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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.

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. [ABSTRACT FROM AUTHOR]

Purpose: Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system. Materials and Methods: Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gyx5 with two cycles of XELOX (capecitabine 1000 mg/m² and oxaliplatin 130 mg/m² every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups. Results: Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. Conclusion: SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant chemoradiation (CRT) is standard of care for locally advanced rectal cancer. However short course radiotherapy (SCRT) was developed for the benefit of a shorter treatment duration and early surgical intervention which also helped in reducing the case burden to the hospital. SCRT is routinely practised in European countries, Indian experience with the SCRT is limited and hence a pilot study was conducted to compare the morphological difference and pathological response between SCRT and CRT. Objectives: A) Evaluate the morphological changes and pathological response between SCRT and CRT. B) Compare the pathologic response with outcome between SCRT and CRT. Materials and Methods: All rectal cancer patients in clinical stage II and III diagnosed during 2016 to 2020, who underwent SCRT or CRT were selected. Altered histopathologic findings due to therapy such as tumor cell morphology, necrosis and stromal response along with pathological response between the study groups were compared along with the outcome. Results: Ten (12.6%) patients were subjected to SCRT and 69 (87.4%) patients underwent CRT. Morphological changes such as necrosis was noted in nine (90%) and eight (11.5%) cases in SCRT and CRT group respectively. Pathologic complete response (pCR) was noted in 12 (17.5%) cases of CRT only. Near complete response was seen in one (10%) and 14 (20.5%) cases of SCRT and CRT respectively. Despite lower rates of pCR in SCRT, no difference in survival or outcome was noted between the two study groups. Conclusion: pCR as expected is less in patients who received SCRT, despite this the outcome during follow up was similar in both the groups. Indian data is very limited and large multi-centre studies should be carried as SCRT offers an advantage of early definitive surgical intervention in addition to shorter duration of hospitalisation when compared with CRT.

Background and purpose: The use of external beam radiotherapy (EBRT) and contact X-Ray brachytherapy (CXB) is emerging as an effective alternative in patients with early stage rectal cancer with the intent of organ preservation (OP). Short course radiotherapy (SCRT) is an alternative EBRT schedule for patients not fit for chemotherapy or for longer courses of EBRT. There are no multicentre studies that have reported on the outcomes of SCRT with a CXB boost, therefore we present these from patients from centres from the UK and Sweden. Materials and methods: From the Guildford Colorectal Database or local databases, 258 patients who underwent SCRT and CXB with the intent of OP from five centres treated between 2007 and 2019 were identified. Response and survival data was analysed and presented. Results: With a median age of 81, 226 patients were treated with radiotherapy alone (RTA) and 32 immediately after local excision (ILE). Median follow-up was 24 months. 70% and 97% of patients in the RTA and ILE groups respectively had a complete clinical response (cCR) after SCRT with CXB. Of those, local relapse was seen in 16% of the RTA and 3% of the ILE group. Median survival was 40 months after CXB in the RTA and 52 months in the ILE group. 94% of patients remained stoma-free to the point of latest follow-up. Conclusion: This data suggests that CXB when combined with SCRT, in a mainly elderly and comorbid population, provides good palliation with stoma-avoidance. Oncological outcomes compare with previously published work. A greater focus is required on quality of life outcomes after OP.

There is no specific guideline for the treatment of locally advanced rectal cancers in the elderly. Here we compared R0 resection rate and degradation of autonomy based on the instrumental activities of daily living score between neoadjuvant, short course radiotherapy and chemoradiotherapy in this specific population. Patients ≥75 years with resectable T3–T4 rectal adenocarcinoma within 12 cm of the anal verge or T2 of the very low rectum were randomised between short course radiotherapy (5 × 5 Gy in one week) and chemoradiotherapy (50 Gy, 2 Gy/f, 5 weeks with capecitabine: 800 mg/m2 twice daily, 5 days per week), with delayed surgery 7 ± 1 weeks for the two arms. One hundred and three eligible patients were enrolled between January 2016 and December 2019 when the trial was closed due to poor accrual. The R0 resection rate (first co-primary objective) was 84.3%; confidence interval 95% [73.26–94.18] in the short course group and 88%; confidence interval 95% [77.77–96.60] in the chemoradiotherapy group (non-inferiority p = 0.28). The deterioration of the instrumental activities of daily living score was not different during the pre-operative phase, it was significantly more deteriorated in the chemoradiotherapy group at 3 months post-operative (44.8% versus 14.8%; p = 0.032) but was not different at 12 months post-operative (second co-primary objective). During pre-operative phase, 9.8% of patients in short course group and 22% of patients in chemoradiotherapy group presented a serious adverse event, but we observed no difference during the post-operative phase between the two groups. Although the main objectives of the study were not achieved, the short course radiotherapy followed by delayed surgery could represent a preferred treatment option in patients ≥75 years with locally advanced rectal cancer; a new study must be performed to confirm the improvement in overall and specific survival results. • This is the first randomised study for locally advanced rectal cancers in the elderly. • The R0 resection rate and the preservation of autonomy were the two co-primaries. • We could not confirm the non-inferiority of 5 × 5 radiotherapy for the co-primary R0. • The tolerance was better for short course radiotherapy. [ABSTRACT FROM AUTHOR]

Aim: A prolonged interval (>4 weeks) between short‐course radiotherapy (25 Gy in five fractions) (SCRT‐delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient‐reported bowel dysfunction and physician‐reported radiation‐induced toxicity for 8 weeks following SCRT‐delay. Method: Patients who were referred for SCRT‐delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient‐reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician‐reported radiation‐induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. Results: Fifty‐one patients were included; 31 (61%) were men and the median age was 67 years (range 44–91). Patient‐reported bowel dysfunction and physician‐reported radiation‐induced toxicity peaked at weeks 1–2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT‐delay. Grade 3 radiation‐induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4–5 radiation‐induced toxicity occurred. Conclusion: During SCRT‐delay, almost every patient experiences temporary mild–moderate radiation‐induced toxicity and major LARS, but life‐threatening toxicity is rare. SCRT‐delay is a safe alternative to SCRT‐direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies. [ABSTRACT FROM AUTHOR]

Background: The most common neoadjuvant therapy for locally advanced rectal cancer is fluoropyrimidine-based chemotherapy combined with radiation (45-50.4 Gy) (LARC). Recently many studies focusing on shifting systemic chemotherapy to preoperative setting to increase pathological complete response rate (pCR). Patients & Methods: This is a randomized controlled trial (RCT) of stage II-III rectal cancer patients treated from October 2020 to April 2022. They were randomized into: Experimental group: Total neoadjuvant therapy (TNT) with short course radiotherapy (25 Gy) then chemotherapy (Capecitabine and Oxaliplatin) for 6 cycles followed by total mesorectal excision (TME). Control group: Standard long course concurrent chemo radiotherapy (LC-CCRT, 45-50.4Gy) with Capecitabine followed by TME and adjuvant chemotherapy. Primary end points were pathological complete response (pCR) and disease related treatment failure (DrTF). Secondary end points were restricted mean survival time at 12 months (RMST), toxicity and surgical complications. Results: High risk criteria as N2 and infiltrated mesorectal fascia (MRF) were statistically higher in TNT group (p=0.005, p= 0.04 respectively). Complete response was achieved radiologically in 11.5% and pathologically in 33.3 % exclusively in TNT group. Restricted mean survival time (RMST) at 12 months was 11.6 months in TNT group and 11.1 months in control group. Pathological complete response was statistically correlated to improvement in DrTF and RMST at 12 months (p =0.01). Conclusion: Short course radiotherapy with neoadjuvant chemotherapy is a good alternative to the standard LC-CCRT with less hospital treatment days and cost especially after COVID 19 pandemic. [ABSTRACT FROM AUTHOR]

Background: The trial hypothesis was that short-course radiotherapy followed by near-total neoadjuvant chemotherapy would increase patient adherence to treatment compared to standard chemo-radiotherapy for locally advanced rectal cancer, without affecting oncological results. Methods: In this open-label RCT, patients with cT3, cT4, or node-positive non-metastatic rectal cancer were randomly assigned to receive complete mesorectal excision after receiving either 5*5 Gy of radiation and FOLFOX or concomitant chemo-radiotherapy and capecitabine. Adjuvant chemotherapy cycles were administered to patients using the FOLFOX regimen. The primary endpoint was to evaluate the response rate after the completion of treatment. The secondary goal was to assess the failure rate (local or distant) and treatment toxicity. Results: Of 100 patients, 50 were in arm 1 and 50 in arm 2. Patients’ characteristics differences between the two groups were not significant except for mutant BRAF and pre-treatment CEA levels p=0.043 and p<0.001. Tumour regression grade 1 was 18% in arm 1 and 2% in arm 2. The pathological response was statistically significant with BRAF mutation (p<0.001), pretreatment CEA level (p=0.006), treatment arms (p=0.031), and pre-treatment GPS (p<0.001). For Overall Survival (OS), the 3-year OS was 94% which was statistically insignificant between the two arms (p=0.564). Three years OS was higher in patients with GPS zero, normal pre-treatment CEA level, wild-type BRAF mutation, and TRG 1 and 2. For disease-free survival, the 3-year DFS was 90% that was statistically insignificant between the two arms (p=0.627). Three-year DFS was higher in TRG1 and 2 100% for both, normal pre-treatment CEA level and pre-treatment GPS zero. The chemotherapy adverse events were vomiting, anaemia, and neurotoxicity which were almost the same in both arms 1 and 2. As regard radiation therapy side effects, the main genitourinary toxicity in the form of dysuria and urinary tract infection46% in arm 1 and 66% in arm 2 (p=0.292), lower GIT toxicity proctitis occur in 40% in arm 1 and 30% of arm 2 (p=0.022) with no grade 3 or grade 4 toxicity in both arms. Conclusion: Short course radiotherapy followed by chemotherapy (near total neoadjuvant therapy) then TME offers comparable results *Watch and wait strategy may be the appropriate option in patients developing a complete pathological response. [ABSTRACT FROM AUTHOR]

Neoadjuvant short course radiotherapy (SCRT) followed by consolidation chemotherapy (CCT) is an alternative treatment for locally advanced rectal cancer (LARC). We performed this systematic review and meta-analysis to explore the tumor response and oncological outcomes of this new approach compared to conventional chemoradiotherapy (CRT). An online search of the PubMed, Embase, and Cochrane Library databases was performed. This review included 7507 patients from 14 different cohorts. The pCR rate was higher with SCRT + CCT than that with CRT (RR: 1.60; 95% CI: 1.35–1.91; p < 0.01). SCRT + CCT provided a higher ypN0 response (RR: 1.06; 95% CI: 1.01–1.12; p = 0.02). There were no differences in R0 resection and positive CRM rates; however, more sphincter-preservation surgeries were performed in the SCRT + CCT arm (RR: 1.06; 95% CI: 1.01–1.11; p = 0.02). There was no difference in the OS and DFS between the SCRT + CCT and the CRT arms (OS: HR: 0.85, p = 0.07; DFS: HR: 0.88, p = 0.08). The compliance and toxicity were comparable between the SCRT and CRT groups. In the subgroup analysis, patients who underwent four or more cycles of CCT had better pCR and DFS events. Therefore, SCRT followed by consolidation chemotherapy might be an effective alternative treatment for LARC.

Background and Purpose: Limited evidence exists for dose escalation in neoadjuvant short course radiotherapy (SCRT) for rectal cancer. With enhanced imaging and radiotherapy techniques over the past decades along with the valuable endpoint of pathological complete response (pCR), we believe SCRT with simultaneous integrated boost could potentially provide deeper pathological responses and improve local control., Methods and Materials: Between January 2020 and December 2022, locoregional-advanced rectal cancer patients that were treated with neoadjuvant SCRT with simultaneous integrated boost up to 5.5-6Gy per fraction with five daily fractions followed by response-adapted chemotherapy was retrospectively reviewed. The pCR rates, R0 resection rates, tumor downstaging, toxicities, and early pattern of recurrence are reported., Results: Among the 76 patients, 67 (88%) were able to undergo curative intent surgery. R0 resection was achieved in 99% (n = 66) of patients with pCR rates of 28% (n = 19). Forty-six percent (n = 31) of patients had significant pathological downstaging (ypT2N0) and 55% (n = 37) of patients had both T and N downstaging. Most common grade 3 or above radiotherapy-related side-effects were proctitis, rectal pain, and dermatitis found in 5% (n = 4), 3% (n = 2) and 3% (n = 2) of patients, respectively. Grade 3 or above surgical complications were observed in 15% (n = 10) of patients. There were no treatment-related deaths. With a median follow-up of 27 months, only 6% (n = 4) had local recurrence after surgery., Conclusions: Neoadjuvant short course radiotherapy with simultaneous boost for rectal cancer is feasible with no added toxicities. Patients who underwent surgery achieve a high R0 resection and pCR rates. Early data suggest low rates of locoregional recurrence. Further follow-up and research is needed to validate and optimize the dose, method, and schedule of dose escalation., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Neoadjuvant short course radiotherapy (SCRT) followed by consolidation chemotherapy (CCT) is an alternative treatment for locally advanced rectal cancer (LARC). We performed this systematic review and meta-analysis to explore the tumor response and oncological outcomes of this new approach compared to conventional chemoradiotherapy (CRT). An online search of the PubMed, Embase, and Cochrane Library databases was performed. This review included 7507 patients from 14 different cohorts. The pCR rate was higher with SCRT + CCT than that with CRT (RR: 1.60; 95% CI: 1.35–1.91; p < 0.01). SCRT + CCT provided a higher ypN0 response (RR: 1.06; 95% CI: 1.01–1.12; p = 0.02). There were no differences in R0 resection and positive CRM rates; however, more sphincter-preservation surgeries were performed in the SCRT + CCT arm (RR: 1.06; 95% CI: 1.01–1.11; p = 0.02). There was no difference in the OS and DFS between the SCRT + CCT and the CRT arms (OS: HR: 0.85, p = 0.07; DFS: HR: 0.88, p = 0.08). The compliance and toxicity were comparable between the SCRT and CRT groups. In the subgroup analysis, patients who underwent four or more cycles of CCT had better pCR and DFS events. Therefore, SCRT followed by consolidation chemotherapy might be an effective alternative treatment for LARC. [ABSTRACT FROM AUTHOR]

Organ saving treatment for early-stage rectal cancer can reduce patient reported side effects compared to standard total mesorectal excision (TME) and preserve quality of life (QOL). An optimal strategy for achieving organ preservation and longer-term oncological outcomes are unknown, thus there is a need for high quality trials. Can we Save the rectum by watchful waiting or TransAnal surgery following (chemo)Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC) is an international 3-arm multi-centre, partially randomised controlled trial incorporating an external pilot. In phase III, patients with cT1-3b N0 tumours, ≤40mm in diameter, who prefer organ preservation are randomised 1:1 between mesorectal long course chemoradiation versus mesorectal short course radiotherapy, with selective transanal microsurgery. Patients preferring radical surgery receive TME. STAR-TREC aims to recruit 380 patients to organ preservation and 120 to TME surgery. The primary outcome is the rate of organ preservation at 30 months. Secondary clinician reported outcomes include acute treatment-related toxicity, rate of non-operative management, non-regrowth pelvic tumour control at 36 months, non-regrowth disease free survival at 36 months, and overall survival at 60 months and patient reported toxicity, health related QOL at baseline, 12 and 24 months. Exploratory biomarker research uses circulating tumour DNA to predict response and relapse. STAR-TREC will prospectively evaluate contrasting therapeutic strategies and implement new measures including a smaller mesorectal target volume, 2-step response assessment and non-operative management for complete response. The trial will yield important information to guide routine management of patients with early-stage rectal cancer. [ABSTRACT FROM AUTHOR]

The optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases. Forty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4, <2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed. At the time of initial diagnosis, 20 patients had <3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien–Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively. Upfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity. [ABSTRACT FROM AUTHOR]

The endpoint of the present study was to evaluate the outcomes of short-course radiotherapy (SCRT) and SCRT with delayed surgery (SCRT-DS) on a selected subgroup of frail patients with locally advanced middle/low rectal adenocarcinoma. From January 2008 to December 2018, a total of 128 frail patients with locally advanced middle-low rectal adenocarcinoma underwent SCRT and subsequent restaging for eventual delayed surgery. Rates of complete pathological response, down-staging, disease free survival (DFS) and overall survival (OS) were analyzed. 128 patients completed 5 × 5 Gy pelvic radiotherapy. 69 of these were unfit for surgery; 59 underwent surgery 8 weeks (average time: 61 days) after radiotherapy. Downstaging of T occurred in 64% and down-staging of N in 50%. The median overall survival (OS) of SCRT alone was 19.5 months. The 1-year, 2-year, 3-year and 5-year OS was 48%, 22%, 14% and 0% respectively. In the surgical group, the median disease-free survival (DFS) and median OS were, respectively, 67 months (95% CI 49.8–83.1 months) and 72.1 months (95% CI 57.5–86.7 months). The 1, 2, 3, 5-year OS was 88%, 75%, 51%, 46%, respectively. Post-operative morbidity was 22%, mortality was 3.4%. Frail patients with advanced rectal cancer are often "unfit" for long-term neoadjuvant chemoradiation. A SCRT may be considered a valid option for this group of patients. Once radiotherapy is completed, patients can be re-evaluated for surgery. If feasible, SCRT and delayed surgery is the best option for frail patients. [ABSTRACT FROM AUTHOR]

Introduction: Neoadjuvant chemoradiation (CRT) is standard of care for locally advanced rectal cancer. However short course radiotherapy (SCRT) was developed for the benefit of a shorter treatment duration and early surgical intervention which also helped in reducing the case burden to the hospital. SCRT is routinely practised in European countries, Indian experience with the SCRT is limited and hence a pilot study was conducted to compare the morphological difference and pathological response between SCRT and CRT., Objectives: A) Evaluate the morphological changes and pathological response between SCRT and CRT. B) Compare the pathologic response with outcome between SCRT and CRT., Materials and Methods: All rectal cancer patients in clinical stage II and III diagnosed during 2016 to 2020, who underwent SCRT or CRT were selected. Altered histopathologic findings due to therapy such as tumor cell morphology, necrosis and stromal response along with pathological response between the study groups were compared along with the outcome., Results: Ten (12.6%) patients were subjected to SCRT and 69 (87.4%) patients underwent CRT. Morphological changes such as necrosis was noted in nine (90%) and eight (11.5%) cases in SCRT and CRT group respectively. Pathologic complete response (pCR) was noted in 12 (17.5%) cases of CRT only. Near complete response was seen in one (10%) and 14 (20.5%) cases of SCRT and CRT respectively. Despite lower rates of pCR in SCRT, no difference in survival or outcome was noted between the two study groups., Conclusion: pCR as expected is less in patients who received SCRT, despite this the outcome during follow up was similar in both the groups. Indian data is very limited and large multi-centre studies should be carried as SCRT offers an advantage of early definitive surgical intervention in addition to shorter duration of hospitalisation when compared with CRT.

Introduction Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands. Methods In the population based Netherlands Cancer Registry, clinical stage III rectal cancer patients, diagnosed between 2008 and 2014, who underwent CRT or SCTR-delay were selected. pCR (ypT0N0), near pCR (ypT0-1N0), and tumor and nodal downstaging were compared between the treatment groups using multivariable logistic regression analysis. Results 386 patients underwent SCRT-delay and 3659 patients underwent CRT. The pCR-rate in the SCRT-delay group was significantly lower compared to the CRT-group (6.4% vs. 16.2%, p < 0.001). After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, SCRT-delay patients were significantly less likely to reach pCR (adjusted odds ratio 0.3, 95%CI 0.2–0.5). Also, near-pCR (ypT0–1N0) as well as tumor and nodal downstaging was observed less often in the SCRT-delay group. Conclusion Compared to patients treated with neoadjuvant CRT, those receiving SCRT and delayed surgery are less likely to develop pCR. Novel neoadjuvant treatment strategies for patients not fit enough for CRT are needed to increase their eligibility for organ-sparing treatments. [ABSTRACT FROM AUTHOR]

Purpose: Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system., Materials and Methods: Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m² and oxaliplatin 130 mg/m² every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups., Results: Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively ( p =0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p =0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p <0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p <0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost., Conclusion: SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Rectal cancers stages II-III are presenting many various clinical situations. Neoadjuvant chemoradiotherapy is a standard of care in many cases, and in association with TME surgery, local relapses are becoming uncommon. None of these neoadjuvant treatments have so far improved survival, and quality of life remains non-optimal after abdomino-perineal resection and quite often after anterior resection. To increase survival through sterilization of subclinical distant metastases, new induction chemotherapy is tested. In T4 tumors, radiation dose escalation should be able to further improve local control, and in elderly patients, reduction of nCRT toxicity may provide better compliance to TME surgery. A promising approach is the use of optimal neoadjuvant treatment in early tumors in order to achieve a clinical complete response and propose an organ preservation either after local excision or using a meticulous and prolonged watch and wait strategy. Well-conducted randomized trials will be necessary to modify the present standard of care. [ABSTRACT FROM AUTHOR]

Background and Purpose: The use of external beam radiotherapy (EBRT) and contact X-Ray brachytherapy (CXB) is emerging as an effective alternative in patients with early stage rectal cancer with the intent of organ preservation (OP). Short course radiotherapy (SCRT) is an alternative EBRT schedule for patients not fit for chemotherapy or for longer courses of EBRT. There are no multicentre studies that have reported on the outcomes of SCRT with a CXB boost, therefore we present these from patients from centres from the UK and Sweden., Materials and Methods: From the Guildford Colorectal Database or local databases, 258 patients who underwent SCRT and CXB with the intent of OP from five centres treated between 2007 and 2019 were identified. Response and survival data was analysed and presented., Results: With a median age of 81, 226 patients were treated with radiotherapy alone (RTA) and 32 immediately after local excision (ILE). Median follow-up was 24 months. 70% and 97% of patients in the RTA and ILE groups respectively had a complete clinical response (cCR) after SCRT with CXB. Of those, local relapse was seen in 16% of the RTA and 3% of the ILE group. Median survival was 40 months after CXB in the RTA and 52 months in the ILE group. 94% of patients remained stoma-free to the point of latest follow-up., Conclusion: This data suggests that CXB when combined with SCRT, in a mainly elderly and comorbid population, provides good palliation with stoma-avoidance. Oncological outcomes compare with previously published work. A greater focus is required on quality of life outcomes after OP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In the last few decades we have witnessed a great advancement in the treatment of rectal carcinoma. This advancement has partly been enabled by the development of new surgical techniques, magnetic resonance imaging as an optimal diagnostic tool and of new histopathological techniques for resected specimen evaluation. Other important contributions include the development of sophisticated radiotherapy treatment techniques which, applied with new cytostatics and smart drugs, induce a better tumor response while reducing toxicity. Although each discipline has contributed to a better understanding of the disease, it is the multidisciplinary approach that has yielded success in treatment so far. [ABSTRACT FROM AUTHOR]

Transanal endoscopic microsurgery (TEMS) is a well established method of accurate resection of specimens from the rectum under binocular vision. This review examines its role in the treatment of benign conditions of the rectum and the evidence to support its use and compliment existing endoscopic treatments. The evolution of TEMS in early rectal cancer and the concepts and outcomes of how it has been utilised to treat patients so far are presented. The bespoke nature of early rectal cancer treatment is changing the standard algorithms of rectal cancer care. The future of TEMS in the organ preserving treatment of early rectal cancer is discussed and how as clinicians we are able to select the correct patients for neoadjuvant or radical treatments accurately. The role of radiotherapy and outcomes from combination treatment using TEMS are presented with suggestions for areas of future research. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate long-term quality-of-life (QoL) after neoadjuvant short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. Methods: Between 1999 and 2008, 225 patients were treated with curative intent for locally advanced rectal cancer using neoadjuvant SC-RT (n =108) or LC-RCHT (n =117). SC-RT delivered 10×2.9Gy twice daily with immediate surgery. LC-RCHT delivered 28×1.8Gy concomitant with 5-FU based chemotherapy and delayed surgery. A cross-sectional QoL analysis was performed in disease-free patients using the EORTC-QLQ-C30 and EORTC-QLQ-CR29 questionnaires. Results: After a median follow-up of 67months, 133 patients were disease-free of which 120 (90%) returned the QoL questionnaires. Patients in the LC-RCHT cohort had a higher rate of uT4, uN+ and low tumor location. No difference in QoL was observed between SC-RT and LC-RCHT except an improved physical functioning in the LC-RCHT group (p =0.04). Comparing our total patient cohort with the general German population showed no difference in global health status but decreased QoL in several functional and bowel symptom scores. Conclusions: The finding of comparable long-term QoL after SC-RT and LC-RCHT adds to our knowledge of equivalent oncological outcome and may be useful in the decision making process between the two neoadjuvant approaches. [Copyright &y& Elsevier]

Objective: Short-course radiotherapy (25 Gy in 5 fractions) has been shown to be non-inferior to standard course radiotherapy in elderly and frail patients (60 Gy in 30 fractions). The purpose of this study was to determine the effects of temozolomide combined with short-course radiotherapy on the outcome of elderly and frail patients., Methods: Between January 2017 and November 2018, 90 patients (65 years old and KPS score of 50-70; 65 years old and KPS score of 80-100; and 65 years old and KPS score of 50-70) were assessed for eligibility. Nine patients were excluded because they did not meet the inclusion criteria, six patients declined to participate, and four patients were unable to complete the quality-of-life questionnaire. The remaining 71 patients were divided into two arms at random in a 1:1 ratio. Short-course radiotherapy with concurrent temozolomide and adjuvant temozolomide was given to Arm 1, while short-course radiotherapy alone was given to Arm 2., Results: In terms of overall survival and progression-free survival, radiotherapy with concurrent temozolomide and adjuvant temozolomide outperformed short-course radiotherapy alone. The median overall survival in arm 1 was 146 days and 121 days in arm 2 (P=0.146). The median progression-free survival in arm 1 was 109.50 days, while it was 77 days in arm 2 (P=0.028). With a median follow-up time of 6 months, the quality of life at 4 weeks and 12 weeks after treatment was not different between the two arms., Conclusion: We concluded that adding temozolomide to short-course radiotherapy significantly improved progression-free survival and showed an increasing trend in overall survival without compromising the quality of life.

Neoadjuvant short-course radiotherapy and long-course chemoradiation (CRT) reduce local recurrence rates when compared to surgery alone and remain widely accepted as standard of care for patients with locally advanced rectal cancer. However, surgery is not without complications and a non-surgical approach in carefully selected patients warrants evaluation. A pathological complete response to CRT is associated with a significant improvement in survival and it has been suggested that a longer time interval between the completion of CRT and surgery increases tumor downstaging. Intensification of neoadjuvant treatment regimens to increase tumor downstaging has been evaluated in a number of clinical trials and more recently the introduction of neoadjuvant chemotherapy prior to CRT has demonstrated high rates of radiological tumor regression. Careful selection of patients using high-resolution MRI may allow a non-surgical approach in a subgroup of patients achieving a complete response to neoadjuvant therapies after an adequate time period. Clearly this needs prospective evaluation within a clinical trial setting, incorporating modern imaging techniques, and tissue biomarkers to allow accurate prediction and assessment of response. [ABSTRACT FROM AUTHOR]

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