Decreased detection rate of disseminated tumor cells of rectal cancer patients after preoperative chemoradiation: a first step towards a molecular surrogate marker for neoadjuvant treatment in colorectal cancer.
OBJECTIVE
To compare the detection rates for rectal cancer cells in blood and bone marrow in patients with or without preoperative chemoradiation.


BACKGROUND
Previous reports have postulated a resistance of disseminated tumor cells to antiproliferative agents because of tumor cell dormancy.


METHODS
Blood samples from 142 patients (pre, intra-, and postoperative samples) and bone marrow samples from 127 patients undergoing resection of rectal adenocarcinoma were analyzed for tumor cells using a cytokeratin (CK) 20-reverse transcription polymerase chain reaction. The results were stratified according to preoperative therapy.


RESULTS
In patients without preoperative chemoradiation, tumor cell detection in blood and bone marrow correlated to tumor stage (Cochran Armitage trend test, P < 0.05). Tumor cells were detected in 34 of 103 (33%) bone marrow and 65 of 117 (55.6%) blood samples of patients without neoadjuvant treatment versus in 4 of 24 (16.7%) bone marrow and in 10 of 25 (40%) blood samples of patients with neoadjuvant treatment. The tumor cell detection rate was significantly lower in the group having undergone chemoradiation (binary logistic regression analysis, P < 0.05). The overall and disease-free survival were significantly worse in patients with tumor cell detection in the bone marrow after neoadjuvant therapy.


CONCLUSIONS
Preoperative chemoradiation is associated with a decreased detection rate of rectal cancer cells in blood and bone marrow. These findings may explain the observed clinical benefit of patients with rectal cancer receiving chemoradiation. This is the first study suggesting that detection of disseminated rectal cancer cells may be useful for assessing the efficacy of neoadjuvant therapy.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D001853:Bone Marrow / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins; D053554:Keratin-20; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009360:Neoplastic Cells, Circulating; D011300:Preoperative Care; D011882:Radiotherapy, High-Energy; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20