Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer: Final Report of the OCUM Study.

PURPOSE: We investigated whether neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer can be restricted to those at high risk of locoregional recurrence (LR) without compromising oncological outcomes. PATIENTS AND METHODS: In a prospective multicenter interventional study, patients with rectal cancer (cT2-4, any cN, cM0) were classified according to the minimal distance between the tumor, suspicious lymph nodes or tumor deposits, and mesorectal fascia (mrMRF). Patients with a distance >1 mm underwent up-front total mesorectal excision (TME; low-risk group), whereas those with a distance ≤1 mm and/or cT4 and cT3 tumors in the lower rectal third received nCRT followed by TME surgery (high-risk group). The primary end point was 5-year LR rate. RESULTS: Of the 1,099 patients included, 884 (80.4%) were treated according to the protocol. A total of 530 patients (60%) underwent up-front surgery, and 354 (40%) had nCRT followed by surgery. Kaplan-Meier analyses revealed 5-year LR rates of 4.1% (95% CI, 2.7 to 5.5) for patients treated per protocol, 2.9% (95% CI, 1.3 to 4.5) after up-front surgery, and 5.7% (95% CI, 3.2 to 8.2) after nCRT followed by surgery. The 5-year rate of distant metastases was 15.9% (95% CI, 12.6 to 19.2) and 30.5% (95% CI, 25.4 to 35.6), respectively. In a subgroup analysis of 570 patients with lower and middle rectal third cII and cIII tumors, 257 (45.1%) were at low-risk. The 5-year LR rate in this group was 3.8% (95% CI, 1.4 to 6.2) after up-front surgery. In 271 high-risk patients (involved mrMRF and/or cT4), the 5-year rate of LR was 5.9% (95% CI, 3.0 to 8.8) and of metastases 34.5% (95% CI, 28.6 to 40.4); disease-free survival and overall survival were the worst. CONCLUSION: The findings support the avoidance of nCRT in low-risk patients and suggest that in high-risk patients, neoadjuvant therapy should be intensified to improve prognosis.

Selection of patients with rectal cancer for neoadjuvant therapy using pre-therapeutic MRI - Results from OCUM trial.

PURPOSE: No consensus is available on the appropriate criteria for neoadjuvant chemoradiotherapy selection of patients with rectal cancer. The purpose was to evaluate the accuracy of MRI staging and determine the risk of over- and undertreatment by comparing MRI findings and histopathology. METHOD: In 609 patients of a multicenter study clinical T- and N categories, clinical stage and minimal distance between the tumor and mesorectal fascia (mrMRF) were determined using MRI and compared with the histopathological categories in resected specimen. Accuracy, sensitivity, specificity, positive predictive, and negative predictive value (NPV) were calculated. Overstaging was defined as the MRI category being higher than the histopathological category. mrMRF and circumferential resection margin (CRM) were judged as tumor free at a minimal distance > 1 mm. The chi-squared test or Fisher's exact test were used. P < 0.05 was considered significant. RESULTS: The T category was correct in 63.5% (386/608) of patients; cT was overstaged in 22.9% (139/608) and understaged in 13.5% (82/608). MRI accuracy for lymph node involvement was 56.5% (344/609); 22.2% (28/126) of patients with clinical stage II and 28.1% (89/317) with clinical stage III disease were diagnosed by histopathology as stage I. The accuracy for tumor free CRM was 86.5% (527/609) and the NPV was 98.1% (514/524). In 1.7% (9/524) mrMRF was false negative. CONCLUSION: MRI prediction of the tumor-free margin is more reliable than the prediction of tumor stage. MRF status as determined MRI should therefore be prioritized for decision making.

Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer carries a high risk of adverse effects. The aim of this study was to examine the selective application of nCRT based on patient risk profile, as determined by MRI, to find the optimal range between undertreatment and overtreatment. STUDY DESIGN: In this prospective multicenter observational study, nCRT before total mesorectal excision (TME) was indicated in high-risk patients with involved or threatened mesorectal fascia (≤1 mm), or cT4 or cT3 carcinomas of the lower rectal third. All other patients received primary surgery. RESULTS: Of the 1,093 patients, 878 (80.3%) were treated according to the protocol, 526 patients (59.9%) underwent primary surgery, and 352 patients (40.1%) underwent nCRT followed by surgery. The 3-year locoregional recurrence (LR) rate was 3.1%. Of 604 patients with clinical stages II and III, 267 (44.2%) had primary surgery; 337 (55.8%) received nCRT followed by TME. The 3-year LR rate was 3.9%, without significant differences between groups. In patients with clinical stages II and III who underwent primary surgery, 27.3% were diagnosed with pathological stage I. CONCLUSIONS: The results justify the restriction of nCRT to high-risk patients with rectal cancer classified by pretreatment MRI. Provided that a high-quality MRI diagnosis, TME surgery, and standardized examination of the resected specimen are performed, nCRT, with its adverse effects, costs, and treatment time can be avoided in more than 40% of patients with stage II or III rectal cancer with minimal risk of undertreatment. (clinicaltrials.gov NCT325649).

MRI-Based Use of Neoadjuvant Chemoradiotherapy in Rectal Carcinoma: Surgical Quality and Histopathological Outcome of the OCUM Trial.

BACKGROUND: Preoperative magnetic resonance imaging (MRI) allows highly reliable imaging of the mesorectal fascia (mrMRF) and its relationship to the tumor. The prospective multicenter observational study OCUM uses these findings to indicate neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. METHODS: nCRT was indicated in patients with positive mrMRF (≤ 1 mm) in cT4 and cT3 carcinomas of the lower rectal third. RESULTS: A total of 527 patients (60.2%) underwent primary total mesorectal excision, and 348 patients (39.8%) underwent long-term nCRT followed by surgery. The mrMRF was involved in 4.6% of the primary surgery group and 80.7% of the nCRT group. Rates of resections within the mesorectal plane (90.8%), sparing of pelvic nerves on both sides (97.8%), and number of regional lymph nodes (95.3% with ≥ 12 lymph nodes examined) are indicative of high-quality surgery. Resection was classified as R0 in 98.3%, the pathological circumferential resection margin (pCRM) was negative in 95.1%. Patients in the nCRT group had more advanced carcinomas with a significantly higher rate of abdominoperineal excision. Independent risk factors for pCRM positivity were advanced stage (T4), metastatic lymph nodes, resection in the muscularis propria plane, and location in the lower third. CONCLUSIONS: The risk classification of rectal cancer patients by MRI seems to be highly reliable and allows the restriction of nCRT to approximately half of the patients with clinical stage II and III rectal carcinoma, provided there is a high-quality MRI diagnostic protocol, high-quality surgery, and standardized examination of the resected specimen.

Simulation-Based Training - Evaluation of the Course Concept "Laparoscopic Surgery Curriculum" by the Participants.

INTRODUCTION: The learning curve in minimally invasive surgery is much longer than in open surgery. This is thought to be due to the higher demands made on the surgeon's skills. Therefore, the question raised at the outset of training in laparoscopic surgery is how such skills can be acquired by undergoing training outside the bounds of clinical activities to try to shorten the learning curve. Simulation-based training courses are one such model. METHODS: In 2011, the surgery societies of Germany adopted the "laparoscopic surgery curriculum" as a recommendation for the learning content of systematic training courses for laparoscopic surgery. The curricular structure provides for four 2-day training courses. These courses offer an interrelated content, with each course focusing additionally on specific topics of laparoscopic surgery based on live operations, lectures, and exercises carried out on bio simulators. RESULTS: Between 1st January, 2012 and 31st March, 2016, a total of 36 training courses were conducted at the Vivantes Endoscopic Training Center in accordance with the "laparoscopic surgery curriculum." The training courses were attended by a total of 741 young surgeons and were evaluated as good to very good during continuous evaluation by the participants. CONCLUSION: Training courses based on the "laparoscopic surgery curriculum" for acquiring skills in laparoscopy are taken up and positively evaluated by young surgeons.