Effect Of Neoadjuvant Chemoradiation Research Articles

Effect of neoadjuvant chemoradiation on anorectal function assessed with anorectal manometry: A systematic review and meta-analysis.

Improvement in oncological survival for rectal cancer increases attention to anorectal dysfunction. Diagnostic questionnaires can evaluate quality of life but are subjective and dependent on patients' compliance. Anorectal manometry can objectively assess the continence mechanism and identify functional sphincter weakness and rectal compliance. Neoadjuvant chemoradiotherapy is presumed to affect anorectal function. We aim to assess anorectal function in rectal cancer patients who undergo total mesorectal excision, with or without neoadjuvant chemoradiation, using anorectal manometry measurements. MEDLINE, Embase, and Cochrane databases were searched for studies comparing perioperative anorectal manometry between neoadjuvant chemoradiation and upfront surgery for rectal cancers. Primary outcomes were resting pressure, squeeze pressure, sensory threshold volume and maximal tolerable volume. Eight studies were included in the systematic review, of which seven were included for metanalysis. 155 patients (45.3%) had neoadjuvant chemoradiation before definitive surgery, and 187 (54.6%) underwent upfront surgery. Most patients were male (238 vs. 118). The standardized mean difference of mean resting pressure, mean and maximum squeeze pressure, maximum resting pressure, sensory threshold volume, and maximal tolerable volume favored the upfront surgery group but without statistical significance. Currently available evidence on anorectal manometry protocols failed to show any statistically significant differences in functional outcomes between neoadjuvant chemoradiation and upfront surgery. Further large-scale prospective studies with standardized neoadjuvant chemoradiation and anorectal manometry protocols are needed to validate these findings.

Neoadjuvant Chemoradiation Impacts the Prognostic Effect of Surgical Margin Status in Pancreatic Adenocarcinoma.

Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (-SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with -SM compared with +SM in both groups (p=0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p<0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04-4.24; p<0.001) and older age (HR 1.01, 95% CI 1.00-1.03, per year; p=0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72-1.65; p=0.70). Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections.

The effects of neoadjuvant chemoradiation on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal adenocarcinoma.

101 Background: Exosomes mediate intercellular communications and have pivotal roles in cancer development. CD63 and CD9 are widely accepted exosomal markers. The effect of concurrent chemoradiation on the expression of exosomal markers is unknown. Here we explored the effect of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal cancer (LARC). Methods: Between 2015 and 2018, 33 patients had LARC treated with NCCR and had pre NCCR biopsy and post NCCR resected rectum examined for exosomal markers expression using immunohistochemistry. Two pathologists independently scored CD63 and CD9 staining in the tumor. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Un-Paired t test was used for statistical analysis. Results: In our cohort, median age was 59 years. Males represented 79% of the patients. Caucasians, African American and other ethnic groups represented 70%, 27% and 3% respectively.The mean tumor CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 106 vs 165 (p = 0.0022). The mean tumor CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 136 vs 215 (p &lt; 0.0001). The exosomal markers expression in the adjacent normal mucosa (ANM) from pre NCCR biopsy and post NCCR resected rectum was only performed in16 out of 33 patients (due to ANM tissue availability). The mean ANM CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 166 vs 183 (p = 0.37). The mean ANM CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 104 vs 145 (p = 0.0897). Conclusions: In patients with LARC, the expression of exosomal markers (CD63 and CD9) increased after treatment with NCCR. Our results show that the expression of CD63 and CD9 is relatively higher in rectal cancer specimens treated with NCCR and thus suggest a possible role of these exosomes in adaptive response to NCCR. Further follow-up and laboratory studies are required to precisely understand the underlying mechanism(s).

The long-term influence of hospital and surgeon volume on local control and survival in the randomized German Rectal Cancer Trial CAO/ARO/AIO-94

BackgroundThe association of treatment volume and oncological outcome of rectal cancer patients undergoing multidisciplinary treatment is subject of an ongoing debate. Prospective data on long-term local control and overall survival (OS) are not available so far. This study investigated the long-term influence of hospital and surgeon volume on local recurrence (LR) and OS in patients with locally advanced rectal cancers. MethodsIn a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with stage II/III rectal cancers were evaluated. LR-rates and OS were stratified by hospital recruitment volume (≤20 vs. 21–90 vs. >90 patients) and by surgeon volume (≤10 vs. 11–50 vs. >50 procedures). ResultsPatients treated in high-volume hospitals had a longer OS than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was adversely associated with LR (p = 0.01) but had no influence on overall survival. The positive effect of neoadjuvant chemoradiation (CRT) on local control was the strongest in patients being operated by medium-volume surgeons, less in patients being operated by high-volume surgeons and missing in those being operated by low-volume surgeons. ConclusionsPatients with locally advanced rectal cancers might benefit from treatment in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on long-term local tumour control. The effect of neoadjuvant CRT on local tumour control may likewise depend on the surgeon volume.

The Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer-The Impact in Intratumoral Heterogeneity.

Purpose: Intratumoral genetic heterogeneity (ITGH) is a common feature of solid tumors. However, little is known about the effect of neoadjuvant chemoradiation (nCRT) in ITGH of rectal tumors that exhibit poor response to nCRT. Here, we examined the impact of nCRT in the mutational profile and ITGH of rectal tumors and its adjacent irradiated normal mucosa in the setting of incomplete response to nCRT.Methods and Materials: To evaluate ITGH in rectal tumors, we analyzed whole-exome sequencing (WES) data from 79 tumors obtained from The Cancer Genome Atlas (TCGA). We also compared matched peripheral blood cells, irradiated normal rectal mucosa and pre and post-treatment tumor samples (PRE-T and POS-T) from one individual to examine the iatrogenic effects of nCRT. Finally, we performed WES of 7 PRE-T/POST-T matched samples to examine how nCRT affects ITGH. ITGH was assessed by quantifying subclonal mutations within individual tumors using the Mutant-Allele Tumor Heterogeneity score (MATH score).Results: Rectal tumors exhibit remarkable ITGH that is ultimately associated with disease stage (MATH score stage I/II 35.54 vs. stage III/IV 44.39, p = 0.047) and lymph node metastasis (MATH score N0 35.87 vs. N+ 45.79, p = 0.026). We also showed that nCRT does not seem to introduce detectable somatic mutations in the irradiated mucosa. Comparison of PRE-T and POST-T matched samples revealed a significant increase in ITGH in 5 out 7 patients and MATH scores were significantly higher after nCRT (median 41.7 vs. 28.8, p = 0.04). Finally, we were able to identify a subset of “enriched mutations” with significant changes in MAFs between PRE-T and POST-T samples. These “enriched mutations” were significantly more frequent in POST-T compared to PRE-T samples (92.9% vs. 7.1% p < 0.00001) and include mutations in genes associated with genetic instability and drug resistance in colorectal cancer, indicating the expansion of tumor cell subpopulations more prone to resist to nCRT.Conclusions: nCRT increases ITGH and may result in the expansion of resistant tumor cell populations in residual tumors. The risk of introducing relevant somatic mutations in the adjacent mucosa is minimal but non-responsive tumors may have potentially worse biological behavior when compared to their untreated counterparts. This was an exploratory study, and due to the limited number of samples analyzed, our results need to be validated in larger cohorts.

The influence of hospital and surgeon volume on survival and local control in rectal cancer: Long-term results of the CAO/ARO/AIO-94 trial.

738 Background: The association of hospital and surgeon volume with the outcome of rectal cancer patients is under debate. In this study the long-term influence of the hospital as well as the surgeon volume on overall survival and local recurrence were investigated. Methods: In a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with locally advanced rectal cancers were evaluated. Survival and local recurrence rates were stratified by the hospital recruitment volume (≤20 vs. 21-90 vs. &gt; 90 patients) and by the surgeon volume (≤10 vs. 11-50 vs. &gt; 50 procedures). Results: Patients treated in „high-volume“ hospitals had a longer overall survival than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was significantly associated with decreased local recurrences (p = 0.01) but had no influence on overall survival. The effect of neoadjuvant chemoradiation on local control was the strongest in patients being operated by medium-volume surgeons. Conclusions: Patients with locally advanced rectal cancers might benefit from treatment in in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on local control.

The Effect of Neoadjuvant Chemoradiation on Anastomotic Leak and Additional 30-Day Morbidity and Mortality in Patients Undergoing Total Gastrectomy for Gastric Cancer

IntroductionIn addition to increased perioperative morbidity, anastomotic leak following gastric resection for gastric cancer can have detrimental effects on overall and disease-free survival. The risk of anastomotic leak following neoadjuvant therapy remains unknown. The purpose of this study is to investigate the association of preoperative chemotherapy and radiation therapy with postoperative anastomotic leak and additional 30-day morbidity and mortality outcomes following total gastrectomy with reconstruction for gastric cancer using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). MethodsPatients who underwent total gastrectomy with reconstruction for gastric cancer from 2005 to 2012 were identified. Within the NSQIP database, anastomotic leak is captured as an organ space infection. The association of preoperative chemotherapy and radiation therapy with anastomotic leak and additional 30-day morbidity and mortality outcomes was investigated using chi-squared analysis, Fisher’s exact test, and Student’s t test. ResultsA total of 1135 patients met inclusion criteria; 121 (10.7%) patients underwent preoperative chemotherapy within 30 days of surgery, and 53 (4.7%) patients underwent preoperative radiation therapy within 90 days of surgery. Neither preoperative chemotherapy nor radiation therapy was associated with an increased risk of anastomotic leak (p = 0.12 and p = 0.58, respectively). When compared to patients who did not undergo neoadjuvant therapy, patients who underwent either preoperative chemotherapy or radiation therapy did not experience a higher frequency of 30-day mortality (p = 0.41), cardiac (p = 0.49), wound (p = 0.76), renal (p = 0.13), septic (p = 0.55), or venous thromboembolism (p = 0.19) events and were significantly less likely to experience a pulmonary event (p = 0.02). ConclusionNeoadjuvant therapy prior to gastric resection for gastric cancer is not associated with an increased risk of anastomotic leak or other additional short-term morbidity or mortality.

Effect of neoadjuvant chemoradiation on the tumor microenvironment in rectal cancer.

e15115 Background: Chemoradiotherapy (CRT) followed by surgery is standard treatment for most rectal cancers. This creates an inflammatory reaction which recruits and enhances T-cell mediated killing. Tumors can evade destruction by expressing immune modulating proteins such as PD-L1. Inhibitors of PD-L1 can circumvent immune evasion potentially enhancing neoadjuvant treatment. We assessed CD8+ infiltrates and PD-L1 expression before and after neoadjuvant CRT. We correlated these changes with clinical and pathological endpoints. Methods: We obtained tissue from 22 patients treated with neoadjuvant CRT followed by primary surgery for rectal adenocarcinoma from 2005-2015. Patients received 5FU based chemotherapy with concurrent radiation (mean 51.2 Gy in 27 fractions). Pre- and post-CRT samples were stained with VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody to quantitate PD-L1 expression. CD8 + lymphocytes were assessed over one high power field (40x objective) in the area of densest expression. Analysis of 8 patients was completed at the time of this submission. Results: 37.5% of cases had upregulated PD-L1 expression post-CRT. 62.5% maintained similar PD-L1 expression in the biopsy and resection specimen. All patients had a CD8+ infiltrate after CRT with 87.5% demonstrating an increase in CD8+ lymphocytes. Patients without increased PD-L1 expression had a trend toward improved pathologic response. Conclusions: A majority of patients had an increased inflammatory infiltrate post-CRT indicating immune activation within the tumor microenvironment. A subset of tumors had increased PD-L1 expression. This population might benefit from neoadjuvant PD-L1 inhibition, which could translate to better pathological response and clinical outcomes. We will present the results from 22 patients currently under study. [Table: see text]

Clinical effect of neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy

Objective To explore the clinical effect of neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy for esophageal cancer. Methods The retrospective cohort study was conducted. The clinicopathological data of 111 esophageal cancer patients who underwent neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy in the Cancer Hospital of Chinese Academy of Medical Sciences between January 2010 and December 2016 were collected. Among 111 patients, 68 with interval time between neoadjuvant chemo-radiation and thoracoscopic and laparoscopic three-incision esophagectomy <8 weeks were allocated into the <8 weeks group and 43 with interval time between neoadjuvant chemo-radiation and thoracoscopic and laparoscopic three-incision esophagectomy ≥8 weeks were allocated into the ≥8 weeks group. Patients underwent preoperative radiotherapy and chemotherapy with TP regimen, and then underwent selective thoracoscopic and laparoscopic three-incision esophagectomy. Observation indicators: (1) neoadjuvant chemo-radiation situations; (2) surgical and postoperative situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients and tumor recurrence or metastasis up to March 2017. Measurement data with normal distribution were represented as ±s and comparison between groups was analyzed using the t test. Count data were analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data was done by the nonparametric test. Results (1) Neoadjuvant chemo-radiation situations: all the patients underwent neoadjuvant chemo-radiation, without severe adverse reaction. Number of patients with complete remission based on oncopathology were 34 in the 0.05). (2) Surgical and postoperative situations: all the patients underwent successful thoracoscopic and laparoscopic three-incision esophagectomy, with negative surgical margins. Operation time, volume of intraoperative blood loss, number of lymph node dissected, time of postoperative intrathoracic drainage-tube removal, time of postoperative neck drainage-tube removal, hoarseness, upper gastrointestinal hemorrhage, anastomotic fistula, respiratory complication, pleural effusion and empyema, cardiovascular complication, incision abnormal healing, death within postoperative 30 days and duration of hospital stay were (354±103)minutes, (400±76)mL, 19±4, (11±4)days, (4.9±1.6)days, 5, 1, 12, 3, 6, 5, 8, 0, (19±17) days in the 0.05). (3) Follow-up: 90 of 111 patients were followed up for 3-82 months, with a median time of 25 months, including 55 in the <8 weeks group and 35 in the ≥8 weeks group. During follow-up, death and tumor recurrence were detected in 9, 11 patients in the <8 weeks group and 6, 11 patients in the ≥8 weeks group, respectively. Conclusion Neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy is safe and effective, and it doesn′t increase the perioperative risks based on preoperative 8-week interval time. Key words: Esophageal neoplasms; Surgical resection, three-incision; Neoadjuvant chemo-radiation; Thoracoscopy; Laparoscopy

Effect of neoadjuvant chemoradiation on local control and disease-free survival in locally advanced rectal neoplasms

Effect of neoadjuvant chemoradiation on local control and disease-free survival in locally advanced rectal neoplasms

Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

The aim of the present study was to examine the effect of neoadjuvant chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in patients with locally advanced rectal adenocarcinoma. A total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4-6 weeks after the chemoradiation. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. Patients with an increase of EGFR expression during chemoradiation had significantly shorter disease-free survival (DFS; p = 0.003) and overall survival (OS; p = 0.005) compared to patients with either no change or decrease in EGFR expression. The 5-year DFS in patients with increased EGFR expression was only 29% compared to 61% in patients without an increase of EGFR expression. Similarly, the 5-year OS of the patients with increased EGFR expression was 29% compared to 66% in patients without an increase of EGFR expression. All recurrences in patients who had an increase of EGFR expression occurred within the first 2 years after the treatment. The increase in EGFR expression was the only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using multivariate Cox regression analysis. An increase of EGFR expression during chemoradiation may be associated with significantly shorter DFS and OS. The increase of EGFR could identify a population of patients in whom the effect of the treatment with anti-EGFR therapy should be studied.

Effect of Neoadjuvant Chemoradiation and Surgical Technique on Recurrence of Localized Pancreatic Cancer

ObjectivesTo determine the influence of neoadjuvant chemoradiation and standardized dissection of the superior mesenteric artery upon the oncologic outcome of patients with localized pancreatic adenocarcinoma. MethodsOne hundred ninety-four patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy between 2004 and 2008 were evaluated. The retroperitoneal dissection was performed directly along the superior mesenteric artery in all cases. A standard histopathologic protocol that measured the “superior mesenteric artery (SMA) margin distance” between cancer cells and the superior mesenteric artery was employed. ResultsSeventy-six percent of patients received neoadjuvant chemoradiation. The SMA margin was positive in 4% of patients but an additional 22% of patients with a negative margin had a SMA margin distance of ≤1 mm. Preoperative CT images overestimated the SMA margin distance in 73% of cases. Patients who received chemoradiation had longer SMA margin distances than those who did not. Patients who received chemoradiation and had a SMA margin of >1 mm had the lowest recurrence rates. Administration of neoadjuvant chemoradiation and lower estimated blood loss were independently associated with longer progression-free survival on multivariate analysis. ConclusionsPreoperative chemoradiation and meticulous dissection of the superior mesenteric artery maximize the distance between cancer cells and the SMA margin and may influence locoregional control.

Effect of neoadjuvant chemoradiation and postoperative radiotherapy on expression of heat shock protein 70 (HSP70) in head and neck vessels

BackgroundPreoperative radiotherapy and chemotherapy in patients with head and neck cancer result in changes to the vessels that are used to construct microsurgical anastomoses. The aim of the study was to investigate quantitative changes and HSP70 expression of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses.MethodsOf 20 patients included in this study five patients received neoadjuvant chemoradiation, another five received conventional radiotherapy and 10 patients where treated without previous radiotherapy. During surgical procedure, vessel specimens where obtained by the surgeon. Immunhistochemical staining of HSP70 was performed and quantitative measurement and evaluation of HSP70 was carried out.ResultsConventional radiation and neoadjuvant chemoradiation revealed in a thickening of the intima layer of recipient vessels. A increased expression of HSP70 could be detected in the media layer of the recipient veins as well as in the transplant veins of patients treated with neoadjuvant chemoradiation. Radiation and chemoradiation decreased the HSP70 expression of the intima layer in recipient arteries. Conventional radiation led to a decrease of HSP70 expression in the media layer of recipient arteries.ConclusionOur results showed that anticancer drugs can lead to a thickening of the intima layer of transplant and recipient veins and also increase the HSP70 expression in the media layer of the recipient vessels. In contrast, conventional radiation decreased the HSP70 expression in the intima layer of arteries and the media layer of recipient arteries and veins. Comparing these results with wall thickness, it was concluded, that high levels of HSP70 may prevent the intima layer of arteries and the media layer of vein from thickening.

Prospective analysis of KRAS, BRAF, and PIK3CA mutational status and EGFR copy number in patients (pts) with locally advanced rectal cancer: A translational substudy of a clinical trial (SAKK 41/07) evaluating the effect of neoadjuvant chemoradiation (CRT) with or without panitumumab.

3549 Background: The prevalence of possible prognostic and predictive markers is of great importance for future study designs and essential for the interpretation of clinical trials incorporating a...

Reduction of nodal micrometastases in patients with histological node-negative esophageal cancer after neoadjuvant treatment.

73 Background: Neoadjuvant chemoradiation (CRT) is important in the treatment ofesophageal cancer. Rationales are tumor-downstaging and elimination of micrometastases improving resectability and curability rate. In this study we evaluated the effect of neo-adjuvant CRT on nodal micrometastases (NMM) in pN0 esophageal cancer patients. Methods: From a prospective database, we selected a matched group of patients on cT-stage, histological type and treatment without (group 1) or with neo-adjuvant CRT (group 2). Patients were staged by EUS, PET-scan, CT-scan and EUS guided cytology. CRT was given in a randomized clinical trial and consisted of paclitaxel 50 mg/m2 and carboplatin AUC = 2 for 5 weeks and concurrent radiotherapy (41.4 Gy/23 frs). All patients (n = 19) underwent a curative intended transthoracic esophagectomy with extended 2-field nodal dissection. After reviewing routine pathological examination all tumors were confirmed as stage pN0. Four sections of every examined lymph node (n = 261) were made at different levels according to a sentinel node protocol and further analyzed immunohistochemically with anti-CK8/18 (CAM 5.2) to detect NMM. Results: Patients characteristics were equally distributed. All patients had a microscopically radical (R0) resection. In group 2 (n = 9) the response rate was 55% which was complete (CR) in 33%. The median number of resected nodes was comparable: 15 ± 6.5 and 15 ± 5.6 in both groups. Thirtheen of the 261 (5%) pN0 nodes in these 19 pts contained NMM. In group 1 (n = 10); 12 of the 136 (9%) examined pN0 lymph nodes were positive and in group 2 only one of the 125 (0.8%) examined pN0 nodes was positive (p = 0.003). NMM were found in 7 pts (70%) in group 1 and in only one patient (11%) in group 2 (p = 0.02). Interestingly, this last patient had responded well to CRT. Conclusions: Neo-adjuvant CRT seems to have a significant impact on the numbers of NMMs in esophageal cancer. Based on the presence of NMM even in patients with good responses, we still advocate a curatively intended nodal dissection. No significant financial relationships to disclose.

Effect of neoadjuvant chemoradiation on postoperative fecal continence and anal sphincter function in rectal cancer patients

Neoadjuvant chemoradiation (nCRT) followed by curative surgery has gained acceptance as the therapy of choice in locally advanced rectal cancer. This prospective study evaluates the effect of nCRT on postoperative anorectal function and continence. Group A consisted of 12 patients (59.8 +/- 11.9 years, male:female = 8:4) who received nCRT (5-FU, CPT-11. 45 + 5.4 Gy boost) before surgery and Group B of 27 patients (61.9 +/- 10.6 years, male:female = 16:11) who were treated by surgery alone. All patients received a questionnaire to evaluate stool continence and anorectal function before as well as after surgery. Anorectal function was further analyzed by perfusion manometry pre- and postoperatively. Preoperatively, none of the patients had signs or symptoms of fecal incontinence, and preoperative measurements showed values within normal limits. Postoperatively, fecal continence was impaired in both groups, but no significant difference was found between patients with or without nCRT. Anorectal manometry revealed an impairment of anorectal function after low anterior resection regardless of the treatment regime. nCRT does not impair anorectal function and fecal continence. The deterioration of continence and anal sphincter function after sphincter preserving surgery is solely caused by the surgical procedure.