Node-positive Rectal Cancer Research Articles

Postoperative Morbidity and Factors Predicting the Development of Lymphoceles Following Lateral Pelvic Node Dissection for Rectal Cancer: A Cohort Study.

Lateral pelvic node dissection (LPLND) is indicated inthe surgical management of clinically significant pelvic lymphadenopathy associated with rectal malignancies. However, procedure-related morbidity, including the incidence and predisposing factors for lymphoceles arising in this setting have not been adequately evaluated. This retrospective single-institution study included 183 patients with nonmetastatic, lateral node-positive rectal cancer undergoing total mesorectal excision with LPLND between June 2014 and May 2023 to determine the incidence and severity of postoperative complications using the Clavien-Dindo system, with logistic regression performed to model a relationship between lymphocele-development and potentially-predictive variables. In this cohort, mean age was 45.3 ± 12.81 years, 62.8% were male, and 27.9% had body mass index ≥ 25kg/m2. Median tumor-distance from the verge was 3.0 (interquartile range [IQR] 1.0-5.0)cm. Following radiotherapy in 86.9%, all patients underwent surgery: 30.1% had open resection and 26.2% had bilateral LPLND. Median nodal-yield was 6 (IQR 4-8) per side. Postoperatively, 45.3% developed complications, with 18% consideredclinically significant. Lymphoceles, detected in 21.3%, comprised the single-most common sequelae following LPLND, 46.2%arising within 30 days of surgery and 33.3% requiring intervention. On multivariate analyses, obesity (hazard ratio [HR] 2.496; 95% confidence interval [CI] 1.094-5.695), receipt of preoperative radiation (HR 10.026; 95% CI 1.225-82.027), open surgical approach (HR 2.779; 95% CI 1.202-6.425), and number of harvested nodes (HR 1.105; 95% CI 1.026-1.190) were significantly associated with lymphocele-development. Pelvic lymphoceles and its attendant complications represent the most commonly encountered morbidity following LPLND for rectal cancer, with obesity, neoadjuvant radiotherapy, open surgery, and higher nodal-yield predisposing to their development.

Uterine Anastomosis with Low Anterior Resection.

In this surgical teaching video, we demonstrate the technique of robot-assisted uterine anastomosis combined with low anterior resection in a 27-year-old patient with T2 node-positive rectal cancer. The patient had undergone uterine transposition for fertility preservation prior to upfront chemotherapy and radiation therapy for rectal cancer. In this video, we review the key steps of both surgical procedures. We emphasize robot trocar placement and docking, demonstrate optimal organ manipulation and tissue handling, and include key operative modifications and pearls for successful perioperative management.

Adjuvant chemotherapy in patients with clinically node-negative but pathologically node-positive rectal cancer in the Netherlands: A retrospective analysis

IntroductionAccurate clinical staging of rectal cancer is hampered by suboptimal sensitivity of MRI in the detection of regional lymph node metastases. Consequently, some patients may be understaged and have been withheld neoadjuvant (chemo)radiotherapy in retrospect. Although Dutch guidelines do not advocate adjuvant chemotherapy (ACT) in rectal cancer, some of these clinically understaged patients receive ACT according to local policy. We aim to assess the benefit of ACT in these patients. MethodsPopulation-based data from patients with clinically node-negative (cN0) but pathologically node-positive (pN+) rectal cancer that underwent total mesorectal excision (TME) without neoadjuvant treatment between 2008 and 2018 were obtained from the Netherlands Cancer Registry. Missing data were handled by multiple imputation. Stabilised inverse probability treatment weighting (sIPTW) was used to balance clinical characteristics. Overall survival (OS) was compared in ACT and non-ACT patients. ResultsOf 34,724 patients, 13,861 had cN0 disease of whom 3016 were pN+ (21.8%). 1466 (48.6%) of these patients underwent upfront TME and were included. Median follow-up was 84 months (95% confidence interval [CI] 76–97) versus 79 months (95% CI 77–81) in patients that did (n = 290, 19.8%) and did not (n = 1176, 80.2%) receive ACT, respectively. After sIPTW adjustment, ACT was associated with improved OS (hazard ratio 0.70; 95% CI 0.49–0.99; p = 0.04). The estimated 5-year OS rate was 74.2% versus 65.3%, respectively. ConclusionIn this population-based cohort of patients with cN0 but pN+ rectal cancer who underwent upfront TME, ACT was associated with a significant OS benefit. These data support to discuss ACT in this population.

Lateral Pelvic Nodal Management and Patterns of Failure in Patients Receiving Short-Course Radiation for Locally Advanced Rectal Cancer.

Management of lateral pelvic lymph nodes in locally advanced rectal cancer is controversial, with limited data indicating the optimal approach. Additionally, no data exists regarding treatment of lateral nodes in the setting of short course radiation and nonoperative intent. We evaluate a novel approach incorporating simultaneous integrated boost to suspicious lateral nodes. This was a retrospective study. This study was conducted at a large, tertiary referral center. Patients treated with radiation and consolidation chemotherapy were included. All primary tumors were biopsy confirmed and disease-staged with pelvic magnetic resonance imaging. Primary tumors were biopsy proven and staged with pelvic magnetic resonance imaging. A subset of lateral pelvic lymph nodes patients received simultaneous integrated boost to 35 Gy in 5 fractions. Then, chemotherapy was administered with the majority receiving mFOLFOX (modified folinic acid, fluorouracil, and oxaliplatin). Clinical partial response required total mesorectal excision. Patterns of failure and survival analyses by subgroup were assessed. Outcomes based on receipt of radiation were compared across node status. Between January 2017 - January 2022, 155 patients were treated with short course and chemotherapy with 121 included in final analysis. Forty-nine percent underwent nonoperative management. Median follow-up was 36 months and median age was 58 years. Thirty-eight patients (26%) had positive lateral pelvic lymph nodes. Comparing lateral node status, progression-free survival was significantly worse for patients with positive disease (p < 0.001) with a trend for worse overall survival. Receipt of nodal boost in patients with lateral nodes resulted in meaningful locoregional control. Nodal boost did not contribute to additional acute or late GI toxicity. Limitations included retrospective nature and lack of lateral nodes pathology; however, thorough radiographic review was performed. Lateral node positive rectal cancer is correlated with worse oncologic outcomes and higher locoregional failure. Boost to clinically positive lateral nodes is a safe approach in the setting of short course and in those receiving nonoperative intent.

Bibliometric analysis and visualization of research trends in total mesorectal excision in the past twenty years.

Rectal cancer leads a major disease burden worldwide. Total mesorectal excision (TME) is the standard treatment for locally advanced or node-positive rectal cancer, while attempts to improve the surgery such as laparoscopic and transanal TME are widely used but have their inherent limitations. This bibliometric study analyzed research trends, cooperation, and knowledge dissemination on TME over the past 20 years to inform future directions. Relevant literature from 2003 to 2023 was extracted from the Web of Science Core Collection and analyzed with VOSviewer, CiteSpace, and R for publication patterns, countries, institutions, authors, and research hotspots. Five thousand three hundred forty-five related publications were included, with rising annual output and citations. The US and China contributed the most studies, while the Netherlands had greater influence. Leiden University ranked first in publications. The top authors were Heald, Kapiteijn, Sauer, Nagtegaal, and Peeters. Research shifted from cancer-focused to patient-centered care and from radiotherapy/chemotherapy to advanced surgery. Multicenter trials became more common. Although the United States and China have the largest number of publications, it should be noted that the influence of these two countries in the field of TME research is not the highest, which does not match the number of publications. In addition, telemedicine, interdisciplinary, medical-industrial integration, etc. may be potential directions for future research in the field of TME.

Magnetic resonance imaging radiomics modeling predicts tumor deposits and prognosis in stage T3 lymph node positive rectal cancer.

To develop a magnetic resonance imaging radiomics model to predict tumor deposits (TDs) and prognosis in stage T3 lymph node positive (T3N+) rectal cancer (RC). This retrospective study included 163 patients with pathologically confirmed T3N + RC from December 2013 to December 2015. The patients were divided into two groups for training and testing. Extracting radiomic features from MR images and selecting features using principal component analysis (PCA), then radiomic scores (rad-scores) were obtained by logistic regression analysis. Finally, a combined TDs prediction model containing rad-scores and clinical features was developed. A receiver operating characteristic (ROC) curve was used to assess the prediction performance. The overall survival (OS) rate in patients with high-risk and low-risk TDs predicted by rad-scores was validated by Kaplan-Meier survival curves. Of the 163 patients included, histological TDs was diagnosed in 45 patients. The area under the curve (AUC) of the final model was 0.833 (training) and 0.844 (testing). The patients with rad-scores predicted high-risk were associated with OS. In addition, postoperative adjuvant therapy improved the OS of the high-risk TDs group (P < 0.05). MRI-based radiomics modeling helps in the preoperative prediction of patients with TDs+ in T3N + RC and provides risk stratification for neoadjuvant therapy. In addition, the rad-scores of TDs could suggest different survival benefits of postoperative adjuvant therapy for T3N + RC patients and guide clinical treatment.

An International Multicenter Prospective Study Evaluating the Long-term Oncological Impact of Adjuvant Chemotherapy in ypN+ Rectal Cancer.

To assess the oncological benefit of adjuvant chemotherapy (AC) in node positive (ypN+) rectal cancer after neoadjuvant chemoradiotherapy and radical surgery. The evidence for AC after total mesorectal excision for locally advanced rectal cancer is conflicting and the net survival benefit is debated. An international multicenter comparative cohort study was performed comparing oncological outcomes in tertiary rectal cancer centers from the Netherlands and France. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision surgery and with positive lymph nodes on histologic examination (ypN+) were included for analysis. Kaplan-Meier curves were generated to compare disease-free (DFS) and overall survival in AC and non-AC groups. Of 1265 patients screened, a total of 239 rectal cancer patients with ypN+ disease were included. Demographic and clinical characteristics were similar in both groups. Higher systemic recurrence rates were observed in the non-AC group compared with those who received AC [32.0% (n=40) vs 17.5% (n=11), respectively, P =0.034]. DFS at 1 and 5 years postoperatively were significantly better in the AC group (92% vs 80% at 1 year; 72% vs 51% at 5 years, P =0.024), whereas no difference in overall survival was observed. In this multicenter comparative cohort study, we identified an oncological benefit of AC in both systemic recurrence and DFS in ypN+ rectal cancer patients. From this data, systemic chemotherapy continues to confer oncological benefit in locally advanced ypN+ rectal cancer.

Are We Overestimating Rectal Cancer Nodal Involvement?

<h3>Purpose/Objective(s)</h3> Per current guidelines, rectal cancer is staged with pelvic MRI (or EUS if MRI contraindicated) to determine T- and N-stage. Those with ≥ clinical stage T3 (cT3) or N1 (cN1) are recommended to neoadjuvant treatment (NT). The specificity of MRI for N-staging of rectal cancer is ∼ 70% - this is lower than the specificity of MRI for T-staging. Thus, for those cancers for which NT is recommended based on N-staging, there is the potential that up to 30% of patients are over-staged. The current retrospective study aims to quantify the percentage of clinically lymph node positive (cN+) rectal cancers treated with NT that have pathologic complete nodal response (ypN0) with no treatment effect noted at surgical resection. <h3>Materials/Methods</h3> Cases of cN+ rectal cancer treated at our COC-Accredited INCP institutions between 2015 - 2020 were identified. Data were collected with regard to staging modality, clinical T- and N-stage, size of largest suspicious lymph node (LN) on MRI, NT-type (total neoadjuvant therapy (TNT) with capecitabine/RT (CRT), TNT with short course RT (SCRT), or neoadjuvant radiation or chemoradiation alone), ypN-stage, and treatment effect. We compared proportions of ypN0 cases by cT- and cN-stage, size of largest suspicious LN on MRI, and NT-type using multivariable logistic regression. <h3>Results</h3> A total of 64 cases of cN+ rectal cancer were identified. Fifty-three were staged by MRI, 2 by EUS, 2 by PET, and 7 by CT. Primary tumor staging was as follows: cTx = 2, cT1 = 1, cT2 = 10, cT3 = 36, cT4 = 15. Clinical N-stage was as follows: cN1 = 41, cN2 = 23. For 13 patients (20%), the recommendation for NT was based entirely on MRI N+ staging. Fifty-seven patients were treated with TNT: All with FOLFOX followed by 44 with CRT and 13 with SCRT. Seven patients were treated with neoadjuvant CRT or SCRT without neoadjuvant FOLFOX. Pathologic results showed residual ypN2 disease in 4 cases, ypN1 disease in 19 cases and ypN0 disease in 42 cases (65%) with treatment effect (n = 5) or possible treatment effect (n = 3) noted in 8 of those cases. ypN0 disease was seen in 57% (n = 4) receiving no TNT, 46% (n = 6) receiving TNT with SCRT, and 72% (n = 32) receiving TNT with CRT. Of the 13 patients with cTx-T2 tumors who received NT based on cN+ status, 10 (77%) had ypN0 disease and 1 had signs of treatment effect in a LN. On multivariable logistic regression, cN-stage (cN1 vs cN2) predicated for ypN+ disease with a hazard ratio of 5.15 for cN2 disease (<i>p</i> = 0.0076). cT-stage, size of largest suspicious LN on MRI and NT-type did not predict for yp nodal status. <h3>Conclusion</h3> In patients with cN+ rectal cancer (staged predominately by MRI), more than half of patients had no pathologic residual nodal disease and no treatment effect noted in the LN. While this finding is in line with the results of major randomized trials such as RAPIDO, it confirms a 65% rate of ypN0 disease following neoadjuvant treatment for cN+ rectal cancer in the setting of a 70% specificity of MRI for rectal cancer nodal staging. cN2 disease predicts for residual pathologic LN disease.

Total Neoadjuvant Therapy Treatment Sequence and its Impact on Pathologic Complete Response and Survival in Patients with Locally Advanced Rectal Cancer

Several recent studies have suggested that total neoadjuvant therapy (TNT) provides improved pathologic response and disease-free survival over neoadjuvant chemoradiation. However, the timing of the radiation as a part of the total neoadjuvant paradigm is unclear. In some studies radiation has been used first and others it has been used after chemotherapy. This study compares pathologic complete response (pCR) and survival patterns with TNT using upfront chemotherapy followed by chemoradiation (C-CRT) versus upfront chemoradiation followed by chemotherapy (CRT-C) in patients with locally advanced rectal cancer using the National Cancer Database.Patients with cT3/4 or node positive rectal cancer, diagnosed between 2004-2017 were included. TNT with chemotherapy first was defined as chemotherapy given at least two months before concurrent chemoradiotherapy followed by definitive surgery. CRT-C was defined as chemotherapy and radiation starting within 14 days of each other, followed by chemotherapy, followed by definitive surgery four to six months later. Minimum follow up was 6 months, in order to account for immortal time bias. Multivariable logistic regression was performed to assess whether upfront chemotherapy followed by chemoradiation versus upfront chemoradiation followed by chemotherapy was significantly associated with pCR, defined as ypT0N0. Overall survival (OS) was analyzed via Kaplan-Meier method with the log-rank test. Multivariable Cox regression analysis was used to assess the impact of covariates on OS.There were 9,393 TNT cases identified. Of these, 1522(16.2%) received C-CRT and 7871(83.8%) received CRT-C. The pCR was 12.2% in both groups. On multivariable logistic regression analyses, there was no difference in pCR based on the timing of the radiation (OR 0.987, 95% CI 0.824-1.183, P = .89). Kaplan-Meier analysis revealed that the 5-year OS rates for TNT was superior for C-CRT over CRT-C, with 5-year OS of 66.5% vs. 65.9% (P = 0•020). However, on multivariable Cox regression, there was no significant difference in OS between C-CRT and CRT-C (HR = 0.981, 95% CI 0.864-1.115, P = 0•772).In this large hospital-based study, most patients receiving TNT received chemoradiation upfront. There were no differences in pCR or overall survival based on the timing of the radiation treatments.

CTSE Overexpression Is an Adverse Prognostic Factor for Survival among Rectal Cancer Patients Receiving CCRT.

The introduction of preoperative concurrent chemoradiotherapy (CCRT) increases the rate of anal preservation and allows tumor downstaging for clinical stage T3/T4 or node-positive rectal cancer patients. However, there is no precise predictive tool to verify the presence of residual tumor apart from surgical resection. The gastrointestinal (GI) tract not only digests nutrients but also coordinates immune responses. As the outermost layer of the GI tract, mucus plays a key role in mediating the interaction between the digestive and immune systems, and aberrant mucus mesh formation may cause chemoresistance by impeding drug delivery. However, the correlations among digestion-related genes, mucin synthesis, and chemoresistance remain poorly understood. In the present study, we evaluated genes related to digestion (GO: 0007586) and identified cathepsin E (CTSE), which is involved in immune regulation, as the most significantly upregulated gene associated with CCRT resistance in rectal cancer in a public transcriptome dataset (GSE35452). We recovered 172 records of rectal cancer patients receiving CCRT followed by surgical resection from our biobank and evaluated the expression level of CTSE using immunohistochemistry. The results revealed that tumors with CTSE overexpression were significantly correlated with pre-CCRT and post-CCRT positive nodal status (both p < 0.001), advanced pre-CCRT and post-CCRT tumor status (p < 0.001 and p = 0.002), perineural invasion (p = 0.023), vascular invasion (p < 0.001), and a lesser degree of tumor regression (p = 0.003). At the univariate level, CTSE overexpression was an adverse prognostic factor for all three endpoints: disease-specific survival (DSS), metastasis-free survival (MeFS) (both p < 0.0001), and local recurrence-free survival (LRFS) (p = 0.0001). At the multivariate level, CTSE overexpression remained an independent prognostic factor for poor DSS, MeFS (both p = 0.005), and LRFS (p = 0.019). Through bioinformatics analysis, we speculated that CTSE overexpression may confer CCRT resistance by forming a defensive mucous barrier. Taken together, these results suggest that CTSE overexpression is related to CCRT resistance and inferior survival in rectal cancer patients, highlighting the potential predictive and prognostic value of CTSE expression.

Predictive factors associated with complete pathological response after neoadjuvant treatment for rectal cancer

PurposeA proportion of 10 to 30% of patients treated by chemoradiotherapy followed by total mesorectal excision surgery for a locally advanced rectal cancer can achieve a complete pathological response. We aimed to identify predictive factors associated with complete pathological response or no response and to assess the impact of each response on survival rates. Patients and methodsPatients treated with long course chemoradiotherapy for locally advanced and/or node positive rectal cancer from 2010 to 2016 were retrospectively reviewed. Statistical analysis was carried out to determine predictors of tumor regression and treatment outcomes. ResultsRecords were available on 70 patients. In the univariate analysis, clinical factors associated with complete tumor response were tumor mobility in digital rectal examination (P=0.047), a limited parietal invasion (P=0.001), clinically negative lymph node (P<0.001) and a circumferential extent greater than 50% (P=0.001). On the other hand, a T4 classification and an endoscopic tumor size greater than 6cm were associated with no response to treatment (P=0.049 and P=0.017 respectively). On multivariate analysis, T2 clinical classification and N0 statement before treatment were independent predictive factors of pathologic complete response (P<0.001 and P=0.001) and a delayed surgery after 12 weeks was associated with no response to treatment (P=0.001). ConclusionThe identification of predictive factors of histological response may help clinicians to predict the prognosis and to propose organ preservation for good responders.

Lymph Node Ratio as a Prognostic Marker in Rectal Cancer Survival: A Systematic Review and Meta-Analysis.

Introduction The lymph node ratio (LNR) is defined as the ratio of the number of positive lymph nodes to the total number of nodes retrieved. LNR has recently emerged as a prognostic factor in rectal cancer. The objective of our study was to pool eligible studies to elucidate the prognostic role of LNR on overall survival (OS) and disease-free survival (DFS) in rectal cancer patients using a meta-analysis.MethodsA systematic database search was performed in MEDLINE and Embase for relevant studies that reported LNR in rectal cancer. Two authors independently screened the relevant articles for selection and data extraction. As a result, a list of such studies and references, published in English up to December 2019, was obtained, and a total of 4,486 node-positive patients in 18 studies were included in this meta-analysis. RevMan software 5.3 (Cochrane Collaboration, the Nordic Cochrane Centre, Copenhagen) was used for conducting all statistical analyses.ResultsA higher LNR was significantly correlated with worse OS [hazard ratio (HR): 2.60; 95% confidence interval (CI): 2.21-3.06; p≤.00001] and DFS (HR: 2.43; 95% CI: 2.11-2.80; p≤.00001) in node-positive rectal cancer patients. Besides, LNR is an independent predictive and prognostic marker of OS and DFS (HR: 2.52; 95% CI: 2.17-2.94; p≤.00001 with I2=0%; p=.32 and HR: 2.63; 95% CI: 2.17-3.18; p≤.00001 with I2=0%; p=.63 respectively, irrespective of lymph nodal harvest).ConclusionsOur present study demonstrates that LNR is an independent predictor of survival in rectal cancer. LNR should be considered as a parameter in future oncological staging systems. Further well-designed randomized control trials to prospectively assess LNR as an independent predictor of rectal cancer survival are necessary before its application in daily practice.

87P - Negative to positive lymph node ratio-prognostic marker of survival in node positive rectal cancer

BackgroundSurvival outcome in rectal cancer primarily determined by nodal status and stage of tumour. Though nodal invasion is strong prognostic indicator in rectal cancer, there exists marked heterogenecity within stage III patients. We investigated the prognostic impact of ratio of positive lymph nodes to total number of retrieved nodes (LNR), ratio of positive to negative lymph nodes (PN-LNR) and negative to positive nodes (NP-LNR) on survival in patients with node positive rectal cancers. MethodsThis is a retrospective analysis of 336 patients of rectal cancer who underwent surgery and adjuvant therapy between 2011 to 2014. The node positive patients were grouped into two groups based on quartiles of LNR <0.2 and >0.2, PN-LNR <0.36 and >0.36 and NP-LNR <2.38 and >2.38. The association between LNR, PN-LNR and NP-LNR and survival was evaluated by the Kaplan-Meier method and multivariate analysis with covariates of prognostic significance in univariate analysis. ResultsPatients classified as LNR <0.2 and >0.2 had a 5-year OS of 86.8 and 64.4 (p < 0.001) and DFS of 85.4 and 59.9 respectively (p < 0.001). The 5-year OS rate for PN-LNR <0.36 and >0.36 were 85.1 and 55.1 (p < 0.001) and DFS of 83.9 and 49.3 respectively (p < 0.001). The 5-year OS rate for NP-LNR <2.38 and >2.38 were 53.1 and 87.3 (p < 0.001) and DFS of 47.5 and 85.6 respectively (p < 0.001). OS and DFS of stage III A, III B, III C were 80.3,75.3, and 53.3 (p < 0.001) and 79.5,71.8 and 47.8 respectively (p < 0.001). On univariate analysis, pN status, sex, grade, histology of tumour, LNR, PN-LNR, NP-LNR were found to be significator factors for OS. On multivariate analysis, NP-LNR was found to be significant factor for OS. (p < 0.001, HR = 17.857; [3.557-89.657]). Factors that were found to be significant for DFS were pN status, LNR, PN-LNR, NP-LNR on univariate analysis and NP-LNR on multivariate analysis. (p < 0.001, HR = 11.41; [1.928-67.634]). NP-LNR is found to a significant factor for OS and DFS both on univariate and multivariate analysis. ConclusionsThe NP-LNR was recognised as an independent prognostic factor in node positive rectal cancer patients. Hence, it can be used as an independent prognostic factor and permits superior prognostic stratification in stage III rectal cancer. Legal entity responsible for the studyKidwai Memorial Institute of Oncology. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Organ Preservation Among Patients With Clinically Node-Positive Rectal Cancer: Is It Really More Dangerous?

Select patients with complete clinical response to chemoradiation have been managed without radical surgery. The presence of radiologic evidence of nodal metastases at baseline could be a risk factor for local tumor regrowth, more advanced stage at the time of recurrence, and worse distant metastases-free survival. The purpose of this study was to compare the outcomes of patients with baseline node-positive and node-negative cancer after neoadjuvant chemoradiation and complete clinical response managed nonoperatively. This was a retrospective review of consecutive patients with nonmetastatic distal rectal cancer undergoing neoadjuvant chemoradiation. Consecutive patients with clinical and radiologic evidence of complete clinical response at 8 to 10 weeks were managed nonoperatively and enrolled in a strict follow-up program (watch and wait). Patients with incomplete clinical response or tumor regrowth after initial complete clinical response were referred to surgery. Surgery-free and distant metastases-free survival were compared between patients according to nodal status at baseline. A total of 117 patients with node-positive and 218 with node-negative cancer at baseline were reviewed. Overall, 62 (53.0%; node positive) and 135 (61.9%; node negative) achieved a complete clinical response and were managed nonoperatively (p = 0.13). Patients with baseline node-positive cancer had similar rates of pathologic nodal metastases at the time of recurrence. Five-year surgery-free (39.7% vs 46.8%; p = 0.2) and distant metastases-free survival (77.5% vs 80.5%; p = 0.49) were similar between baseline node-positive and node-negative patients. This was a retrospective study with a small sample size and possible inaccurate nodal staging. Patients with rectal cancer with node-positive cancer at baseline who develop a complete clinical response after neoadjuvant chemoradiation are not at increased risk for local tumor regrowth or development of more advanced disease at the time of recurrence. These patients seem to be safe candidates for organ-preserving strategies after achieving complete clinical response. See Video Abstract at http://links.lww.com/DCR/A902.

Total Mesorectal Excision Versus Local Excision After Preoperative Chemoradiotherapy in Rectal Cancer With Lymph Node Metastasis: A Propensity Score–Matched Analysis

Todetermine whether local excision (LE) outcomes were comparable to total mesorectal excision (TME) outcomes in node-positive (cN+) rectal cancer patients who were good responders. This retrospective study included clinical T2-3 and cN+low rectal cancer patient who received preoperative chemoradiotherapy (PCRT) followed by TME or LE. Clinical stage T1 or T4 tumors, upper-to-middle rectal tumors (>7cm from anal verge), and synchronous distant metastases were excluded. Lymph nodes ≥5mm in size were defined as tumor-positive, and patients with metastatic lymph nodes >20mm in size were excluded. Preoperative chemoradiotherapy comprised radiation (50-50.4Gy/25-28 fractions over 5weeks) with 2 cycles of 5-fluorouracil or oral capecitabine. Propensity scores were computed from tumor and patient variables and used for 1-to-1 matched analysis. Local recurrence-free survival, disease-free survival, and overall survival were compared between the 2 matched groups. Between January 2007 and December 2013, 563 and 55 patients underwent TME and LE, respectively. The median follow-up period was 54months. In propensity score-matched analysis, 48 patients were included in each group. No statistical differences were observed in 3-year local recurrence-free survival (97.9% vs 97.9%, P=.994), 3-year disease-free survival (91.5% vs 91.4%, P=.968), or 3-year OS (93.7% vs 97.9%, P=.809) between the TME and LE groups. In clinical N+ rectal cancer patients, oncologic outcomes of PCRT followed by LE were comparable to those of TME; this finding might be applicable only to those patients with good response in the primary tumor and small lymph node metastases.

The negative impact of understaging rectal cancer patients

BackgroundNeo-adjuvant chemoradiation followed by surgery and adjuvant therapy is standard treatment of clinical node positive rectal cancer. Understaging leads to delay in treatment with possible detrimental results. This study analyses effects of understaging stage III rectal cancer on long-term outcomes. MethodsA consecutive series of patients, operated on in MGH between 2004 and 2015 was included. Outcomes of non-neoadjuvantly treated clinical stage I patients who turned out to have pathological stage III disease and neoadjuvantly treated clinical stage III patients were retrospectively reviewed. The latter group was subdivided into patients who had persistent nodal disease (ypN+) and patients without positive lymph nodes after neoadjuvant treatment (ypN0). ResultsOf the 204 included patients, 30 had unexpected nodal disease on pathology. Clinical stage I-patients had higher rates of local recurrence, and rectal cancer and overall mortality than ypN0-patients. ConclusionUnderstaging stage III rectal cancer led to poorer oncologic outcomes, when compared to patients without positive lymph nodes on pathology after neoadjuvant. Future research should focus on identifying patients with treatment susceptible lymph node involvement.

Prognostic significance of the distribution of lymph node metastasis in rectal cancer after neoadjuvant chemoradiation.

This study aimed to evaluate the prognostic significance of lymph node distribution (LND) in rectal cancer after neoadjuvant chemoradiation. A total of 519 patients with primary rectal cancer who underwent curative resection after neoadjuvant chemoradiation were included. LND was classified into four groups: LND0, no lymph node metastasis (368/519, 70.9%); LNDp, lymph node metastasis along the inferior mesenteric artery (proximal) (15/519, 2.9%); LNDm, lymph node metastasis at the mesorectum (109/519, 21.0%); and LNDpm, lymph node metastasis at both the proximal and mesorectal areas (27/519, 5.2%). Clinicopathologic characteristics were analyzed to identify independent prognostic factors. In patients with positive lymph nodes, LND showed superior discrimination for 3-year DFS (LNDp 67.7%, LNDm 48.9%, and LNDpm 26.8%, P = 0.003) and 3-year LRFS (LNDp 93.3%, LNDm 81.4%, and LNDpm 60.5%, P = 0.009) compared to ypN stage (3-year DFS, N1 47.8%, N2 40.0%, P = 0.184; 3-year LRFS, N1 79.4%, N2 75.2%, P = 0.527). On multivariate survival analysis, LND was an independent prognostic factor for LRFS (P = 0.030) in patients with positive lymph nodes. LND may improve the prognostic value of the ypTNM staging system for patients with node-positive rectal cancer after neoadjuvant chemoradiation, particularly in terms of local recurrence.

Clinically Node Negative, Pathologically Node Positive Rectal Cancer Patients Who Did Not Receive Neoadjuvant Therapy

PurposeNeoadjuvant chemoradiotherapy is the preferred standard of care for clinical stages II–III rectal cancer. It is uncertain whether clinically node negative (cN−) tumors found to be pathologically stage III could be optimally treated with surgery alone and avoid adjuvant treatments. The aim of our study was to define the outcomes of such patients. MethodsPatients undergoing radical surgery using total mesorectal excision (TME) techniques for rectal cancer (≤12 cm from the anal verge) with curative intent during 2000–2012 and found to have stage III disease on final pathology were identified from a prospectively maintained database. Patients were staged with abdominopelvic CT, transrectal endoscopic ultrasound, and/or pelvic MRI. Exclusion criteria were cN+ without neoadjuvant chemoradiotherapy, hereditary colorectal syndromes, inflammatory bowel diseases, lack of preoperative nodal staging, intraoperative radiotherapy, and follow-up <3 years. We compared cN−/pN+ patients according to the postoperative treatment received (group 1 if no further treatment, group 2 if any postoperative treatments), using ypN+ patients (neoadjuvant chemoradiotherapy + surgery) as controls (group 3). Oncological outcomes evaluated included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence (LR), and distant recurrence (DR). ResultsOut of 218 patients included in the study, 77 cN− patients underwent initial surgery with a pN+ surgical specimen. Eighteen of these patients received no postoperative treatment due to associated comorbidity, patient preference, or postoperative complications while the remaining 59 (group 2) patients received chemoradiotherapy (n = 21) or chemotherapy alone (n = 38), respectively, and group 3 included 141 patients. Distal, radial resection margins and TME grading when available were comparable among groups. cN−/pN+ patients treated with surgery alone were associated with significantly poorer cancer outcomes compared with cN−/pN+ patients who received any form of adjuvant therapy and to ypN+ patients. ConclusionTME surgery is not sufficient to optimize outcomes among rectal cancer patients believed to be node negative and found to be stage III based on specimen pathology.

Pre-operative chemoradiotherapy using capecitabine and cetuximab followed by definitive surgery in patients with operable rectal cancer

BackgroundAchieving a high rate of complete pathological response with pre-operative chemoradiotherapy in rectal cancer is an unmet need. We evaluated the efficacy and toxicity of the combination of cetuximab, capecitabine and radiation therapy in the pre-operative setting of localized rectal cancer. Patients and methodsPatients with clinically staged T3, T4 or nodepositive rectal cancer were treated with concurrent capecitabine and radiotherapy with weekly cetuximab starting one week before the start of radiation. This was followed by total mesorectal excision within 6-8 weeks. All patients achieving R0 resection received adjuvant capecitabine for 6 cycles. ResultsFifteen patients were treated and all underwent surgery. Sphincter preservation was achieved in 11 patients (73.3%) and pathological complete response in two. With a median follow up of 48 months (range 8.4-57.5), 12 patients were relapse-free and 14 were alive with 4-year relapse free survival of 80%. Overall survival was 93%. Significant grade 3 and 4 toxicity was mainly cetuximab-induced skin reactions (33%), radiation-induced skin toxicity (13%) and diarrhea (20%). ConclusionsAdding cetuximab to pre-operative concurrent capecitabine and radiotherapy provides modest efficacy with manageable toxicity.

Prediction of tumor response after neoadjuvant chemoradiotherapy in rectal cancer using (18)fluorine-2-deoxy-D-glucose positron emission tomography-computed tomography and serum carcinoembryonic antigen: a prospective study.

To investigate the association between (18)fluorine-2-deoxy-D-glucose positron emission tomography-computed tomography ((18)F-FDG PET/CT) parameters, serum carcinoembryonic antigen (CEA), and tumor response in patients with rectal cancer receiving neoadjuvant chemoradiotherapy (nCRT). Sixty-four patients with T3-4 and/or node-positive rectal cancer receiving nCRT followed by surgery were prospectively studied. PET/CT was performed before, and in 28 patients, both before and after nCRT. The pre-/post-nCRT maximum standardized uptake (SUVmax) values, differences between pre-/post-nCRT SUVmax (∆SUVmax), response index of SUVmax (RI-SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and CEA were measured. The ability of PET/CT parameters and CEA to predict Mandard's tumor regression grade (TRG) and pathological complete remission (pCR) were evaluated. 31 patients were identified as responders (TRG 1-2), and 19 exhibited pCR. For responders, significant differences were found for ΔSUVmax (24.88 vs. 15.39g/ml, p=0.037), RI-SUVmax (0.76 vs. 0.63, p=0.025), ΔSUVmean (14.43 vs. 8.65g/ml, p=0.029), RI-SUVmean (0.77 vs. 0.63, p=0.011), CEA-pre (6.30 vs. 27.86μg/L, p<0.001), CEA-post (2.22 vs. 5.49μg/L, p=0.002), ΔCEA (4.08 vs. 23.13μg/L, p<0.001), and RI-CEA (0.25 vs. 0.55, p=0.002). Differences between pCR and non-pCR patients were noted as RI-SUVmean (0.77 vs. 0.65, p=0.043), MTV-pre (9.87 vs. 14.62cm(3), p=0.045), CEA-pre (5.62 vs. 22.27μg/L, p=0.002), CEA-post (1.95 vs. 4.72μg/L, p=0.001), and ΔCEA (3.68 vs. 17.99μg/L, p=0.013). Receiver operating characteristic analysis revealed that RI-SUVmean exhibited the greatest accuracy in predicting responders, whereas CEA-post and ΔCEA exhibited the greatest accuracy in predicting pCR. (18)F-FDG PET/CT parameters and CEA are accurate tools for predicting tumor response to nCRT in rectal cancer.