Clear Circumferential Resection Margin Research Articles

Resection margins, lymph node harvest and 3 year survival in open and laparoscopic colorectal cancer surgery; a prospective cohort study

IntroductionLaparoscopic colorectal cancer surgery has been gaining popularity in the last decade. However, there are concerns about adequate lymph node dissection and safe resection margins in laparoscopic colorectal cancer surgery. This study was aimed at comparing the lymph node (LN) clearance and surgical resection margins and 3-year survival for open and laparoscopic colorectal cancer surgery.MethodA pre-tested interviewer administered questionnaire was used to assess the adoption of the laparoscopic approach by Sri Lankan surgeons. Data was collected prospectively from patients who underwent open or laparoscopic colorectal cancer surgery at the University Surgical Unit of the National Hospital of Sri Lanka from April 2016 to May 2019. The histopathology records were analysed to determine the longitudinal and circumferential resection margins(CRM) and the number of lymph nodes harvested. The resection margins were classified as positive or negative. The total number of LN examined was evaluated. Presence of local recurrence and liver metastasis was determined by contrast enhanced CT scan during 3-years of follow up. Chi square, T test and z test for proportions were used to compare CRM, LN harvest and survival rates between the groups.ResultsOf the surgeons interviewed only 11 (18.4%) performed laparoscopic colorectal cancer surgery. A total of 137 patients (83 males and 54 females) were studied. Eighty-one procedures were laparoscopic and 56 procedures were open. All patients had clear longitudinal resection margins. Seventy-eight patients in the laparoscopic group (96%) and 51 patients (91%) in the open group had clear CRM (p > 0.05). A total of 2188 LNs (mean 15.9) were resected in all procedures. Six-hundred-eighty-nine lymph nodes were removed during open procedures (mean 12.3, SD 0.4) and 1499 (mean 18.5, SD 0.6) were removed during laparoscopy (p < 0.05). At 3 years follow-up the disease-free survival in the laparoscopic and open colon cancer patients was 27/41 (65.8%) and 16/29 (55.1%) respectively (p = 0.35). Disease free survival in the laparoscopic and open rectal cancer patients was 23/38 (60.5%) and 13/25 (52.0%) respectively (p = 0.40). Four patients were lost during follow-up.Discussion and conclusionCRM was comparable in the two groups. Laparoscopic group had a significantly higher LN harvest. Three-year survival rates were similar in the two groups. Acceptable results can be obtained with laparoscopic colorectal cancer surgery.

Outcomes of open vs laparoscopic vs robotic vs transanal total mesorectal excision (TME) for rectal cancer: a network meta-analysis.

Total mesorectal excision (TME) for rectal cancer can be achieved using open (OpTME), laparoscopic (LapTME), robotic (RoTME), or transanal techniques (TaTME). However, the optimal approach for access remains controversial. The aim of this network meta-analysis was to assess operative and oncological outcomes of all four surgical techniques. Ovid MEDLINE, EMBASE, and PubMed databases were searched systematically from inception to September 2020, for randomised controlled trials (RCTs) comparing any two TME surgical techniques. A network meta-analysis using a Bayesian random-effects framework and mixed treatment comparison was performed. Primary outcomes were the rate of clear circumferential resection margin (CRM), defined as > 1mm from the closest tumour to the cut edge of the tissue, and completeness of mesorectal excision. Secondary outcomes included radial and distal resection margin distance, postoperative complications, locoregional recurrence, disease-free survival, and overall survival. Surface under cumulative ranking (SUCRA) was used to rank the relative effectiveness of each intervention for each outcome. The higher the SUCRA value, the higher the likelihood that the intervention is in the top rank or one of the top ranks. Thirty-two RCTs with a total of 6151 patients were included. Compared with OpTME, there was no difference in the rates of clear CRM: LapTME RR = 0.99 (95% (Credible interval) CrI 0.97-1.0); RoTME RR = 1.0 (95% CrI 0.96-1.1); TaTME RR = 1.0 (95% CrI 0.96-1.1). There was no difference in the rates of complete mesorectal excision: LapTME RR = 0.98 (95% CrI 0.98-1.1); RoTME RR = 1.1 (95% CrI 0.98-1.4); TaTME RR = 1.0 (95% CrI 0.91-1.2). RoTME was associated with improved distal resection margin distance compared to other techniques (SUCRA 99%). LapTME had a higher rate of conversion to open surgery when compared with RoTME: RoTME RR = 0.23 (95% CrI 0.034-0.70). Length of stay was shortest in RoTME compared to other surgical approaches: OpTME mean difference in days (MD) 3.3 (95% CrI 0.12-6.0); LapTME MD 1.7 (95% CrI -1.1-4.4); TaTME MD 1.3 (95% CrI -5.2-7.4). There were no differences in 5-year overall survival (LapTME HR 1.1, 95% CrI 0.74, 1.4; TaTME HR 1.7, 95% CrI 0.79, 3.4), disease-free survival rates (LapTME HR 1.1, 95% CrI 0.76, 1.4; TaTME HR 1.1, 95% CrI 0.52, 2.4), or anastomotic leakage (LapTME RR = 0.92 (95% CrI 0.63, 1.1); RoTME RR = 1.0 (95% CrI 0.48, 1.8); TaTME RR = 0.53 (95% CrI 0.19, 1.2). The overall quality of evidence as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessments across all outcomes including primary and secondary outcomes was deemed low. In selected patients eligible for a RCT, RoTME achieved improved distal resection margin distance and a shorter length of hospital stay. No other differences were observed in oncological or recovery parameters between (OpTME), laparoscopic (LapTME), robotic (RoTME), or trans-anal TME (TaTME). However, the overall quality of evidence across all outcomes was deemed low.

450 FACTORS AFFECTING CIRCUMFERENTIAL RESECTION MARGIN AFTER ESOPHAGECTOMY AND ITS PROGNOSTIC SIGNIFICANCE-LARGE SINGLE CENTRE EXPERIENCE

Abstract The evidence regarding the importance of circumferential resection margin (CRM) as a prognostic factor after esophagectomy is inconclusive in the era of neoadjuvant therapy. We retrospectively analysed our prospectively maintained database for factors that affect CRM positivity, and whether a positive CRM affects event free and overall survival. 2843 patients underwent esophagectomy with curative intent from October 2004 to 2019 at our centre. CRM was analysed as negative, close but technically free (&amp;lt;1 mm) and involved. Methods Data on the following variables was retrospectively extracted from prospective database. CRM status was noted for clinic-radiological T and N stage, level of growth, histology, differentiation grade and neoadjuvant treatment. Intra-operative details such as surgical procedure, approach, surgeon grade, lymphadenectomy and resection status were analysed. On final histopathology; proximal and distal margins, lymph node positivity, lymphovascular invasion(LVI), tumour regression grade(TRG) were analysed. The effect of CRM on development of recurrence and overall survival was evaluated. CRM data was available for 2439 (85.78%) patients. 71.2% of the patients received neoadjuvant chemotherapy. Factors were analysed separately for both close and positive margins. Results 75.8% had negative, 15.6% close and 8.6% positive CRM. Univariately, T stage, adenocarcinoma, poor differentiation, transhiatal approach, R+ resection, positive margins, TRG &amp;gt; 3, LVI and upfront surgery predicted positive CRM. On multivariate, negative CRM was seen in T1/T2 stage [OR 0.325, 95% CI-0.144-0.732, p = 0.007], squamous carcinoma [OR 0.574, 95% CI-0.351-0.958, p = 0.027], R0 resection [OR 0.228, 95% CI-0.086-0.599, p = 0.003] while positive CRM was seen in upfront surgery [OR 2.32, 95% CI-1.55-3.46, p &amp;lt; 0.001], positive nodes [OR 1.748, 95% CI-1.19-2.56, p = 0.004] and LVI [OR 2.73, 95% CI-1.87-3.98, p &amp;lt; 0.001]. Median event-free survival in CRM negative was 64 months compared to 14 months in CRM positive (p &amp;lt; 0.001). Conclusion Positive CRM involvement is a prognostic indicator in patients undergoing esophagectomy and associated with worse event-free and overall survival. CRM-positive disease in esophageal cancer may represent residual tumor, advanced disease, aggressive biology, or poor response to neoadjuvant treatment. All attempts should be made to achieve a clear circumferential resection margin. More evidence is needed to evaluate if adjuvant therapy is justified in these patients and the type of therapy also needs to be determined.

Oncological outcomes of laparoscopic versus open rectal cancer resections: meta-analysis of randomized clinical trials.

The role of laparoscopic rectal cancer surgery has been questioned owing to conflicting reports on pathological outcomes from recent RCTs. However, it is unclear whether these pathological markers and the surgical approach have an impact on oncological outcomes. This study assessed oncological outcomes of laparoscopic and open rectal cancer resections. A meta-analysis of RCTs was performed. Primary endpoints included oncological outcomes (disease-free survival (DFS), overall survival (OS), local recurrence). Secondary endpoints included surrogate markers for the quality of surgical resection. Twelve RCTs including 3744 patients (2133 laparoscopic, 1611 open) were included. There was no significant difference in OS (hazard ratio (HR) 0.87, 95 per cent c.i. 0.73 to 1.04; P = 0.12; I2 = 0 per cent) and DFS (HR 0.95, 0.81 to 1.11; P = 0.52; I2 = 0 per cent) between laparoscopic and open rectal resections. There was no significant difference in locoregional (odds ratio (OR) 1.03, 95 per cent c.i. 0.72 to 1.48; P = 0.86; I2 = 0 per cent) or distant (OR 0.87, 0.70 to 1.08; P = 0.20; I2 = 7 per cent) recurrence between the groups. Achieving a successful composite score (intact mesorectal excision, clear circumferential resection margin and distal margin) was significantly associated with improved DFS (OR 0.55, 0.33 to 0.74; P < 0.001; I2 = 0 per cent). An intact or acceptable mesorectal excision (intact mesorectal excision with or without superficial defects) had no impact on DFS. Finally, a positive CRM was associated with worse DFS. Well performed surgery (laparoscopic or open) achieves excellent oncological outcomes with very little difference between the two modalities. The advantage and benefit of minimally invasive surgery should be assessed on an individual basis.

Surgical techniques in the management of rectal cancer: a modified Delphi method by colorectal surgeons in Australia and New Zealand.

Technological developments have allowed advances in minimally invasive techniques for total mesorectal excision such as laparoscopy, robotics, and transanal surgery. There remains an ongoing debate about the safety, benefits, and appropriate clinical scenarios for which each technique is employed. The aim of this study was to provide a panel of expert opinion on the role of each surgical technique currently available in the management of rectal cancer using a modified Delphi method. Surveys were designed to explore the key patient- and tumor-related factors including clinical scenarios for determining a surgeon's choice of surgical technique. Open surgery was favoured in obese patients with an extra-peritoneal tumor and a positive circumferential resection margin (CRM) or T4 tumor when a restorative resection was planned. Laparoscopy was favoured in non-obese males and females, in both intra- and extra-peritoneal tumors with a clear CRM. Robotic surgery was most commonly offered to obese patients when the CRM was clear and if an abdominoperineal resection was planned. Transanal total mesorectal excision (taTME) was preferred in male patients with a mid or low rectal cancer, particularly when obese. Transanal endoscopic microsurgery/transanal minimally invasive surgery local excision was only offered to frail patients with small, early stage tumors. All surgical techniques for rectal cancer dissection have a role and may be considered appropriate. Some techniques have advantages over others in certain clinical situations, and the best outcomes may be achieved by considering all options before applying an individualised approach to each clinical situation.

Surgical treatment of colorectal cancer

Surgical treatment of colorectal cancer Abstract. For the last two decades, colorectal surgery has been evolving driven by technical innovation, new findings in clinical trials and better understanding of the pathophysiology and biology of the tumours. Efforts to improve oncological outcomes led to a centralisation of care and nowadays surgery for colorectal cancer is mainly performed in certified high-volume centres. Standardised surgical techniques have been developed in order to facilitate training and improve oncological outcome. The introduction of total mesorectal excision (TME) resulted in a better postoperative outcome, reduced local recurrence rate and better overall survival for rectal cancer. Complete mesocolic excision (CME) was described as an attempt to standardise the operative technique for colon cancer and follows the same principles of the TME in order to improve the oncological outcome. In this approach, sharp precise dissection of the embryological planes allows the maintenance of integrity of the mesocolic envelope with its lymphatic drainage. However, CME has not yet been adopted universally by surgeons and data about long-term oncological outcome are awaited. One of the most substantial recent developments in the surgery of colon cancer is the implementation of minimally invasive approach. Randomised controlled trials demonstrated comparability of laparoscopic versus open surgery for colonic cancer. However, with the recent evidence, non-inferiority of the laparoscopic approach for TME could not be proven. Obtaining a clear circumferential resection margin especially in male patients with narrow pelvis is a major issue that has a direct impact on the local recurrence of rectal cancer. In an attempt to improve quality of the TME, new surgical techniques such as transanal total mesorectal excision and robotic surgery are now widely performed. However, oncological long-term data are lacking. Preservation of function and quality of life are factors which need to be addressed when counselling the patient with rectal cancer. Organ preservation with local excision for low-risk lesions is an appropriate approach for selected patients.

Short course radiotherapy (SCRT) and delayed surgery by 8-10 weeks for MRI defined high-risk rectal cancer.

e15145 Background: Pelvic MRI can identify rectal cancer patients at risk of an incomplete (R1) resection, allowing pre-operative treatment, usually with pelvic chemo-radiotherapy (CRT) over 5 weeks. Co-morbidities (eg IHD) may make CRT high risk, &amp; SCRT with delayed surgery 8-10 weeks later may be an option, but with relatively little published data on efficacy. Methods: Between 2004 &amp; 2016 our database identified 573 patients with MRI defined high risk rectal adenocarcinomas, and 55 (9.6%) had SCRT &amp; delayed surgery. Results: Patient characteristics: m 35, F 20, mean age 75 years (55- 90). Main co-morbidities were active IHD &amp; frailty. Major post-operative complications were an anastomic leak in 1 (1.8%) patient &amp; septicaemia/shock in 1 (1.8%) patient, with the latter being the only 30 day post-operative death (1.8%). The R1 resection rate was 7 (12.7%), affecting the circumferential resection margin (CRM) in 6, with 2 subsequently developing local recurrence. 4 CRM +ve patients are dead, all of systemic relapse. Distal margin involved in 1 patient, alive with no recurrence on follow up. Local recurrence (with systemic relapse) occurred in 1 patent with a clear CRM, 4 years after SCRT/surgery. Overall local recurrence rate was 5.4%. Pathology response was minimal 4 (7.3%), partial 28 (51%), good partial 15 (27%), &amp; complete (pCR) 8 (14.5%). The 5 year disease specific survival rates, accepting small numbers in each group, were 60% for minimal, 96% for partial, 93% for good partial &amp; 100% for pCR patients respectively. Systemic relapse occurred in 12 (22%) patients, with liver surgery &amp; liver ablation in 2 patients respectively. 18 (33%) patients have died, 10 of infection, 2 of IHD, 2 of progressive disease, 2 of separate cancers, &amp; 2 unknown. Conclusions: In a MRI defined high risk rectal cancer population &amp; co-morbidities, the outcomes from SCRT with delayed surgery 8-10 weeks later are similar to CRT, &amp; a reasonable option to consider.

Reduced pelvic field sparing anastomosis for postoperative radiotherapy in selected patients with mid-upper rectal cancer.

The aim of this study was to report the clinical results of reduced pelvic field radiotherapy (RT), excluding the anastomotic site, after total mesorectal excision in selected patients with rectal cancer. Between 2011 and 2014, 99 patients underwent upfront surgery for clinically less-advanced tumors but were finally diagnosed as pT3/N+. Among them, 50 patients with mid–upper rectal cancer who received postoperative RT with a reduced pelvic field were included in this retrospective review. This group was composed of patients with high seated tumors, complete resection with a clear circumferential resection margin, and no complication during surgery. We investigated treatment outcomes, toxicity and the effect of RT-field reduction on organs-at risk in 5 randomly selected patients. During the median follow-up period of 42 months (range: 15−59 months), tumors recurred in 9 patients (18%). The 3-year overall and disease-free survival were 98% and 81%, respectively. Distant metastasis was the dominant failure pattern (n = 8, 16%), while no recurrences occurred at or near anastomotic sites. No anastomotic complications were found on pelvic examination, images and/or colonoscopy. Reported acute and late RT-related toxicities were mostly mild to moderate, with only small numbers of Grade 3 toxicities. None of the patients developed Grade 4−5 acute or late toxicity. With a caudally reduced field, 64% reduction in absolute anastomotic exposure at the maximum dose was achieved compared with the traditional whole-pelvic field (P = 0.008). The reduced pelvic field RT was able to minimize late anastomotic complication without increasing its recurrence in selected patients with mid–upper rectal cancer in the postoperative setting.

Combined robotic transanal total mesorectal excision (R-taTME) and single-site plus one-port (R-SSPO) technique for ultra-low rectal surgery-initial experience with a new operation approach.

Robot-assisted rectal surgery is gaining popularity, and robotic single-site surgery is also being explored clinically. We report our initial experience with robotic transanal total mesorectal excision (R-taTME) and radical proctectomy using the robotic single-site plus one-port (R-SSPO) technique for low rectal surgery. Between July 2015 and March 2016, 15 consecutive patients with ultra-low rectal lesions underwent R-taTME followed by radical proctectomy using the R-SSPO technique by a single surgeon. The clinical and pathological results were retrospectively analyzed. The median operative time was 473 (range, 335-569)min, and the estimated blood loss was 33 (range, 30-50)mL. The median number of lymph nodes harvested was 12 (range, 8-18). The median distal resection margin was 1.4 (range, 0.4-3.5)cm, and all patients had clear circumferential resection margins. We encountered a left ureteric transection intraoperatively in one patient, and another patient required reoperation for postoperative adhesive intestinal obstruction. There was no 30-day mortality. R-taTME followed by radical proctectomy using the R-SSPO technique for patients with low rectal lesions is technically feasible and safe without compromising oncologic outcomes. However, there were considerable limitations and a steep learning curveusing current robotic technology.

Total mesorectal excision for the treatment of rectal cancer.

IntroductionIn the surgical treatment of rectal cancer, a clear circumferential resection margin and distal resection margin should be obtained. The aim of this study was to determine the morbidity, mortality, survival outcome, and local failure after total mesorectal excision (TME) in the surgical treatment of rectal cancer.MethodsThis retrospective study was conducted on 101 patients treated for rectal cancer using low anterior resection (LAR), abdominoperinial resection (APR), or Hartmaan’s technique. In all operative procedures, total mesorectal excisions (TMEs) were done. The patients were treated from November 2000 to April 2011 in the South Egypt Cancer Institute (SECI) of Assuit University (Egypt). Neo-adjuvant therapy was given to those patients with serosalin filtration, lymph node involvement, and sexual and urinary function impairment. Data were analyzed using IBM-SPSS version 21, and survival rates were estimated using the Kaplan-Meier method.ResultsOne hundred one patients were evaluable (61 males, 40 females). Regarding the operative procedure used, it was: (APR), LAR, Hartmaan’s technique in 15.8%, 71.3%, and 12.9% of patients, respectively. Operation-related mortality during the 30 days after surgery was 3%. The operations resulted in morbidity in 25% of the patients, anastomotic site leak in 5.9% of the patients, urinary dysfynction in 9.9% of the patients, and erectile dysfunction in 15.8% of the male patients. Regarding safety margin, the median distances were distal/radial margin, 23/12 mm, distal limit 7 cm. Median lymph nodes harvest 19 nodes. Primary tumor locations were anteriorly 23.8%, laterally 13.9%, posteriorly 38.6%, and circumferential 23.8%. Protective stoma 16.8%. Primary Tumor TNM classification (T1, T2, T3, and T4; 3, 28.7, 55.4, and 12.9%, respectively). Nodes Metastases (N0, N1, and N2; 57.4, 31.7, and 10.9%, respectively). TNM staging (I, II, III, and IV; 15.8, 29.7, 46.5, and 7.9%, respectively). Chemotherapy was administered to 67.3% of the patients. Radiotherapy (short course neoadjuvant, long course neoadjuvant, and adjuvant postoperative used in 33.7, 20.8, and 19.8% of patients, respectively). Survival 5-years CSS was 73% and 5-years RFS 71%. Mean operative time was 213 minutes. The average amount of intraoperative blood loss was 344 mL.ConclusionTotal mesorectal excision (TME) represents the gold-standard technique in rectal cancer surgery. It is safe with neoadjuvent chemoradiotherapy and provides both maximal oncological efficiency (local control and long-term survival and maintenance of a good quality of life).

PWE-311 Extra-levator abdomino-perineal resection for low rectal cancer

Introduction Extra-levator abdomino-perineal resection (eLAP) has superseded standard abdomino-perineal excision (APER) for low rectal cancer. Reduction in rates of circumferential resection margin (CRM) involvement and tumour perforation offer improved oncological outcome. There is no consensus regarding management of the larger perineal defect that results. We report outcomes following primary closure following an eLAP. Method All eLAPs undertaken in a single centre over five years were identified. eLAP and primary closure is the local standard of care. A retrospective review recorded CRM involvement, primary wound healing and infection rates, the incidence of perineal herniae, and subsequent intervention if required. Results Fifty-one patients were identified, with a mean age of 70.2, and a male preponderance of 63%. Ten patients were classified ASA 3 (19.6%); the remainder were ASA 1–2. Thirty-two patients had a laparoscopic operation (63%), with a further 6 converted to open (12%). 14 patients had an open operation (27%). 38/51 patients (75%) had a clear CRM. There were no tumour perforations. EMVI was present in 13 patients (25%). Wound healing problems were identified in 12 patients (24%), with 6 requiring intervention (12%). The incidence of perineal hernia was 9/51 (18%) of which 5 (9.8%) were repaired surgically. Conclusion This series suggests that eLAP combined with primary closure of the perineum may offer the benefits of low rates of CRM involvement and tumour perforation yet minimal perineal wound related morbidity compared to published data. Disclosure of interest None Declared.

The prognostic value of circumferential resection margin in esophageal squamous cell carcinoma after concurrent chemoradiation therapy and surgery

BackgroundDespite the significant advances in surgical techniques and multimodality treatments for esophageal cancer, the overall survival remains unsatisfactory. During the past years, efforts were made to determine the prognostic factors that would help in identifying patients suitable for surgery or guiding adjuvant therapy. Positive circumferential resection margins (CRMs) in esophageal cancer have been previously linked with poor prognosis, but their impact on survival remains controversial in patients treated by a multimodality protocol. The aim of our study was to examine the significance of tumor involvement of CRM in patients with esophageal squamous cell carcinoma after concurrent chemoradiation therapy followed by esophagectomy. MethodsBetween 2000 and 2010, 94 esophageal squamous cell carcinoma patients who received preoperative concurrent chemoradiation therapy followed by surgery were enrolled in our study. We focused on the CRM, which was defined microscopically as clear (negative) or involved (positive). Univariate and multivariate survival analyses were performed with overall survival as the endpoint. ResultsOur cohort was predominantly male (94.7%) with a median age of 57 years. All of them received concurrent chemoradiation therapy followed by esophagectomy. Overall, 17 patients (18.1%) had positive CRM. Kaplan–Meier survival analysis demonstrated that the 5-year overall survival of patients with clear and involved CRM is 60.1% and 11.8%, respectively (log rank p < 0.001). Multivariate analysis with the Cox proportional hazard model demonstrated that CRM involvement is a significant prognostic factor for overall survival (p < 0.001). ConclusionIn patients with esophageal squamous cell carcinoma who underwent trimodality treatment, CRM involvement is a significant risk factor predicting survival. Additional effort is required to achieve a clear CRM in esophageal cancer treatment.

Current practice in preoperative therapy and surgical management of locally advanced rectal cancer: a bi‐national survey1

The Australasian colorectal surgeon's current approach to preoperative rectal cancer management was compared with international guidelines. Members of the Colorectal Surgical Society of Australia and New Zealand were surveyed in 2010, on the use of MRI and the management of locally advanced rectal cancer. Surgeons had to decide the appropriate management in five scenarios that were developed from national guidelines. Of 174 invitations sent, 108 (62.1%) replies were received. Most surgeons (98.1%) had access to MRI. Ninety-three (86.1%) would use MRI routinely for staging. The majority selected a tumour-specific mesorectal resection for upper rectal cancer (58.2%) and a total mesorectal excision for distal cancer (100%). Almost all restorative operations included a covering ileostomy. One third of surgeons recommended that patients with a favourable cT3 mid-rectal tumour (N0, clear circumferential resection margins) should not have preoperative therapy and should proceed directly to surgery. When high-risk features, such as threatened resection margins or cN1 stage, were present, 5% and 15% of surgeons, respectively, would continue to treat by standard resection without preoperative therapy. Evidence-based international guidelines for the management of rectal cancer have changed little in the last 10 years. Despite this, there is a clear gap between these and clinical practice. The main variance relates to the role of radiotherapy in locally advanced rectal cancer. Despite considerable evidence that radiotherapy reduces local recurrence for all stages of rectal cancer, current practice in Australasia is for its selective use.

P-0296 Could Pre-Treatment Cea be an Effective Predictor of Relapse in High Risk Rectal Cancer?

ABSTRACT Introduction Over 14,000 cases of rectal cancer occur per year in the UK. Radical surgery with total mesorectal excision (TME) is the main curative treatment for disease localised to the pelvis. Some cases are judged on pelvic MRI to be at high risk of positive margins from surgery alone. They are offered pre-operative chemo-radiotherapy (CRT) before surgery with TME. This hopes to downsize and downstage tumors to provide clear circumferential resection margins and reduce the likelihood of relapse. Good pathological responses to CRT are associated with improved cancer outcomes. We investigated whether carcinoembryonic antigen (CEA) levels at presentation could act as a simple predictor of relapse when using CRT followed by TME for patients with high-risk rectal cancers. Methods Retrospective data was collected on high-risk rectal cancer patients treated radically with pre-op CRT and TME surgery at Ipswich Hospital between March 2005 and Jan 2012. All received at least 45 Gy in 25 fractions of radiotherapy using a three-field CT plan and 5 weeks of oral capecitabine chemotherapy. CEA levels were obtained prior to radiotherapy. Following surgery, rectal specimens were assessed by our pathologists to evaluate response to treatment and whether complete pathological response (pCR) was achieved. Follow-up was by our oncology department and colorectal surgeons with annual CT scanning, 1-3 yearly colonoscopies and clinical surveillance for 5 years. Results 56 patients met inclusion criteria. Male to female ratio: 1.8:1. 96% (n=54) patients received pre-op chemotherapy alongside radiotherapy: 2 patients were considered too high-risk for this component of treatment. Mean follow-up from commencing radiotherapy was 33 months (range 7-69). Mean time from last dose of radiotherapy to surgery was 11 weeks (range 5-18). 93% (n=52) had (R0) resection margins following surgery. 7.1% (n=4) had (R1) incomplete resection margins following surgery; 2 of these 4 suffered local relapse in the pelvis. 30% (n=17) achieved a pCR following CRT, none of the patients who achieved a pCR have relapsed. 77% (n=43) presented with a normal CEA (≤5, range 5, range 6-54). Normal CEA group: 35%, (n=15) achieved pCR following CRT and 14% (n=6) relapsed. High CEA group: 15% (n=2) achieved pCR following CRT and 46%, (n=6) relapsed. There was a significant between group difference in relapse (Fisher's exact test p=0.02). Further survival analysis for relapse revealed a statistically significant hazard ratio of 4.5 (95% CI 1.04 to 19.4). Conclusion 1. High CEA on presentation was associated with an estimated relative risk of relapse 4.5 times greater than presenting with a normal CEA. 2. Therefore high CEA at presentation could be a useful biomarker to identify patients with the highest risk of relapse who may benefit from more intensive treatment. 3. Our high rates of R0 resection margin (93%) and pCR (30%) could be due to a relatively prolonged time from radiotherapy to surgery in our cohort.

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m−2 to 60 mg m−2 to 70 mg m−2 to identify the maximum tolerated dose (60 mg m−2). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m−2 per day) for 5 weeks. Irinotecan (60 mg m−2) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity.

Magnetic resonance imaging in rectal cancer downstaged using neoadjuvant chemoradiation: accuracy of prediction of tumour stage and circumferential resection margin status

The aim was to examine the accuracy of magnetic resonance imaging (MRI) in predicting circumferential resection margin (CRM) involvement, T- and N-stage in patients with locally advanced carcinoma of the rectum, who had undergone long-course downstaging chemoradiation (CRT). Patients with rectal cancer were selected for long-course downstaging CRT if their tumour was considered to threaten (< or = 1 mm) or involve the CRM on MRI. Eighty such patients had a repeat MRI at a median of 6 weeks post-CRT followed by surgical excision soon thereafter. The findings on the post-CRT MRI were compared with histological examination of the surgical specimen. For CRM involvement, post-CRT restaging MRI had an accuracy of 81% (65/80) a sensitivity of 54% (7/13), a specificity of 87% (58/67), a positive predictive value of 44% (7/16) and a negative predictive value of 91% (58/64). Accuracy for T- and N-staging was 43% (34/80) and 78% (62/80), respectively. 38% of T-stages were overstaged and 20% understaged. 4% of N-stages were overstaged and 19% understaged. The 13 patients with histological positive CRM had worse clinical outcomes than the 67 patients with negative CRM in terms of disease-free survival (relative risk of reduced DFS 4.6, P = 0.001) and overall survival (relative risk of death 3.6, P = 0.016). Magnetic resonance imaging has good specificity and negative predictive value for predicting an uninvolved CRM post downstaging CRT in locally advanced rectal cancer although sensitivity and positive predictive value for an involved CRM were unsatisfactory. The shortcomings of MRI stem from poor differentiation of viable tumour from posttreatment changes and inability to identify small nodal and tumour deposits. Clinical correlates in this group of patients have confirmed the importance of achieving a clear CRM at surgery.

Neoadjuvant chemotherapy enables R0 resection of locally advanced rectal cancer in a patient with a previously irradiated pelvis

Pre-operative chemoradiation is frequently employed in an attempt to downstage locally advanced rectal cancer which threatens or involves the circumferential resection margin (CRM) on MRI scanning. We present a case where radiotherapy was contraindicated as the patient had previously been irradiated to a radical dose for prostatic adenocarcinoma. Neoadjuvant capecitabine and oxaliplatin were used to downsize the tumour to permit resection with a clear CRM.

Considerations and restrictions for non-operative treatment of rectal cancer in selected patients

Surgery is the corner stone of curative treatment for rectal cancer and the reference for new treatments. Proper treatment consists of complete surgical removal of the tumour, with clear circumferential resection margins, checked with adequate pathological examination, the results of which can be used as a reference for adjuvant treatment. In the past decade, preoperative chemoradiotherapy (CRT) has been introduced for rectal cancer to downstage and downsize the tumour. A pathological complete response (pCR), defined as no tumour detectable during pathological examination of the resection specimen, has been reported in 10–30% of patients treated with preoperative CRT.

A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group Study

The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m−2) administered on days 1–5 and 29–33 followed by low dose LV (20 mg m−2) and 5FU (350 mg m−2 over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6–10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26–75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m−2 when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m−2 dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 (24%) and 12 out of 57 (21%) overall. A histologically confirmed clear circumferential resection margin (CRM) was achieved in 39 out of 49 (80%) of those resected, and 39 out of 57 (68%) overall. In conclusion, MTD with this scheduled regimen of irinotecan is 20 mg m−2 (days 1–5 and 29–33). The acceptable toxicity and compliance at 18 mg m−2 recommend testing this dose in future phase III studies. The tumour downstaging and complete resection rates (negative CRM) are encouragingly high for this very locally advanced group.

Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study

Objective To assess the accuracy of preoperative staging of rectal cancer with magnetic resonance imaging to predict surgical circumferential resection margins.Design Prospective observational study of rectal cancers treated by colorectal...