Rectal Cancer Outcomes Research Articles

Predictors of Positive Circumferential Resection Margin in Rectal Cancer: A Current Audit of the National Cancer Database.

Positive circumferential resection margin is a predictor of local recurrence and worse survival in rectal cancer. National programs aimed to improve rectal cancer outcomes were first created in 2011 and continue to evolve. The impact on circumferential resection margin during this time frame has not been fully evaluated in the United States. The purpose of this study was to determine the incidence and predictors of positive circumferential resection margin after rectal cancer resection, across patient, provider, and tumor characteristics. This was a retrospective cohort study. The study was conducted using the National Cancer Database, 2011-2016. Adults who underwent proctectomy for pathologic stage I to III rectal adenocarcinoma were included. Rate and predictors of positive circumferential resection margin, defined as resection margin ≤1 mm, were measured. Of 52,620 cases, circumferential resection margin status was reported in 90% (n = 47,331) and positive in 18.4% (n = 8719). Unadjusted analysis showed that patients with positive circumferential resection margin were more often men, had public insurance and shorter travel, underwent total proctectomy via open and robotic approaches, and were treated in Southern and Western regions at integrated cancer networks (all p < 0.001). Multivariate analysis noted that positive proximal and/or distal margin on resected specimen had the strongest association with positive circumferential resection margin (OR = 15.6 (95% CI, 13.6-18.1); p < 0.001). Perineural invasion, total proctectomy, robotic approach, neoadjuvant chemoradiation, integrated cancer network, advanced tumor size and grade, and Black race had increased risk of positive circumferential resection margin (all p < 0.050). Laparoscopic approach, surgery in North, South, and Midwest regions, greater hospital volume and travel distance, lower T-stage, and higher income were associated with decreased risk (all p < 0.028). This was a retrospective cohort study with limited variables available for analysis. Despite creation of national initiatives, positive circumferential resection margin rate remains an alarming 18.4%. The persistently high rate with predictors of positive circumferential resection margin identified calls for additional education, targeted quality improvement assessments, and publicized auditing to improve rectal cancer care in the United States. See Video Abstract at http://links.lww.com/DCR/B584. ANTECEDENTES:El margen positivo de resección circunferencial es un predictor de recurrencia local y peor sobrevida en el cáncer de recto. Los programas nacionales destinados a mejorar los resultados del cáncer de recto se crearon por primera vez en 2011 y continúan evolucionando. La repercusión del margen de resección circunferencial durante este período de tiempo no se ha evaluado completamente en los Estados Unidos.OBJETIVO:Determinar la incidencia y los predictores para un margen positivo de resección circunferencial posterior a la resección del cáncer de recto, según las características del paciente, el proveedor y el tumor.DISEÑO:Estudio de cohorte retrospectivo.AMBITO:Base de datos nacional de cáncer, 2011-2016.PACIENTES:Adultos que se sometieron a proctectomía por adenocarcinoma de recto con un estadío por patología I-III.PRINCIPALES VARIABLES EVALUADAS:Tasa y predictores para un margen positivo de resección circunferencial, definido como margen de resección ≤ 1 mm.RESULTADOS:De 52,620 casos, la condición del margen de resección circunferencial se informó en el 90% (n = 47,331) y positivo en el 18.4% (n = 8,719). El análisis no ajustado mostró que los pacientes con margen positivo de resección circunferencial se presentó con mayor frecuencia en hombres, tenían un seguro social y viajes más cortos, se operaron de proctectomía total abierta y robótica, y fueron tratados en las regiones del sur y el oeste en redes integradas de cáncer (todos p <0,001). El análisis multivariado destacó que el margen proximal y / o distal positivo de la pieza resecada tenía la asociación más fuerte con el margen postivo de resección circunferencial (OR 15,6; IC del 95%: 13,6-18,1, p <0,001). La invasión perineural, la proctectomía total, el abordaje robótico, la quimioradioterapia neoadyuvante, la red de cáncer integrada, el tamaño y grado del tumor avanzado y la raza afroamericana tenían un mayor riesgo de un margen de una resección positiva circunferencial (todos p <0,050). El abordaje laparoscópico, la cirugía en las regiones Norte, Sur y Medio Oeste, un mayor volumen hospitalario y distancia de viaje, estadio T más bajo y mayores ingresos se asociaron con una disminución del riesgo (todos p <0,028).LIMITACIONES:Estudio de cohorte retrospectivo con variables limitadas disponibles para análisis.CONCLUSIONES:A pesar del establecimiento de iniciativas nacionales, la tasa de margen positivo de resección circunferencial continúa siendo alarmante, 18,4%. El índice continuamente elevado junto a los predictores de un margen positivo de resección circunferencial hace un llamado para una mayor educación, evaluaciones específicas de mejora de la calidad y difusión de las auditorías para mejorar la atención del cáncer de recto en los Estados Unidos. Vea el resumen de video en http://links.lww.com/DCR/B584. Consulte Video Resumen en http://links.lww.com/DCR/B584.

Five‐year oncological outcomes for rectal cancer treated by upfront laparoscopic total mesorectal excision

AbstractAimThe study aimed to evaluate the long‐term recurrence rates and survival following upfront laparoscopic total mesorectal excision (TME) for rectal adenocarcinoma.Patient and MethodsThis was a retrospective cohort of 94 patients with rectal adenocarcinoma undergoing upfront radical resection in New Territories West Cluster between 2010 and 2015. Tumours with safe circumferential resection margin (&gt;1 mm) on magnetic resonance imaging (MRI) staging were selected for upfront surgery. Demographic data, tumour characteristics, operative details, and histopathological and postoperative outcomes were collected from patients' records. The primary outcome was local recurrence. Secondary outcomes were distant recurrence and overall (OS) and disease‐free survival (DFS).ResultsA total of 224 patients were diagnosed with rectal adenocarcinoma, of which 94 received upfront surgery after a multidisciplinary team discussion by surgeons and oncologists. The median follow‐up period after surgery was 60 months (range 4.7‐60.9 months), with four patients lost to follow‐up. Six patients (6.3%) developed local recurrence (two with isolated local recurrence and four with local and distant recurrence). Twelve patients (12.8%) experienced distant recurrence. The 5‐year OS and DFS rates were 84.3% and 76.2%, respectively. Possible prognostic factors for local recurrence (including distal tumour level ≤ 5 cm, clinical nodal stage, clinical threatened margin, pathological stage, harvested lymph nodes &lt;12, distal margin &lt;1 cm, positive extramural venous invasion, and circumferential resection margin) were evaluated by multivariable logistic regression, and were shown to be insignificant.ConclusionUpfront laparoscopic TME for MRI‐selected rectal cancer patients can achieve favourable oncological outcomes in our centre. Routine neoadjuvant treatment for all T3 or nodal positive disease is not necessary.

Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): 10-year follow-up of an open-label, non-inferiority, randomised controlled trial

Laparoscopic surgery has been widely used for rectal cancer; however, its long-term outcomes remain controversial. This study aimed to assess the long-term oncological safety of laparoscopic surgery for rectal cancer using 10-year follow-up data of the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. The COREAN trial is a, open-label, non-inferiority, randomised controlled trial. Eligible participants were aged 18-80 years, had cT3N0-2M0 middle or low rectal cancer with lesions located within 9 cm of the anal verge, and had been treated with preoperative chemoradiotherapy. Patients were randomly assigned (1:1) to open or laparoscopic surgery with a computer-generated random allocation sequence with a random permuted block design. Neither patients nor clinicians were masked to treatment assignment. Open or laparoscopic total mesorectal excision was done 6-8 weeks after the administration of preoperative concurrent chemoradiotherapy (fluoropyrimidines alone, doublet therapy, or triplet therapy) at a dose of 50·5 Gy over 5·5 weeks. Postoperative adjuvant chemotherapy was administered for 4 months. The primary endpoint of 3-year disease-free survival was published previously. Here, we report 10-year overall survival, disease-free survival, and local recurrence. Analyses were done in the modified intention-to-treat population of all participants who were randomly assigned and provided follow-up data. This study is registered with ClinicalTrials.gov, NCT00470951. Of the 340 patients enrolled in the COREAN trial between April 4, 2006, and Aug 26, 2009 (170 patients in each group), two patients in the laparoscopic surgery group moved abroad and were lost to follow-up, so were not included in this 10-year analysis. The median duration of follow-up was 143 months (IQR 122-156). No differences were observed in 10-year overall survival (74·1% [95% CI 66·8-80·0] in the open surgery group vs 76·8% [69·6-82·5] in the laparoscopic surgery group; p=0·44), 10-year disease-free survival (59·3% [51·1-66·5] vs 64·3% [56·0-71·5]; p=0·20), or 10-year local recurrence (8·9% [5·2-15·0] vs 3·4% [1·4-7·9]; p=0·050) between the open surgery and laparoscopic surgery groups at 10 years after surgery. The stratified hazard ratios, adjusted for ypT and ypN classification and tumour regression grade, for open surgery versus laparoscopic surgery were 0·94 (95% CI 0·63-1·43) for overall survival, 1·05 (0·74-1·49) for disease-free survival, and 2·22 (0·78-6·34) for local recurrence. The 10-year follow-up of the COREAN trial confirms the long-term oncological safety of laparoscopic surgery in patients with rectal cancer treated with preoperative chemoradiotherapy. Similar to open surgery, laparoscopic surgery does not compromise long-term survival outcomes in rectal cancer when performed by well trained surgeons. National Cancer Center, Goyang, South Korea.

Robotic versus laparoscopic total mesorectal excision for rectal cancer: a meta-analysis of long-term survival and urogenital functional outcomes.

Robotic surgical technology has been widely introduced and applied in various fields of surgery. The aim of this study was to analyze long-term oncological and urogenital functional outcomes following laparoscopic/robotic total mesorectal excision (TME) in rectal cancer surgery. We identified studies that compared oncological and functional outcomes following laparoscopic TME (LTME) and robotic TME (RTME) for treatment of rectal cancer over the past 16 years. Data related to overall survival (OS), disease-free survival (DFS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) were subjected to meta-analysis. There was no difference in long-term OS and DFS in the pooled data. Compared with LTME, there were significant differences in the score of IPSS at 3, 6 and 12 months for RTME, in the pooled data for male patients. There were significant differences in IIEF score for male patients at 3 and 6 months. Compared with LTME, RTME has better preservation of urinary and sexual functions and comparable long-term oncological outcome in rectal cancer.

Serum calcium improved systemic inflammation marker for predicting survival outcome in rectal cancer

Systemic inflammation markers have shown prognostic values with variability in rectal cancer. Considering the association of serum calcium with inflammation, we aimed to examine whether it could improve systemic inflammation markers for survival prediction. We enrolled 508 patients with stage I to III rectal cancer who underwent curative resection. The cohort was grouped by corrected serum calcium (cCa), platelet-to-lymphocyte ratio (PLR), and CaPLR (a score model combining cCa with PLR) for survival analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare models in survival prediction. The primary endpoint was disease-free survival (DFS). A total of 26.7% (136/508) patients reached recurrence after curative surgery. Both high cCa (HR 1.486; 95% CI, 1.018-2.171; P=0.040) and high PLR (HR 1.452; 95% CI, 1.059-1.991; P=0.021) were significantly associated with worse DFS. In model comparison, the AIC and LR were improved after cCa was added to PLR model in DFS prediction (AIC: 1,704.83 vs. 1,707.14 vs. 1,707.15; LR: 8.68 vs. 4.37 vs. 4.36; P=0.037). The CaPLR was developed for DFS prediction with adjusted HRs of 2.216 (95% CI, 1.256-3.909; P=0.006) and 1.679 (95% CI, 1.004-2.836; P=0.047) for high and intermediate score group respectively compared to low score group. A nomogram for predicting DFS was generated by using CaPLR and other clinical predictors, with a concordance index of 0.705 (95% CI, 0.620-0.789; P<0.001). Serum calcium could improve systemic inflammation markers in survival prediction for patients with rectal cancer.

The effect of different inferior mesenteric artery ligation levels and different lymph node dissection areas on the short- and long-term outcomes of rectal cancer.

Surgery is the most effective treatment for rectal cancer patients, but its key steps, including selection of the level of inferior mesenteric artery ligation and removal of 253 lymph nodes, are still inconclusive. This study aimed to analyze the effects of different surgical methods, including levels of ligation (low vs. high) and lymph node dissection areas (D2 vs. D3) on the short-term and long-term outcomes. Between March 2014 and August 2018, 253 rectal cancer patients were retrospectively analyzed; 113 patients underwent low ligation D2 lymph node dissection (LLD2), 75 patients underwent low ligation D3 lymph node dissection (LLD3), and 65 patients underwent high ligation (HL). We compared the short-term and long-term outcomes among the different groups. There were no significant differences among the groups in terms of the intraoperative variables, including operative time, blood transfusion, and conversion from laparoscopic to open surgery. The median blood loss was significantly lower in LLD3 (50 mL) than in LLD2 (100 mL) and HL (100 mL), but it was not significantly different between LLD2 and HL. There were no significant differences among the LLD2, LLD3, and HL groups in the incidence of postoperative complications (9.7% vs. 12.0% vs. 10.8%, respectively) and hospital stay (14 vs. 15 vs. 14, respectively). The anastomotic leakage Clavien-Dindo grade was significantly lower with LLD2 and LLD3 than with HL, but it was the same between LLD2 and LLD3. The total number of lymph nodes harvested in the LLD3 group (n=14) was higher than that in the LLD2 group (n=12), but it was not significantly different than that in the HL group (n=13). There were no significant differences among the groups in terms of 3-year overall survival rate and disease-free survival rate. Low ligation was similar to HL in terms of major intraoperative and postoperative parameters, but it can reduce the severity of anastomotic leakage to a certain extent. D3 lymph node dissection can increase the total number of lymph nodes harvested, but it did not improve long-term prognosis.

Sphincter preservation in patients with low rectal cancer: striking the right oncological balance

BackgroundThe surgical treatment options for low rectal cancer patients include the Abdominoperineal Resection and the sphincter saving Low Anterior Resection. There is growing evidence towards better outcomes for patients being treated with a Low Anterior Resection compared to an Abdominoperineal Resection.ObjectiveThe aim of this study was to evaluate the short term and oncological outcomes in low rectal cancer treatment.DesignThis is a retrospective cohort study of prospectively collected data.SettingRectal cancer patients from a single center in the United Kingdom.PatientsPatients included all low rectal cancer patients (≤ 6 cm from the anal verge) undergoing Low Anterior Resection or Abdominoperineal Resection between 2006 and 2016.Outcome measuresTo identify differences in postoperative complications and disease free and overall survival.ResultsA total of 262 patients were included for analysis (Low Anterior Resection n = 170, Abdominoperineal Resection n = 92). Abdominoperineal Resection patients were significantly older (69 versus 66 years), had lower tumours (3 versus 5 cm), received more neo-adjuvant radiation, had longer hospital stay and more complications (wound infections and wound dehiscence). Low Anterior Resections had a significantly higher number of harvested lymph nodes (17 versus 12) however there was no difference in nodal involvement and R0 resection rate. No significant difference was found for recurrence, overall survival and disease free survival.LimitationRetrospective review of cancer database and single center data.ConclusionIn the treatment of low rectal cancer Abdominoperineal Resection is associated with higher rates of postoperative complications and longer hospital stay compared to the Low Anterior Resection, with similar oncological outcomes.

Short-Term and Long-Term Outcomes in Mid and Low Rectal Cancer With Robotic Surgery.

ObjectiveTo investigate the risk factors for postoperative complications and anastomotic leakage after robotic surgery for mid and low rectal cancer and their influence on long-term outcomes.MethodsA total of 641 patients who underwent radical mid and low rectal cancer robotic surgery at Zhongshan Hospital Fudan University from January 2014 to December 2018 were enrolled in this study. The clinicopathological factors of the patients were collected. The risk factors for short-term outcomes of complications and anastomotic leakage were analyzed, and their influences on recurrence and overall survival were studied.ResultsOf the 641 patients, 516 (80.5%) underwent AR or LAR procedures, while 125 (19.5%) underwent the NOSES procedure. Only fifteen (2.3%) patients had stoma diversion. One hundred and seventeen patients (17.6%) experienced surgical complications. Anastomotic leakage occurred in 44 patients (6.9%). Eleven patients (1.7%) underwent reoperation within 90 days after surgery. Preoperative radiotherapy did not significantly increase anastomotic leakage in our study (7.4% vs. 6.8%, P = 0.869). The mean postoperative hospital stay was much longer with complication (10.4 vs. 7.1 days, P<0.05) and leakage (12.9 vs. 7.4 days, P < 0.05). Multivariate analysis showed that male sex (OR = 1.855, 95% CI: 1.175–2.923, P < 0.05), tumor distance 5 cm from the anus (OR = 1.563, 95% CI: 1.016–2.404, P < 0.05), and operation time length (OR = 1.563, 95% CI: 1.009–2.421, P < 0.05) were independent risk factors for complications in mid and low rectal cancer patients. The same results for anastomotic leakage: male sex (OR = 2.247, 95% CI: 1.126–4.902, P < 0.05), tumor distance 5 cm from the anus (OR = 2.242, 95% CI: 1.197–4.202, P < 0.05), and operation time length (OR = 2.114, 95% CI: 1.127–3.968, P < 0.05). The 3-year DFS and OS were 82.4% and 92.6% with complication, 88.4% and 94.0% without complication, 88.6% and 93.1% with leakage, and 87.0% and 93.8% without leakage, respectively. The complication and anastomotic leakage showed no significant influences on long-term outcomes.ConclusionBeing male, having a lower tumor location, and having a prolonged operation time were independent risk factors for complications and anastomotic leakage in mid and low rectal cancer. Complications and anastomotic leakage might have no long-term impact on oncological outcomes for mid and low rectal cancer with robotic surgery.

Short-term outcomes of medium-low rectal cancer treated by taTME and experience of 22 cases.

Transanal total mesorectal excision (taTME) is a novel radical resection technique that may address the unsatisfactory functional and oncological outcomes of medium-low rectal cancers. Although its oncological safety remains unclear, taTME has demonstrable value in surgery, complications, and oncological outcomes. Here, we explore the short-term outcomes of rectal cancer after taTME and discuss the surgical experience. Twenty-two patients with medium-low rectal cancer who underwent taTMEwere retrospectively evaluated. Comprehensive demographic, oncological, and clinical data were analyzed and the perioperative state and postoperative follow-up were evaluated. Over a median follow-up period of 24.4 (4-36) months, local recurrence occurred in one patient at 6 months postsurgery. Fecal incontinence was the most common postoperative complication, and 3-6 months of pelvic-floor-rehabilitation training greatly improved anal function CONCLUSIONS: taTME achieved satisfactory short-term outcomes in oncological complications and postoperative functions. Accurate intraoperative anatomical location, identification of the rectovesical fascia, and neuroprotection are critical. However, this procedure has a steep learning curve, and large samples and multicenter studies are required to substantiate its effectiveness. We retrospectively analyzed the oncological and functional prognosis of 22 patients with colorectal cancer undergoing taTME surgery and preliminarily concluded taTME can be regarded as a safe and feasible treatment.

Difference in surgical outcomes of rectal cancer by study design: meta-analyses of randomized clinical trials, case-matched studies, and cohort studies.

BackgroundRCTs are considered the standard in surgical research, whereas case-matched studies and propensity score matching studies are conducted as an alternative option. Both study designs have been used to investigate the potential superiority of robotic surgery over laparoscopic surgery for rectal cancer. However, no conclusion has been reached regarding whether there are differences in findings according to study design. This study aimed to examine similarities and differences in findings relating to robotic surgery for rectal cancer by study design.MethodsA comprehensive literature search was conducted using PubMed, Scopus, and Cochrane CENTRAL to identify RCTs, case-matched studies, and cohort studies that compared robotic versus laparoscopic surgery for rectal cancer. Primary outcomes were incidence of postoperative overall complications, incidence of anastomotic leakage, and postoperative mortality. Meta-analyses were performed for each study design using a random-effects model.ResultsFifty-nine articles were identified and reviewed. No differences were observed in incidence of anastomotic leakage, mortality, rate of positive circumferential resection margins, conversion rate, and duration of operation by study design. With respect to the incidence of postoperative overall complications and duration of hospital stay, the superiority of robotic surgery was most evident in cohort studies (risk ratio (RR) 0.83, 95 per cent c.i. 0.74 to 0.92, P < 0.001; mean difference (MD) –1.11 (95 per cent c.i. –1.86 to –0.36) days, P = 0.004; respectively), and least evident in RCTs (RR 1.12, 0.91 to 1.38, P = 0.27; MD –0.28 (–1.44 to 0.88) days, P = 0.64; respectively).ConclusionResults of case-matched studies were often similar to those of RCTs in terms of outcomes of robotic surgery for rectal cancer. However, case-matched studies occasionally overestimated the effects of interventions compared with RCTs.

Alcohol Consumption, HDL-Cholesterol and Incidence of Colon and Rectal Cancer: A Prospective Cohort Study Including 250,010 Participants.

AimsAlcohol consumption has been linked to colorectal cancer (CRC) and also to the high-density lipoprotein cholesterol level (HDL-C). HDL-C has been associated with the incidence of CRC. The aim of this study was to investigate the association between self-reported alcohol consumption, HDL-C and incidence of CRC, separately for the two sites.MethodsAltogether, 250,010 participants in Norwegian surveys have been followed-up for an average of 18 years with respect to a first-time outcome of colon or rectal cancer. During follow-up, 3023 and 1439 colon and rectal cancers were registered.ResultsFor men, the HR per 1 drink per day was 1.05 with 95% confidence interval (0.98–1.12) for colon and 1.08 (1.02–1.15) for rectal cancer. The corresponding figures for women were 1.03 (0.97–1.10) and 1.05 (1.00–1.10). There was a positive association between alcohol consumption and HDL-C. HDL-C was inversely associated with colon cancer in men (0.74 (0.62–0.89) per 1 mmol/l) and positively associated with rectal cancer, although not statistically significant (1.15 (0.92–1.44). A robust regression that assigned weights to each observation and exclusion of weights ≤ 0.1 increased the HRs per 1 drink per day and decreased the HR per 1 mmol/l for colon cancer. The associations with rectal cancer remained unchanged.ConclusionOur results support a positive association between alcohol consumption and colon and rectal cancer, most pronounced for rectal cancer. Considering the positive relation between alcohol consumption and HDL-C, the inverse association between HDL-C and colon cancer in men remains unsettled.

Persistent extramural vascular invasion positivity on magnetic resonance imaging after neoadjuvant chemoradiotherapy predicts poor outcome in rectal cancer

BackgroundIn rectal cancer, extramural vascular invasion (EMVI) is the presence of tumour cells in blood vessels outside the muscular layer, which is associated with poor prognosis. Regression of EMVI on MRI following neoadjuvant chemoradiotherapy or its persistence may have prognostic implications. MethodsThis retrospective study included 52 patients with rectal cancer who underwent total mesorectal excision following long-course neoadjuvant chemoradiotherapy (CRT). EMVI assessments were done on previous pelvic MRIs obtained before neoadjuvant CRT and eight weeks after the completion of neoadjuvant chemoradiotherapy in initially EMVI positive cases. ResultsPersistently EMVI positive patients had worse overall survival and disease-free survival compared to initially EMVI negative patients and patients who returned to negative (p < 0.001 for both). Multivariate analysis identified persistent EMVI positivity after neoadjuvant treatment (HR, 102.9; p = 0.003) as significant independent predictor of worse overall survival; and persistent EMVI positivity (HR, 17.0; p = 0.002), mesorectal fascia involvement after neoadjuvant treatment (HR, 8.0; p = 0.017), and poor differentiation (HR, 10.3, p = 0.012) as significant independent predictors of worse disease-free survival. ConclusionPersistent EMVI positivity after neoadjuvant therapy appears to be an independent factor for poor overall survival; and persistent EMVI positivity as well as mesorectal fascia involvement on post neoadjuvant therapy MRI and poor differentiation appears to be important predictors of poor disease-free survival in rectal cancer patients.

Severe lymphopenia predicts poorer survival in patients with rectal cancer undergoing neoadjuvant chemoradiation.

138 Background: Chemoradiation (CRT) induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. The objective of this study was to evaluate the prognostic impact of lymphopenia in patients with rectal cancer undergoing neoadjuvant CRT. We hypothesized that severe lymphopenia would correlate with worse survival. Methods: The inclusion criteria for this single-institution retrospective study were: 1) biopsy-proven diagnosis of rectal adenocarcinoma, 2) receipt of neoadjuvant CRT followed by surgery, and 3) absolute lymphocyte count (ALC) available prior to and within 12 weeks of CRT. In general, CRT consisted of 5-fluorouracil or capecitabine and RT with 50.4 Gy over 28 fractions. Lymphopenia was graded according to CTCAE v5.0. The primary variable of interest was ALC nadir within 12 weeks of CRT, dichotomized by ALC of &lt; 0.5 k/μl (Grade 3 lymphopenia). The primary endpoint was overall survival (OS). Cox modeling and Kaplan-Meier methods were used to perform survival analyses. Results: 193 patients were identified. Median follow-up for the entire cohort was 68 months. Median age was 58. 62% were male, 82% were Caucasian, and 90% had ECOG ≤1. Median tumor distance from anal verge was 8 cm. Overall clinical stage was 1 or 2 in 23% and 3 in 77%. Median baseline CEA was 3.2 ng/ml. 83% received chemotherapy following RT. Following CRT, 70% underwent low anterior resection and 30% underwent abdominoperineal resection. Median baseline ALC for the entire cohort was 1.7 k/ul. ALC nadir within 12 weeks of initiating CRT was &lt; 0.5 k/ul among 110 (57%) patients. Patients who developed severe lymphopenia with CRT had a lower baseline hemoglobin (median 13.3 vs. 14.0 g/dl, p = 0.022) and lower baseline ALC (median 1.6 vs. 1.8 k/ul, p = 0.010) compared to those who did not develop severe lymphopenia. There were no differences in disease and treatment characteristics between the two groups. On multivariable Cox model, severe lymphopenia was significantly associated with increased hazards of death (HR = 3.52 [95% CI 1.47-8.44], p = 0.005). Receipt of chemotherapy post-CRT (HR = 0.22 [95% CI 0.09-0.54], p = 0.001) predicted better OS while higher pathologic T (HR = 8.01 [95% CI 2.98-17.21], p &lt; 0.001) and N stage (HR = 9.43 [95% CI 3.19-27.86], p &lt; 0.001) and positive surgical margin (HR = 3.77 [95% CI 1.13-12.62], p = 0.031) predicted worse OS. The 5-year OS was 79% vs. 92% in the cohort with vs. without severe lymphopenia, respectively (log-rank p = 0.001). Conclusions: CRT-induced lymphopenia is common and severe lymphopenia may be a prognostic marker of poorer survival in rectal cancer. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating CRT-induced lymphopenia. Our findings also suggest an important role of the host immunity in rectal cancer outcomes, supporting the ongoing efforts of immunotherapy trials in rectal cancer.

Epidural analgesia does not impact recurrence or mortality in patients after rectal cancer resection

The relationship between epidural analgesia and rectal cancer outcome is not fully clarified. We aimed to investigate the putative effect of epidural analgesia on the risks of recurrence and mortality after rectal tumour resection. In this monocentric cohort study, we consecutively enrolled patients with stage I–III rectal cancer who underwent tumour resection from 2005 to 2014. Patients received epidural analgesia or intravenous opioid-based analgesia for postoperative pain control. Primary endpoint was first cancer recurrence. Secondary endpoints were all-cause mortality and cancer-specific mortality. We collected 1282 patients in the inverse probability of treatment weighting analyses, and 237 (18.5%) used epidurals. Follow-up interval was median 46.1 months. Weighted Cox regression analysis showed the association between epidural analgesia and recurrence-free survival was non-significant (adjusted hazard ratio [HR] 0.941, 95% CI 0.791–1.119, p = 0.491). Similarly, the association between epidural analgesia and overall survival (HR 0.997, 95% CI 0.775–1.283, p = 0.984) or cancer-specific survival (HR 1.113, 95% CI 0.826–1.501, p = 0.482) was non-significant either. For sensitivity tests, quintile stratification and stepwise forward model selection analyses showed similar results. We did not find a significant association between epidural analgesia and risk of recurrence, all-cause mortality, or cancer-specific mortality in patients with rectal cancer undergoing tumour resection.

Transanal total mesorectal excision outcomes for advanced rectal cancer in a complex surgical population.

Total mesorectal excision (TME) is the gold standard for oncologic resection in low and mid rectal cancers. However, abdominal approaches to TME can be hampered by poor visibility, inadequate retraction, and distal margin delineation. Transanal TME (taTME) is a promising hybrid technique that was developed to mitigate the difficulties of operating in the low pelvis and to optimize the circumferential resection and distal margins. The objective of this study was to characterize our experience implementing taTME at our institution in a technically challenging patient population. We performed a retrospective review of consecutive patients who underwent taTMEs between November 2013 and May 2019 for rectal cancer at a tertiary community cancer center. Outcome measures included pathologic grading of TME specimen, post-operative complications, and oncologic outcomes. Forty-four patients with mid and low rectal cancer underwent low anterior resection via taTME. The most common staging modality was rectal MRI which demonstrated T3 or T4 tumors in 89% of our patients prior to neoadjuvant. Eighty-six percent of patients underwent neoadjuvant chemoradiation. The initial cases were performed sequentially as a single team, but we later transitioned to a synchronous, two-team approach. Ninety-one percent of TME grades were complete or near complete. Only one patient (2.3%) had a positive circumferential margin. Six patients developed anastomotic leaks with an overall anastomotic complication rate of 18.2%. Two patients (4.5%) with primary rectal cancer developed local recurrence, one of which developed multifocal local recurrence. Using the taTME approach on selected locally advanced low rectal cancers, especially in technically complex irradiated and obese male patients, has yielded comparably safe and effective outcomes to laparoscopic proctectomy.

Postoperative non-steroidal anti-inflammatory drug use and oncological outcomes of rectal cancer.

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are known to suppress the inflammatory response after surgery and are often used for pain control. This study aimed to investigate NSAID use after radical surgical resection for rectal cancer and long-term oncological outcomes.MethodsA cohort of patients who underwent anterior resection for rectal cancer between 2007 and 2013 in 15 hospitals in Sweden was investigated retrospectively. Data were obtained from the Swedish Colorectal Cancer Registry and medical records; follow-up was undertaken until July 2019. Patients who received NSAID treatment for at least 2 days after surgery were compared with controls who did not, and the primary outcome was recurrence-free survival. Cox regression modelling with confounder adjustment, propensity score matching, and an instrumental variables approach were used; missing data were handled by multiple imputation.ResultsThe cohort included 1341 patients, 362 (27.0 per cent) of whom received NSAIDs after operation. In analyses using conventional regression and propensity score matching, there was no significant association between postoperative NSAID use and recurrence-free survival (adjusted hazard ratio (HR) 1.02, 0.79 to 1.33). The instrumental variables approach, including individual hospital as the instrumental variable and clinicopathological variables as co-variables, suggested a potential improvement in the NSAID group (HR 0.61, 0.38 to 0.99).ConclusionConventional modelling did not demonstrate an association between postoperative NSAID use and recurrence-free survival in patients with rectal cancer, although an instrumental variables approach suggested a potential benefit.

Development and validation of magnetic resonance imaging-based radiomics models for preoperative prediction of microsatellite instability in rectal cancer.

BackgroundMicrosatellite instability (MSI) is a predictive biomarker for response to chemotherapy and a prognostic biomarker for clinical outcomes of rectal cancer. The purpose of this study was to develop and validate radiomics models for preoperative prediction of the MSI status of rectal cancer based on magnetic resonance (MR) images.MethodsThis study retrospectively recruited 491 rectal cancer patients with pathologically confirmed MSI status. Patients were randomly divided into a training cohort (n=327) and a validation cohort (n=164). The most predictive radiomics features were selected using intraclass correlation coefficient (ICC) analysis, the two-sample t test, and the least absolute shrinkage and selection operator (LASSO) method. XGBoost models were constructed in the training cohort to discriminate the MSI status using clinical factors, radiomics features, or a combined model incorporating both the radiomics signature and independent clinical characteristics. The diagnostic performance of these three models was evaluated in the validation cohort based on their area under the curve (AUC), sensitivity, specificity, and accuracy.ResultsAmong the 491 rectal cancer patients, the prevalence of MSI was 10.39% (51/491). Following ICC analysis, two-sample t test, and LASSO regression, six radiomics features were selected for subsequent analysis. The combined model, which incorporated both the clinical factors and radiomics features achieved an AUC of 0.895 [95% confidence interval (CI), 0.838–0.938] in the validation cohort, and showed better performance in predicting MSI status than the other two models using either clinical factors (P=0.015) or radiomics features (P=0.204) alone.ConclusionsRadiomics features based on preoperative T2-weighted MR imaging (MRI) are associated with the MSI status of rectal cancer. Combinational analysis of clinical factors and radiomics features may improve predictive performance and potentially contribute to noninvasive personalized therapy selection.

Improved Survival Outcome and Access to Cancer Screening from Hemorrhoid in Patients with Rectal Cancer.

Background The interventions for hemorrhoid increase access to rectal cancer screening and thus might reduce cancer death. We aimed to examine the impact of hemorrhoid on survival outcomes in rectal cancer. Methods We identified 510 patients with stage I to III rectal cancer from a prospectively collected database. Patients were divided into hemorrhoid and non-hemorrhoid group. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Results Hemorrhoid group had significantly more stage I-II diseases in comparison to nonhemorrhoid group (71.1% vs. 55.9%, P = 0.049). The hemorrhoid group had significantly better DFS and OS compared to nonhemorrhoid group, the hazard ratios (HRs) of which were 0.39 (95% CI 0.17-0.88, P = 0.018) and 0.33 (95% CI 0.12-0.92, P = 0.034), respectively. Multivariate analysis revealed that hemorrhoid was independently associated with DFS [adjusted HR 0.43 (95% CI 0.17-0.95, P = 0.045)]. A nomogram for predicting DFS outcome was generated based on hemorrhoid history, with a concordance index of 0.71 (95% CI 0.66-0.75, P < 0.001). Conclusions There may exist a screening effect and survival benefit from hemorrhoid in rectal cancer, which supports the significance of rectal cancer screening in lowering its mortality.

Rectal Cancer Care: Does One Size Fit All?

Over the past decade, rectal cancer care in the US has continued to advance rapidly. New innovations such as robotic surgery, nonoperative management, total neoadjuvant therapy, and advances in molecular diagnostics have changed the way we treat and care for rectal cancer patients. 1 Cercek A. Roxburgh C.S.D. Strombom P. et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018; 4e180071 Crossref PubMed Scopus (152) Google Scholar , 2 Smith J.J. Strombom P. Chow O.S. et al. Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy. JAMA Oncol. 2019; 5e185896 Crossref PubMed Scopus (137) Google Scholar , 3 Jayne D. Pigazzi A. Marshall H. et al. Effect of robotic-assisted vs conventional laparoscopic surgery on risk of conversion to open laparotomy among patients undergoing resection for rectal cancer: The ROLARR Randomized Clinical Trial. JAMA. 2017; 318: 1569-1580 Crossref PubMed Scopus (419) Google Scholar Despite paradigm shifts in treatment and new technology, there continues to be persistent variation in access to high quality, guideline-concordant multidisciplinary care for patients with rectal cancer. Barriers to patient access affects both overall survival and potential surgical options. The National Accreditation Program for Rectal Cancer (NAPRC), the OSTRiCh Consortium (Optimizing the Surgical Treatment of Rectal Cancer), and the Commission on Cancer (CoC), a quality program of the American College of Surgeons, aim to accredit hospitals by evaluating a hospital's structure and processes for treating rectal cancer patients. 4 Monson J.R.T. Dietz D.W. Boughey J.C. You Y.N. Improving rectal cancer outcomes through advocacy, education, and research: The OSTRiCh Consortium and the new NAPRC. Bull Am Coll Surg United States. 2016; 101: 45-46 PubMed Google Scholar Accredited hospitals are held accountable for delivering multidisciplinary, evidence-based care. Enthusiasm has been strong. NAPRC is in its early phase, with 19 hospitals successfully completing the accreditation process and dozens more in the process. NAPRC is an important first step in improving rectal cancer care in the US, but the US is a complex, large, and diverse country, and truly improving access for broad swaths of the population is going to take a coordinated effort that harnesses the passions of providers, hospitals, payors, and patients. Fragmented Care in the Treatment of Rectal Cancer and Time to Definitive TherapyJournal of the American College of SurgeonsVol. 232Issue 1PreviewThe National Accreditation Program for Rectal Cancer (NAPRC) emphasizes a multidisciplinary approach for treating rectal cancer and has developed performance measures to ensure that patients receive standardized care. We hypothesized that rectal cancer patients receiving care at multiple centers would be less likely to receive timely and appropriate care. Full-Text PDF

Association of certification, improved quality and better oncological outcomes for rectal cancer in a specialized colorectal unit.

Centralization of cancer care is expected to yield superior results. In Germany, the national strategy is based on a voluntary certification process. The effect of centre certification is difficult to prove because quality data are rarely available prior to certification. This observational study aims to assess outcomes for rectal cancer patients before and after implementation of a certified cancer centre. All consecutive patients treated for rectal cancer in our certified centre from 2009 to 2017 were retrieved from a prospective database. The dataset was analyzed according to a predefined set of 19 quality indicators comprising 36 quality goals. The results were compared to an identical cohort of patients, treated from 2000 to 2008 just before centre implementation. In total, 1059 patients were included, 481 in the 2009-2017 interval and 578 in the 2000-2008 interval. From 2009 to 2017, 25 of 36 quality goals were achieved (vs. 19/36). The proportion of anastomotic leaks in low anastomoses was improved (13.5% vs. 22.1%, p = 0.018), as was the local 5-year recurrence rate for stage (y)pIII rectal cancers (7.7% vs. 17.8%, p = 0.085), and quality of mesorectal excision (0.3% incomplete resections vs. 5.5%, p = 0.002). Furthermore, a decrease of abdominoperineal excisions was noted (47.1% vs. 60.0%, p = 0.037). For the 2009-2017 interval, local 5-year recurrence rate in stages (y)p0-III was 4.6% and 5-year overall survival was 80.2%. Certification as specialized centre and regular audits were associated with an improvement of various quality parameters. The formal certification process has the potential to enhance quality of care for rectal cancer patients.