Neoadjuvant Treatment For Rectal Cancer Research Articles

Diverting ostomy prior to neoadjuvant treatment in rectal cancer should be used selectively: A retrospective single-center cohort study.

Rectal cancer patients commonly benefit from neoadjuvant therapy before resection surgery. For these patients, an elective ostomy diversion is frequently considered, despite the absence of conclusive evidence when a diversion is advantageous. This is a retrospective observational single-center study on a 4-year consecutive rectal cancer cohort undergoing neoadjuvant therapy, aiming at improving the understanding of risks and benefits associated with ostomy diversion. Baseline characteristics, tumor-specific data, clinical events, and outcomes were collected using the Swedish Colorectal Cancer Registry and medical records. Thirty-two (30.2%) of the 106 included patients presented with endoscopic impassable tumors at diagnosis, of which 18 (56.2%) had diverting ostomy. Three out of 14 with impassable tumor and no diversion developed a bowel obstruction. None of the patients with an endoscopically passable tumor at diagnosis (n = 74) experienced a bowel obstruction. The elective diversions (n = 40) were not associated with serious complications (Clavien-Dindo grade ⩾ 3b). Patients with a diverting ostomy (n = 30) had similar time intervals from diagnosis to neoadjuvant treatment and to definite tumor resection as those without diversion but experienced more complex primary tumor resections in terms of blood loss and operation time. An elective diverting ostomy is a relatively safe procedure in rectal cancer patients requiring neoadjuvant therapy. More than one out of five non-diverted patients with endoscopically impassable rectal tumors developed bowel obstruction and would potentially have benefited from an elective diversion.

Changes in clinical guidelines for the treatment of colorectal cancer in 2024

Aim. The ensuring that changes to clinical guidelines can be discussed more widely before they are formally introduced into clinical practice.Materials and methods. A brief review of the literature and rationale for each proposed major change in the treatment section is presented. The refusal to carry out preoperative radiation therapy for cancer of the upper ampullary rectum, the narrowing of indications for preoperative radiation therapy for cancer of the mid-ampullary rectum, as well as the expansion of indications for total non-adjuvant chemotherapy for rectal cancer with damage to the circular resection margin are discussed. Changes to the drug treatment section are discussed.Results. This article presents planned changes to clinical guidelines for the treatment of non-metastatic colorectal cancer in 2024. The most significant alterations concerned neoadjuvant treatment of rectal cancer and adjuvant treatment of colon cancer. A new algorithm was proposed for choosing rectal cancer neoadjuvant therapy, considering individual treatment decisions.Conclusion. A consensus was achieved concerning the necessity to expand indications for neoadjuvant rectal cancer chemotherapy, but only in patients with good functional status. The most benefit can be achieved in patients, for whom complete clinical response is the aim of the treatment and in patients with positive circumferential resection margin.

Loss of psoas muscle during neoadjuvant treatment for rectal cancer is associated with poor oncological and surgical outcomes.

Sarcopenia has been associated with poor outcomes in rectal cancer patients. This study aims to assess the degree of muscle loss during neoadjuvant therapy in patients with rectal cancer, and its relationship with tumour response, post-operative complications and long-term disease recurrence. The change in the psoas muscle area was determined by measuring the psoas muscle area at L4 on initial staging PET CT scans and comparing this with the restaging scan 8-10 weeks after radiation treatment had been completed. The average change in the psoas muscle area was compared between patients who had residual disease versus complete clinical/pathological response, anastomotic leak vs. no leak, and distant recurrence vs. no recurrence on follow-up imaging. Ninety-two patients were included in the study. The mean loss of psoas muscle area was 5%. Patients who had a complete response to chemoradiotherapy showed a statistically significant difference in muscle mass loss (2.8%) compared to those with residual tumour present after therapy (6.2%), P = 0.02 on multivariable analysis. There was a statistically significant greater loss of muscle in patients who had an anastomotic leak versus those that did not (10.2% vs. 4.1%) and in those who developed metastatic disease versus those that did not (10.7% vs. 4.1%) (P < 0.05). Our study adds to the growing body of evidence that sarcopenia is a predictor of poor surgical and oncological outcomes in rectal cancer patients. We postulate that the loss of muscle is an indication of disease burden and worse tumour biology.

Does complete pathological response increase perioperative morbidity risk in rectal cancer?

The optimal management of patients with clinical complete response after neoadjuvant treatment for rectal cancer is controversial. The aim of this study is to compare the morbidity between patients with locally advanced rectal cancer who have had a pathological complete response (pCR) or not after neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The study hypothesis was that pCR may impact the surgical complication rate. A retrospective cohort study was conducted of a prospectively maintained database in Australia and New Zealand, the Binational Colorectal Cancer Audit, that identified patients with locally advanced rectal cancer (<15 cm from anal verge) from 1 January 2007 to 31 December 2019. Patients were included if they had locally advanced rectal cancer and had undergone NCRT and proceeded to surgical resection. There were 4584 patients who satisfied the inclusion criteria, 65% being male. The mean age was 63 years and 11% had a pCR (ypT0N0). TME with anastomosis was performed in 67.8% of patients, and the majority of the cohort received long-course radiotherapy (81.7%). Both major and minor complications were higher in the TME without anastomosis group (17.3% vs. 14.7% and 30.6% vs. 20.8%, respectively), and the 30-day mortality was 1.31%. In the TME with anastomosis group, pCR did not contribute to higher rates of surgical complications, but male gender (p < 0.0012), age (p < 0.0001), preoperative N stage (p = 0.0092) and American Society of Anesthesologists (ASA) score ≥3 (p < 0.0002) did. In addition, pCR had no significant effect (p = 0.44) but male gender (p = 0.0047) and interval to surgery (p = 0.015) contributed to higher rates of anastomotic leak. In the TME without anastomosis cohort, the only variable that contributed to higher rates of complications was ASA score ≥3 (p = 0.033). Patients undergoing TME dissection for rectal cancer following NCRT showed no difference in complications whether they had achieved pCR or not.

The Impact on Survival of Neoadjuvant Treatment Interruptions in Locally Advanced Rectal Cancer Patients.

The standard oncologic treatment of locally advanced rectal cancer is long-course radio-chemotherapy followed by surgery and adjuvant chemotherapy. This can result in a lengthy total treatment duration, sometimes up to one year from the diagnosis. Interruptions to neoadjuvant treatment can occur for a variety of reasons, forced or unforced. The main purpose of this study is to analyze the survival data of locally advanced rectal cancer patients who received neoadjuvant treatment and to find a cut-off point showing exactly how many days of interruption of neoadjuvant treatment the risk of death or disease relapse increases. We conducted a retrospective study on 299 patients with locally advanced rectal cancer using survival analysis (Kaplan-Meier curve and Cox regression) to determine survival probabilities for overall survival, local control, and disease-free survival. Patients with 0 to 3 days of neoadjuvant therapy interruption had a higher overall survival probability compared to patients with 4 or more days (90.2% compared to 57.9%, p-value < 0.001), hazard ratio 5.89 (p < 0.001). Local control and disease-free survival had a higher probability in patients with 0-2 days of interruption compared to people with 3 or more days (94% vs. 75.4%, and 82.2% vs. 50.5%, respectively, both p-values < 0.001). Patients with tumoral or nodal downstaging experienced fewer days of interruption than patients with no downstage. These findings reinforce the need for radiation oncologists to be well-organized when starting neoadjuvant treatment for rectal cancer, in order to anticipate and prevent potential treatment interruptions and achieve the best therapeutic results.

Comparison of preoperative magnetic resonance imaging with postoperative pathology results in rectal cancer patients undergoing neoadjuvant therapy.

Locally advanced rectal cancer often requires neoadjuvant treatment (NAT) before surgical intervention. This study aimed to assess the concordance between preoperative magnetic resonance imaging (MRI) findings and postoperative pathology results after NAT in rectal cancer patients. A retrospective analysis of 52 patients who underwent NAT and subsequent surgery at Ankara Bilkent City Hospital between May 2019 and May 2023 was conducted. Demographics, preoperative MRIs, time intervals between NAT, MRI, and surgery, and postoperative pathology were assessed. The median age of the cohort was 59 years, with a male predominance (76.9%). Tumour T stage (κ = 0.157), lymph node stage (κ = 0.138), and circumferential resection margin (κ = 0.138) concordance showed poor agreement between post-neoadjuvant treatment (PNT) MRI and pathology. PNT MRI demonstrated a limited correlation with postoperative pathology. While preoperative MRI is commonly used for restaging after NAT in rectal cancer, our study highlights its limited concordance with postoperative pathology. The sensitivity and specificity metrics, although reported in the literature, should be interpreted alongside concordance assessments for a comprehensive evaluation.

A paradigm shift in the neoadjuvant treatment of rectal cancer: a single-institution real-world cohort study using the COVID-19 pandemic to compare clinical outcomes between long-course chemoradiotherapy and RAPIDO-style total neoadjuvant therapy

A paradigm shift in the neoadjuvant treatment of rectal cancer: a single-institution real-world cohort study using the COVID-19 pandemic to compare clinical outcomes between long-course chemoradiotherapy and RAPIDO-style total neoadjuvant therapy

Long-term efficacy of transanal local excision versus total mesorectal excision after neoadjuvant treatment for rectal cancer: A meta-analysis.

The purpose of this meta-analysis is to compare the long-term efficacy of transanal local excision (TLE) versus total mesorectal excision (TME) following neoadjuvant therapy for rectal cancer. The Web of Science, Pubmed, Medline, Embase, and the Cochrane Library were systematically searched for correlational research. The Newcastle-Ottawa Scale and the Cochrane risk of bias tool were used to assess the quality of cohort studies (CSs) and randomized controlled trials (RCTs), respectively. Statistically analyzed using RevMan5.4. A total of 13 studies, including 3 randomized controlled trials (RCTs) and 10 cohort studies (CSs), involving 1402 patients, were included in the analysis. Of these, 570 patients (40.66%) underwent TLE, while 832 patients (59.34%) underwent TME. In the meta-analysis of CSs, no significant difference was observed between the TLE group and TME group regarding 5-year overall survival (OS) and 5-year disease-free survival (DFS) (P > 0.05). However, the TLE group had a higher rates of local recurrence (LR) [risk ratio (RR) = 1.93, 95%CI (1.18, 3.14), P = 0.008] and a lower rates of 5-years local recurrence-free survival (LRFS) [hazard ratio (HR) = 2.79, 95%CI (1.04, 7.50), P = 0.04] compared to the TME group. In the meta-analysis of RCTs, there was no significant difference observed between the TLE group and TME group in terms of LR, 5-year OS, 5-year DFS, and 5-year disease-specific survival (P > 0.05). After undergoing neoadjuvant therapy, TLE may provide comparable 5-year OS and DFS to TME for rectal cancer. However, neoadjuvant therapy followed by TLE may has a higher LR and lower 5-year LRFS compared to neoadjuvant therapy followed by TME, so patients should be carefully selected. Neoadjuvant therapy followed by TLE may be a suitable option for patients who prioritize postoperative quality of life. However, the effectiveness of this approach requires further research to draw a definitive conclusion.

Methylglyoxal from gut microbes boosts radiosensitivity and radioimmunotherapy in rectal cancer by triggering endoplasmic reticulum stress and cGAS-STING activation

BackgroundPreoperative radiation therapy (preRT) is a fundamental aspect of neoadjuvant treatment for rectal cancer (RC), but the response to this treatment remains unsatisfactory. The combination of radiation therapy (RT) and...

Extramural Venous Invasion and Tumor Deposit at Diffusion-weighted MRI in Patients after Neoadjuvant Treatment for Rectal Cancer.

Background Diffusion-weighted (DW) imaging is useful in detecting tumor in the primary tumor bed in locally advanced rectal cancer (LARC) after neoadjuvant therapy, but its value in detecting extramural venous invasion (EMVI) and tumor deposit is not well validated. Purpose To evaluate diagnostic accuracy and association with patient prognosis of viable EMVI and tumor deposit on DW images in patients with LARC after neoadjuvant therapy using whole-mount pathology specimens. Materials and Methods This retrospective study included patients who underwent neoadjuvant therapy and surgery from 2018 to 2021. Innovative five-point Likert scale was used by two radiologists to independently evaluate the likelihood of viable EMVI and tumor deposit on restaging DW MRI scans in four axial quadrants (12 to 3 o'clock, 3 to 6 o'clock, 6 to 9 o'clock, and 9 to 12 o'clock). Diagnostic accuracy was assessed at both the per-quadrant and per-patient level, with whole-mount pathology as the reference standard. Weighted κ values for interreader agreement and Cox regression models for disease-free survival and overall survival analyses were used. Results A total of 117 patients (mean age, 56 years ± 12 [SD]; 70 male, 47 female) were included. Pathologically proven viable EMVI and tumor deposit was detected in 29 of 117 patients (25%) and in 44 of 468 quadrants (9.4%). Per-quadrant analyses showed an area under the receiver operating characteristics curve of 0.75 (95% CI: 0.68, 0.83), with sensitivity and specificity of 55% and 96%, respectively. Good interreader agreement was observed between the radiologists (κ = 0.62). Per-patient analysis showed sensitivity and specificity of 62% and 93%, respectively. The presence of EMVI and tumor deposit on restaging DW MRI scans was associated with worse disease-free survival (hazard ratio [HR], 5.6; 95% CI: 2.4, 13.3) and overall survival (HR, 8.9; 95% CI: 1.6, 48.5). Conclusion DW imaging using the five-point Likert scale showed high specificity and moderate sensitivity in the detection of viable extramural venous invasion and tumor deposits in LARC after neoadjuvant therapy, and its presence on restaging DW MRI scans is associated with worse prognosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Méndez and Ayuso in this issue.

Development and multicenter validation of a multiparametric imaging model to predict treatment response in rectal cancer

ObjectivesTo develop and validate a multiparametric model to predict neoadjuvant treatment response in rectal cancer at baseline using a heterogeneous multicenter MRI dataset.MethodsBaseline staging MRIs (T2W (T2-weighted)-MRI, diffusion-weighted imaging (DWI) / apparent diffusion coefficient (ADC)) of 509 patients (9 centres) treated with neoadjuvant chemoradiotherapy (CRT) were collected. Response was defined as (1) complete versus incomplete response, or (2) good (Mandard tumor regression grade (TRG) 1–2) versus poor response (TRG3-5). Prediction models were developed using combinations of the following variable groups:(1) Non-imaging: age/sex/tumor-location/tumor-morphology/CRT-surgery interval(2) Basic staging: cT-stage/cN-stage/mesorectal fascia involvement, derived from (2a) original staging reports, or (2b) expert re-evaluation(3) Advanced staging: variables from 2b combined with cTN-substaging/invasion depth/extramural vascular invasion/tumor length(4) Quantitative imaging: tumour volume + first-order histogram features (from T2W-MRI and DWI/ADC)Models were developed with data from 6 centers (n = 412) using logistic regression with the Least Absolute Shrinkage and Selector Operator (LASSO) feature selection, internally validated using repeated (n = 100) random hold-out validation, and externally validated using data from 3 centers (n = 97).ResultsAfter external validation, the best model (including non-imaging and advanced staging variables) achieved an area under the curve of 0.60 (95%CI=0.48–0.72) to predict complete response and 0.65 (95%CI=0.53–0.76) to predict a good response. Quantitative variables did not improve model performance. Basic staging variables consistently achieved lower performance compared to advanced staging variables.ConclusionsOverall model performance was moderate. Best results were obtained using advanced staging variables, highlighting the importance of good-quality staging according to current guidelines. Quantitative imaging features had no added value (in this heterogeneous dataset).Clinical relevance statementPredicting tumour response at baseline could aid in tailoring neoadjuvant therapies for rectal cancer. This study shows that image-based prediction models are promising, though are negatively affected by variations in staging quality and MRI acquisition, urging the need for harmonization.Key PointsThis multicenter study combining clinical information and features derived from MRI rendered disappointing performance to predict response to neoadjuvant treatment in rectal cancer.Best results were obtained with the combination of clinical baseline information and state-of-the-art image-based staging variables, highlighting the importance of good quality staging according to current guidelines and staging templates.No added value was found for quantitative imaging features in this multicenter retrospective study. This is likely related to acquisition variations, which is a major problem for feature reproducibility and thus model generalizability.

Comment on: Watch and wait after neoadjuvant treatment in rectal cancer: comparison of outcomes in patients with and without a complete response at first reassessment in the International Watch & Wait Database (IWWD).

Comment on: Watch and wait after neoadjuvant treatment in rectal cancer: comparison of outcomes in patients with and without a complete response at first reassessment in the International Watch & Wait Database (IWWD).

P-374 Total neoadjuvant treatment of rectal cancer by MRI-guided radiotherapy

P-374 Total neoadjuvant treatment of rectal cancer by MRI-guided radiotherapy

Develop and validate a radiomics space-time model to predict the pathological complete response in patients undergoing neoadjuvant treatment of rectal cancer: an artificial intelligence model study based on machine learning

ObjectiveIn this study, we aimed to investigate the predictive efficacy of magnetic resonance imaging (MRI) radiomics features at different time points of neoadjuvant therapy for rectal cancer in patients with pathological complete response (pCR). Furthermore, we aimed to develop and validate a radiomics space–time model (RSTM) using machine learning for artificial intelligence interventions in predicting pCR in patients.MethodsClinical and imaging data of 83 rectal cancer patients were retrospectively analyzed, and the patients were classified as pCR and non-pCR patients according to their postoperative pathological results. All patients received one MRI examination before and after neoadjuvant therapy to extract radiomics features, including pre-treatment, post-treatment, and delta features. Delta features were defined by the ratio of the difference between the pre- and the post-treatment features to the pre-treatment feature. After feature dimensionality reduction based on the above three feature types, the RSTM was constructed using machine learning methods, and its performance was evaluated using the area under the curve (AUC).ResultsThe AUC values of the individual basic models constructed by pre-treatment, post-treatment, and delta features were 0.771, 0.681, and 0.871, respectively. Their sensitivity values were 0.727, 0.864, and 0.909, respectively, and their specificity values were 0.803, 0.492, and 0.656, respectively. The AUC, sensitivity, and specificity values of the combined basic model constructed by combining pre-treatment, post-treatment, and delta features were 0.901, 0.909, and 0.803, respectively. The AUC, sensitivity, and specificity values of the RSTM constructed using the K-Nearest Neighbor (KNN) classifier on the basis of the combined basic model were 0.944, 0.871, and 0.983, respectively. The Delong test showed that the performance of RSTM was significantly different from that of pre-treatment, post-treatment, and delta models (P < 0.05) but not significantly different from the combined basic model of the three (P > 0.05).ConclusionsThe RSTM constructed using the KNN classifier based on the combined features of before and after neoadjuvant therapy and delta features had the best predictive efficacy for pCR of neoadjuvant therapy. It may emerge as a new clinical tool to assist with individualized management of rectal cancer patients.

Watch and wait after neoadjuvant treatment in rectal cancer: comparison of outcomes in patients with and without a complete response at first reassessment in the International Watch & Wait Database (IWWD).

In rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment. This registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for near-cCR groups based on the response evaluation according to modality. A total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI. Oncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment.

Accurate tumor segmentation and treatment outcome prediction with DeepTOP

BackgroundAccurate outcome prediction prior to treatment can facilitate trial design and clinical decision making to achieve better treatment outcome. MethodWe developed the DeepTOP tool with deep learning approach for region-of-interest segmentation and clinical outcome prediction using magnetic resonance imaging (MRI). DeepTOP was constructed with an automatic pipeline from tumor segmentation to outcome prediction. In DeepTOP, the segmentation model used U-Net with a codec structure, and the prediction model was built with a three-layer convolutional neural network. In addition, the weight distribution algorithm was developed and applied in the prediction model to optimize the performance of DeepTOP. ResultsA total of 1889 MRI slices from 99 patients in the phase III multicenter randomized clinical trial (NCT01211210) on neoadjuvant treatment for rectal cancer was used to train and validate DeepTOP. We systematically optimized and validated DeepTOP with multiple devised pipelines in the clinical trial, demonstrating a better performance than other competitive algorithms in accurate tumor segmentation (Dice coefficient: 0.79; IoU: 0.75; slice-specific sensitivity: 0.98) and predicting pathological complete response to chemo/radiotherapy (accuracy: 0.789; specificity: 0.725; and sensitivity: 0.812). DeepTOP is a deep learning tool that could avoid manual labeling and feature extraction and realize automatic tumor segmentation and treatment outcome prediction by using the original MRI images. ConclusionDeepTOP is open to provide a tractable framework for the development of other segmentation and predicting tools in clinical settings. DeepTOP-based tumor assessment can provide a reference for clinical decision making and facilitate imaging marker-driven trial design.

Neoadjuvant Treatment for Rectal Cancer and Nonoperative Management/Total Neoadjuvant Therapy

AbstractTreatment of locally advanced rectal cancer remains one of the most challenging in colorectal surgery. It has had an evolving landscape over the past three decades. This review describes the introduction of total neoadjuvant therapy—a term aimed to describe an approach where both systemic chemotherapy and chemoradiation are administered in the preoperative setting. This novel strategy has come to the fore with the strength of well-documented results of recent trials. Its implementation has begun globally, but long-term outcomes and data analysis to identify optimal schedules are eagerly awaited.

Toxicities and outcomes of neoadjuvant treatment in elderly patients with locally advanced rectal cancer: A scoping review.

91 Background: Neoadjuvant treatment (NAT) followed by surgery has become the standard treatment for locally advanced rectal cancer (LARC). This scoping review aims to assess the toxicity and outcomes of the currently available NAT of rectal cancer in elderly patients with age-associated frailty. Methods: Six thousand seventy-nine records were identified on Ovid Medline, Embase, Cochrane database, and CINAHL. Two independent reviewers screened the articles. Fifteen articles were identified through a hand search. Articles on NAT in LARC in elderly patients were included. Results: Thirty-three studies from 2005 to 2022 met inclusion criteria, including 27 retrospective reviews, 4 clinical trials (Phase 1 and 2) and 2 prospective studies; 5 were multicentred. The median age of the sample was 70-75 in 24 studies and 76-83 in 11 studies. One study examined only patients above 80. Twenty-four studies examined NAT with long course concurrent chemoradiotherapy (LCCRT), 5 examined both LCCRT and RT alone, 3 examined short-course radiotherapy (SCRT), one examined SCRT with sequential chemotherapy (CT), and one study examined neoadjuvant CT followed by LCCRT. Concurrent CT with 5 FU-based treatments was given in 23 studies with either intravenous or oral, and oxaliplatin was added to 5 FU in 10 studies. Interruption of concurrent treatment was reported with dose reduction, delay or discontinuation in 26 studies. Diarrhea, nausea/vomiting and radiation dermatitis were reported as significant side effects (G3 -4), with G3-4 diarrhea reported in 18 studies. Haematological toxicities were very frequent, with a 20-60% rate in the studies. No dose interruption of RT was required in the three studies that included only SCRT, except for one patient. The study on CT followed by LCCRT showed that CT was completed in 82% and LCCRT in 76% of patients. A preliminary result of PRODIGE 42-GERICO 12 NACRE, a randomised trial comparing SCRT with chemoradiotherapy (CRT), showed that 14% of patients in the CRT arm did not receive all of the planned treatment compared to 0% in SCRT arm, and the 6 months death rate was 10.0% in CRT arm and 3.92% in SCRT. Conclusions: Toxicities are frequently reported with Neoadjuvant LCCRT in the elderly and lead to treatment interruption. SCRT is well tolerated and probably associated with better survival (pending final results of the NACRE trial). Studies in this scoping review are over-represented by retrospective studies, and we suggest that future clinical trials focus on elderly patients to investigate treatment strategies with fewer toxicities.

Rectal Sparing Approaches after Neoadjuvant Treatment for Rectal Cancer: A Systematic Review and Meta-Analysis Comparing Local Excision and Watch and Wait.

Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to perform a systematic review of the literature, and to compare rectal-sparing approaches, in terms of rectum-preservation rate, local control, and distant recurrences. A systematic review and meta-analysis were performed of studies published until July 2022 (PROSPERO, registration CRD42022341480), and the quality of evidence was assessed using a GRADE approach. Seven retrospective studies and one prospective trial were included. In six studies, patients were treated with standard long-course nCRT, and in two with Total Neoadjuvant Therapy (TNT). Overall, there were 213 and 188 patients in WW and LE group, respectively, and no difference was found between WW and LE when considering rectum-preservation rate (OR 0.80 95%CI 0.31-2.01, p = 0.63), local disease (OR 1.60 95%CI 0.75-3.42, p = 0.22), locoregional failure (OR 0.85 95%CI 0.20-3.66, p = 0.83) and distant recurrence (OR 0.76 95%CI 0.37-1.55, p = 0.45). Studies directly comparing WW and LE are still lacking, even though no differences between WW and LE in terms of rectum-preservation, local control, and distant recurrences have been found.

Extralevator Abdominoperineal Excision (ELAPE) is Not Superior to Abdominoperineal Excision (APE) in the Era of Neoadjuvant Treatment in Rectal Cancer.

Aim: To evaluate the effect of extralevator abdominoperineal excision of the rectum (ELAPE) on the circumferential resection margin (CRM) and overall survival in comparison to standard abdominoperineal excision of the rectum (APE) in patients with advanced rectal cancer. Material and Methods: This retrospective study encompasses patients with advanced rectal cancer operated on with two different methods: prone Jack-Knife position ELAPE and APE. In part of them, neoadjuvant chemoradiation was conducted. Postoperative patient, tumor, and outcome data were analyzed in terms of differences in CRM positivity and overall survival. Results: Of 67 patients treated with either APE (52) or ELAPE (15), 43 were male and 24 were female. Neoadjuvant treatment was conducted on 49 of the total patients. Complete pathological response (T0) was achieved in 3 patients. Positive CRM was reported in 7 patients (11.5 %), 3 in ELAPE and 4 in APE group (p = 0.348). The overall postoperative complication rate was 56.7%. Mean survival period was 42.2 months. Overall survival rate for both groups was 67.2 %. No statistical differences were seen between the ELAPE and APE procedure in terms of overall survival (p = 0.483). Conclusions: Differences between the use of ELAPE and APE in terms of CRM positivity and overall survival were not statistically significant. Therefore, we conclude that ELAPE is not superior to standard APE in the treatment of advanced rectal cancer.