Prognostic impact of micrometastases in colon cancer: interim results of a prospective multicenter trial.
OBJECTIVE
The 25% rate of recurrence after complete resection of stage II colon cancer (CC) suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance.


METHODS
Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival.


RESULTS
The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P<0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P=0.002).


CONCLUSIONS
This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.
Bilchik
Anton J
AJ
Department of Gastrointestinal Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, and Michigan State University McLaren Regional Medical Center, Flint, MI, USA. bilchika@jwci.org
Hoon
Dave S B
DS
Saha
Sukamal
S
Turner
Roderick R
RR
Wiese
David
D
DiNome
Maggie
M
Koyanagi
Kazuo
K
McCarter
Martin
M
Shen
Perry
P
Iddings
Douglas
D
Chen
Steven L
SL
Gonzalez
Maria
M
Elashoff
David
D
Morton
Donald L
DL
D000368:Aged; D003082:Colectomy; D003110:Colonic Neoplasms / Q000473:pathology*; D004396:Coloring Agents; D018572:Disease-Free Survival; D005260:Female; D005456:Fluorescent Dyes; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012394:Rosaniline Dyes; D021701:Sentinel Lymph Node Biopsy / Q000379:methods; D015996:Survival Rate
D004396:Coloring Agents; D005456:Fluorescent Dyes; D012394:Rosaniline Dyes; C025484:iso-sulfan blue; D007633:Keratins