Analysis of clinical outcomes and prognostic factors of neoadjuvant chemoradiotherapy combined with surgery: intraperitoneal versus extraperitoneal rectal cancer.

Neoadjuvant chemoradiotherapy (CRT) is a widely purposed and performed treatment for rectal cancer. Downstaging effects possibly enhance the rate of curative surgery and may enable sphincter preservation in low-lying tumours. The current study examines the clinical outcomes in patients enrolled in a neoadjuvant CRT-surgery protocol for rectal cancer, distinguishing between intraperitoneal and extraperitoneal cancer. From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were enrolled in a single-centre, not randomized study based on 5-week sessions of radiotherapy associated with a 30-day protracted venous 5-FU infusion followed by surgical resection. The study population was divided into two groups according to the localization of the tumour: 18 intraperitoneal and 40 extraperitoneal (EPt). Fifty-eight patients were treated with neoadjuvant CRT and surgery. Overall mortality rate was 25.9%, no deaths were recorded during hospitalization; 10 patients (all EPt) died because of recurrence. Significant differences in disease-free survival and overall survival rates were found between intraperitoneal vs. extraperitoneal tumours (P = 0.006), both intraperitoneal vs. extraperitoneal tumours N(0) (P = 0.04 and P < 0.05) and intraperitoneal vs. extraperitoneal tumours N(+) (P < 0.05). We diagnosed all local recurrence and liver metastasis in extraperitoneal tumours (t = 0.02 and t = 0.04), and only one case of lung metastasis arose from intraperitoneal cancer. Extraperitoneal tumours could be more aggressive than intraperitoneal ones, spreading more precociously, and/or less responsive to the neoadjuvant CRT because of their localization rather than biological differences. Aside from lymph node status, the location of the tumour with respect to the peritoneum border, is also a prognostic factor of survival in rectal cancer treated by neoadjuvant CRT and surgery.

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.