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Outcomes of Clinically Node Negative but Pathologically Node Positive Rectal Cancer Patients Who Did Not Receive Neoadjuvant Therapy
Nouf Akeel*, Nan Lan, Luca Stocchi, Meagan Costedio, David Dietz, Emre Gorgun, Matthew Kalady, Georgios Karagkounis, Hermann Kessler, Feza H. Remzi
Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH

Purpose: Neoadjuvant chemoradiotherapy is the preferred standard of care for clinical stage II-III rectal cancer. It is uncertain whether clinically node negative (cN-) tumors found to be pathologically stage III could be optimally treated with surgery alone and avoid adjuvant treatments. The aim of our study was to define the outcomes of such patients.
Methods: Patients undergoing radical surgery using TME techniques for rectal cancer (<12 cm from the anal verge) with curative intent during 2000-2012 and found to have stage III disease on final pathology were identified from a prospectively maintained database. Patients were staged with abdominopelvic CT, transrectal endoscopic ultrasound and/ or pelvic MRI. Exclusion criteria were cN+ without neoadjuvant chemoradiotherapy, hereditary colorectal syndromes, inflammatory bowel diseases, lack of preoperative nodal staging, intraoperative radiotherapy and follow-up <3 years. We compared cN-/pN+ patients according to the postoperative treatment received (group 1 if no further treatment, group 2 if any postoperative treatments), using ypN+ patients (neoadjuvant chemoradiotherapy + surgery) as controls (group 3). Oncological outcomes evaluated included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence (LR) and distant recurrence (DR).
Results: Out of 218 patients included in the study, 77 cN- patients underwent initial surgery with a pN+ surgical specimen. Eighteen of these patients received no postoperative treatment due to associated comorbidity, patient preference or postoperative complications while the remaining 59 (group 2) patients received chemoradiotherapy (n=21) or chemotherapy alone (n=38), respectively, while group 3 included 141 patients. Distal, radial resection margins and TME grading when available were comparable among groups (table 1). cN-/pN+ patients treated with surgery alone were associated with significantly poorer cancer outcomes compared with cN-/pN+ patients who received any form of adjuvant therapy and to ypN+ patients (table 2).
Conclusion: TME surgery is not sufficient to optimize outcomes among rectal cancer patients believed to be node negative and found to be stage III based on specimen pathology.
Table 1: Pathological characteristics
Pathologic parameters, n (%)Group 1Group 2Group 3p value
Microscopically involved margins (≤1mm)Distal001 (0.7%)>0.99
 Radial07 (12.1%)14 (10.0%)0.33
Mesorectal grade*Complete10 (83.3%)30 (96.8%)64 (73.6%)0.1
 Near Complete007 (8.0%) 
 Incomplete2 (16.7%)1 (3.2%)16 (18.4%) 
 Not assessed62854 
Nodal substagingN1a7 (38.9%)14 (23.7%)52 (36.9%)0.52
 N1b7 (38.9%)22 (37.3%)41 (29.1%) 
 N1c02 (3.4%)1 (0.7%) 
 N2a2 (11.1%)10 (16.9%)19 (13.5%) 
 N2b2 (11.1%)11 (18.6%)28 (19.9%) 

* Denominator based on the number of patients with assessed mesorectal grading (routinely reported since 2009)
Table 2: Oncological outcomes
Oncological outcomes, %Group 1Group 2Group 3p value
5-yr OS42.373.566.40.004
5-yr DFS42.867.257.30.005
5-yr DSS54.785.774.10.021
5-yr LR16.
5-yr DR42.420.437.20.016

OS overall survival, DFS disease-free survival, DSS disease-specific survival, LR local recurrence, DR distant recurrence

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