Abstract The management of locally advanced rectal cancer has evolved significantly with the introduction of total neoadjuvant therapy, which increases rates of clinical complete response and enables select patients to pursue non-operative management through a watch-and-wait strategy. While total mesorectal excision remains the standard curative approach, it is associated with considerable morbidity and long-term impacts on bowel, urinary, and sexual function. In contrast, non-operative management offers organ preservation and improved functional outcomes but carries oncologic uncertainty and requires intensive surveillance. This review examines the comparative benefits and limitations of total mesorectal excision and non-operative management, highlighting their impact on quality of life, recurrence risk, and patient-centered care. It also explores emerging strategies to support shared decision-making, including decision aids and predictive modeling, including risk preference assessments. These tools are essential to support informed, individualized decisions and to promote ethically grounded, evidence-based care in the evolving landscape of rectal cancer management.

ASO Visual Abstract: Robotic Intracorporeal Single-Stapled Anastomosis (RISS) is Associated with Lower Anastomotic Leakage Rates than the Double-Stapled Technique after Minimally Invasive Total Mesorectal Excision for Rectal Cancer.

ABSTRACT Aim Minimally invasive total mesorectal excision is widely used in rectal cancer surgery because of its better surgical field‐of‐view and recognition of microanatomy, compared with open surgery; however, it remains difficult to perform deep pelvic manipulation. Transanal total mesorectal excision (TaTME) is expected to overcome these difficulties, especially in two‐team surgeries with simultaneous abdominal and transanal approaches. Methods Data were collected from patients with rectal cancer who underwent TaTME between January 2012 and December 2019 at 26 specialized rectal cancer institutions in Japan. Patients in the two‐team surgery group were propensity score‐matched in a 2:1 ratio to those in the one‐team surgery group. Surgical outcomes, postoperative complications, transanal approach‐related outcomes, and survival rates were compared between the two surgical groups. Results Overall, 444 patients (296 and 148 in the two‐ and one‐team surgery groups, respectively) were included in the analyses. The median operation time was significantly shorter ( p < 0.001), the median estimated blood loss ( p < 0.001) and positive distal margin rates ( p = 0.020) were significantly lower, the number of lymph nodes dissected was significantly higher ( p = 0.011) in the two‐team surgery group versus the one‐team surgery group. The two groups did not differ in postoperative complications. The 5‐year relapse‐free survival rate was slightly higher in the two‐team surgery group than in the one‐team surgery group, although there was not statistically significant ( p = 0.244). Conclusion Two‐team surgery has advantages of shorter operation time, decreased estimated blood loss, increased number of lymph nodes dissected and decreased positive distal margin rates and potential to decrease recurrence rates.

The standard treatment for locally advanced rectal cancer (RC) in Japan is TME with or without lateral lymph node dissection (LLND) and subsequent adjuvant chemotherapy. The efficacy of chemotherapy after TME without LLND remains unclear, so we aimed to assess this efficacy. We retrospectively reviewed patients who underwent TME without LLND and received adjuvant chemotherapy between January 2010 and December 2020 at our institution. Relapse-free survival (RFS) and overall survival (OS) were assessed. Prognostic factors for RFS, including tumor location, chemotherapy regimen, and T and N factors were analyzed using univariate and multivariate analyses. Of 197 patients, 117 were eligible. The median age was 66 years (range 26–82). Tumor locations were Ra and Rb in 67 (57%) and 50 (43%) patients. Eighty (68%) and 37 (32%) patients received fluoropyrimidine monotherapy (single agent) and oxaliplatin-based therapy (doublet) as adjuvant chemotherapy. The 3-year RFS rate and 3-year OS rate were 73.6% (95% confidence interval [CI], 64.7–81.0%) and 95.5% (95% CI, 89.6–98.1%), respectively. In the univariate and multivariate analysis, none of these variables were identified as independent prognostic factors for RFS. TME without LLND followed by adjuvant chemotherapy in patients with RC demonstrated favorable 3-year RFS and OS rates.

The EAES released guidelines on the role of taTME in the management of rectal cancer in 2022. To develop updated, evidence-informed recommendations to support clinicians involved in the management of taTME; to provide guidance for hospital managers, policymakers, and patients with low- and mid-rectal cancers. We performed a systematic review to identify randomized trials and matched nonrandomized studies comparing transanal total mesorectal excision (taTME) to laparoscopic TME (laTME) or robotic TME (roTME) in patients with low- and mid-rectal cancer. A panel of general and colorectal surgeons, a radiologist, a pathologist, and patient partners appraised the certainty of the evidence using GRADE. The panel developed recommendations using an evidence-to-decision framework during an in-person consensus meeting. We applied a Delphi survey to establish consensus. The panel recommends taTME over laTME in patients with low- and selected mid-rectal cancers when access to surgeons with expertise in performing taTME in high-volume rectal cancer centers is available (strong recommendation). This recommendation applies to patients eligible for sphincter preservation who are at high risk for conversion to abdominoperineal resection, including male gender with BMI > 30kg/m2. The recommendation is supported by a reduction in 30-day major complications and disease recurrence at 2years with taTME compared to laTME. When access to a surgeon with expertise in performing taTME is not available, the panel recommends against taTME over laTME (strong recommendation). Further, the panel suggests roTME as an alternative to taTME in patients with low- and selected mid-rectal cancers when access to surgeons with expertise in performing taTME is not available (conditional recommendation). We provide evidence-informed guidance on the role of taTME in the surgical management of patients with low- and mid-rectal cancers. Patients and surgeons should exercise shared-decision making to apply patient-tailored decisions when considering treatment options.

C-reactive protein's (CRP) diagnostic utility for early detection of anastomotic leakage is based on heterogeneous patient groups, including different pathologies and surgical approaches, without accounting for the presence of faecal diversion. This study assessed the diagnostic accuracy of CRP in detecting anastomotic leakage after minimally invasive total mesorectal excision (TME) for rectal cancer, stratified by the presence or absence of a primary diverting stoma. Patients from 11 high-volume centers in the Netherlands who underwent minimally invasive TME for rectal cancer between 2015 and 2021 were included. CRP levels were analyzed from postoperative days 1-4, and diagnostic accuracy was assessed using receiver operating characteristic analysis. Subgroup analyses were performed for patients with and without a primary diverting stoma. A total of 1418 patients were included, with anastomotic leakage occurring in 232 (16.4%). In patients without a stoma, the highest diagnostic accuracy was on day 4 at a cut-off of 104.5mg/L, with sensitivity of 84.1%, specificity of 71.1%, PPV of 38.1%, and NPV of 95.5% (AUC = 0.83, P < 0.001). In patients with a stoma, diagnostic accuracy was lower, with maximum performance at a cut-off of 132.5mg/L on day 4 (sensitivity 57.6%, specificity 78.7%, PPV 36.5%, NPV 89.7%, AUC = 0.71, P < 0.001). The difference in AUC was significant (P = 0.018). CRP has poor diagnostic accuracy for detecting anastomotic leakage in patients with a primary diverting stoma after minimally invasive rectal cancer surgery. Additional diagnostic tests should be considered for this group to allow for early detection of anastomotic leaks.

Both transanal total mesorectal excision (TaTME) and robotic total mesorectal excision (robotic TME) have been developed to optimize mesorectal dissection quality in rectal cancer surgery. However, current evidence remains inconclusive regarding the comparative advantages between these two minimally invasive approaches. Patients who underwent curative TaTME or robotic TME for rectal cancer at our institution from 2015 to 2021 were retrospectively reviewed. The primary outcomes were circumferential resection margin (CRM) involvement and oncological outcomes (local recurrence, disease-free survival, and overall survival). Secondary outcomes included operative time, blood loss, conversion rate, postoperative complications, and functional recovery. To adjust for baseline differences, inverse probability of treatment weighting (IPTW) was employed. A total of 174 patients were included in the final analysis, comprising 110 who underwent TaTME and 64 who underwent robotic TME. While operative duration was comparable, the TaTME group exhibited increased intraoperative blood loss and higher rates of diverting stoma (72.6% vs. 51.7%, p < 0.001) and hand-sewn anastomosis (43.6% vs. 24.1%, p < 0.001) than the robotic TME group. Minor complications (Clavien-Dindo grade I) were more frequent in the TaTME group, though major morbidity was similarly low in both cohorts. Pathologically, TaTME was associated with a greater incidence of positive circumferential resection margins (CRM) (6.1% vs. 0%, p = 0.001) and shorter distal margins. Long-term oncological endpoints, including local recurrence, distant metastasis, overall survival, and disease-free survival were statistically similar. Despite certain technical drawbacks observed in TaTME, such as increased blood loss and CRM positivity, both techniques demonstrated equivalent long-term oncologic safety, indicating their appropriateness in selected patients undergoing rectal cancer resection.

Robotic total mesorectal excision (R-TME) is widely used to treat rectal cancer; however, data on robotic beyond TME (R-bTME) remain limited. The present study compared the short-term outcomes between robotic standard TME (R-sTME) and R-bTME in patients with primary rectal cancer. This retrospective multicenter study included patients with mid-to-low rectal cancer who underwent robotic surgery between 2017 and 2024. The primary endpoint was postoperative morbidity, defined as Clavien-Dindo grade ≥ II. Of the 462 patients, 391 underwent R-sTME, and 71 underwent R-bTME. In the R-bTME group, the resected sites most commonly involved the lateral compartment (72%), particularly lateral lymph nodes (63%), followed by the anterior compartment (18%), where uterine resection was most frequent, and the posterior compartment (11%), predominantly involving the hypogastric nerve. Overall morbidity was higher in the R-bTME group than in the R-sTME group (26.8% vs. 16.4%), primarily due to increased urinary dysfunction. However, the rates of severe complications (Clavien-Dindo grade ≥ III), infectious complications, anastomotic leakage, and conversion were comparable between the groups. The rate of positive radial margin (RM) was higher in the R-bTME group than in the R-sTME group (8.5% vs. 1.0%), reflecting more advanced local disease. R-bTME is feasible for advanced primary rectal cancer when performed in select patients at experienced centers.

Transanal total mesorectal excision has been increasingly adopted in the curative resection of low rectal cancer. Obesity is a known risk factor for conversion and morbidity during laparoscopic and robotic total mesorectal excision. We sought to compare short-term postoperative and pathologic outcomes and long-term oncologic outcomes of transanal total mesorectal excision between nonobese and obese patients across high-volume rectal cancer centers in the United States. Retrospective cohort study. Eight tertiary centers in the United States of America. Eligible patients underwent transanal total mesorectal excision for curative resection of primary rectal adenocarcinoma between November 2011 and June 2020. Intraoperative complications, 30-day postoperative complications, local recurrence, distant recurrence, overall survival, and disease-free survival. A total of 390 transanal total mesorectal excision procedures were performed in 271 (69.5%) nonobese (BMI <30) and 120 (30.5%) obese (BMI ≥30) patients. The median BMI was 27.4 (interquartile range, 24.1-31.0), and the median follow-up was 29 months (interquartile range, 14-44 months). There were no significant differences in tumor stage or neoadjuvant treatment across groups. Tumors were located ≤6 cm from the anal verge in 60.6% of patients. Operative time was longer in the obese group, with no significant differences in conversion rates or intraoperative complications. No significant differences in postoperative complications, including Clavien-Dindo grade 3 or higher complications, anastomotic complications, or reoperation rates were noted between nonobese and obese cohorts. At a median follow-up of 29 months, local recurrence, overall survival, and disease-free survival were comparable between groups, whereas patients with obesity had a significantly lower rate of distant recurrence than nonobese patients. Retrospective design, short median follow-up time. In this multicenter retrospective study, transanal total mesorectal excision resulted in similar conversion and morbidity rates among patients with obesity and nonobese patients. Obesity was associated with a significantly lower 3-year distant recurrence with no differences in other mid-term oncologic outcomes. See Video Abstract. ANTECEDENTES:La disección mesorrectal total transanal (taTME) se utiliza cada vez más en la resección curativa del cáncer rectal bajo. La obesidad es un factor de riesgo conocido para la conversión y la morbilidad durante la TME laparoscópica y robótica.OBJETIVO:Buscamos comparar los resultados posoperatorios y patológicos a corto plazo y los resultados oncológicos a largo plazo de la taTME entre pacientes no obesos y obesos en centros de cáncer rectal de alto volumen en los Estados Unidos.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO:Ocho centros terciarios de los Estados Unidos de América.PACIENTES:Los pacientes elegibles se sometieron a taTME para la resección curativa de adenocarcinoma rectal primario entre noviembre de 2011 y junio de 2020.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones intraoperatorias, complicaciones posoperatorias a los 30 días, recidiva local, recidiva a distancia, supervivencia global, supervivencia libre de enfermedad.RESULTADOS:Se realizaron un total de 390 procedimientos de taTME en 271 (69,5 %) pacientes no obesos (IMC < 30 kg/m 2 ) y 120 (30,5 %) obesos (IMC ≥ 30 kg/m 2 ), con un IMC medio de 27,4 kg/m 2 (IQR 24,1-31,0). La mediana del seguimiento fue de 29 meses (IQR 14-44 meses). No hubo diferencias significativas en el estadio tumoral ni en el tratamiento neoadyuvante entre los grupos. Los tumores se localizaron a ≤ 6 cm del borde anal en el 60,6 % de los pacientes. El tiempo quirúrgico fue mayor en el grupo obeso, sin diferencias significativas en las tasas de conversión ni en las complicaciones intraoperatorias. No se observaron diferencias significativas en las complicaciones posoperatorias, incluidas las complicaciones de grado ≥3 según Clavien-Dindo, las complicaciones anastomóticas o las tasas de reintervención entre las cohortes no obesas y obesas. En una mediana de seguimiento de 29 meses, la recurrencia local, la supervivencia global y la supervivencia libre de enfermedad fueron comparables entre los grupos, mientras que los pacientes obesos tuvieron una tasa significativamente menor de recurrencia a distancia que los pacientes no obesos.LIMITACIONES:Diseño retrospectivo, tiempo medio de seguimiento corto.CONCLUSIONES:En este estudio retrospectivo multicéntrico, la taTME dio lugar a tasas de conversión y morbilidad similares entre los pacientes obesos y no obesos. La obesidad se asoció con una recurrencia a distancia a 3 años significativamente menor, sin diferencias en otros resultados oncológicos a medio plazo. ( AI-generated translation ).

Proficiency-based progression is key to analyzing and improving surgical performance. Objective assessment has demonstrated a direct link between operative performance and outcomes in laparoscopic surgery but not in robotics. There is current research to automate assessment processes with sensor data and machine learning. This requires granular, reliable annotations to train clinically implementable, trusted models, to improve patient safety. To evaluate objective skill and error tools in robotic rectal cancer surgery, to provide a granular validated dataset from which to train and test deep learning models. A national, ethically approved, multicentre study, Video Analysis in Minimally Invasive Surgery (VAMIS) (ClinicalTrials.gov NCT05279287), recorded robotic-assisted total mesorectal excision (RTME). Recruited participants were pseudonymised and clinical data were collected. Operations were recorded and uploaded to Touch Surgery™ using the DS1 computer (Digital Technologies, a Medtronic company) and annotated by independent, blinded raters. Objective assessment employed error, Objective Clinical Human Reliability Analysis (OCHRA), Modifiable-Global Evaluative Assessment in Robotic Skills (M-GEARS) and TME performance tools. Correlational and multivariable regression analyses were performed, investigating associations between intraoperative skill and errors with clinical outcomes. 30 RTME operations were recorded, annotating 538 errors (median 13/operation). Major consequential errors were significantly associated with complications (p = 0.031). Weighted error variables, accounting for error severity, were significantly associated with increased odds of prolonged operative time (p = 0.025). Inter-rater reliability demonstrated an excellent matched error agreement percentage of two raters (mean agreement 90% (range 68-100%), after calibration sessions). OCHRA was significantly correlated with M-GEARS (r = -0.54 to -0.77, p < 0.001-0.002) and the RTME performance tool (r = 0.74, p = 0.007). This feasibility study validated the concept that granular error and skill annotations can be objectively measured and associated with clinical outcomes in robotic rectal cancer surgery. This is an important step for larger studies and in aiding the development of deep learning models to predict errors and skill.

This study aimed to evaluate whether the pelvic index/mesorectal length (PI/ML) ratio is an effective factor in recurrence, anastomotic leakage, mesorectal excision status, and low anterior resection syndrome (LARS) development in rectal cancer patients undergoing total mesorectal excision. A total of 47 patients who underwent surgery for rectal cancer between January 2016 and December 2021 were included. Demographics, clinical data, and pre-operative PI measurements were recorded. Post-operative LARS was assessed using the LARS questionnaire in patients followed for at least 12 months. A significant association was found between PI/ML ratio and tumor recurrence (p < 0.0001). Receiver operating characteristic analysis identified a cutoff value of PI/ML < 1.6 for predicting tumor recurrence, with 100% sensitivity and 84.6% specificity. After applying Bonferroni correction for multiple comparisons (n = 4, adjusted significance threshold p < 0.0125), this association remained statistically significant. The association between PI/ML ratio and anastomotic leakage (cutoff < 2.15; sensitivity 100%, specificity 53.7%) showed marginal significance (p = 0.009). No significant association was found between PI/ML ratio and LARS or mesorectal excision status after correction. PI/ML ratio appears to be a useful predictor for tumor recurrence and may help identify patients at risk for anastomotic leakage in rectal cancer surgery. However, this ratio was not significantly associated with the development of LARS. Further research with larger cohorts is needed to validate these findings and clarify the potential prognostic value of the ratio.

Background: Reliable and accurate prediction of treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) is usually demanding and continues to pose a challenge. Kurtosis as a histogram parameter calculated on T2-weighted MRI sequences might be an additional tool, as it represents a quantitative biomarker for response prediction. It is defined as a measure of distributions’ tails relative to the center of the distribution curve, which reflects tissue heterogeneity. The aim of the study was to evaluate the added value of T2-weighted kurtosis in predicting pathological response to nCRT in patients with LARC. Methods: a single-center cohort study included 71 patients with LARC who underwent both initial and post-nCRT MRI examinations followed by surgical resection in the form of the total mesorectal excision (TME). Histogram analysis was performed using software MIPAV (Medical Image Processing, Analysis, and Visualization, version 11.3.2, developed by the National Institutes of Health, Bethesda, MD, USA) on T2-weighted sequences, extracting kurtosis along with other histogram parameters. Pathological tumor regression grade (pTRG) in accordance with Mandard classification was considered the gold standard. Patients were classified as responders (pTRG 1–2) or non-responders (pTRG 3–5). Results: while other histogram parameters did not show statistically significant differences between groups, post-treatment values of kurtosis were significantly higher in responders compared to non-responders (4.28 ± 0.73 vs. 3.01 ± 0.17, p = 0.024). The F1 score as a classification metric (0.821) indicates an improvement in classification performance following therapy. Conclusions: T2-weighted kurtosis might be a significant tool in predicting pathological response to nCRT, representing a potentially valuable quantitative biomarker that could improve treatment response assessment.

Temporary ileostomy is a valuable aid in reducing the severity of complications associated with rectal cancer surgery. The purpose of the present study was to determine the reasons for delays in ileostomy closure in patients who underwent laparoscopic rectal cancer surgery and protective loop ileostomy and to prevent delays in closure timing. A retrospective analysis was conducted with patients who underwent loop ileostomy and its reversal in laparoscopic rectal surgery for rectal cancer at the Surgical Oncology Clinic of Tokat Gaziosmanpaşa University. Patients who had loop ileostomy closure between 2018 and 2023 were included in the study. Demographic data of the patients, neoadjuvant status, adjuvant chemotherapy, presence of comorbidities, smoking, American Society of Anesthesiologist's classification (ASA) score, primary surgical method [low anterior resection (LAR), very low anterior resection (VLAR), transanal total mesorectal excision (TaTME)], pathologic stage, anticoagulant use, presence of anastomotic leak, postoperative bleeding, presence of ileus, length of hospital stay, time from index surgery to closure, 90-day complications (Clavien-Dindo classification), unexpected 30-day readmission, reoperation status, and ileostomy closure time values were recorded, and a database was created. Multivariate regression analysis was used to identify clinically significant risk factors for delayed closure. A total of 129 patients underwent loop ileostomy closure during the study. The median time to closure in patients with rectal cancer was 5.47 months (range: 1 to 22). Thirty-nine of the 129 patients (30.2%) underwent reversal >6 months after index surgery. Anastomotic level ( P =0.004), Clavien-Dindo complication grade ( P =0.005), and hospital readmission after index surgery ( P =0.004) were associated with delayed ileostomy closure ( P <0.005). Reasons for delay included factors such as degree of complication, hospital readmission, and anastomosis level. Addressing these causes would benefit patients in terms of improving their quality of life after closure.

In rectal cancer patients with a clinical complete response managed nonoperatively, local regrowth occurs in up to 35%. Although prior studies suggest a higher metastatic risk after regrowth, most data are derived from conventional chemoradiotherapy cohorts. The risk in a total neoadjuvant therapy setting remains unclear. To assess whether local regrowth after clinical complete response in patients treated with total neoadjuvant therapy increases the risk of distant metastasis and to evaluate whether the risk could be reduced by upfront surgery performed after total neoadjuvant therapy. Retrospective cohort study. Single tertiary care center. Patients with locally advanced rectal cancer treated with total neoadjuvant therapy between 2018 and 2024 who achieved a clinical complete response, were managed nonoperatively, developed local regrowth, and subsequently underwent salvage total mesorectal excision, compared with those who underwent upfront total mesorectal excision after total neoadjuvant therapy, with final pathology demonstrating a near-complete response, were included in this study. Total neoadjuvant therapy followed by either watch and wait and salvage total mesorectal excision or upfront total mesorectal excision. The primary outcome was distant metastasis. Secondary outcomes included distant metastasis-free survival and independent predictors of distant spread. Seventy-four patients were included (median age, 58 years [interquartile range 51-67]; 58% men): 32 who had local regrowth managed by salvage total mesorectal excision and 42 who underwent upfront total mesorectal excision. The distant metastasis-free survival was comparable between groups, and local regrowth was not independently associated with distant metastasis (OR 0.99; 95% CI, 0.25-4.00). ypT3 to 4 stage was independently associated with increased risk of distant metastasis (OR 5.8; 95% CI, 1.3-25.3), whereas complete mesorectal excision was protective (OR 0.08; 95% CI, 0.01-0.59). Retrospective design, small sample size, and limited follow-up were the limitations of this study. Patients treated with total neoadjuvant therapy who developed local regrowth and underwent salvage total mesorectal excision achieved distant metastasis rates comparable to those who underwent upfront surgery after total neoadjuvant therapy and demonstrated a pathologic near-complete response. High-quality salvage surgery and close surveillance are essential for optimizing oncologic outcomes. See Video Abstract. ANTECEDENTES:En pacientes con cáncer rectal con respuesta clínica completa tratados sin cirugía, se produce un recidiva local en hasta un 35% de los casos. Aunque estudios previos sugieren un mayor riesgo de metástasis tras la recidiva, la mayoría de los datos proceden de cohortes de quimiorradioterapia convencional. El riesgo en un contexto de terapia neoadyuvante total sigue sin estar claro.OBJETIVO:Evaluar si el recidiva local tras una respuesta clínica completa en pacientes tratados con terapia neoadyuvante total aumenta el riesgo de metástasis a distancia, y evaluar si el riesgo podría reducirse mediante una cirugía inicial realizada después de la terapia neoadyuvante total.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO:Centro único de atención terciaria.PACIENTES:Pacientes con cáncer rectal localmente avanzado tratados con terapia neoadyuvante total entre 2018 y 2024 que lograron una respuesta clínica completa, fueron tratados de forma no quirúrgica, desarrollaron un recidiva local y posteriormente se sometieron a una escisión mesorrectal total de rescate, en comparación con aquellos que se sometieron a una escisión mesorrectal total inicial después de la terapia neoadyuvante total, con una patología final que demostró una respuesta casi completa.INTERVENCIÓN:Terapia neoadyuvante total seguida de vigilancia y espera y escisión mesorrectal total de rescate o escisión mesorrectal total inicial.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue la metástasis a distancia. Los resultados secundarios incluyeron la supervivencia libre de metástasis a distancia y los predictores independientes de diseminación a distancia.RESULTADOS:Se incluyeron 74 pacientes (mediana de edad: 58 años [IQR, 51-67]; 58 % hombres): 32 con recidiva local tratada mediante mesorrectal total de rescate y 42 con mesorrectal total inicial. La supervivencia libre de metástasis a distancia fue comparable entre los grupos, y el recidiva local no se asoció de forma independiente con la metástasis a distancia (OR, 0,99; IC del 95 %, 0,25-4,00). El estadio ypT3-4 se asoció de forma independiente con un mayor riesgo de metástasis a distancia (OR, 5,8; IC del 95 %, 1,3-25,3), mientras que la extirpación mesorrectal completa fue protectora (OR, 0,08; IC del 95 %, 0,01-0,59).LIMITACIONES:Diseño retrospectivo, tamaño reducido de la muestra y seguimiento limitado.CONCLUSIÓN:Los pacientes tratados con terapia neoadyuvante total que desarrollaron recidiva local y se sometieron a una extirpación mesorrectal total de rescate alcanzaron tasas de metástasis a distancia comparables a las de los que se sometieron a cirugía inicial después de la terapia neoadyuvante total y mostraron una respuesta patológica casi completa. La cirugía de rescate de alta calidad y la vigilancia estrecha son esenciales para optimizar los resultados oncológicos. (AI-generated translation ).

PURPOSE There is increasing interest in organ preservation for early-stage rectal cancer. Circulating tumor DNA (ctDNA) for detection of molecular residual disease may aid in clinical decision making for these approaches. METHODS The Canadian Cancer Trials Group (CCTG) CO.28 NEO trial was a phase II study of 58 patients with early-stage, clinically node-negative rectal cancers exploring the impact of 3 months of neoadjuvant infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin chemotherapy followed by transanal excision surgery (TES) in patients with treatment-responsive tumors. Patients without a clinical response were recommended total mesorectal excision (TME). A total of 52 patients had blood available for retrospective ctDNA analysis with the tumor-informed ctDNA assay FoundationOneTracker. Blood samples were taken prechemotherapy, postchemotherapy but before TES and/or TME, on surveillance (months 12, 24, and 46), and at progression. RESULTS ctDNA was detected in 24.5% of patients before chemotherapy and detection increased with clinical T stage ( P = .022). The ctDNA detection rate decreased to 6.7% of patients postchemotherapy but pre-TES ( P = .024). Two thirds of patients with ctDNA detected after neoadjuvant chemotherapy (66.7%) had been recommended TME based on lack of clinical response or TES pathology. Of patients (n = 3) with a sample taken at the time of progression, 33.3% (n = 1) had detectable ctDNA; however, no surveillance samples had ctDNA detected for any patient who had a clinical recurrence. CONCLUSION Early-stage node-negative rectal cancers shed ctDNA that can be detected in a subset of patients, particularly those with a higher clinical stage. This offers a potential future decision aid to augment endoscopy and MRI, particularly in cases of clinical uncertainty. More data in larger studies with denser surveillance sampling are needed to support ctDNA integration into clinical decision making for organ preservation.

Rectal cancer surgery timing after neoadjuvant therapy: balancing downstaging and perioperative outcomes.

Current treatments for locally advanced rectal cancer (LARC) include preoperative radiotherapy, chemotherapy and chemoradiotherapy followed by total mesorectal excision (TME), which can severely impact quality of life. Recently, anti-PD1 immunotherapy in microsatellite instability high (MSI-H) LARC has shown 100% clinical complete responses, allowing patients to avoid surgery with minimal toxicity. This review assesses the safety, toxicity, pathological impact, and long-term benefits of incorporating immunotherapy into the neoadjuvant treatment of microsatellite stable (MSS) and MSI-H LARC. This systematic review, conducted following PRISMA guidelines, investigates neoadjuvant immunotherapy in LARC. Data on study characteristics, treatment protocols, and outcomes were extracted. Quality assessment was conducted by using the Methodological Index for nonrandomized studies (MINORS) and the RoB2 tool. Patients were categorized into MSI-H, MSS, and unknown microsatellite status cohorts. We found twelve published studies including 547 patients. In the MSS cohort, postneoadjuvant surgery rates ranged from 57.6% to 100%, with a watch-and-wait approach adopted in up to 27.1% of cases. For MSI-H patients, surgery and watch-and-wait rates varied widely (0%-100%), reflecting heterogeneity in management. R0 resection rates were high across cohorts (70%-100% MSS, 80%-100% MSI-H). Pathological complete response (pCR) rates were 25% to 50% in MSS and 50% to 60% in MSI-H cohorts. Grade 3-4 adverse events ranged from 3.9% to 45.2% (MSS), 0% to 60% (MSI-H), with immune-related events generally below 10%. The role of immunotherapy in MSS rectal cancer remains unclear; phase III trials and translational research are needed urgently for guidance.

IntroductionLocally advanced rectal cancer (LARC) remains a therapeutic challenge, with significant risks of both locoregional and distant relapse. Total neoadjuvant therapy (TNT), which combines induction chemotherapy and chemoradiotherapy (CRT) prior to surgery, has emerged as a potentially more effective strategy than traditional approaches, yet data from low- and middle-income countries (LMICs) remain limited. This study evaluates the efficacy and toxicity of induction FOLFIRINOX followed by concurrent CRT in Vietnamese patients with lower–middle LARC.MethodsA retrospective analysis was conducted on adult patients (n = 72) with clinical stage T3–T4 M0 rectal adenocarcinoma. All patients received induction FOLFIRINOX for six cycles and preoperative CRT, followed by total meso-rectal excision (TME), and adjuvant chemotherapy as indicated. The primary endpoint was pathologic complete response (pCR, ypT0N0); secondary endpoints were 3-year disease-free survival (DFS) and safety. The study conforms to STROBE guidelines.ResultsPathological complete response was achieved in 25.0% of patients. The 3-year DFS reached 90.6%. Treatment feasibility was high, with 93.06% completing all 6 induction cycles; hematologic adverse events, particularly leukopenia and neutropenia, were the most common toxicities but were generally manageable with supportive care, while nonhematological toxicities were predominantly mild. R0 resection rate was 100% and sphincter-preserving surgery was 86.1%.ConclusionIn a LMIC setting, induction FOLFIRINOX followed by CRT shows promising efficacy and tolerable toxicity in LARC. These findings support early, intensified systemic therapy to enhance local control and mitigate metastatic spread.

Neoadjuvant chemotherapy alone (with radiation omission) for locally advanced rectal cancer has been evaluated in several randomized controlled trials. Although oncologic outcomes have been well described, the impact of this treatment strategy on surgical outcomes is unknown. To evaluate how important surgical outcomes were reported in previous trials comparing neoadjuvant chemotherapy to chemoradiation therapy for locally advanced rectal cancer and to perform a meta-analysis of available data. A systematic review was conducted using MEDLINE, Embase, and the Cochrane Library Databases. All published randomized controlled trials that compared neoadjuvant chemotherapy to chemoradiation for MRI-staged rectal adenocarcinoma. Neoadjuvant chemotherapy alone (with radiation omission). Postoperative surgical outcomes, including anastomotic leak, diverting ostomy use, ostomy nonreversal, 30-day postoperative morbidity, and postoperative bowel function. Four randomized controlled trials met eligibility criteria and were included for data analysis. Oncologic outcomes demonstrated that neoadjuvant chemotherapy was equivalent or noninferior to chemoradiation therapy. Anastomotic leak and use of diverting ostomy were reported in 3 of the 4 trials, whereas 30-day postoperative morbidity and ostomy nonreversal were reported in only 2 trials. Bowel function was measured in 3 trials but was measured and reported differently in each trial. On meta-analysis, neoadjuvant chemotherapy was associated with a significant reduction in anastomotic leak (relative risk [RR] 0.54; 95% CI, 0.35-0.81), use of diverting ostomy (RR 0.79; 95% CI, 0.70-0.88), and ostomy nonreversal (RR 0.37; 95% CI, 0.15-0.93). There was no association between neoadjuvant chemotherapy and 30-day postoperative morbidity (RR 0.88; 95% CI, 0.53-1.45). A small number of included trials with heterogeneity in outcome definitions was the limitation. Important surgical outcomes were not reported in trials comparing neoadjuvant chemotherapy alone to chemoradiation therapy for locally advanced rectal cancer. Based on the limited data available, chemotherapy alone was associated with reduced risk of anastomotic leak, diverting ostomy use, and ostomy nonreversal. See Video Abstract .

BackgroundPathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) is associated with favorable outcomes; however, pre-treatment biomarkers that reliably predict pCR remain limited. We evaluated whether the Tumor Marker Index (TMI; geometric mean of normalized CEA and CA19-9) predicts pCR and examined its relationship with recurrence and survival.MethodsThis single-center retrospective study included 123 stage III LARC patients treated with nCRT followed by total mesorectal excision (2015–2022). The primary endpoint was pCR (ypT0N0). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) analysis assessed TMI discrimination and identified a cut-off. Predictors of pCR were evaluated by univariable and multivariable logistic regression. Systemic inflammatory markers (NLR, PLR, SII) were also analyzed.ResultsMedian age was 67 years; 61.0% were male. pCR occurred in 18.7% (23/123). Patients with pCR had lower baseline CEA and TMI. TMI predicted pCR (AUC 0.633, 95% CI 0.509–0.756; p = 0.036); the Youden cut-off ≤ 0.79 yielded sensitivity 86.96% and NPV 92.31%. In multivariable analysis (outcome coded as non-pCR), comorbidity (aOR 3.871; p = 0.035), cT3 vs. cT2 (aOR 4.447; p = 0.026) and higher TMI (per unit; aOR 3.343; p = 0.036) independently increased the odds of non-pCR, whereas a longer RT–surgery interval (per week) reduced it (aOR 0.940; p = 0.016). NLR/PLR/SII were not independent predictors. Recurrence was lower in low-TMI patients (20.5% vs. 57.5%, p < 0.001). pCR was associated with longer PFS (91.6 vs. 62.2 months; log-rank p = 0.012) but not OS (81.9 vs. 64.2 months; p = 0.165).ConclusionsPre-treatment TMI is an independent predictor of pCR and correlates with lower recurrence in LARC after nCRT. Given its high sensitivity/NPV at the identified threshold, TMI may support organ-preservation discussions and guide treatment intensification strategies; prospective validation is warranted.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12957-025-04081-w.