Lack of Pathological Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy is Associated with Poorer Long-Term Oncological Outcomes

Purpose: Tumor regression scores are used to evaluate local response to preoperative treatment. Complete pathological response (tumor regression score=0) is associated with excellent prognosis. In this study we evaluated the prevalence and impact of poor-to-no pathological response to neoadjuvant treatment (tumor regression score=3), based on a recently revised grading system on long term oncologic outcomes among rectal cancer patients. Methods: This retrospective study included rectal cancer patients who received. neoadjuvant chemoradiotherapy and surgical resection at our medical center. Pathological specimens were ren evaluated and graded (grades 0-3) based on the revised tumor regression scores. Disease free survival and cancer specific survival rates were documented and matched with the patients’ tumor regression scores. Results: Initially 78 patients were included. 6 patients were later excluded from the long-term follow up since they developed disease progression during neoadjuvant treatment. Among the other 72 patients, 38 (52.8%) were classified as tumor regression score=3 (no response) and 34 (47.2%) tumor regression score=0-2 (any level of response). Conversion from laparoscopy to open surgery was higher in the tumor regression score=3 group (21% vs. 2.9%, p=0.02). Follow-up ranged from 5 months to 12 years. Nine (12.5%) patients experienced disease recurrence, 8 with tumor regression score=3. Most recurrences were metastases to liver and lungs. Disease free survival was lower in tumor regression score=3 patients as compared to tumor regression score=0-2. Conclusions: Non-responders to neoadjuvant therapy are at higher risk for disease recurrence, conversion to open surgery and disease-related mortality. Systemic recurrence of tumor regression score=3 tumors suggests an aggressive biology of these tumors. Further studies are needed to characterize tumors that are less likely to respond to radiotherapy and to personalize preoperative treatment decisions.