Plasma serine and glycine in relation to clinical outcomes following neoadjuvant radiotherapy for rectal cancer.

Concerns have been raised regarding the risk of local recurrence (LR) following transanal total mesorectal excision (TaTME), particularly during the learning curve. This study aimed to evaluate the impact of hospital case volume on LR after TaTME in Japan. This multicenter retrospective cohort study included 710 patients who underwent TaTME for rectal cancer at 25 institutions between 2014 and 2019. Hospitals were categorized as low volume (1-38 cases) or high volume (≥ 39 cases). The primary outcome was 5-year local recurrence rate (LRR). Multivariable Cox regression was performed to identify risk factors for LR. Of 710 patients, 277 were treated in low-volume hospitals and 433 in high-volume hospitals. The median follow-up was 46 months. Cumulative incidence of LR was significantly different (P = 0.048), and 5-year LRR was higher in the low-volume than in the high-volume groups (12.9% versus 6.8%). Multifocal LR was also more frequent in low-volume centers (4.1% versus 1.2%, P = 0.041). In multivariable analysis, treatment in low-volume hospitals was an independent predictor of LR (hazard ratio 2.15, 95% CI 1.25-3.69; P < 0.01). Subgroup analysis revealed increased LR in low-volume centers for patients undergoing anterior resection with the single stapling technique and for those with pT3/4 disease, nodal metastasis, or pathological lateral lymph node involvement. Hospital case volume was independently associated with LR after TaTME. Although increased recurrence was observed in low-volume centers, particularly among certain subgroups, the volume effect likely reflects multifactorial institutional influences rather than technical aspects alone.

ASO Visual Abstract: Impact of Hospital Volume on Local Recurrence of Rectal Cancer After Transanal Total Mesorectal Excision: A Nationwide Multicenter Cohort Study in Japan.

Using agile development methodology to develop a decision aid for complex rectal cancer.

The treatment of locally advanced (LARC) and locally recurrent (LRRC) rectal cancers poses significant challenges due to the anatomical complexity and the aggressive nature of tumor invasion. The adoption of multidisciplinary team (MDT) treatment models has become key to improving patient outcomes. Within the MDT framework, advances in imaging and pathology facilitate accurate assessment of disease. In minimally invasive surgery, urinary system reconstruction and pelvic floor reconstruction techniques have significantly improved outcomes for patients undergoing surgery. MDT decision-making plays a particularly important role in the selection of neoadjuvant treatment strategies: The MDT must weigh up the benefits and risks while taking into account the patient's primary disease, as well as their physical and mental condition, and strictly adhere to the indications for pelvic exenteration (PE) surgery. For patients without mesorectal involvement, neoadjuvant chemotherapy alone has demonstrated comparable efficacy to neoadjuvant chemoradiotherapy while exhibiting lower toxicity, but its application in T4b patients requires further validation. In conclusion, the treatment of LARC/LRRC has entered the era of multidisciplinary precision, and the MDT model is the core mechanism for integrating technological innovation and evidence to continuously improve patients' survival and quality of life. The future direction of development under the MDT model focuses on the integration of imaging and liquid biopsy for precise stratification, the optimization of the cost of robotic surgery and the innovation of bioprosthetic materials, the clarification of the optimal preoperative plan through multicenter studies, and exploring immune-based/targeted combination strategies.

With the implementation of surgical techniques, such as total pelvic exenteration, and improvements in perioperative management, an increasing number of patients with locally recurrent rectal cancer (LRRC) are potential targets for curative surgery. Negative pathological margins (R0 resection) and favorable pathological complete response (pCR) have been identified as independent predictors of better oncological outcomes in LRRC. However, achieving R0 resection and optimal tumor regression remain primary concerns and significant challenges for colorectal surgeons. Based on the latest research both domestically and internationally, along with the clinical experience of authors' team, this article provides an overview to enhance the likelihood of achieving R0 resection and pCR from surgical strategies and perioperative therapies, aiming to offer a reference for colorectal surgeons specializing in locally recurrent rectal cancer.

This literature‐based systematic review and associated guidelines provide evidence‐based paradigms for the management of locoregionally recurrent rectal cancer (LRRC). This multispecialty committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and colorectal surgery. As is the standard, the previously described American Radium Society Appropriate Use Criteria methodology for this project was followed rigorously, with the Population, Intervention, Comparator, Outcome, Timing, and Study Design framework and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses methodology to assess the evidence. RAND/University of California Los Angeles consensus methodology (modified Delphi) was used to rate the appropriateness of treatment options. Published between January 1, 2013, and July 16, 2025, 116 peer‐reviewed trials provided the evidence: 10 were well‐designed randomized phase 2/3 trials, 29 were moderately well designed trials that accounted for most common biases (matched cohort and phase 2), 76 trials had design limitations (retrospective), and one was a meta‐analysis. Clinical cases were created as examples to illustrate current acceptable management of LRRC. Treatment and prognosis are influenced by prior therapy and the site(s) and extent of LRRC. The ability to achieve a margin‐negative surgical resection is the ultimate determinant of survival and local control. Preoperative systemic therapy, radiation therapy, or a combination of the two can facilitate tumor downsizing and improve the likelihood of a margin‐negative resection. An individualized multidisciplinary approach is required to ensure the best outcome. Although this review does not suggest a major alteration of current practice, it provides reassuring evidence of the importance of combined‐modality therapy.

Extended pelvic exenteration (EPE) is a key therapeutic strategy for locally advanced or recurrent rectal cancer. However, conventional postoperative assessments-including histopathology, serum tumor markers, and standard imaging-are limited by low sensitivity and a considerable temporal lag in detecting residual disease. Detection of molecular residual disease (MRD) via circulating tumor DNA (ctDNA) may provide a reliable biomarker to enable more precise postoperative management following EPE. This study evaluates the utility of ctDNA-based MRD assessment in determining molecular R0 resection status and in monitoring disease recurrence after pelvic exenteration for rectal cancer. Between May 2022 and October 2023, a real-world study was conducted involving 100 patients with locally advanced or recurrent rectal cancer without evidence of distant metastasis who underwent radical resection at Shanghai Changzheng Hospital. Peripheral blood samples were collected preoperatively, postoperatively, following adjuvant therapy, and at 3-month intervals thereafter. MRD status was assessed using a personalized, tumor-informed panel based on whole-exome sequencing of the primary tumor. The cohort comprised 52 male patients (52%), with a mean (standard deviation) age of 50.8 (13.24) years. While all patients achieved pathologically negative margins, the postoperative MRD positivity rate (MRD1) remained at 35%, increasing to 41% following adjuvant therapy (MRD2). Over a median follow-up of 745 days (95% confidence interval, 697-793days), the 1-year and 2-year disease-free survival (DFS) rates were 85.0% and 71.9%, respectively. Positivity at the MRD1 and MRD2 timepoints conferred an 8-fold and a 60-fold increased risk of recurrence, respectively, compared with MRD-negative status. Notably, MRD positivity detected tumor recurrence or metastasis significantly earlier than radiological confirmation, with a median lead time of 361 days (interquartile range, 158.5-468 days). ctDNA-based MRD detection demonstrates substantial clinical utility for recurrence surveillance and prognostic stratification. Postoperative MRD status provides a more accurate reflection of molecular R0 resection than conventional pathological margin assessment. Furthermore, MRD status upon completion of initial adjuvant therapy serves as an early indicator of therapeutic efficacy and a robust predictor of long-term prognosis.

Half of patients experience moderate to severe long-term urination dysfunction after rectal cancer surgery: a prospective cohort study.

Anatomic distribution of postoperative recurrence and radiotherapy target volume optimization in rectal cancer: A large-scale real-world study.

Evaluation of the National Accreditation Program for Rectal Cancer and Association with Oncologic Outcomes After Proctectomy.

Chemotherapy followed by pelvic reirradiation versus chemotherapy alone as preoperative treatment for locally recurrent rectal cancer (GRECCAR 15): superiority open-label phase III randomized clinical trial.

The role of adjuvant chemotherapy (ACT) in pathologic T3N0 (pT3N0) rectal cancer, which has a favorable prognosis, remains controversial because high-risk groups for recurrence are not well defined. This study investigated prognostic factors for survival in this patient group and evaluated the benefit of ACT based on these factors. This retrospective study analyzed 352 patients with pT3N0 rectal cancer who underwent upfront radical surgery at three referral hospitals between November 2003 and December 2020. A multivariable Cox regression model was used to identify the prognostic factors for 5-year recurrence-free survival (RFS). Patients were categorized as high or low risk based on these factors, and survival outcomes were compared between those who received ACT and those who did not, using the log-rank test. Median follow-up was 52.8 months. 193 (54.8%) patients received ACT. Multivariable analysis revealed that ACT, circumferential resection margin (CRM) ≤ 2mm, vascular invasion, and perineural invasion were independent predictors of 5-year RFS. In patients with ≥ 1 risk factor, ACT significantly improved RFS (92.5% vs. 72.8%, hazard ratio [HR] 0.247, 95% confidence interval [CI] 0.090-0.683, p < 0.01). In those without risk factors, no significant benefit was observed (98.0% vs. 91.6%, HR 0.272, 95% CI 0.057-1.313, p=0.082). This study identified CRM ≤ 2mm, vascular invasion, and perineural invasion as high-risk features for recurrence in pT3N0 rectal cancer. ACT improved RFS only in patients with these features. While these findings support risk-based ACT administration in this patient population, further validation of our risk stratification system is needed.

Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is the standard treatment for advanced low rectal cancer; however, long-term oncological outcomes vary widely, and reliable prognostic biomarkers remain limited. Carcinoembryonic antigen (CEA) is commonly used in colorectal cancer management, but the prognostic value of post-CRT CEA levels has not been fully clarified. This study aimed to identify clinically relevant prognostic factors for recurrence and survival, with particular focus on pre- and post-CRT CEA levels. A retrospective review was conducted of 41 consecutive patients with advanced low rectal cancer (Rb, cT3/4 or N1/2 and no lateral lymph node metastasis) who underwent long-course preoperative CRT followed by radical surgery. CRT consisted of 45 Gy in 25 fractions with concurrent tegafur/uracil, followed by total mesorectal excision 8-10 weeks after CRT completion. Clinicopathological factors were analyzed in relation to recurrence, disease-free survival (DFS), and overall survival (OS). With a median follow-up of 69.3 months, recurrence occurred in 16 patients. Five-year DFS and OS rates were 59.4% and 73.2%, respectively. Univariate analysis identified postoperative complications, pathological complete response, and pre- and post-CRT CEA levels as significant factors associated with recurrence. Multivariate analysis demonstrated that post-CRT CEA was the only independent prognostic factor. Receiver operating characteristic analysis identified a post-CRT CEA cut-off value of 3.9 ng/ml. Patients with lower post-CRT CEA showed significantly better DFS and OS. Post-CRT CEA is a valuable prognostic biomarker for recurrence and survival in advanced low rectal cancer, and patients with elevated post-CRT CEA may benefit from additional consolidation chemotherapy.

ASO Visual Abstract: Locally Recurrent Rectal Cancer in the Lateral Compartment: Imaging Features and Association with Primary Tumor Characteristics.

Surgical resection, the primary treatment for locally recurrent rectal cancer (LRRC), is technically challenging. Transanal/transperineal minimally invasive surgery (Ta/Tp MIS) improves visualization and access through undisturbed planes. This study compared the short- and mid-term outcomes of Ta/Tp MIS with those of conventional non-Ta/Tp MIS for LRRC. This retrospective observational study involved 98 patients who underwent curative-intent surgery for LRRC at a single tertiary cancer center between April 2008 and March 2022. Patients were classified into Ta/Tp MIS (n = 34) and non-Ta/Tp MIS (n = 64) groups. Perioperative and mid-term oncologic outcomes were compared, including operative time, blood loss, intraoperative transfusion, postoperative complications, pathological R0 resection, recurrence-free survival, local recurrence, and overall survival. Ta/Tp MIS was associated with reductions in resection time (median, 225 versus 252min; p = 0.0176), blood loss (median, 420.5 versus 1068mL; p < 0.0001), and intraoperative transfusions (17.7% versus 48.4%, p = 0.0041), and tended toward a shorter operative time (median, 366.5 versus 418.5min; p = 0.1170). R0 resection (91.2% versus 89.1%), postoperative complications (overall Clavien-Dindo complication grade: 76.5% versus 75.0%, p = 1; grade ≥ 3: 41.2% versus 37.5%, p = 0.8282), 3-year recurrence-free survival (46.3% versus 44.2%, p = 0.9079), local recurrence (24.8% versus 37.7%, p = 0.3130), and 3-year overall survival (89.7% versus 77.7%, p = 0.2271) were comparable between groups. Ta/Tp MIS appears to be a feasible surgical approach for selected patients with LRRC, and in this retrospective analysis, was associated with shorter resection time and reduced blood loss. No clear differences were observed in postoperative complications or short- to mid-term oncologic outcomes compared with conventional approaches.

Locally recurrent rectal cancer (LRRC) is an emerging area for research; however, it represents significant challenges as a relatively rare form of advanced pelvic malignancy, from both a recruitment and study setup and delivery perspective. To date, there have been relatively few published trials in this setting. High-quality, multi-centre, prospective studies could offer helpful insights regarding the challenges associated with delivering studies in rare disease settings such as LRRC, and how to effectively address them. The Locally Recurrent Rectal Cancer-Quality of Life (LRRC-QoL) study is an international, multi-centre, mixed-methods study of health-related quality of life (HrQoL) in LRRC. The International Surgical Trials Toolkit was utilised as a guideline in navigating site setup processes and to describe the challenges encountered during this study. A modified Quintet Recruitment Intervention (QRI) was used as a framework to identify recruitment challenges and drive improvements. Overall, 227 patients were recruited to the LRRC-QoL study across 14 countries. Significant challenges were encountered during site setup, including issues related to legal agreements which were further complicated by Brexit, expenses related to translation, and requirements for multiple ethical approvals. Delays during study setup and recruitment challenges occurred due to the COVID-19 pandemic. Several strategies were identified through the modified QRI with a positive impact on recruitment. Recruitment pathways were refined to a more streamlined, centralised approach, facilitated by verbal consent to contact. Recruitment rates also improved with the introduction of multiple options for participation, including traditional paper-based methods, online, and via telephone. Patient information leaflets were refined following patient and public involvement (PPI) work. Several approaches identified during the LRRC-QoL study should be considered in the development of future studies and trials recruiting patients with LRRC. These include undertaking PPI during study development, identifying flexible recruitment strategies which complement sites' existing clinical processes, and partnering with existing collaborative networks. Study registration The LRRC-QoL study registration reference: ISRCTN13692671 ( https://doi.org/10.1186/ISRCTN13692671 ).

Standard of care for locally advanced rectal cancers includes total neoadjuvant therapy followed by surgery or non-operative management based on response. There remains significant risk of both local and distant recurrence, despite close surveillance. The use of circulating tumor DNA in rectal cancer surveillance has not yet been standardized. To assess the utility of circulating tumor DNA as an adjunct to surveillance for recurrence following definitive therapy. Single institution retrospective review. Single National Cancer Institute designated and National Accreditation Program for Rectal Cancer accredited institution. All patients diagnosed with rectal cancer from 2021-2024 with circulating tumor DNA data available. Circulating tumor DNA status at the time of clinical recurrence. Subgroup analysis of recurrence location. A total of 241 patients were diagnosed with rectal cancer between 2021-2024. Circulating tumor DNA data was available for 144/241 (59.8%). 28 patients with clinical recurrences were studied, 20 (71.4%) occurred after surgery and 8 (28.6%) during watch and wait. 20/28 (71.4%) recurrences had a positive circulating tumor DNA prior to detection of recurrence clinically. Circulating tumor DNA was positive a median of 100 days (range, 10-532 days) prior to recurrence being detected. 11/12 (91.7%) distant recurrences were circulating tumor DNA positive, compared to 10/17 (58.8%) local recurrences. Retrospective single institution study with limited sample size. Circulating tumor DNA can be an asset during surveillance in both patients undergoing watch and wait or surgery, with identification of recurrences earlier than traditional methods. Within our study, a positive circulating tumor DNA was suggestive of distant metastases rather than local recurrence, which may impact decision making in the way we manage these patients, particularly when considering salvage surgery. Large prospective studies are needed to determine the ideal implementation of circulating tumor DNA into surveillance protocols. (See Video Abstract).

Lateral lymph node dissection via robotic surgery: technical feasibility and patterns of lateral lymph node recurrence in rectal cancer.

Advancements in the multidisciplinary management of locally advanced and recurrent rectal cancer, as well as advanced pelvic malignancies, have significantly improved oncological outcomes. Pelvic exenteration is a complex procedure involving en bloc resection of the involved organs with the aim of achieving a microscopic negative margin (R0)1. Since 2012, the Royal Brisbane and Women's Hospital (RBWH) has been performing pelvic exenteration surgery and is now the statewide referral centre in Queensland. This study aims to present our oncological and surgical outcomes since establishment. This is a retrospective cohort study utilising data collected from medical records of patients who underwent pelvic exenteration at the RBWH between 1 January 2012 and 31 August 2023. Ethics approval was obtained from the Metro North Hospital and Health Service Human Research Ethics Committee (HREC 102257). A total of 139 patients underwent pelvic exenteration surgery over the 11-year period. 117 of those were total exenteration, 22 were partial. The indications were locally advanced rectal cancer (56.8%), locally recurrent rectal cancer (22.3%), other primary or recurrent malignancy or benign, (10.8%, 7.9%, 2.2% respectively). The proportion of patients with an R0 resection was 90.4%. The overall survival (using Kaplan-Meier analysis) at 1, 2 and 5 years was 89.9%, 82.0%, and 62.9%, respectively. Disease-free survival at 1, 2 and 5 years was 76.1%, 67.0% and 59.2%. Disease-specific survival at 1, 2 and 5 years was 92.7%, 83.8% and 66.8%. Our results were comparable to national data and PelvEx Collaborative group data and demonstrate that pelvic exenteration surgery can be safely performed in a lower volume centre with equivalent outcomes to higher volume centres.