Prognostic value of tumour regression grading and depth of neoplastic infiltration within the perirectal fat after combined neoadjuvant chemo-radiotherapy and surgery for rectal cancer

Objective: To evaluate histological variables correlated with pathological response to chemo-radiotherapy protocols for rectal cancer and with local recurrence and survival. Methods: From 1994 to 2003, 58 patients with rectal cancer were enrolled in a non-randomised study based on standardised treatment with radiotherapy, 5-fluorouracil, and surgical resection, followed by histological examination, including tumour regression grading and depth of neoplastic infiltration within the perirectal fat. All patients were followed up. Mean (SD) length of follow up was 55.3 (28.1) months, range 5 to 108. Results: No case was found with no regression (grade 0). Tumour regression was defined as grade 1 in 24.5% of cases, grade 2 in 58.5%, grade 3 in 7.5%, and grade 4 (complete regression) in 9.5%. Neoplastic infiltration of >4 mm within the perirectal fat was found in 25.6% of cases in grade 1, 55.8% in grade, 2.7% in grade 3, and 11.6% in grade 4. In 80% cases of pT4 depth of neoplastic infiltration within the perirectal fat was >4 mm (100% were pN+), and the same spread was also found in 53.4% of pT2 and 86.2% of pT3. Pathological response was associated with regression grade (p = 0.006) and depth of neoplastic infiltration within the perirectal fat (p = 0.04). Tumour regression grading was an independent variable for pT (p = 0.0002), pN status (p = 0.00004), pathological staging (p = 0.000001), and local recurrence (p = 0.003). Conclusions: Involvement of the lateral resection margins correlates with a poor prognosis and indicates the likelihood of local recurrence of rectal cancer. Tumour regression grading and the depth of neoplastic infiltration within the perirectal fat are important prognostic factors that need to be evaluated routinely.