The authors are to be complimented on a thoughtful and complete review of the application of the sentinel node paradigm to colorectal cancer. This paradigm is inherently quite different for colorectal cancer because, except for the occasional demonstration of variant anatomy, the technique will not alter the extent of surgery as it has done in melanoma and breast cancer.
The authors are to be complimented on a thoughtful and complete review of theapplication of the sentinel node paradigm to colorectal cancer. This paradigm isinherently quite different for colorectal cancer because, except for theoccasional demonstration of variant anatomy, the technique will not alter theextent of surgery as it has done in melanoma and breast cancer.
Potential Clinical Utility
The authors review the many technical issues that remain unresolved inapplying the sentinel node concept to colorectal cancer including dye and/orisotopes, in vivo vs ex vivo injections, subserosal vs submucosal injections,colon vs extraperitoneal rectum, and the identification of nodes in the fattymesentery before the marker progresses to more central nodes. The latter issueis the most problematic, with the sentinel and other close regional nodes buriedin the mesentery. For right colon cancers, nodes may be more easily identifiedfrom the posterior retroperitoneal side after full mobilization.
Despite all these problems, the potential clinical utility of such studiesjustify continued attempts to improve and standardize the technique. Although inthe future it is likely that analysis of molecular markers within the primarytumor will provide the prognostic determinants for use of adjuvant regimens, thepresence of regional lymph node metastases is currently the primary indicatorfor such treatments.
The prognostic significance of colon cancer micrometastases is reviewed bythese authors, and the conclusion remains to be drawn. In a series ofstandard node-negative stage II colon cancer patients whose regional nodeswere retrospectively examined for micrometastases by immunohistochemistry,four-fifths of those alive without recurrence at 5 years hadimmunohistochemistry-positive regional nodes. If positive sentinel nodesdetected by immunohistochemistry or polymerase chain reaction (PCR) areidentified in otherwise node-negative patients, and are shown by prospectivestudies to have an adverse prognostic impact, studies will still need to beconducted to demonstrate the potential survival advantage of adjuvant therapyand the risks associated with this incremental benefit.
A major challenge in defining the effect of micrometastatic-only nodal spreadon prognosis will be the ethical and logistical challenges to blinding suchfindings from patients and treating physicians. Retrospectiveimmunohistochemical nodal analyses from a large multicenter cohort of routinenode-negative patients may be a more practical strategy for defining theprognostic impact by multivariate analysis.
Surgical pathologists may find that a focused analysis of a few sentinelnodes in colon cancer patients, representing over 100,000 operative specimenseach year, may provide far more valuable data than would laborious analysis ofdozens of nodes. Surgeons and other oncologists need to be aware of the time andcost implications associated with step-section and immunohistochemical analysesin their continued quest for "ultra-staging."
1. Tschmelitsch J, Klimstra DS, Cohen AM: Lymph node metastases do notpredict relapse in stage II colon cancer. Ann Surg Oncol 7(8):601-608, 2000.