Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.

Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows:

Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin.

Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin.

High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.

All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard.

Tumor regression grade groups were identified as:

Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes

Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.

Morbidity will be assessed according to the classification of Clavien-Dindo as follows:

Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.

Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death

Both pelvic recurrence and distant metastasis will be assessed.

Recurrence free survival

Total survival with or without disease