diseases occurred in 5 patients (5/36, 13.9%). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes all patient, tumor and treatment characteristics regarding the primary rectal cancer diagnosis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient, procedure and tumor characteristics at the time of the primary tumor resection\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian or absolute number\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIQR\u003csup\u003ea\u003c/sup\u003e or percentage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime till Recurrence\u003c/b\u003e (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.75-30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGrading\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eG3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultimodal Therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u0026thinsp;+\u0026thinsp;Chemo-/Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemo-/Radiotherapy only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBest Supportive Care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOperative Procedure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPR\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPR\u003csup\u003eb\u003c/sup\u003e, Sacrectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPR,\u003csup\u003eb\u003c/sup\u003e Adjacent Organ Resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAR\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLAR\u003csup\u003ec\u003c/sup\u003e, Adjacent Organ Resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePelvic Exenteration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePelvic Exenteration, Sacrectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePalliative Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntraoperative Radiotherapy\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Applicable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eR Status\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003ea\u003c/sup\u003e interquartile range, \u003csup\u003eb\u003c/sup\u003e abdominoperineal resection, \u003csup\u003ec\u003c/sup\u003e low anterior resection\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eLocal recurrence patterns and outcomes after surgery for LRRC\u003c/h3\u003e\n\u003cp\u003eMedian time until rectal cancer recurrence in our cohort was 20.5 months (IQR: 16.75\u0026ndash;30) with a range from 2 months minimum up to 84 months. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents tumor and treatment characteristics at the time of tumor recurrence.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTumor and treatment characteristics at the time of tumor recurrence\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eprevious treatment (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003etherapy for LRRC\u003csup\u003ea\u003c/sup\u003e (n)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elocalisation (Memorial Sloan Kettering Classification)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eneoadjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eadjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRT\u003csup\u003eb\u003c/sup\u003e/CT\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRT\u003csup\u003eb\u003c/sup\u003e/CT\u003csup\u003ec\u003c/sup\u003e/Surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003esurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eIORT\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaxial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eanterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eposterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1x only RT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (1x only RT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaxial\u0026thinsp;+\u0026thinsp;anterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaxial\u0026thinsp;+\u0026thinsp;lateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eposterior\u0026thinsp;+\u0026thinsp;lateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eanterior\u0026thinsp;+\u0026thinsp;posterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003ea\u003c/sup\u003e locally recurrent rectal cancer, \u003csup\u003eb\u003c/sup\u003e radiotherapy, \u003csup\u003ec\u003c/sup\u003e chemotherapy; \u003csup\u003ed\u003c/sup\u003e intraoperative radiotherapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn total, 26 patients (26/36, 72.2%) received a therapy regimen for their local recurrence that included surgery. Seven patients (7/36, 19.4%) were treated with surgery only, and 19 patients (19/36, 52.8%) were treated with a combination of radiotherapy, chemotherapy and surgery. Eight patients (8/36, 22.2%) received only radiotherapy and/or chemotherapy. No patient received best supportive care. For 2 patients (2/36, 5.6%), the further course of the disease is unknown as they refused any further diagnostics and treatment.\u003c/p\u003e \u003cp\u003eThe operative group covers a wide range of procedures: 9 abdominoperineal resections (9/26, 34.6%), one with sacrectomy (1/26, 3.8%), and 2 with additional organ resection (2/26, 7.7%), as well as 4 low anterior resections (4/26, 15.4%). All these patients had undergone an anterior resection or a low anterior resection in the context of their primary surgery. A complete exenteration was necessary in 5 patients (5/26, 19.2%).\u003c/p\u003e \u003cp\u003eMost recurrences occurred around the anastomosis, with a total of 15 patients (15/36, 41.7%). Of these 15 patients, 5 patients (5/15, 66.7%) had tumor mass in the former tumor region and anterior of that with infiltration of vagina, bladder, or prostate, and one patient had tumor recurrence in the former tumor region with additional tumor mass laterally. Five patients had only anterior recurrence, and 4 only posterior tumor with infiltration of the sacrum. For 2 patients (2/36, 5.6%), the exact location of the recurrent tumor is unknown because they refused further diagnostic examinations.\u003c/p\u003e \u003cp\u003eOnly one of the 36 patients with LRRC had an anastomotic leakage after the primary operation. However, the local recurrence in this case did not occur in the area of the old anastomosis, but posteriorly and laterally, which may have corresponded anatomically to the former leakage cavity.\u003c/p\u003e \u003cp\u003eAmong the cohort of patients who underwent resection of their LRRC, an R0 resection was achieved in 12 individuals (12/22; 54.5%).\u003c/p\u003e \u003cp\u003eNine patients (9/36, 25.0%) had tumor recurrence only in the region of the anastomosis or at the site of the former tumor without infiltration of adjacent organs or tumor mass in any other region than the anastomotic site. Of these 9 patients, 2 had undergone an anterior resection as the original surgery, 2 had had a local resection which could be performed transanally, and the remaining 5 patients had undergone a low anterior resection as the initial surgery. 8 out of these 9 patients qualified for a second surgery for their recurrent cancer. Both patients with previous local transanal tumor resection received an abdominoperineal resection, 3 patients had again a low anterior resection, one patient with recurrent tumor mass in the region of the anastomosis had palliative stoma placement due to colon ileus and one patient had a low anterior resection with additional ileocecal resection. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the sites of recurrence and corresponding multimodal treatments.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLocations of tumor recurrence and corresponding multimodal treatments\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"9\" nameend=\"c10\" namest=\"c2\"\u003e \u003cp\u003eProcedures (n)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elocalisation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAPR\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAPR\u003csup\u003ea\u003c/sup\u003e, sacretomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAPR\u003csup\u003ea\u003c/sup\u003e, adjacent organres.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLAR\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLAR\u003csup\u003eb\u003c/sup\u003e + adjacent organres.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003epelvic exenteration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003epelvic exenteration\u0026thinsp;+\u0026thinsp;sacrectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003epalliative surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eother\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaxial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eanterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eposterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaxial\u0026thinsp;+\u0026thinsp;anterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaxial\u0026thinsp;+\u0026thinsp;lateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eposterior\u0026thinsp;+\u0026thinsp;lateral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eanterior\u0026thinsp;+\u0026thinsp;posterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003csup\u003ea\u003c/sup\u003e abdominoperineal resection, \u003csup\u003eb\u003c/sup\u003e low anterior resection\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIntraoperative radiotherapy was administered in 6 patients (6/26, 23.1%). All six patients had a complex recurrence pattern of their tumor, including lateral positions and infiltration of adjacent organs. Two patients needed pelvic exenteration, and one patient needed exenteration with sacrectomy. Another patient received sacrectomy alone, and two patients underwent abdominoperineal resection. Table\u0026nbsp;4 presents the surgical approach depending on the site of recurrence.\u003c/p\u003e \u003cp\u003eThe postoperative complication rate after resection of LRRC was 57.7% (15 patients suffered at least one postoperative complication), and complications were various. One out of 3 patients (1/3, 33.3%) with low anterior resection without restoration of bowel continuity had leakage of the rectal stump which needed intervention (endoluminal vacuum therapy). 7 out of 14 patients (7/14, 50.0%) after abdominoperineal resection or pelvic exenteration had a perineal wound healing disorder. Of the 14 patients, 9 (9/14, 64.3%) had received an omentoplasty, one patient each had a VRAM (vertical rectus abdominis myocutaneous) or gluteal flap (each 7.1%), and in 3 patients (3/14, 21.4%), no omentoplasty was used and the perineal wound was closed primarily. Five of the perineal wound infections occurred after omentoplasty, one after the gluteal flap and one after primary closure of the perineal wound. Postoperative ileus occurred in 2 patients (2/26; 7.7%) and non-surgical complications including respiratory disorders or renal failure were found in one patient each (3.8% each).\u003c/p\u003e \u003cp\u003eFor survival analysis, 6 patients were lost to follow up. Thus, we could analyze the remaining 30 patients with a median follow up of 23 months (IQR: 12\u0026ndash;30 months). The 3- and 5-year overall survival rates were 79% and 72%, respectively. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the survival of the cohort over time (Kaplan-Meier curve).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis retrospective analysis of an almost 12-year period at a colorectal surgery center of excellence at a German university hospital revealed a local recurrence rate after curative treatment for rectal cancer of 5.4% (36/666). This is consistent with the recent literature which reports a recurrence rate of 4 to 11% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e. The primary and, to date, most significant surgical milestone in the development of rectal cancer surgery was the introduction of \u0026ldquo;total mesorectal excision\u0026rdquo; by Heald in the second half of the 20th century [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Heald was able to achieve a local recurrence rate of less than four percent, which was previously unthinkable. Most recurrent tumors have a simultaneous local and distant recurrence or only distant recurrence [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Jung et al. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] who conducted a retrospective analysis regarding risk factors for local recurrence over a time period of 15 years divided their cohort in 3 groups depending on the time interval since the primary operation. The analysis showed that the recurrence rate decreased over time from up to 13% (2002\u0026ndash;2006) down to only 5% (2012\u0026ndash;2017). This is in concordance with our results.\u003c/p\u003e \u003cp\u003eJankowski et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] conducted a retrospective study over a 7-year period (2001\u0026ndash;2008) regarding the incidence of and risk factors for LRRC. In their cohort, the local recurrence rate was 7.4% (27/365). They found that the subgroup that was treated with short-term radiotherapy only, using 5x5 Gy, showed a good control regarding local recurrence with a recurrence rate of only 4.2% [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This treatment is not used very often nowadays and mostly applied in older patients who are not able to receive chemotherapy. At present, neoadjuvant radio-chemotherapy or total neoadjuvant therapy are the most common preoperative therapy regimes for locally advanced rectal cancer [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, there a multiple potential risk factors for local recurrence after rectal cancer resection apart from the absence of neoadjuvant treatment. Jankowski et al. identified a low location in the rectum of the primary tumor as another relevant risk factor for local recurrence [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our study cohort, more than one third of the patients with LRRC, (38.9% (n\u0026thinsp;=\u0026thinsp;14)) had their primary tumor in the lower third of the rectum (circumferential resection margin (CRM) was involved in one of the 14 patients, whereas 10 patients had a negative CRM, one patient had a local excision, and in two cases, data one CRM were missing), whereas only 16.7% (n\u0026thinsp;=\u0026thinsp;6) had their primary tumor in the upper third of the rectum (3 of the 6 patients had a negative CRM, and in the remaining 3 patients CRM was unknown). This risk factor may be due to the narrow anatomy in the pelvis with closer resection margins even with a correctly performed total mesorectal excision (TME) in the lower third of the rectum.\u003c/p\u003e \u003cp\u003eAnother retrospective single center study from Mayo Medical Center, Rochester, Minnesota, conducted by Hahnloser et al. found no correlation between the initial tumor treatment and local recurrence. They included a total of 429 patients with LRRC between 1981 and 1996 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. All patients had previously undergone curative surgery and received multimodal treatment for their recurrent tumor. After re-staging, 304 patients were thought to be eligible for surgery, but only 138 patients underwent curative resection (R0). 139 patients had palliative resection due to gross tumors that could not be completely resected due to technical limitations and 27 patients had microscopically residual tumor mass. Looking at these subgroups, survival was best when the tumor was completely removed (5-year survival 37%), second best with only microscopically residual tumor mass (5-year survival 22%) and poorest when larger masses of tumor had to remain (5-year survival 16%). These data are relatively old and radio-chemotherapy regimens and surgical techniques have advanced since then, but we can still conclude that the most important principle in successful treatment of LRRC is to achieve an R0 resection.\u003c/p\u003e \u003cp\u003eThis was also found by Caricato et al. in their meta-analysis regarding prognostic factors [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] after surgery for locally LRRC. They identified a total of 8 studies which confirmed that an R0 resection was a statistically significant prognostic factor and associated with better survival outcomes compared to R1 and R2 resection [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This is further supported by a Swedish nationwide analysis conducted by Westberg [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. They included all patients with LRRC in the period between 1995 and 2002 and collected data in their nationwide colorectal cancer registry. They found a 5-year survival rate of 43% for patients after R0 resection and 14% for patients after R1 resection.\u003c/p\u003e \u003cp\u003eA systematic review by Fadel et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] regarding oncological outcomes after multimodal treatments and surgery in patients with LRRC found that a neoadjuvant treatment for recurrence is highly beneficial and should be done as a combination of radiation and chemotherapy whenever possible. Furthermore, Fadel at al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] report that neoadjuvant radio-chemotherapy was helpful in achieving an R0-resection and that patients even benefited from neoadjuvant radiation alone (followed by radical resection) compared to upfront surgery with potential adjuvant systemic treatment. Likewise, R\u0026ouml;del et al. found that 8% of patients with recurrent cancer that were primarily classified as nonresectable could be subjected to surgery after neoadjuvant radio-chemotherapy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs Klose et al. showed in their multivariate analysis of 90 patients with LRRC, curative resection is more likely for intraluminal local recurrence compared to extraluminal recurrence and curative resection is significantly associated with prolonged survival [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The fact that almost half of our cohort (15 patients, 41.7%) had a recurrence at the previous anastomotic site may at least in part explain the good R0 resection rate of 54.5% (12/22), and depending on that, the good survival. Rahbari and colleagues have also shown that R0 resection of the LRRC is a decisive prognostic factor for survival, even in the presence of extrapelvic tumor recurrence: in their multivariate analysis of 107 patients with LRRC, R0 resection could be achieved in 58.7%. The R0 rate is thus comparable to the rate of 54.5% described by us. Three- and 5-year survival rates were 61% and 47%, which is lower than in our cohort. On multivariate analysis, surgical morbidity, presence of extrapelvic disease, and R1/2 resection were independent predictors of a poorer survival [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe found a 3-year overall survival of 79% without separating the patients in any groups due to the small sample size. Our results are in concordance with the results of Kim et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] who conducted a retrospective analysis of early and late recurrent rectal cancer patients in Asia. They found a 3-year overall survival of 76% for early and 90% for the late recurrence group.\u003c/p\u003e \u003cp\u003eAnother study by Agas et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] reported a relatively poor overall survival for locally recurrent rectal cancer (68%, 41%, 37% for 3-, 5-, 7-year overall survival (OS), respectively), who were eligible for surgery and had undergone intraoperative radiotherapy (IORT).\u003c/p\u003e \u003cp\u003eFadel et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] described a lower 5-year OS in their meta-analysis compared to our and Kim\u0026rsquo;s results. They could include 14 retrospective studies and one prospective study regarding treatment and survival in locally recurrent rectal cancer patients. The patients could be divided into 4 different treatment groups and reported a 5-year OS of: 35% for the neoadjuvant radio-chemotherapy group, 30% for the surgery only group, and 29% for the neoadjuvant radiotherapy group. The poorest 5-year survival was seen in the adjuvant chemo-radiotherapy group with 21%. This is not in line with our results, which might be due to older data (the included studies included were mainly published between 1997 and 2006) and other treatments and chemotherapeutics provided in their study cohort.\u003c/p\u003e \u003cp\u003eOur results showed that the recurrent tumor mass was mostly located at the former tumor site or anastomotic site, which is also described by Park et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. They report similar recurrence patterns as found in our study cohort. The central type of pelvic recurrence was the most common (n\u0026thinsp;=\u0026thinsp;21, 33.9%) followed by the lateral (n\u0026thinsp;=\u0026thinsp;14, 22.6%), posterior (n\u0026thinsp;=\u0026thinsp;13, 21%), perineal (n\u0026thinsp;=\u0026thinsp;8, 12.9%), and anterior types (n\u0026thinsp;=\u0026thinsp;6, 9.7%). This is in accordance with our results with a rate of central recurrences of 41% (15/36), lateral recurrences of 25% (9/36), and posterior recurrences of 22% (8/36). The results differ only in regard of LRRC affecting the anterior region, where we found a much higher recurrence rate of 30% (11/36) compared to 9.7%.\u003c/p\u003e \u003cp\u003eA large systematic review suggests that the risk of local recurrence of colorectal cancer triples after postoperative anastomotic leakage [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This is not fully reflected in our data: only one of the 36 patients with LRRC had had anastomotic leakage after primary surgery. Another independent risk factor for local recurrence is CRM involvement [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Again, our data are not entirely conclusive, partly because no data on CRM were available from the external primary surgeries: CRM was negative in 21 of 36 patients (58.3%), in 13 (36.1%) there were no data on CRM available due to external primary surgeries, and a local procedure was used in two patients. However, the R status was only not specified in 2 cases, whereas in 32 of 36 patients (88.9%), an R0 resection could be achieved, and in two patients, R1 was reported. There were no cases of R2 resection. It can therefore be concluded that most local relapses in our cohort occurred despite previous R0 resection and negative CRM.\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, selection bias cannot be excluded due to the retrospective study design. Second, despite the long observation period, the sample size is small. Nevertheless, the strengths of our study are also evident: the data summarize a period of almost 12 years of treatment of rectal cancer recurrences at a nationally recognized colorectal surgery center. This can contribute to filling the evidence gaps regarding therapeutic algorithms for local recurrences of rectal cancer.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eLRRC remains a challenging topic, even in interdisciplinary teams and for highly educated and trained experts. With an individualized therapeutic approach, an R0 resection of the LRRC can be achieved in almost two-thirds of cases. The resulting good 5-year survival rate of 72% supports a multimodal therapeutic approach with surgical resection of the local recurrence, with acceptable postoperative morbidity. To tailor multimodal therapy even more precisely and specifically to the individual localization and tumor biology, further findings from prospective studies with large numbers of cases are required.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest disclosure:\u003c/h2\u003e \u003cp\u003eNone of the authors has a conflict of interest to declare.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval statement:\u003c/strong\u003e\u003cp\u003e This study (ID: 2022-812-AF 11) has been approved by the institutional ethics committee, the Ethikkommission II of the University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding statement:\u003c/h2\u003e \u003cp\u003eNone of the authors received external financial support for preparation, conduct, or analysis of the study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eP.H., J.H. and C.R. were involved in study conception and design. P.H. was in charge of data acquisition. P.H. and J.H. analyzed and interpreted the data, drafted the manuscript and prepared tables and figures.All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are available on request from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGuren MG, Undseth C, Rekstad BL et al (2014) Reirradiation of locally recurrent rectal cancer: A systematic review. 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Eur J Surg Oncol. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejso.2024.108641\u003c/span\u003e\u003cspan address=\"10.1016/j.ejso.2024.108641\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 50:\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"recurrent rectal cancer, colorectal cancer, abdominoperineal resection, complications, survival","lastPublishedDoi":"10.21203/rs.3.rs-5694880/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5694880/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTreatment of locally recurrent rectal cancer (LRRC) is still challenging because of inhomogeneous patient cohorts regarding previous treatments as well as different recurrence patterns and locations. The aim of this study was to investigate the local treatments and surgical approaches tailored to them.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe included all patients who were treated for LRRC without distant metastasis at the University Medical Center Mannheim, Germany, between 2010 and 2022. We collected data from our electronic clinical data management system regarding the initial diagnosis and treatment as well as locations and treatment of the recurrent tumor.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe identified a total of 666 patients who were curatively treated for rectal cancer of whom 36 patients (5.4%) developed LRRC without distant recurrence. Most patients (26/36) had a tailored therapy regimen that included surgery with or without perioperative radiation and/or chemotherapy. The most common site of local relapse was around the former colorectal anastomosis (15/36, 41.7%). The operative procedures ranged from anterior resection to multi-organ resection and exenteration. A complete resection (R0) could be achieved in 12 patients (12/22; 54.5%). The 3- and 5-year overall survival rates were 79% and 72%, respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eMost local recurrences happen at the anastomotic site and are mostly eligible for curative surgical therapy with good long-term survival.\u003c/p\u003e","manuscriptTitle":"Recurrence patterns and management of locally recurrent rectal cancer: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 16:53:24","doi":"10.21203/rs.3.rs-5694880/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorAssigned","content":"","date":"2024-12-31T06:00:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-12-30T13:31:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"Langenbeck's Archives of Surgery","date":"2024-12-22T17:10:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4cca645a-d3f7-4135-b081-ad30586ca638","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-07T15:59:39+00:00","versionOfRecord":{"articleIdentity":"rs-5694880","link":"https://doi.org/10.1007/s00423-025-03692-x","journal":{"identity":"langenbecks-archives-of-surgery","isVorOnly":false,"title":"Langenbeck's Archives of Surgery"},"publishedOn":"2025-04-02 15:56:58","publishedOnDateReadable":"April 2nd, 2025"},"versionCreatedAt":"2025-01-01 16:53:24","video":"","vorDoi":"10.1007/s00423-025-03692-x","vorDoiUrl":"https://doi.org/10.1007/s00423-025-03692-x","workflowStages":[]},"version":"v1","identity":"rs-5694880","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5694880","identity":"rs-5694880","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}