PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer.

BACKGROUND: Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced rectal cancer. METHODS: We initiated a prospective phase 2 study in which single-agent dostarlimab, an anti-PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair-deficient stage II or III rectal adenocarcinoma. This treatment was to be followed by standard chemoradiotherapy and surgery. Patients who had a clinical complete response after completion of dostarlimab therapy would proceed without chemoradiotherapy and surgery. The primary end points are sustained clinical complete response 12 months after completion of dostarlimab therapy or pathological complete response after completion of dostarlimab therapy with or without chemoradiotherapy and overall response to neoadjuvant dostarlimab therapy with or without chemoradiotherapy. RESULTS: A total of 12 patients have completed treatment with dostarlimab and have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose-positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported. CONCLUSIONS: Mismatch repair-deficient, locally advanced rectal cancer was highly sensitive to single-agent PD-1 blockade. Longer follow-up is needed to assess the duration of response. (Funded by the Simon and Eve Colin Foundation and others; ClinicalTrials.gov number, NCT04165772.).

Comparison of etiological and physiological characteristics of fecal incontinence in men and women.

Fecal incontinence (FI) is often underreported and underestimated in men. Our aims were to clarify the causes and the physiological characteristics of FI in men and to underline the differences between etiological and physiological factors in men and women diagnosed with FI. The study cohort encompassed 200 men and 200 women who underwent anatomical and physiological evaluation for FI in a tertiary referral center specializing in pelvic floor disorders. All patients underwent endoanal ultrasound and anorectal manometry. Evacuation proctography was performed in some patients. Demographic, medical, anatomical, and physiological parameters were compared between the two study groups. Urge incontinence was the most frequent type of FI in both genders. In men, anal fistula, history of anal surgeries, rectal tumors, and pelvic radiotherapy were common etiologic factors, whereas history of pelvic surgeries was more common in women. Associated urinary incontinence was reported more frequently by women. External anal sphincter defects, usually anterior, were more common in women (M: 1.5%, F: 24%, P < 0.0001), whereas internal anal sphincter defect prevalence was similar in men and women (M: 6%, F: 12%, P = 0.19). Decreased resting and squeeze pressures were less common in men (M: 29%, F: 46%, P < 0.0001: M: 44%, F: 66%, P < 0.0001). The incidence of rectal hyposensitivity was higher in men (M: 11.1%, F: 2.8%, P < 0.0001), whereas rectal hypersensitivity was higher in women (M: 5.8%, F: 10.8%, P < 0.0001). Anorectal dyssynergia was more common in men (M: 66%, F: 37%, P < 0.0001). Significantly different etiological factors and physiological characteristics for FI were found in men. Acknowledging these differences is significant and may yield better treatment options.NEW & NOTEWORTHY Fecal incontinence (FI) in men has different etiological factors when compared with women. The prevalence of internal anal sphincter defect among men with FI was similar to women. Different manometric measurements were found among men with FI: decreased anal pressures were less common among men, whereas rectal hyposensitivity and anorectal dyssynergia were more common among men.

Complications Following Transrectal and Transperineal Prostate Biopsy: Results of the ProBE-PC Randomized Clinical Trial.

PURPOSE: Transrectal prostate biopsy has come under scrutiny due to potential for postbiopsy infections and transperineal prostate biopsy is being offered as the safer alternative. However, there is a lack of randomized comparative studies. Our goal was to directly evaluate infectious and noninfectious complications following the 2 biopsy procedures. MATERIALS AND METHODS: We conducted a prospective, pragmatic, randomized clinical study in men undergoing prostate biopsy. The participants underwent either transrectal or transperineal prostate biopsy in the office under local anesthesia. The primary outcome was a 30-day composite infectious complication rate, comprising of 1 or more components including fever, genitourinary infection, antibiotic prescriptions, office or emergency visits, hospitalization, or sepsis. Secondary outcomes included 30-day composite noninfectious complications (urinary or hemorrhagic). RESULTS: Of the 763 randomized participants, 718 underwent either transrectal (351) or transperineal (367) prostate biopsy. A composite infectious complication event occurred in 9 participants (2.6%) in the transrectal and 10 participants (2.7%) in the transperineal group (odds ratio, 1.06; 95% CI, 0.43 to 2.65; P = .99). None of the participants developed sepsis in either group. There were no between-group differences in any of the individual component infectious events. A composite noninfectious complication occurred in 6 (1.7%) and 8 (2.2%) participants in the transrectal and transperineal groups, respectively (odds ratio, 1.28; 95% CI, 0.44 to 3.73; P = .79). No participants required hospitalization or other interventions. CONCLUSIONS: Among men undergoing transperineal or transrectal prostate biopsy, we could not demonstrate any difference in the infectious or noninfectious complications. Both biopsy approaches remain clinically viable and safe.

Clinically Significant Prostate Cancer Detection Following Transrectal and Transperineal Biopsy: Results of the Prostate Biopsy Efficacy and Complications Randomized Clinical Trial.

PURPOSE: The comparative effectiveness of transrectal and transperineal prostate biopsy in detecting clinically significant prostate cancer is not well understood. We conducted a randomized clinical trial to determine whether transperineal biopsy improves the detection of clinically significant prostate cancer. MATERIALS AND METHODS: Of the 840 men randomized, 93% were White, 44% had a previous biopsy, with a median age of 66 years and median PSA density of 0.14. Of these, 384 underwent transrectal and 398 underwent transperineal prostate biopsy. Prebiopsy prostate MRI was performed in 96% of men. Grade Group ≥ 2 prostate cancer was classified as clinically significant. Odds ratios were calculated using logistic regression to evaluate the effect of biopsy procedures on cancer detection rates. RESULTS: The detection rates of clinically significant prostate cancer were 47.1% and 43.2% (odds ratio 1.17; 95% CI, 0.88-1.55) for transrectal and transperineal biopsy, respectively. Age, PSA density, clinical stage and Prostate Imaging Reporting and Data System score were associated with the diagnosis of clinically significant cancer, whereas history of previous biopsy, anterior tumors, and biopsy procedure (transrectal or transperineal) were not. Clinically significant cancer detection rates in biopsy-naïve men undergoing MRI-targeted transrectal or transperineal biopsy were 59% and 62%, respectively. The overall cancer detection rates following transrectal and transperineal biopsy were 72.1% and 70.4%, respectively. CONCLUSIONS: There was no significant difference noted in the detection of clinically significant prostate cancer following transrectal or transperineal prostate biopsy. Urologists may utilize either biopsy procedure that best suits their patients' needs and practice setting.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Computed Diffusion-Weighted Images of Rectal Cancer: Image Quality, Restaging, and Treatment Response after Neoadjuvant Therapy.

BACKGROUND: Computed diffusion-weighted images (cDWI) of random b value could be derived from acquired DWI (aDWI) with at least two different b values. However, its comparison between aDWI and cDWI images in locally advanced rectal cancer (LARC) patients after neoadjuvant therapy (NT) is needed. PURPOSE: To compare the cDWI and aDWI in image quality, restaging, and treatment response of LARC after NT. STUDY TYPE: Retrospective. POPULATION: Eighty-seven consecutive patients. FIELD STRENGTH/SEQUENCE: 3.0 T/DWI. ASSESSMENT: All patients underwent two DWI sequences, including conventional acquisition with b = 0 and 1000 s/mm2 (aDWIb1000 ) and another with b = 0 and 700 s/mm2 on a 3.0-T MR scanner. The images of the latter were used to compute the diffusion images with b = 1000 s/mm2 (cDWIb1000 ). Four radiologists with 3, 4, 14, and 25 years of experience evaluated the images to compare the image quality, TN restaging performance, and treatment response between aDWIb1000 and cDWIb1000 . STATISTICAL TESTS: Interclass correlation coefficients, weighted κ coefficient, paired Wilcoxon, and McNemar or Fisher test were used. A significance level of 0.05 was used. RESULTS: The cDWIb1000 images were superior to the aDWIb1000 ones in both subjective and objective image quality. In T restaging, the overall diagnostic accuracy of cDWIb1000 images was higher than that of aDWIb1000 images (57.47% vs. 49.43%, P = 0.289 for the inexperienced radiologist; 77.01% vs. 63.22%, significant for the experienced radiologist), with better sensitivity in determining ypT0-Tis tumors. Additionally, it increased the sensitivity in detecting ypT2 tumors for the inexperienced radiologist and ypT3 tumors for the experienced radiologist. N restaging and treatment response were found to be similar between two sequences for both radiologists. DATA CONCLUSION: Compared to aDWIb1000 images, the computed ones might serve as a wise approach, providing comparable or better image quality, restaging performance, and treatment response assessment for LARC after NT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Outcomes and potential impact of a virtual hands-on training program on MRI staging confidence and performance in rectal cancer.

OBJECTIVES: To explore the potential impact of a dedicated virtual training course on MRI staging confidence and performance in rectal cancer. METHODS: Forty-two radiologists completed a stepwise virtual training course on rectal cancer MRI staging composed of a pre-course (baseline) test with 7 test cases (5 staging, 2 restaging), a 1-day online workshop, 1 month of individual case readings (n = 70 cases with online feedback), a live online feedback session supervised by two expert faculty members, and a post-course test. The ESGAR structured reporting templates for (re)staging were used throughout the course. Results of the pre-course and post-course test were compared in terms of group interobserver agreement (Krippendorf's alpha), staging confidence (perceived staging difficulty), and diagnostic accuracy (using an expert reference standard). RESULTS: Though results were largely not statistically significant, the majority of staging variables showed a mild increase in diagnostic accuracy after the course, ranging between + 2% and + 17%. A similar trend was observed for IOA which improved for nearly all variables when comparing the pre- and post-course. There was a significant decrease in the perceived difficulty level (p = 0.03), indicating an improved diagnostic confidence after completion of the course. CONCLUSIONS: Though exploratory in nature, our study results suggest that use of a dedicated virtual training course and web platform has potential to enhance staging performance, confidence, and interobserver agreement to assess rectal cancer on MRI virtual training and could thus be a good alternative (or addition) to in-person training. CLINICAL RELEVANCE STATEMENT: Rectal cancer MRI reporting quality is highly dependent on radiologists' expertise, stressing the need for dedicated training/teaching. This study shows promising results for a virtual web-based training program, which could be a good alternative (or addition) to in-person training. KEY POINTS: • Rectal cancer MRI reporting quality is highly dependent on radiologists' expertise, stressing the need for dedicated training and teaching. • Using a dedicated virtual training course and web-based platform, encouraging first results were achieved to improve staging accuracy, diagnostic confidence, and interobserver agreement. • These exploratory results suggest that virtual training could thus be a good alternative (or addition) to in-person training.

Prediction of Pathologic Complete Response for Rectal Cancer Based on Pretreatment Factors Using Machine Learning.

BACKGROUND: Pathologic complete response after neoadjuvant therapy is an important prognostic indicator for locally advanced rectal cancer and may give insights into which patients might be treated nonoperatively in the future. Existing models for predicting pathologic complete response in the pretreatment setting are limited by small data sets and low accuracy. OBJECTIVE: We sought to use machine learning to develop a more generalizable predictive model for pathologic complete response for locally advanced rectal cancer. DESIGN: Patients with locally advanced rectal cancer who underwent neoadjuvant therapy followed by surgical resection were identified in the National Cancer Database from years 2010 to 2019 and were split into training, validation, and test sets. Machine learning techniques included random forest, gradient boosting, and artificial neural network. A logistic regression model was also created. Model performance was assessed using an area under the receiver operating characteristic curve. SETTINGS: This study used a national, multicenter data set. PATIENTS: Patients with locally advanced rectal cancer who underwent neoadjuvant therapy and proctectomy. MAIN OUTCOME MEASURES: Pathologic complete response defined as T0/xN0/x. RESULTS: The data set included 53,684 patients. Pathologic complete response was experienced by 22.9% of patients. Gradient boosting showed the best performance with an area under the receiver operating characteristic curve of 0.777 (95% CI, 0.773-0.781), compared with 0.684 (95% CI, 0.68-0.688) for logistic regression. The strongest predictors of pathologic complete response were no lymphovascular invasion, no perineural invasion, lower CEA, smaller size of tumor, and microsatellite stability. A concise model including the top 5 variables showed preserved performance. LIMITATIONS: The models were not externally validated. CONCLUSIONS: Machine learning techniques can be used to accurately predict pathologic complete response for locally advanced rectal cancer in the pretreatment setting. After fine-tuning a data set including patients treated nonoperatively, these models could help clinicians identify the appropriate candidates for a watch-and-wait strategy. See Video Abstract . EL CNCER DE RECTO BASADA EN FACTORES PREVIOS AL TRATAMIENTO MEDIANTE EL APRENDIZAJE AUTOMTICO: ANTECEDENTES:La respuesta patológica completa después de la terapia neoadyuvante es un indicador pronóstico importante para el cáncer de recto localmente avanzado y puede dar información sobre qué pacientes podrían ser tratados de forma no quirúrgica en el futuro. Los modelos existentes para predecir la respuesta patológica completa en el entorno previo al tratamiento están limitados por conjuntos de datos pequeños y baja precisión.OBJETIVO:Intentamos utilizar el aprendizaje automático para desarrollar un modelo predictivo más generalizable para la respuesta patológica completa para el cáncer de recto localmente avanzado.DISEÑO:Los pacientes con cáncer de recto localmente avanzado que se sometieron a terapia neoadyuvante seguida de resección quirúrgica se identificaron en la Base de Datos Nacional del Cáncer de los años 2010 a 2019 y se dividieron en conjuntos de capacitación, validación y prueba. Las técnicas de aprendizaje automático incluyeron bosque aleatorio, aumento de gradiente y red neuronal artificial. También se creó un modelo de regresión logística. El rendimiento del modelo se evaluó utilizando el área bajo la curva característica operativa del receptor.ÁMBITO:Este estudio utilizó un conjunto de datos nacional multicéntrico.PACIENTES:Pacientes con cáncer de recto localmente avanzado sometidos a terapia neoadyuvante y proctectomía.PRINCIPALES MEDIDAS DE VALORACIÓN:Respuesta patológica completa definida como T0/xN0/x.RESULTADOS:El conjunto de datos incluyó 53.684 pacientes. El 22,9% de los pacientes experimentaron una respuesta patológica completa. El refuerzo de gradiente mostró el mejor rendimiento con un área bajo la curva característica operativa del receptor de 0,777 (IC del 95%: 0,773 - 0,781), en comparación con 0,684 (IC del 95%: 0,68 - 0,688) para la regresión logística. Los predictores más fuertes de respuesta patológica completa fueron la ausencia de invasión linfovascular, la ausencia de invasión perineural, un CEA más bajo, un tamaño más pequeño del tumor y la estabilidad de los microsatélites. Un modelo conciso que incluye las cinco variables principales mostró un rendimiento preservado.LIMITACIONES:Los modelos no fueron validados externamente.CONCLUSIONES:Las técnicas de aprendizaje automático se pueden utilizar para predecir con precisión la respuesta patológica completa para el cáncer de recto localmente avanzado en el entorno previo al tratamiento. Después de realizar ajustes en un conjunto de datos que incluye pacientes tratados de forma no quirúrgica, estos modelos podrían ayudar a los médicos a identificar a los candidatos adecuados para una estrategia de observar y esperar. (Traducción-Dr. Ingrid Melo ).

The Enigma That is Rectal Squamous Cell Carcinoma: A Case Series.

INTRODUCTION: Colorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the United States. As rectal squamous cell carcinoma (SCC) is an uncommon colorectal cancer, there is limited data on this clinical entity. We aimed to evaluate the tumor characteristics, treatment, and clinical outcomes of this rare deadly disease. METHODS: Pathological specimens from 2017 to 2022 at a single National Cancer Institute-designated cancer center were screened for all rectal cases with a diagnosis of SCC. All patients with a primary rectal SCC were included. Patients who had extension to the dentate line or evidence of an anal mass, and those who were treated at an outside institution, were excluded. Demographic, treatment, outcome, and surveillance data was extracted. RESULTS: There were 56 specimens identified, nine of which met inclusion criteria. Most patients were White (78%), Hispanic (78%), and female (67%). The average age at diagnosis was 57 y [52-65]. All patients had nodal involvement at the time of clinical staging. All patients were treated with Nigro protocol, with one patient treated with surgery first. The median time of follow-up was 12 mo after initial treatment, 33% had recurrence, with median time to recurrence of 25 mo. Overall, mortality from rectal SCC was 33% at a median time of 37 mo from initial diagnosis. CONCLUSIONS: Rectal SCC is a colorectal cancer that is not fully understood. Our findings showed that treatment mirrors that of anal SCC, with similar rates of survival to both rectal adenocarcinoma and anal SCC.

Leiomyosarcoma of the rectum: A systematic review of recent literature.

Leiomyosarcomas (LMSs) are rare tumors originating from the muscular layer. We performed a literature review of cases of confirmed rectal leiomyosarcomas (rLMSs) to clarify the history of such an infrequent tumor arising at such an uncommon location. In this research local recurrence was related to poorly differentiated rLMS and no other association between recurrence and any criteria was found. Concerning overall survival (OS), rLMS patients developing recurrence presented shorter longevity compared with the group without.

A precise approach to robotic intracorporeal rectal transection and hand-sewn purse-string anastomosis for low anterior resection.

This study presents a new technique for robotic-assisted intracorporeal rectal transection and hand-sewn anastomosis for low anterior resection that overcomes some limitations of conventional techniques. By integrating the advantages of the robotic platform, ensuring standardized exposure during rectal transection, and emphasizing the importance of avoiding complications associated with staple crossings, this innovation has the potential to significantly improve outcomes and reduce costs for patients with lower rectal tumors.

Comparison of conventional MRI analysis versus MRI-based radiomics to predict the circumferential margin resection involvement of rectal cancer.

BACKGROUND: To compare the application of conventional MRI analysis and MRI-based radiomics to identify the circumferential resection margin (CRM) status of rectal cancer (RC). METHODS: A cohort of 301 RC patients with 66 CRM invloved status and 235 CRM non-involved status were enrolled in this retrospective study between September 2017 and August 2022. Conventional MRI characteristics included gender, age, diameter, distance to anus, MRI-based T/N phase, CEA, and CA 19 - 9, then the relevant logistic model (Logistic-cMRI) was built. MRI-based radiomics of rectal cancer and mesorectal fascia were calculated after volume of interest segmentation, and the logistic model of rectal cancer radiomics (Logistic-rcRadio) and mesorectal fascia radiomics (Logistic-mfRadio) were constructed. And the combined nomogram (nomo-cMRI/rcRadio/mfRadio) containing conventional MRI characteristics, radiomics of rectal cancer and mesorectal fascia was developed. The receiver operator characteristic curve (ROC) was delineated and the area under curve (AUC) was calculated the efficiency of models. RESULTS: The AUC of Logistic-cMRI was 0.864 (95%CI, 0.820 to 0.901). The AUC of Logistic-rcRadio was 0.883 (95%CI, 0.832 to 0.928) in the training set and 0.725 (95%CI, 0.616 to 0.826) in the testing set. The AUCs of Logistic-mfRadio was 0.891 (95%CI, 0.838 to 0.936) in the training set and 0.820 (95%CI, 0.725 to 0.905) in the testing set. The AUCs of nomo-cMRI/rcRadio/mfRadio were the highest in both the training set of 0.942 (95%CI, 0.901 to 0.969) and the testing set of 0.909 (95%CI, 0.830 to 0.959). CONCLUSION: MRI-based radiomics of rectal cancer and mesorectal fascia showed similar efficacy in predicting the CRM status of RC. The combined nomogram performed better in assessment.

Anatomic Basis of Rectal Cancer Staging: Clarifying Controversies and Misconceptions.

Rectal MRI provides a detailed depiction of pelvic anatomy; specifically, the relationship of the tumor to key anatomic structures, including the mesorectal fascia, anterior peritoneal reflection, and sphincter complex. However, anatomic inconsistencies, pitfalls, and confusion exist, which can have a strong impact on interpretation and treatment. These areas of confusion include the definition of the rectum itself, specifically differentiation of the rectum from the anal canal and the sigmoid colon, and delineation of the high versus low rectum. Other areas of confusion include the relative locations of the mesorectal fascia and peritoneum and their significance in staging and treatment, the difference between the mesorectal fascia and circumferential resection margin, involvement of the sphincter complex, and evaluation of lateral pelvic lymph nodes. The impact of these anatomic inconsistencies and sources of confusion is significant, given the importance of MRI in depicting the anatomic relationship of the tumor to critical pelvic structures, to triage surgical resection and neoadjuvant chemoradiotherapy with the goal of minimizing local recurrence. Evolving treatment paradigms also place MRI central in management of rectal cancer. ©RSNA, 2024.

Fluorescence guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series.

PURPOSE: Tattoo markings are often used as preoperative markers for colorectal cancer. However, scattered ink markings adversely affect tumor site recognition intraoperatively; therefore, interventions for rectal cancer may lead to an inaccurate distal resection margin (DRM) and incomplete total mesorectal excision (TME). This is the first case series of fluorescence-guided robotic rectal surgery in which near-infrared fluorescence clips (NIRFCs) were used to localize rectal cancer lesions. METHODS: We enrolled 20 consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 in the current study. The primary endpoints were the rate of intraoperative clip detection and its usefulness for marking the tumor site. Secondary endpoints were oncological assessments, including DRM and the number of lymph nodes. RESULTS: Clip locations were confirmed in 17 of 20 (85%) patients. NIRFCs were not detected in 3 out of 7 patients who underwent preoperative chemoradiation therapy. No adverse events, including bleeding or perforation, were observed at the time of clipping, and no clips were lost. The median DRM was 55 mm (range, 22-86 mm) for rectosigmoid (Rs), 33 mm (range, 16-60 mm) for upper rectum (Ra), and 20 mm (range, 17-30 mm) for low rectum (Rb). The median number of lymph nodes was 13 (range, 10-21). CONCLUSION: The rate of intraoperative clip detection, oncological assessment, including DRM, and the number of lymph nodes indicate that the utility of fluorescence-guided methods with NIRFCs is feasible for rectal cancer.

MRI-defined T3, clear mesorectal fascia mid-low rectal cancer: is neoadjuvant treatment necessary?

AIM: Neoadjuvant treatments (nCRT) are becoming the standard treatment for patients with stage II or III mid-low rectal cancer. Recently, some studies have shown that surgery alone may be sufficient for patients with T3 rectal cancer. This raises the question of whether nCRT is necessary for all patients with T3 rectal cancer. Therefore, this study compared the clinical outcomes of patients with MRI-defined T3, clear MRF mid-low rectal cancer treated with surgery alone (TME group) or nCRT followed by surgery (nCRT + TME group). METHODS: A total of 1509 patients were enrolled in this study. After a 1:1 propensity score matching analysis, 480 patients were included in each group. The primary endpoint was 3-year disease-free survival (DFS). The secondary endpoints included the perioperative outcomes, histopathologic outcomes, and other follow-up outcomes. RESULTS: nCRT had advantages in rates of sphincter-preserving surgery and tumor downstaging, but it was accompanied by a higher rate of enterostomies. At 3 years after surgery, local recurrence occurred in 3.3% of patients in the TME group and in 3.5% of patients in the nCRT + TME group (P = 0.914), the DFS rates were 78.3% in the TME group and 75.3% in the nCRT + TME group (P = 0.188), and the overall survival rates were 90.3% in the TME group and 89.9% in the nCRT + TME group (P = 0.776). CONCLUSIONS: Surgery alone versus nCRT followed by surgery may provide similar long-term oncological outcomes for patients with MRI-defined T3, clear MRF, and mid-low rectal cancer. nCRT may cause overtreatment in some patients.

Rectal cancer - avoiding surgery?

Nonoperative treatment of rectal cancer is gaining popularity. Several trials recently demonstrated advantages in disease-free survival with total neoadjuvant treatment (TNT) with the addition of the watch and wait (WW) strategy for locally advanced rectal cancer. On longer follow-up, an unexpected increased risk in local recurrence in the TNT group at the RAPIDO trial suggested early surgery for nonresponding tumours. The WW option is globally accepted for a complete clinical response; however, a high rate of regrowth was found in a registry with an increased risk of distant metastases, questioning the deleterious effect of deferral of surgery in this group. The short- and long-term toxic effects of neoadjuvant treatment are costs to consider in the National Comprehensive Cancer Network guidelines compared with the European Society for Medical Oncology guidelines, which favour surgery alone if good mesorectal resection is assured with increasing surgical proficiency adjusted to the precise anatomical location.

Current treatment of pT1 rectal cancers in Denmark: A retrospective national cohort study.

AIM: Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers. METHOD: This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared. RESULTS: A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors. CONCLUSION: LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate.

Substratifying the risk of covert malignancy in significant rectal polyps: Outcomes from a specialist multidisciplinary team (MDT).

AIM: A treatment strategy for patients with a significant polyp or early colon cancer (SPECC) of the rectum presents a challenge due to the significant rate of covert malignancy and lack of standardized assessment. For this reason, NICE recommends multidisciplinary meetings to improve outcomes. The primary aim of the present study was to report the performance of our specialist early rectal cancer (SERC) multidisciplinary team (MDT) in correctly substratifying the risk of cancer and to discuss the limitations of staging investigations in those patients with "poor outcomes". METHOD: This was a retrospective review of patients referred to our SERC MDT from 2014 to 2019. Lesions were assigned by the MDT to three pre-resection categories (low, intermediate, high) according to the risk of covert malignancy. Resection method and final histology were compared to the pre-resection categories. RESULTS: Of 350 SPECC lesions, 174 were assessed as low-risk, 108 intermediate-risk and 68 high-risk. The cancer incidence was 4.8%, 8.3% and 53%, respectively (15.5% overall). Eight lesions were categorized as low-risk but following piecemeal resection were found to be malignant. Five lesions, three of which were categorized as high-risk, were ultimately benign following conventional surgery. One pT1sm1 cancer, removed by anterior resection, may have been treated by local excision. CONCLUSION: A total of 83% of malignant polyps were triaged to an en bloc resection technique and surgical resection avoided for nearly all benign lesions. However, 12 patients from this cohort were deemed to have a poor outcome because of miscategorization. Further comparative research is needed to establish the optimum strategy for rectal SPECC lesion assessment. ORIGINALITY STATEMENT: There is currently no consensus for staging significant polyps of the rectum. This paper reports the effectiveness of a specialist early rectal cancer MDT to correctly risk-stratify significant rectal polyps. It underscores the importance of accurate categorization for treatment decision-making, while acknowledging the limitations of current staging modalities.

Influence of neoadjuvant treatment strategy on perioperative outcomes in locally advanced rectal cancer.

AIM: Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). The goal of neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) is to further improve local and systemic control. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care. While TNT appears to be noninferior to nCRT with respect to short-term oncological outcomes few data exist on perioperative outcomes. Perioperative morbidity including anastomotic leaks is associated with a negative effect on oncological outcomes, probably due to a delay in proceeding to adjuvant therapy. Thus, we aimed to compare conversion rates, rates of sphincter-preserving surgery and anastomosis formation rates in patients undergoing rectal resection after either TNT or standard nCRT. METHODS: An institutional colorectal oncology database was searched from January 2018 to July 2023. Inclusion criteria comprised patients with histologically confirmed rectal cancer who had undergone neoadjuvant therapy and TME. Exclusion criteria comprised patients with a noncolorectal primary, those operated on emergently or who had local excision only. Outcomes evaluated included rates of conversion to open, sphincter-preserving surgery, anastomosis formation and anastomotic leak. RESULTS: A total of 119 patients were eligible for inclusion (60 with standard nCRT, 59 with TNT). There were no differences in rates of sphincter preservation or primary anastomosis formation between the groups. However, a significant increase in conversion to open (p = 0.03) and anastomotic leak (p = 0.03) was observed in the TNT cohort. CONCLUSION: In this series TNT appears to be associated with higher rates of conversion to open surgery and higher anastomotic leak rates. While larger studies will be required to confirm these findings, these factors should be considered alongside oncological benefits when selecting treatment strategies.

Permanent stoma rate and long-term stoma complications in laparoscopic, robot-assisted, and transanal total mesorectal excisions: a retrospective cohort study.

BACKGROUND: The surgical resection of rectal carcinoma is associated with a high risk of permanent stoma rate. Primary anastomosis rate is suggested to be higher in robot-assisted and transanal total mesorectal excision, but permanent stoma rate is unknown. METHODS: Patients undergoing total mesorectal excision for MRI-defined rectal cancer between 2015 and 2017 in 11 centers highly experienced in laparoscopic, robot-assisted or transanal total mesorectal excision were included in this retrospective study. Permanent stoma rate, stoma-related complications, readmissions, and reoperations were registered. A multivariable regression analysis was performed for permanent stoma rate, stoma-related complications, and stoma-related reoperations. RESULTS: In total, 1198 patients were included. Permanent stoma rate after low anterior resection (with anastomosis or with an end colostomy) was 40.1% in patients undergoing laparoscopic surgery, 21.3% in patients undergoing robot-assisted surgery, and 25.6% in patients undergoing transanal surgery (P < 0.001). Permanent stoma rate after low anterior resection with an anastomosis was 17.3%, 11.8%, and 15.1%, respectively. The robot-assisted and transanal techniques were independently associated with a reduction in permanent stoma rate in patients who underwent a low anterior resection (with anastomosis or with an end colostomy) (OR 0.39 [95% CI 0.25, 0.59] and OR 0.35 [95% CI 0.22, 0.55]), while this was not seen in patients who underwent a restorative low anterior resection. 45.4% of the patients who had a stoma experienced stoma-related complications, 4.0% were at least once readmitted, and 8.9% underwent at least one reoperation. CONCLUSIONS: The robot-assisted and transanal techniques are associated with a lower permanent stoma rate in patients who underwent a low anterior resection.