Kitz J, et al. - In this secondary end point analysis of a phase 3 randomized clinical trial, researchers investigated if the quality of total mesorectal excision (TME) plane affects clinical outcomes in patients with rectal cancer treated with preoperative chemoradiotherapy and adjuvant treatment. Outcomes suggested the quality of the TME plane as an independent prognostic factor for the local recurrence in rectal cancer thereby highlighting the crucial role of pathologists and surgeons in the multidisciplinary management of rectal cancer.

Methods

• In the CAO/ARO/AIO-04 trial, 1,236 patients with cT3-4 and/or node-positive rectal adenocarcinoma were enrolled from 88 centers in Germany between July 25, 2006, and February 26, 2010.
• Treatment with standard fluorouracil-based preoperative chemoradiotherapy (CRT) alone (control arm) or oxaliplatin (experimental arm) followed by TME and adjuvant chemotherapy was provided to the patients.
• In 1,152 operation specimens, they prospectively determined the TME quality (mesorectal, intramesorectal, and muscularis propria plane).
• Pathologists and surgeons independently performed the assessment.
• In this work, the results were correlated with clinicopathologic data and the clinical outcome was tested, including multivariable analysis with the Cox regression model.

Results

• Researchers included 1,152 German Caucasian participants, and of these, 332 (28.8) were women and the mean age was 63 years.
• In 930 patients (80.7%), the plane of TME was mesorectal, in 169 (14.7%) intramesorectal, and in 53 (4.6%) muscularis propria.
• The univariable analysis suggested a significant association of the TME plane with 3-year disease-free survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 73.1-78.8 vs 61.6-76.0 vs 55.6-81.3, respectively; P=.01), cumulative incidence of local and distant recurrences (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 2.0-4.5 vs 1.2-8.1 vs 2.5-20.5, respectively; P < .001; and mesorectal vs intramesorectal vs muscularis propria, 95% CI, 17.0-22.4 vs 18.3-32.0 vs 14.2-39.0, respectively; P=.03, respectively), and overall survival (mesorectal vs intramesorectal vs muscularis propria, 95% CI, 88.3-92.3 vs 79.7-91.0 vs 81.6-98.7, respectively; P=.02).
• In contrast to the pathologist-based evaluation, operating surgeon assessment of TME plane did not demonstrate prognostic significance for any of these clinical end points.
• The multivariable analysis revealed the plane of surgery (mesorectal vs muscularis propria TME) as an independent factor for local recurrence (P=.002).