Search Results (35)

Treatment of locally advanced rectal cancer (LARC), clinical stages II–III, typically involves multimodal treatment options. Over the past decade, the role of radiation therapy as a neoadjuvant treatment for LARC has evolved and is currently a part of total neoadjuvant therapy (TNT). Some recently published studies advocate for the omission of radiation therapy entirely, while others report on a non-operative approach that emphasizes the use of higher radiation therapy doses. This review aims to evaluate the latest literature on the current role of radiation therapy in the management of LARC, with a discussion of how to best select the most appropriate treatment protocol based on individual patient and tumor characteristics, comorbidities, and personal needs and preferences. Full article

Background/Objectives: Nonoperative management (NOM) of patients with locally advanced rectal cancer (LARC) who achieve a complete clinical response (cCR) to total neoadjuvant therapy (TNT) has been shown to be oncologically safe and is an attractive treatment option for patients. However, identifying responders to TNT that may benefit from nonoperative management is clinically challenging. Circulating tumor DNA (ctDNA) testing has shown promise in detecting minimal residual disease but has not yet been studied extensively within this clinical context. Methods: This is a single-institution retrospective case series study of LARC patients treated with TNT from 2019 to 2023 who underwent ctDNA testing as an adjunct to standard clinical response assessments. Results: A total of 28 patients had ctDNA testing as part of their response assessments after TNT. In total, 9 patients had positive ctDNA, and 19 patients had negative ctDNA during surveillance. Baseline characteristics of these two groups were not different. In this study, 6/9 (67%) patients who had positive ctDNA required surgery for residual rectal cancer, whereas only 4/19 (21%) patients who had negative ctDNA required surgery (p = 0.035). Conclusions: ctDNA testing has the potential to detect MRD in LARC patients treated with TNT. Full article

Locally advanced rectal cancer (LARC) remains a major clinical challenge due to its high risk of local recurrence and distant metastasis. Although total mesorectal excision (TME) has been established as the gold standard surgical approach, high recurrence rates associated with surgery alone have driven the development of multimodal preoperative strategies, such as radiotherapy and chemoradiotherapy. More recently, total neoadjuvant therapy (TNT)—which integrates systemic chemotherapy and radiotherapy prior to surgery—and non-operative management (NOM) for patients who achieve a clinical complete response (cCR) have further expanded treatment options. These advances aim not only to improve oncologic outcomes but also to enhance quality of life (QOL) by reducing long-term morbidity and preserving organ function. However, several unresolved issues persist, including the optimal sequencing of therapies, precise risk stratification, accurate evaluation of treatment response, and effective surveillance protocols for NOM. The advent of molecular biomarkers, next-generation sequencing, and artificial intelligence (AI) presents new opportunities for individualized treatment and more accurate prognostication. This narrative review provides a comprehensive overview of the current status of preoperative treatment for LARC, critically examines emerging strategies and their supporting evidence, and discusses future directions to optimize both oncological and patient-centered outcomes. By integrating clinical, molecular, and technological advances, the management of rectal cancer is moving toward truly personalized medicine. Full article

Traditionally, the therapeutic approach to rectal cancer has involved neoadjuvant chemoradiotherapy followed by surgical resection, and, in some cases, adjuvant chemotherapy. This study aims to present current advances and ongoing controversies in the management of patients with locally advanced rectal cancer (LARC), with a particular focus on clarifying the role of total neoadjuvant therapy (TNT) in contemporary treatment strategies. Methods: We conducted a systematic literature review in Medline/PubMed using various keyword combinations, including “rectal cancer/neoplasia” and“therapy” or “neoadjuvant therapy” or “TNT”, and included articles published between 2015 and 2025. Results: The association of neoadjuvant radiochemotherapy with preoperative systemic chemotherapy has led to the current concept of total neoadjuvant therapy. The advantages of preoperative chemotherapy include better patient compliance, a decrease in the rate of local recurrence and distant metastases via the early destruction of infra-clinical micrometastases, and higher rates of pathological complete response. All of these have led to the inclusion of this strategy in treatment guidelines for patients with locally advanced rectal cancer. Conclusions: However, the selection of patients with advanced rectal tumors for optimal therapy requires comprehensive imaging assessments, molecular and genetic testing, and a multidisciplinary team to determine the most appropriate total neoadjuvant therapy approach. Full article

Rectal cancer management necessitates a rigorous multidisciplinary strategy, emphasizing precise staging and detailed risk stratification to inform optimal therapeutic decision-making. Obtaining an accurate histological diagnosis before initiating treatment is essential. Comprehensive staging integrates clinical evaluation, thorough medical history analysis, assessment of carcinoembryonic antigen (CEA) levels, and computed tomography (CT) imaging of the abdomen and thorax. High-resolution pelvic magnetic resonance imaging (MRI), utilizing dedicated rectal protocols, is critical for identifying recurrence risks and delineating precise anatomical relationships. Endoscopic ultrasound further refines staging accuracy by determining the tumor infiltration depth in early-stage cancers, while preoperative colonoscopy effectively identifies synchronous colorectal lesions. In early-stage rectal cancers (T1–T2, N0, and M0), radical surgical resection remains the standard of care, although transanal local excision can be selectively indicated for certain T1N0 tumors. In contrast, locally advanced rectal cancers (T3, T4, and N+) characterized by microsatellite stability or proficient mismatch repair are optimally managed with total neoadjuvant therapy (TNT), which combines chemoradiotherapy with oxaliplatin-based systemic chemotherapy. Additionally, tumors exhibiting high microsatellite instability or mismatch repair deficiency respond favorably to immune checkpoint inhibitors (ICIs). The evaluation of tumor response following neoadjuvant therapy, utilizing MRI and endoscopic assessments, facilitates individualized treatment planning, including non-operative approaches for patients with confirmed complete clinical responses who comply with rigorous follow-up. Recent advancements in molecular characterization, targeted therapies, and immunotherapy highlight a significant evolution towards personalized medicine. The effective integration of these innovations requires enhanced interdisciplinary collaboration to improve patient prognosis and quality of life. Full article

Background and Objectives: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC). Methods: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous. Results: Twelve studies (n = 1354 unique patients, median sample = 73, range 22–735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a “butyrate-rich” baseline profile was 44% (95% CI 35–54) versus 21% (95% CI 15–29) in controls (I² = 18%). Conclusions: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment. Full article

Background: The rectal cancer treatment paradigm is rapidly changing with the advent of total neoadjuvant therapy and non-operative management approaches in responders. A good clinical response to neoadjuvant treatment documented by magnetic resonance imaging, endoscopy and clinical examination corresponds, to a large extent, to a pathologic complete response, as assessed in surgical specimens. Methods: We undertook a systematic review and meta-analysis on the MRI-based omics approach to predicting pathologic complete responses. Results: A total of 29 studies with relevant data available reporting on a total of 4486 patients were eligible for meta-analysis. The calculated values for the area under the curve in receiver operator curves of diagnostic accuracy for radiomics-only and radiomics-combined-with-clinical-data models were 0.80 and 0.88, respectively, for studies incorporating baseline imaging data only. The value for studies using delta radiomic data was 0.86, and those for studies using data from the post-neoadjuvant setting were 0.75 and 0.83, respectively, for the radiomics-only and radiomics-combined-with-clinical-data models. Conclusions: Radiomics-based prediction models for pathologic complete response assessment might further enable individualized treatment decisions to be made in patients with rectal cancer. Full article

Background: The incidence of cancer in older patients is high, reaching 2.3 million world-wide in 2018 for patients aged over 80. Because the characteristics of this population make therapeutic choices difficult, co-management between geriatricians and other cancer specialists has gradually become essential. Methods: This narrative review aims to synthesize current data on the contribution of geriatric assessment in the management of elderly patients with non-colorectal digestive cancers. Oncogeriatric assessment is multi-domain, including the evaluation of co-morbidities, autonomy, nutrition, cognition, mood, and functional assessment. Results: Oncogeriatric parameters are predictive of mortality and adverse events. In the peri-operative phase of non-colorectal digestive cancer surgical management, geriatric management can assist in the decision-making process, identify frailties, and arrange a specific and personalized trimodal preoperative rehabilitation program, including nutritional management, adapted physical activity, and psychological care. Its aim is to limit the risks of confusion and of decompensation of comorbidities, mainly cardio-respiratory, which is associated with the highest morbidity in biliary-pancreatic surgery for older adults, facilitate recovery of previous autonomy when possible, and shorten hospital stay. For metastatic cancers, or during multimodal management, such as peri-operative chemotherapy for localized gastric cancers or pre-operative radio-chemotherapy for oesophageal or rectal cancers, specific assessment of the tolerance of chemotherapy is necessary. Neuropathic toxicity and chemobrain have a greater impact on elderly patients, with an increased loss of autonomy. Joint geriatric management can reduce the rate of grade 3–5 adverse effects of chemotherapy in particular and improve quality of life. Conclusions: Co-management between geriatricians and other specialties should be encouraged wherever possible. Full article

Background/Objectives: Predictive tools are needed to assess the response to treatment and guide treatment decisions for locally advanced rectal cancer (LARC). This study explores the value of combining the immunoscore (IS) and magnetic resonance imaging tumor regression grade (mrTRG) with pathologic and radiologic neoadjuvant rectal (NAR) scores in predicting pathologic complete response (pCRs). Methods: The scores were assessed for patients with LARC enrolled in the Averectal study (NCT03503630), who received five fractions of short-course radiotherapy, followed by six cycles of mFOLFOX-6 plus avelumab, and total mesorectal excision. The IS was calculated using the mean density percentiles of CD3- and CD8-positive T-cells on baseline biopsy samples. Baseline and post-treatment MRIs were reviewed to measure the mrTRG. NAR scores were calculated using the pre-treatment T stage and post-treatment pathologic and radiologic N and T stages. Results: Fifteen out of thirty-five patients whose data were available achieved pCR (42.8%), and seven out of fourteen patients with mrTRG = 1 (complete response) attained pCR. In patients with both a mrTRG = 1 and high IS, the pCR rate was 66.7% (6/9). All of the patients who achieved pCR had a low or intermediate pathologic NAR score with a significant correlation between pCR and pathologic NAR scores (p < 0.0001). Both pathologic and radiologic NAR scores were correlated with overall survival and disease-free survival. Conclusions: The IS can supplement the mrTRG to better predict TNT outcomes, along with the use of the NAR score. This combination could potentially help with patient selection for non-operative management and guide treatment strategies for those with different recurrence risks. Full article

Background/Objectives: The management of locally advanced rectal cancer has evolved significantly, shaped by advances in multimodal neoadjuvant therapy and a growing emphasis on organ preservation through the watch-and-wait approach. These advancements, however, introduce complex treatment decisions that require careful consideration by both patients and clinicians. Methods: This narrative review explores the evolution of the management of locally advanced rectal cancer and the role of shared decision-making in guiding treatment decisions, particularly for patients facing decisions between surgical resection and watch-and-wait. Additionally, it discusses the development of tools to aid in shared-decision making, current challenges in implementing shared decision-making and future directions for improvement patient centered care in locally advanced rectal cancer management. Results: Considerations for decision making include anatomical considerations that influence surgical options, the potential benefits and risks of watch-and-wait versus surgical resection of the rectum, and the impact of treatment on bowel, urinary, and sexual function. Additionally, patients must weigh the long-term implications of their choices on quality of life. Conclusions: Shared decision-making has emerged as a critical component of patient-centered care and ensures that treatment decisions align with patients’ values and priorities. Given the preference-sensitive nature of the management of locally advanced rectal cancer, shared decision-making plays an important role in helping patients navigate these decisions. Full article

Colorectal cancer (CRC) is the second most prevalent cause of cancer-related death and the third most common cancer globally. Early-stage rectal cancer is defined by lesions confined to the bowel wall, without extension beyond the submucosa in T1 or the muscularis propria in T2, with no indication of lymph node involvement or distant metastasis. The gold standard for managing rectal cancer is total mesorectal excision (TME); however, it is linked to considerable morbidities and impaired quality of life. There is a growing interest in local resection and non-operative treatment of early RC for organ preservation. Local resection options include three types of transanal endoscopic surgery (TES): transanal endoscopic microsurgery (TEM), transanal endoscopic operations (TEO), and transanal minimally invasive surgery (TAMIS), while endoscopic resection includes endoscopic mucosal resection (EMR), underwater endoscopic mucosal resection (UEMR), and endoscopic submucosal dissection (ESD). Although the oncological outcome of local resection of early rectal cancer is debated in the current literature, some studies have shown comparable outcomes with radical surgery in selected patients. The use of adjuvant and neoadjuvant chemoradiotherapy in early rectal cancer management is also controversial in the literature, but a number of studies have reported promising outcomes. This review focuses on the available literature regarding diagnosis, staging, and management strategies of early rectal cancer and provides possible recommendations. Full article

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2–3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences. Full article

Background: With rectum-sparing protocols becoming more common for rectal cancer treatment, this study aimed to predict the pathological complete response (pCR) to preoperative chemoradiotherapy (pCRT) in rectal cancer patients using pre-treatment MRI and a radiomics-based machine learning approach. Methods: We divided MRI-data from 102 patients into a training cohort (n = 72) and a validation cohort (n = 30). In the training cohort, 52 patients were classified as non-responders and 20 as pCR based on histological results from total mesorectal excision. Results: We trained various machine learning models using radiomic features to capture disease heterogeneity between responders and non-responders. The best-performing model achieved a receiver operating characteristic area under the curve (ROC-AUC) of 73% and an accuracy of 70%, with a sensitivity of 78% and a positive predictive value (PPV) of 80%. In the validation cohort, the model showed a sensitivity of 81%, specificity of 75%, and accuracy of 80%. Conclusions: These results highlight the potential of radiomics and machine learning in predicting treatment response and support the integration of advanced imaging and computational methods for personalized rectal cancer management. Full article

Total neoadjuvant therapy (TNT) has emerged as a promising approach for managing locally advanced rectal cancer (LARC), aiming to enhance resectability, increase pathological complete response (pCR), improve treatment compliance, survival, and sphincter preservation. This study compares the clinical outcomes of TNT, with either induction or consolidation chemotherapy, to those of the standard chemoradiotherapy (CRT). In this retrospective multi-institutional study, patients with stage II-III LARC who underwent CRT or TNT from seven oncology centers between 2021 and 2024 were retrospectively analyzed. The TNT group was categorized into induction or consolidation groups based on the sequence of chemotherapy and radiotherapy. Clinical and pathological data and treatment outcomes, including pCR, event-free survival (EFS), and overall survival (OS), were analyzed. Among the 276 patients, 105 received CRT and 171 underwent TNT. The TNT group showed significantly higher pCR (21.8% vs. 2.9%, p < 0.001) and lower lymphatic (26.3% vs. 42.6%, p = 0.009), vascular (15.8% vs. 32.7%, p = 0.002), and perineural invasion rates (20.3% vs. 37.6%, p = 0.003). Furthermore, 16.9% of TNT patients opted for non-operative management (NOM), compared to 0.9% in the CRT group (p < 0.001). The median interval between the end of radiotherapy and surgery was longer in the TNT group (17.6 weeks vs. 8.8 weeks, p < 0.001). The 3-year EFS was 58.3% for CRT and 71.1% for TNT (p = 0.06). TNT is associated with higher pCR, lower lymphatic and vascular invasion rates, and higher rates of NOM compared to CRT. This supports the use of TNT as a viable treatment strategy for LARC, offering potential benefits in quality of life. Full article

The management of locally advanced rectal cancer has undergone significant transformations over the decades and optimal treatment approaches continue to evolve. There have been numerous advances in surgery, chemotherapy, and radiation therapy from the first description of the abdominoperineal resection in 1908, timing of chemotherapy and radiation therapy in the late 20th and early 21st century, and most recently, the introduction of organ preservation or nonoperative management in 2004. Alongside these advancements, the concept of shared decision making in medicine has evolved, prompting a focus on patient-centered care. This evolution in practice has been fueled by a growing recognition of the importance of patient autonomy and the alignment of treatment options with patients’ values and preferences. With the growing number of possible treatment options, variability in patient counseling exists, highlighting the need for a standardized approach to shared decision making in locally advanced rectal cancer. This narrative review will describe the evolution of treatment options of locally advanced rectal cancer as well as the concept of shared decision making and decision aids, and will introduce a decision aid for patients with locally advanced rectal cancer who have achieved a complete clinical response and are eligible for watch and wait. Full article