Prognostic value of histologic tumor regression, thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase in rectal cancer UICC stage II/III after neoadjuvant chemoradiotherapy

Abstract

Histologic tumor regression (TR) in rectal cancer after preoperative chemoradiotherapy (CT/RT) may be useful as a surrogate end point for early treatment efficacy, but little is known about its prognostic value. The aim of this follow-up study was to evaluate whether TR is able to predict prognosis in rectal cancer patients. Furthermore, the prognostic value of thymidylate synthase (TS)-gene, thymidine phosphorylase (TP)-gene, and dihydropyrimidine dehydrogenase (DPD)-gene expression after neoadjuvant CT/RT was determined. Forty patients with rectal cancer cUICC stage II/III, receiving preoperative 5-fluorouracil (5-FU) based CT/RT were studied for therapy-induced TR and categorized as "responders" or "nonresponders" according to their TR-grade. Posttherapeutical TS-gene, TP-gene, and DPD-gene expression on surgical resection specimens was quantified by TaqMan real-time PCR after micro dissection. During a median follow-up of 58 months, cancer recurrence occurred in 28%. A significant correlation was seen between disease-free survival and lymph node status (P < 0.001). All patients, who developed cancer recurrence had a posaherapeutical positive lymph node status. The majority of patients with cancer recurrence were "responders" (91%) after CT/RT. There was a significant correlation between posttherapeutical TS-gene expression and cancer recurrence within the subgroup of "responders." TS-gene expression was significantly higher in patients with cancer recurrence than in those, who are disease-free up to date (P = 0,028). In conclusion, lymph node status remains the most important prognostic marker in rectal cancer patients, whereas posttreatment TR by itself has no prognostic significance. Furthermore, measurement of post-therapeutical TS-gene expression may help to identify patients at higher risk for cancer recurrence.