Delay to Surgery May Harm Rectal Cancer Nonresponders to Neoadjuvant Therapy

Preoperative chemoradiotherapy followed by surgery is standard treatment for locally advanced rectal cancer. Increasingly, total neoadjuvant therapy is being applied, with the potential for nonoperative management in patients with a clinical complete response. There are limited data regarding outcomes in patients with little or no response to neoadjuvant therapy.

In a retrospective analysis of patients with rectal cancer who were treated with chemoradiotherapy and surgery and had partial or no response to the chemoradiotherapy, investigators evaluated the impact of the time to surgery after neoadjuvant therapy on oncologic outcomes.

Of 1064 patients from 12 high-volume centers in Italy treated from 2000 to 2014, 54.4% underwent surgery within 8 weeks of completing therapy, and 45.6% underwent surgery after 8 weeks. Most patients had pretreatment clinical T3 (84.1%) or N1 (67.5%) disease, and the majority received additional neoadjuvant chemotherapy (87%) and adjuvant chemotherapy (63.3%). Pathologic stage at surgery in the two groups was similar (ypT3 59.8% and 56.2%; ypN0 59.0% and 69.2%).

A wait time for surgery longer than 8 weeks was associated with inferior outcomes. These include:

• A higher rate of abdominal perineal resection (33.2% vs. 21.9%; odds ratio, 1.71; P<0.001)
• A higher rate of 30-day morbidity (19.6% vs. 14.8%; OR, 1.4; P=0.04)
• A higher rate of surgical complications (15.1% vs. 10.0%; OR, 1.6; P=0.01)
• Inferior 5-year overall survival (67.6% vs. 80.3%) and 10-year OS (40.1% vs. 57.8%)
• Increased local recurrence at 5 years (10.4% vs. 5.3%) and 10 years (13.4% vs. 7.1%)