Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer with [68Ga]Ga-FAPI-04 PET, [18F]FDG PET, and Contrast-Enhanced MRI: Lesion-to-Lesion Comparison with Pathology.

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. 68Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI-04) PET/MRI, [18F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter's sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [68Ga]Ga-FAPI-04 PET/MRI and [18F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [68Ga]Ga-FAPI-04 change in SULpeak percentage, where SULpeak is SUVpeak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [68Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SULpeak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.

The association of preoperative radiotherapy and surgery for AJCC stage I-III rectal adenocarcinoma: a population-based study.

BACKGROUND: With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma. METHODS: This retrospective study analyzed the clinicopathological data from 6,585 AJCC stage I-III rectal adenocarcinoma in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Kaplan-Meier survival analysis and multivariate Cox proportional were used to assess the impact of PR on survival. Propensity score matching (PSM) was employed to balance the baseline covariates between the PR and non-PR groups and to compare postoperative pathological differences. RESULTS: After PSM, PR did not improve overall survival (OS) in stages I (p = 0.33), II (p = 0.37), and III (p = 0.14) patients. Multivariate Cox analysis indicated that PR was not an independent prognostic factor for patients. Restricted cubic spline (RCS) analysis demonstrated a nonlinear negative correlation between OS hazard ratios and both circumferential resection margin (CRM) and lymph node evaluation (LNE). Compared to the non-PR group, patients in the PR group had lower tumor deposits (TD) (p < 0.001), positive CRM (p = 0.191), and perineural invasion (PNI) (p = 0.001). CONCLUSION: PR is not an independent prognostic factor for rectal adenocarcinoma patients. However, PR can reduce the likelihood of TD, CRM, and PNI, thereby potentially influencing the quality of surgery.

Outcomes and failure patterns after chemoradiotherapy for locally advanced rectal cancer with positive lateral pelvic lymph nodes: a propensity score-matched analysis.

PURPOSE: This study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN). MATERIALS AND METHODS: Patients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local-regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109). CONCLUSIONS: Our study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

Tumor response rates based on initial TNM stage and tumor size in locally advanced rectal cancer: a useful tool for shared decision-making.

BACKGROUND: It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size. METHODS: Patients treated with LARC from 2014 to 2021 with cT2-3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version 20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270). RESULTS: The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3 cm to 20% in cT3N+ > 4 cm. Organ preservation without recurrence at 2 years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+. CONCLUSION: There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making.

A large population-based and validated study on the follow-up management and supportive strategy of locally advanced rectal cancer patients.

OBJECTIVE: Our objective was to evaluate the predictive factors and metastatic time for liver and lung metastasis in locally advanced rectal cancer (RC) patients. METHODS: Univariate and multivariate analysis were performed to identify risk factors and prognostic factors for liver metastasis and lung metastasis in RC. Survival probabilities were calculated using the Kaplan-Meier model and compared using the log-rank test between groups. The probability of time-to-event occurrence was calculated using the random survival forest model. Finally, the SEER database was used to verify our findings. RESULTS: Our results indicated that pathological T stage and pathological N stage were independent predictive factors for liver metastasis. Furthermore, CEA level, pathological T stage, and tumor deposit were independent predictive factors for lung metastasis. Based on the results of a multivariate Cox analysis, we categorized patients with liver and lung metastasis into three groups based on their scores. The results revealed that patients with higher scores had a higher probability of experiencing metastasis. For liver metastasis, Groups 1, 2, and 3 all exhibited higher occurrence rates within the first 24 months. However, for lung metastasis, Group 4 showed the highest occurrence rate at the 12th month, while Groups 5 and 6 exhibited the highest occurrence rates at the 15th month. CONCLUSIONS: In summary, we developed predictive models to determine the likelihood of liver and lung metastasis in RC patients. It is crucial to implement a more intensive surveillance program for patients with unfavorable risk profiles in order to facilitate early detection of metastasis.

Advantages of robotic surgery for rectal cancer compared to laparoscopic surgery: pelvic anatomy and its impact on urinary dysfunction.

The anatomical dimensions and the shape of the pelvis influence surgical difficulty for rectal cancer. Compared to conventional laparoscopic surgery, robot-assisted surgery is expected to improve surgical outcomes due to the multi-joint movement of its surgical instruments. The aim of this study was to investigate the impact of pelvic anatomical indicators on short-term outcomes of patients with rectal cancer. A retrospective analysis was conducted using data from 129 patients with rectal cancer who underwent conventional laparoscopic low anterior resection (L-LAR) or robot-assisted low anterior resection (R-LAR) with total mesorectal excision or tumor-specific mesorectal excision between January 2014 and December 2022. The transverse diameter of the lesser pelvis and the sacral promontory angle were used as indicators of pelvic anatomy. The sacral promontory angle was not associated with age and sex while the pelvic width was smaller in male than in female. The pelvic width did not affect postoperative complications in both L-LAR and R-LAR. In contrast, postoperative urinary dysfunction occurred more frequently in patients with a small sacral promontory angle (p = 0.005) in L-LAR although there was no impact on short-term outcomes in R-LAR. Multivariate analysis demonstrated that a small sacral promontory angle was an independent predictive factor for urinary dysfunction (p = 0.032). Sharp angulation of the sacral promontory was a risk factor for UD after L-LAR. Robot-assisted surgery could overcome anatomical difficulties and reduce the incidence of UD.

Effect of radiotherapy on long-term quality of life in recurrence-free rectal cancer survivors (LaTE study): nationwide inverse probability of treatment-weighted registry-based cohort study and survey.

BACKGROUND: Radiotherapy reduces local recurrence in locally advanced rectal cancer, but may cause harm in patients who do not experience recurrence. The aim was to investigate the impact of radiotherapy on long-term quality of life after curative treatment for rectal cancer, i.e. in patients without a recurrence during the follow-up. METHODS: All patients operated on for rectal cancer in Norway under 75 years of age between 30 September 2007 and 1 October 2020 were identified using the Cancer Registry of Norway. Exclusion criteria were distant metastasis, recurrence and dementia. The primary outcome measure was the Gastrointestinal Quality of Life Index. Secondary outcome measures included the 36-item Short Form Survey. Inverse probability weights based on a multiple logistic regression model were used to balance prechosen covariates between the radiotherapy and no radiotherapy groups when assessing differences in outcomes. RESULTS: Of 5014 invited patients, 2142 (43%) eligible patients answered the questionnaires. Of these 762 (36%) were treated with neoadjuvant radiotherapy plus surgery and 1380 (64%) with surgery alone. The mean follow-up time was 6.4 and 7.4 years respectively. After propensity score matching, the Gastrointestinal Quality of Life Index differed significantly between irradiated and non-irradiated patients ((mean(s.d.), mean score 103.8(19.4) versus 110.8(19.6) respectively, mean difference: -6.96 (95% c.i. -8.72 to -5.19); P < 0.001). Among patients without a stoma the mean difference was -8.1 points, whereas it was -5.7 for patients with a stoma. The radiotherapy group also scored significantly lower in 7 of 8 36-item Short Form Survey domains compared with the surgery alone group. CONCLUSION: Long-term quality of life was significantly lower in patients without a recurrence during the follow-up who received radiotherapy compared with patients who did not. These findings warrant a critical re-evaluation of the use of radiotherapy both in traditional neoadjuvant treatment and in modern organ-preserving treatment regimens.

Persistent Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Importance: Patients with locally advanced rectal cancer and persistent lymph node metastases (PLNM) after neoadjuvant treatment are at high risk of developing locoregional and distant metastasis, yet optimal postsurgical treatment of these patients is limited. Objective: To analyze the association of PLNM with pretreatment clinical parameters, intensity of neoadjuvant treatment, and long-term oncological outcomes. Design, Setting, and Participants: This cohort study is a post-hoc analysis of 3 randomized clinical trials (Surgical Oncology Working Group of Germany [CAO], Radiological Oncology Working Group of Germany [ARO], and Working Group for Internal Oncology in the German Cancer Society [AIO]) conducted in Germany in 1994, 2004, and 2012 that included 1948 patients with locally advanced rectal cancer recruited between February 1995 and January 2018. Statistical analysis was conducted between September 2023 and February 2024. Exposures: Receiving preoperative fluorouracil-based chemoradiotherapy (CRT, comprising the preoperative group of CAO/ARO/AIO-94 and the control group of CAO/ARO/AIO-04), fluorouracil-based CRT plus oxaliplatin (experimental group of CAO/ARO/AIO-04), or total neoadjuvant treatment (TNT) with fluorouracil-based CRT plus oxaliplatin with induction or consolidation leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin chemotherapy within the CAO/ARO/AIO-12 trial. Main Outcome and Measures: The associations of PLNM with clinical parameters, intensity of neoadjuvant treatment, and cumulative incidences of LR, DM, and overall survival were assessed. Results: A total of 1888 patients (1333 male participants [70.6%]; median [range] age, 62 [19-84] years) with locally advanced rectal adenocarcinoma (clinical tumor stage 3 to 4 and/or clinically node-positive) treated within 3 consecutive clinical trials were analyzed. A total of 522 (29%) experienced PLNM; 378 had lymph node stage (ypN) 1 (20%) after neoadjuvant treatment (ypN) 1 (20%), and 174 had ypN2 (9%). Age, clinical T-stage, N-stage, grading, carcinoembryonic antigen levels, and time interval from completion of CRT to surgery were significantly associated with PLNM, whereas sex and tumor location were not. The percentage of patients with ypN2 stage was almost halved after TNT (18 of 293 patients [6%]) compared with patients treated with fluorouracil-based CRT (114 of 1009 patients [11.3%]; χ26 = 16.693; P = .01). After a median (IQR) follow-up of 54 (37-62) months, 5-year overall survival was 86.1% (95% CI, 83.9%-88.4%) for ypN0, 74.0% (95% CI, 83.9%-88.4%) for ypN1, and 43% for ypN2 (95% CI, 35.4%-52.2%) (P < .001). The 5-year cumulative incidences of locoregional and distant metastases were, respectively, 3% (95% CI, 2.1%-4.2%) and 20% (95% CI, 18%-23%) for ypN0, 6% (95% CI, 3.4%-8.8%) and 40% (95% CI, 34%-46%) for ypN1, and 19% (95% CI, 13%-26%) and 72% (95% CI, 63%-79%) for ypN2 (both P < .001). Conclusions and Relevance: In this cohort study, PLNM unmasked an unfavorable phenotype of rectal cancer at high risk for treatment failure. More aggressive adjuvant treatment might be considered; however, risk-adapted surveillance strategies and early recurrence-directed surgery, if feasible, are important strategies in this group of patients with CRT- and/or chemotherapy-resistant disease.

Efficacy and safety of MR-guided adaptive simultaneous integrated boost radiotherapy to primary lesions and positive lymph nodes in the neoadjuvant treatment of locally advanced rectal cancer: a randomized controlled phase III trial.

BACKGROUND: In locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC. METHODS: This is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60-65 Gy in 25-28 fractions to primary lesions and positive lymph nodes; 50-50.4 Gy in 25-28 fractions to the pelvis) or intensity-modulated radiotherapy (50-50.4 Gy in 25-28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life. DISCUSSION: Since dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

Prediction of pathological response and lymph node metastasis after neoadjuvant therapy in rectal cancer through tumor and mesorectal MRI radiomic features.

Establishing predictive models for the pathological response and lymph node metastasis in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) based on MRI radiomic features derived from the tumor and mesorectal compartment (MC). This study included 209 patients with LARC who underwent rectal MRI both before and after nCRT. The patients were divided into a training set (n = 146) and a test set (n = 63). Regions of interest (ROIs) for the tumor and MC were delineated on both pre- and post-nCRT MRI images. Radiomic features were extracted, and delta radiomic features were computed. The predictive endpoints were pathological complete response (pCR), pathological good response (pGR), and lymph node metastasis (LNM). Feature selection for various models involved sequentially removing features with a correlation coefficient > 0.9, and features with P-values ≥ 0.05 in univariate analysis, followed by LASSO regression on the remaining features. Logistic regression models were developed, and their performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among the 209 LARC patients, the number of patients achieving pCR, pGR, and LNM were 44, 118, and 40, respectively. The optimal model for predicting each endpoint is the combined model that incorporates pre- and delta-radiomics features for both the tumor and MC. These models exhibited superior performance with AUC values of 0.874 (for pCR), 0.801 (for pGR), and 0.826 (for LNM), outperforming the MRI tumor regression grade (mrTRG) which yielded AUC values of 0.800, 0.715, and 0.603, respectively. The results demonstrate the potential utility of the tumor and MC radiomics features, in predicting treatment efficacy among LARC patients undergoing nCRT.

ctDNA responds to neoadjuvant treatment in locally advanced rectal cancer.

BACKGROUND: Liquid biopsy is a minimally invasive procedure investigating tumor mutations. METHODS: In our retrospective study, we investigated whether molecular therapy monitoring of patients receiving neoadjuvant radio(chemo)therapy on a daily routine is possible in 17 patients with locally advanced rectal cancer. Six patients received short-course radiotherapy (5 × 5 Gy) with subsequent surgery, six patients were treated according RAPIDO protocol with short-course radiotherapy followed by chemotherapy (FOLFOX4) and subsequent surgery and five patients received conventional neoadjuvant radiochemotherapy with 5-FU followed by surgery. Response was assessed by Dworak. Liquid biopsies were taken before and immediately after neoadjuvant radiotherapy to isolate and ultradeeply sequence cell free DNA with a panel of 127 genes. Somatic mutations were determined bioinformatically by comparison with normal DNA from leukocytes to distinguish them from germline variants or aging mutations. RESULTS: In 12 patients (71%) at least one somatic mutation was detected. In 8/12 patients a decrease and in 4/12 an increase or mixed response in ctDNA was seen. Statistical correlation between ctDNA analysis and clinical response could not be seen. CONCLUSION: ctDNA is responding to neoadjuvant therapy and liquid biopsy is easily integrated into a daily routine. As part of translational research this protocol leaves room for further investigations.

Cross-sectional investigation of the distribution characteristics and prognostic significance of lateral lymph nodes in patients with rectal cancer.

BACKGROUND: Information about the distribution characteristics and prognostic significance of lateral lymph nodes (LLNs) on primary computed tomography (CT) scan in rectal cancer patients is lacking. METHODS: Between January 2013 and December 2016, patients with pathologically proved rectal cancer and pretreatment abdominal enhanced CT in our department were screened. We firstly redivided LLNs into seven categories based on their locations. Then, the number and distribution of all measurable LLNs and the characteristics of the largest LLN in each lateral compartment were recorded. Furthermore, we investigated the long-term outcomes in patients with different LLN characteristics and LLN risk scoring. RESULTS: A total of 572 patients were enrolled in this study. About 80% of patients had measurable LLNs, and most patients developed measurable LLNs in the obturator cranial compartment. Lateral local recurrence (LLR) was observed in 20 patients, which accounted for 83.3% of the local recurrence (LR). Patients with the largest LLN short-axis diameter >10 mm had a poor prognosis, which was similar to that in patients with simultaneous distant metastasis (SDM). Patients with LLN risk scoring ≥2 had a worse prognosis than those with LLN risk scoring <2, while better than those with SDM. CONCLUSION: This study suggests that LLR is the main locoregional recurrence pattern. Most rectal cancer patients have measurable LLNs on primary CT scan. However, patients with enlarged LLNs <10 mm or LLN risk scoring <2 still have a significantly better prognosis than patients with SDM, which indicated the potential value of locoregional treatment for these LLNs.

[Distribution pattern of the rectal circumferential fascia and its clinical significance: An anatomical study].

Objective: To investigate the pattern of distribution of the circumferential fascia of the rectum and elucidate its clinical implications. Methods: In this descriptive study, we examined the gross anatomy of four male hemipelvic cadaveric specimens from the Department of Anatomy at Fujian Medical University and the histological features of 16 fresh postoperative specimens from patients who had undergone total mesorectal excision for rectal cancer at the Department of Colorectal Surgery, Union Hospital, Fujian Medical University, between January and December 2022. The resultant combination of gross anatomical and histological features was employed to assess the following areas: (1)the morphology of the anterior mesorectum and fascia at the peritoneal reflection; (2)the caudal attachment point of Denonvilliers' fascia; (3) the fusion area of the pelvic plexus and the pre-hypogastric fascia; (4)the lateral and posterior attachment edges of the rectosacral fascia; and (5) selected histological features. Results: Our findings were as follows. (1) At the peritoneal reflection, the anterior mesorectum forms a triangular fat pad with a dense fascial structure. The base of this pad extends anteriorly across the most caudal point of the peritoneal reflection, with Denonvilliers' fascia originating from the anterior side of the triangle, near the bladder side of the peritoneum craniad to the peritoneal reflection. (2) The caudal attachment of Denonvilliers' fascia is at the angle between the seminal vesicles, the ampulla of the vas deferens, and the prostate. It adheres tightly to the prostatic capsule and vascular bundles pass through its cephalic side. (3) The pre-hypogastric fascia transitions laterally to merge with Denonvilliers' fascia; its middle part being inseparable from the main body of the pelvic plexus, which gives rise to the nerves that innervate the rectum. (4) The rectosacral fascia is formed by fusion of the fascia propria with the pre-hypogastric fascia. The resultant fused fascia bifurcates into two leaves on the right side; the outer leaf being the pre-hypogastric fascia and the inner leaf the fascia propria. (5) Histologically, the peritoneal reflection zone shows cuboidal epithelium of the peritoneum at its lowest point with no detectable origin of Denonvilliers' fascia. The anterior side of the peritoneal reflection, from which Denonvilliers' fascia originates, has a dense double-layered fascial structure comprising thick collagen fiber (16/16). The fascia propria exhibits a thinner and looser collagen fiber structure and its origin varies between individuals, 13/16 originating together with Denonvilliers' fascia from the craniad side of the peritoneal reflection, and 3/16 originating separately from the most caudal point of the peritoneal reflection. The caudal edge of Denonvilliers' fascia has a double-layered fascial structure with multiple S100-stained areas. The posterior edge of the rectosacral fascia has a fused fascial structure, thick nerve fibers being clearly observable between collagen fibers originating from the pre-hypogastric fascia under high magnification. The lateral edge of the rectosacral fascia extends interiorly, maintains the integrity of the fascia propria. Conclusions: In this study, we investigated the pattern of distribution of the circumferential fascia of the rectum by cadaveric dissection and histological examination of postoperative specimens. We found that the anterior mesorectum forms a triangular fat pad that can serve as a reference for dissection anterior to Denonvilliers' fascia, by making incisions 1 cm above the peritoneal reflection. The region of fusion of Denonvilliers' fascia with the prostatic capsule on the caudal side is rich in neurovascular bundles, contradicting the traditional view of a retroprostatic plane. This finding supports the practice of cutting Denonvilliers' fascia 0.5 cm above the base of the seminal vesicles. The fusion of the fascia propria with the pre-hypogastric fascia posteriorly forms the rectosacral fascia, which bifurcates into two leaves on both sides of the rectum, the inner leaf being the fascia propria and the outer leaf the pre-hypogastric fascia. These transition anteriorly to become Denonvilliers' fascia and fuse densely with the main body of the pelvic plexus on both sides. These findings provide a theoretical foundation for protecting the pelvic plexus and hypogastric nerve by transecting Denonvilliers' fascia and then dissecting in a top-to-bottom direction (i.e., from anterior to caudal), ultimately leading to the transection of the pre-hypogastric fascia.

Local excision vs. proctectomy in patients with ypT0-1 rectal cancer following neoadjuvant therapy: a propensity score matched analysis of the National Cancer Database.

BACKGROUND: We aimed to evaluate outcomes of organ preservation by local excision (LE) compared to proctectomy following neoadjuvant therapy for rectal cancer. METHODS: This retrospective observational study using the National Cancer Database (NCDB) included patients with locally advanced non-metastatic rectal cancer (ypT0-1 tumors) treated with neoadjuvant therapy between 2004 and 2019. Outcomes of patients who underwent LE or proctectomy were compared. 1:1 propensity score matching including patient demographics, clinical and therapeutic factors was used to minimize selection bias. Main outcome was overall survival (OS). RESULTS: 11,256 of 318,548 patients were included, 526 (4.6%) of whom underwent LE. After matching, mean 5-year OS was similar between the groups (54.1 vs. 54.2 months; p = 0.881). Positive resection margins (1.2% vs. 0.6%; p = 0.45), pathologic T stage (p = 0.07), 30-day mortality (0.6% vs. 0.6%; p = 1), and 90-day mortality (1.5% vs. 1.2%; p = 0.75) were comparable between the groups. Length of stay (1 vs. 6 days; p < 0.001) and 30-day readmission rate (5.3% vs. 10.3%; p = 0.02) were lower in LE patients. Multivariate analysis of predictors of OS demonstrated male sex (HR 1.38, 95% CI 1.08-1.77; p = 0.009), higher Charlson score (HR 1.52, 95% CI 1.29-1.79; p < 0.001), poorly differentiated carcinoma (HR 1.61, 95% CI 1.08-2.39; p = 0.02), mucinous carcinoma (HR 3.53, 95% CI 1.72-7.24; p < 0.001), and pathological T1 (HR 1.45, 95% CI 1.14-1.84; p = 0.002) were independent predictors of increased mortality. LE did not correlate with worse OS (HR 0.91, 95% CI 0.42-1.97; p = 0.82). CONCLUSION: Our findings show no overall significant survival difference between LE and total mesorectal excision, including ypT1 tumors. Moreover, patients with poorly differentiated or mucinous adenocarcinomas generally had poorer outcomes, regardless of surgical method.

Outcomes of robotic versus laparoscopic-assisted surgery in patients with rectal cancer: a systematic review and meta-analysis.

PURPOSE: Robotic-assisted rectal surgery (RARS) and Laparoscopic-assisted rectal surgery are the two techniques that are increasingly used for rectal cancer, and both have their advantages and disadvantages. This meta-analysis will analyze the outcomes of both techniques to determine their relative performance and suitability. METHODS: An extensive search was carried out on PubMed, Cochrane, Scopus, Embase, and Google Scholar, followed by a meta-analysis of all randomized controlled trials (RCTs) to assess both approaches for rectal cancer. RESULTS: This meta-analysis is comprised of fifteen RCTs. The conversion to open surgery (RR = 0.53, 95% CI: 0.38-0.74, P = 0.0002) was significantly lower in the RARS group. The outcomes like anastomotic leak, postoperative ileus, postoperative urinary retention (POUR), surgical site infection (SSI), and intra-abdominal abscess showed no significant difference between the two groups. The reoperation rate (RR = 0.56, 95% CI: 0.34-0.95, P = 0.03) was lower in the robotic group. High heterogeneity was obtained when pooling data on operative time, length of hospital stay, and blood loss. Oncological outcomes, including local recurrence, the number of harvested lymph nodes (LN) and distal resection margin showed no significant distinction among both groups, while the positive circumferential resection margin (CRM) (RR = 0.67, 95% CI: 0.49-0.91, P = 0.01) was lower in the RARS group. RARS demonstrated a significantly higher rate of total mesorectal excision (TME) (RR = 1.07, 95% CI: 1.01-1.14, P = 0.03). CONCLUSION: RARS is safe and feasible for rectal cancer patients and may be superior or equivalent to Laparoscopic-assisted rectal surgery, but high-standard, large-scale trials are required to determine the best approach.

Validation of a genome-based model for adjusting radiotherapy dose (GARD) in patients with locally advanced rectal cancer.

Neoadjuvant radiotherapy is the standard care of locally advanced rectal cancer. Although a majority of patients received the same dose, the curative efficacy varies among individuals. In recent years, cancer treatment has entered the era of precise medical care, and how to identify patients for proper treatment by molecular signature is an important path of individualized therapy. This study aimed to establish and validate a genome-based model for adjusting radiation dose (GARD) for Chinese locally advanced rectal cancer through gene expression microarrays, and to evaluate the response of the GARD model in predicting the efficacy of neoadjuvant radiotherapy. Fresh-frozen primary tumor from 64 patients with locally advanced rectal cancer undergoing neoadjuvant radiotherapy from 2015 to 2018 were included. The gene expression profile was analyzed using Affymetrix 3000Dx gene-chip scanner. The radiosensitivity index (RSI) and GARD were calculated using the pGRT™ algorithm. Neoadjuvant rectal cancer score (NAR) was selected as efficacy evaluation indicators. Patients were divided into high and low NAR scoring groups, and two-sample t-test was used to analyze the differences in GARD values between different NAR subgroups. ROC curves were used to calculate the cut-off values and the area under the curve (AUC) for assessing the validity of the GARD models. The personalized radiation dose ( pGRT dose )can be computed using the formula nd = GARD / (α + ßd). Among patients, 1.5% T2, 46.3% T3, and 52.2% T4. Wherein pCR (n = 10; 15.6%) and no pCR (n = 54; 84.4%). The median NAR is 8.43 (rang from 0 to 50.34, IQR 3.75-14.98). NAR > 8.43 (n = 27; 42.2%) and NAR ≤ 8.43 (n = 37; 57.8%), suggesting that there are significant individual differences in clinical efficacy of patients with similar tumor stages and under the same treatment conditions. The median RSI is 0.48 (rang from 0.22 to 0.92, IQR 0.41-0.55). Median GARD was 18.40 rang from (rang from 2.26 to 37.52, IQR 14.94-22.28) within tumor tissue, suggesting individual differences in the efficacy of radiation therapy. The RSI value was significantly lower in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (0.44 vs. 0.54, p = 0.0003). The GARD value was significantly higher in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (21.01 vs. 15.88, p = 0.0004). Using the Receiver Operating Characteristic (ROC) curve analysis, a GARD threshold of 17 was identified as optimal, covering 37.5% of the 64-patient sample, with an area under the curve (AUC) of 0.75. In the external validation cohort, the high GARD score group demonstrated superior DFS compared to the low GARD score group(p < 0.001). Only 17% of patients had pGRT dose within the guideline recommended dose (45-50 Gy). The differences in NAR values among LARC patients receiving standard neoadjuvant radiotherapy suggest significant individual differences in clinical outcomes among patients with similar tumor stage and the same treatment conditions. Patients with a GARD value exceeding 17 exhibit a more favorable prognosis. Our results suggest that the gene expression-based pGRT™ algorithm has good efficacy prediction performance in preoperative concurrent radiotherapy for locally advanced rectal cancer, suggesting the potential clinical application of this method to guide the designation of individualized radiotherapy doses.

Baseline MRI predictors of successful organ preservation in the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial.

BACKGROUND: Prospective randomized trials have not yet identified baseline features predictive of organ preservation in locally advanced rectal cancers treated with total neoadjuvant therapy and a selective watch-and-wait strategy. METHODS: This was a secondary analysis of the OPRA trial, which randomized patients with stage II-III rectal adenocarcinoma to receive either induction or consolidation total neoadjuvant therapy. Patients were recommended for total mesorectal excision, or watch and wait based on clinical response at 8 ± 4 weeks after completing treatment. Standardized baseline clinical and radiological variables were collected prospectively. Survival outcomes, including total mesorectal excision-free survival, disease-free survival, and overall survival, were assessed by intention-to-treat analysis. Cox proportional hazards models were used to evaluate associations between baseline variables and survival outcomes. RESULTS: Of the 324 patients randomized for the OPRA trial, 38 (11.7%) had cT4 tumours, 230 (71.0%) cN-positive disease, 101 (32.5%) mesorectal fascia involvement, and 64 (19.8%) extramural venous invasion. Several baseline features were independently associated with recommendation for total mesorectal excision on multivariable analysis: nodal disease (HR 1.66, 95% c.i. 1.12 to 2.48), extramural venous invasion (HR 1.57, 1.07 to 2.29), mesorectal fascia involvement (HR 1.45, 1.01 to 2.09), and tumour length (HR 1.11, 1.00 to 1.22). Of these, nodal disease (HR 2.02, 1.15 to 3.53) and mesorectal fascia involvement (HR 2.02, 1.26 to 3.26) also predicted worse disease-free survival. Age (HR 1.03, 1.00 to 1.06) was associated with overall survival. CONCLUSION: Baseline MRI features, including nodal disease, extramural venous invasion, mesorectal fascia involvement, and tumour length, independently predict the likelihood of organ preservation after completion of total neoadjuvant therapy. Mesorectal fascia involvement and nodal disease are associated with disease-free survival.