A nomogram for predicting the overall survival in rectal cancer patients after total neoadjuvant therapy.

BACKGROUND: Total neoadjuvant therapy (TNT) has been recommended by the National Comprehensive Cancer Network for treating locally advanced rectal cancer (LARC), but extremely rare studies have focused on establishing nomograms to predict the prognosis in these patients after TNT. We aimed to develop a nomogram to predict overall survival (OS) in rectal cancer patients who underwent TNT. METHODS: In retrospective cohort study, we extract the data of the rectal cancer patients from the SEER database between 2010 and 2015, including demographic information and tumor characteristics. The cohort was divided into training set and validation set based on a ratio of 7:3. Univariate logistic regression analysis was utilized for the comparison of variables in training set. Candidate variables with P < 0.1 in training set was entered into the best subset selection, LASSO regression and Boruta feature selection. Finally, the selected variables significantly associated with the 3-year, 5-year, and 8-year OS were used to build a nomogram, followed by validation using receiver operating characteristic (ROC) curve, area under the curve (AUC), and calibration curve. RESULTS: A total of 3265 rectal cancer patients (training set: 2285; test set: 980) were included in the present study. A nomogram was developed to predict the 3-year, 5-year, and 8-year OS based on age, household income, total number of in situ/malignant tumors, CEA, T stage, N stage and perineural invasion. The nomogram showed good efficiency in predicting the 3-year, 5-year and 8-year OS with good AUC for the training set and test set, respectively. CONCLUSION: We established a nomogram for predicting the 3-year, 5-year, and 8-year OS of the rectal cancer patients, which showed good prediction efficiency for the OS after TNT.

Young-Onset Rectal Cancer: Is It for Real?

The incidence of early-onset colorectal cancer has been rising over the last two decades. Tumors in young patients have distinct features compared to older patients. They predominantly arise in the distal colon and rectum and have poor histological features. Patients tend to present at a more advanced stage and be exposed to more aggressive management approaches; however, this has not translated into a significant survival benefit compared to their older counterparts. This chapter will share current evidence on risk factors and management options for early onset colorectal cancer with a focus on rectal cancer.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms: A Chinese multicenter study of 12-year experience.

BACKGROUND: There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). AIM: To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. METHODS: Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. RESULTS: A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. CONCLUSION: The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.

MRI Tumor Regression Response to Neoadjuvant Chemotherapy Alone without Radiation for Rectal Adenocarcinoma.

Background Neoadjuvant chemotherapy (NCT) is gaining acceptance for the management of locally advanced rectal cancer (LARC) in patients without negative prognostic factors. However, the value of MRI in evaluating tumor response after NCT remains unclear. Purpose To investigate the accuracy of MRI in assessing pathologic complete response in participants with LARC who underwent surgery after NCT without radiation. Materials and Methods A retrospective imaging substudy was conducted within two consecutive prospective clinical trials: the expanded phase II trial (from December 2017 to May 2021) and the COPEC trial (comparison of tumor response to two or four cycles of neoadjuvant chemotherapy alone, ongoing from August 2021). All included participants received four cycles of capecitabine combined with oxaliplatin (or CAPOX) before surgery. Three radiologists who were blinded to the clinicopathologic data independently evaluated the tumor response using five methods, namely, MR tumor regression grade (MR-TRG) alone, diffusion-weighted imaging (DWI) alone, DWI-modified MR-TRG (DWImodMR-TRG), MRI complete response, and radiologic neoadjuvant response score. With pathologic assessment serving as the reference standard, the positive and negative predictive values, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined to evaluate the accuracy and performance of these models. The AUCs of the models were compared using the DeLong test. Results A total of 224 participants were included, comprising 119 from the expanded phase II trial (median age, 61 years [IQR, 53-67]; 89 male) and 105 from the COPEC trial (median age, 59 years [IQR, 53-67]; 65 male). MR-TRG, DWI, DWImodMR-TRG, MRI complete response, and the radiologic neoadjuvant response score were associated with pathologic complete response. DWImodMR-TRG achieved the highest AUC of 0.90 (95% CI: 0.85, 0.95), with a specificity of 89% (162 of 182) and a negative predictive value of 93% (162 of 174). Conclusion MRI-based models were accurate for determining pathologic complete response in participants with LARC following NCT. DWI improved the predictive performance of MRI-based assessment. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Santiago and Shur in this issue.

Deciphering the Dilemma: Choosing the Optimal Total Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer.

Rectal cancer management has evolved significantly, particularly with neoadjuvant treatment strategies. This narrative review examines the development and effectiveness of these therapies for locally advanced rectal cancer (LARC), highlighting the historical quest that led to current neoadjuvant alternatives. Initially, trials showed the benefits of adding radiotherapy (RT) and chemotherapy (CT) to surgery, reducing local recurrence (LR). The addition of oxaliplatin to chemoradiotherapy (CRT) further improved outcomes. TNT integrates chemotherapy and radiotherapy preoperatively to enhance adherence, timing, and systemic control. Key trials, including PRODIGE 23, CAO/ARO/AIO 12, OPRA, RAPIDO, and STELLAR, are analyzed to compare short-course and long-course RT with systemic chemotherapy. The heterogeneity and difficulty in comparing TNT trials due to different designs and outcomes are acknowledged, along with their promising long-term results. On the other hand, it briefly discusses the potential for non-operative management (NOM) in select patients, a strategy gaining traction due to favorable outcomes in specific trials. As a conclusion, this review underscores the complexity of rectal cancer treatment, emphasizing individualized approaches considering patient preferences and healthcare resources. It also highlights the importance of interpreting impressive positive or negative results with caution due to the variability in study designs and patient populations.

Mucinous histology is a negative predictor of neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC). Mucinous adenocarcinoma (MAC) is a potential poor prognosis subgroup of rectal cancer. However, the predictive value of MAC in NCRT treatment of LARC is controversial. METHODS: A comprehensive literature search of PubMed, Embase, and the Cochrane Library was performed. All studies examining the effect of MAC on CRT response in LARC were included. Outcomes of MAC were compared with non-specific adenocarcinoma (AC) by using random-effects methods. Data were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The main outcomes were the rates of pathological complete response (pCR), tumor and nodal down-staging, positive resection margin rate, local recurrence, and overall mortality. RESULTS: Fifteen studies containing comparative data on outcomes in a total of 9,238 patients receiving NCRT for LARC were eligible for inclusion. MAC had a reduced rate of pCR (OR, 0.38; 95% CI, 0.18-0.78) and tumor down-staging (OR, 0.31; 95% CI, 0.22-0.44) following NCRT compared with AC. MAC did not significantly affect nodal down-staging (OR, 0.42; 95% CI, 0.16-1.12) after NCRT. CONCLUSION: MAC of LARC was found to be a negative predictor of response to NCRT with lower rates of pCR and tumor down-staging for LARC. The nodal down-staging of MAC was relatively lower than that of AC, although the differences were not statistically significant.

NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024.

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.

Arterial Mucosal Linear Enhancement at Contrast-enhanced MRI to Exclude Residual Tumor after Neoadjuvant Chemotherapy and Radiation Therapy for Rectal Cancer.

Background A watch-and-wait regimen for locally advanced rectal cancer after neoadjuvant chemotherapy and radiation therapy (NCRT) relies on identifying complete tumor response. However, the concordance between a complete response at combined T2-weighted and diffusion-weighted MRI (T2DWI) and pathologic complete response (pCR; ie, ypT0N0) in the tumor is unsatisfactory. Purpose To assess whether identification of mucosal linear enhancement (MLE) at arterial-phase contrast-enhanced (CE) T1-weighted MRI is associated with ypT0 status in patients with locally advanced rectal cancer after NCRT and to evaluate whether combining MLE at CE T1-weighted MRI and negative lymph node metastasis (LNM) at T2DWI can improve identification of pCR. Materials and Methods This retrospective study included patients with locally advanced rectal cancer who underwent total mesorectal excision after NCRT between July 2020 and July 2023 at a tertiary referral academic center. Restaging MRI included T2DWI and arterial-phase CE T1-weighted MRI for primary tumor assessment and T2DWI for evaluation of LNM status. Imaging features associated with ypT0 status were identified at multivariable regression analysis. Results In total, 239 patients (mean age, 58 years ± 12 [SD]; 180 male patients) were assessed. MLE was more common in the ypT0 group than in the ypT1-4 group after NCRT (73% vs 4%, respectively; P < .001). MLE was associated with higher odds of ypT0 status in an adjusted analysis (odds ratio, 137; 95% CI: 25, 767; P < .001). The combination of MLE and negative LNM status achieved an area under the receiver operating characteristic curve of 0.84 (95% CI: 0.79, 0.88) for pCR. Conclusion MLE at CE MRI was associated with higher odds of complete tumor response. Combining MLE and negative LNM status showed good performance for identifying complete tumor response and may exclude residual tumors after NCRT in patients with locally advanced rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Schoellnast in this issue.

Predictive value of flexible proctosigmoidoscopy and laboratory findings for complete clinical responses after neoadjuvant chemoradiotherapy in patients with locally advanced primary rectal cancer: a retrospective cohort study.

PURPOSE: Colorectal cancer is the second leading cause of cancer death worldwide. Standard treatments for locally advanced rectal cancer include neoadjuvant chemoradiotherapy and total mesorectal excision (TME), which are associated with significant morbidity. After neoadjuvant therapy, one-third of patients achieve a pathological complete response (pCR) and are eligible for a watch-and-wait approach without TME. The purpose of this study was to determine the potential predictors of pCR before surgery. METHODS: The demographic, clinical, and endoscopic data of 119 patients with primary locally advanced rectal cancer without distant metastasis who underwent restaging endoscopy and TME 6-8 weeks after the end of neoadjuvant therapy were collected. The absence of tumor cells in the histological examination of the TME specimen after neoadjuvant therapy was considered pCR. Binary logistic regression and receiver operating characteristic curves were utilized for analysis. RESULTS: According to the multivariate logistic regression analysis, flattening of marginal tumor swelling (p value < 0.001, odds ratio = 100.605) emerged as an independent predictor of pCR in rectal cancer patients. Additionally, receiver operating characteristic curve analysis revealed that lower preoperative carcinoembryonic antigen and erythrocyte sedimentation rate levels predict pCR, with cutoffs of 2.15 ng/ml and 19.0 mm/h, respectively. CONCLUSION: Carcinoembryonic antigen and erythrocyte sedimentation rate, along with the presence of flattening of marginal tumor swelling, can predict pCR after neoadjuvant chemoradiotherapy in patients with primary rectal cancer. These factors offer a potential method for selecting candidates for conservative treatment based on endoscopic and laboratory findings.

Assessing neoadjuvant therapy recommendations in 19 national and international guidelines for rectal cancer.

BACKGROUND:  Treatment guidelines belong to the most authoritative sources of evidence-based medicine and are widely implemented by health-care providers. Rectal cancer with an annual incidence of over 730,000 new cases and nearly 340,000 deaths worldwide, remains a significant therapeutic challenge. The total mesorectal excision (TME) leads to a dramatic improvement of local control. The addition of neoadjuvant treatment has been proposed to offer further advancement. However, this addition results in significant functional impairment and a decline in the quality of life. METHODS: This review critically assesses whether the recommendation for neoadjuvant treatment in current international guidelines is substantiated. A comprehensive search was conducted in July 2022 in PubMed resulting in 988 papers published in English between 2012 and 2022. After exclusions and proofs 19 documents remained for further analysis. RESULTS: Of the 19 guidelines considered in this review, 11 do not recommend upfront surgery, and 12 do not address the issue of functional impairment following multimodal treatment. The recommendation for neoadjuvant therapy relies on outdated references, lacking differentiated strategies based on current utilisation of MRI staging; numerous guidelines recommend neoadjuvant treatment also to subgroups of patients, who may not need this therapy. Also statements regarding conflicts of interest are often not presented. CONCLUSIONS: An immediate and imperative step is warranted to align the recommendations with the latest available evidence, thereby affording rectal cancer patients a commensurate standard of care. A meticulous assessment of the guideline formulation process has the potential to avert heterogeneity in the future.

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision.

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. BACKGROUND: The standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision. PURPOSE: To evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision. METHODS: Retrospective study including patients with rectal cancer T3-4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradiotherapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses. RESULTS: 270 patients were included, 57.8% male and mean age 61.7 (30‒88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5‒86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001). CONCLUSION: Local recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.

Rectal adenocarcinoma: Ex vivo 9.4T MRI-correlation with histopathologic treatment response to neoadjuvant chemoradiotherapy.

OBJECTIVES: To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo. METHODS: Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether-filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI-based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings. RESULTS: The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images. CONCLUSION: Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.

Response of various histological types of locally advanced rectal cancer to neoadjuvant multimodality therapy.

Objectives: To determine the response of various histological types of locally advanced rectal cancer to neoadjuvant multimodality therapy. METHODS: The non-randomised, quasi-experimental retrospective cohort study was conducted at the Combined Military Hospital, Rawalpindi, Pakistan, and comprised data of patients treated between January 1, 2020, to September 30, 2021. The data retrieved related to histologically proven and locally advanced rectal cancer patients aged 18-70 years receiving neoadjuvant chemoradiotherapy. Radiotherapy dose was 45 gray to pelvis with a boost to gross tumour of 5.4 gray in 3 fractions by using volumetric arc therapy concurrently with capecitabine 625mg/m² daily. A magnetic resonance imaging scan of pelvis with contrast was done at 5-10 weeks before surgery. Histological response to neoadjuvant treatment of various histological types was evaluated using the Rectal Cancer Regression Grade. Data was analysed using SPSS 22. RESULTS: Of the 182 patients evaluated, 108(59.34%) were included; 64(59.3%) males and 44(40.7%) females. The overall mean age was 45.4±5.2 years. Regression status was grade 1 in 24(22%) patients, grade 2 in 43(40%) and grade 3 in 41(38%) (p=0.074). There were 12(11.11%) patients with signet ring cell and 10(83.3%) showed pathological tumour regression. There were 17(15.74%) patients with mucinous variant, and 12(70.5%) had tumour regression. There were 79(73.15%) patients with adenocarcinoma, and 59(74.6%) of them showed tumour regression. . CONCLUSIONS: There was less tumour regression in mucinous and signet ring cell variants of adenocarcinoma. Modification and intensification of neoadjuvant therapy may be required in such histologies.

Magnetic resonance imaging radiomics-based prediction of severe inflammatory response in locally advanced rectal cancer patients after neoadjuvant radiochemotherapy.

PURPOSE: To predict severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced rectal cancer (RC) patients using magnetic resonance imaging (MRI) radiomics models. METHODS: This retrospective study included patients who underwent radical surgery for RC cancer after neoadjuvant radiochemotherapy between July 2017 and December 2019 at XXX Hospital. MRI radiomics features were extracted from T2WI images before (pre-nRCT-RF) and after (post-nRCT-RF) neoadjuvant radiochemotherapy, and the variation of radiomics features before and after neoadjuvant radiochemotherapy (delta-RF) were calculated. Eight, eight, and five most relevant features were identified for pre-nRCT-RF, post-nRCT-RF, and delta-RF, respectively. RESULTS: Eighty-six patients were included and randomized 3:1 to the training and test set (n = 65 and n = 21, respectively). The prediction model based on delta-RF had areas under the curve (AUCs) of 0.80 and 0.85 in the training and test set, respectively. A higher rate of difficult operations was observed in patients with severe inflammation (65.5% vs. 42.9%, P = 0.045). CONCLUSION: The prediction model based on MRI delta-RF may be a useful tool for predicting severe inflammatory response after neoadjuvant radiochemotherapy in locally advanced RC patients.