Question ID: WS-19
Submitted by: Peter Scardino
January 31, 2011
Do regional lymph nodal metastases from solid tumors differ biologically from metastases to distant sites? Background: Metastases from solid tumors to regional lymph nodes (LN) are relatively common, their frequency varies markedly among tumor types but within type is associated with the aggressiveness of the primary tumor, their presence and extent are usually poor prognostic factors, they are difficult to detect by imaging, and the therapeutic benefit of lymph node dissection remains uncertain. Since the days of Halstead, regional lymph node dissection (LND) – more or less extensive - has generally accompanied surgical (and often radiotherapeutic) treatment of the primary tumor. A sizable minority of patients with regional LN metastases survive long term without recurrence after locoregional therapy alone (no systemic therapy). The few randomized trials performed have left unsettled the therapeutic value of regional LND, yet enthusiasm for more trials is muted by the uncertainty about the biological and clinical significance of nodal metastases. Recent studies suggest tumor induced lymphangiogenesis is an important mechanism that promotes nodal metastases. Feasibility: Modern cancer biology has the tools to discover whether nodal metastases differ in biologically important ways from the primary tumor and distant metastases in the same patient, and to identify the features that distinguish classes of tumors with frequent (e.g., melanoma) versus rare (e.g., sarcoma) nodal metastases. As the TCGA completes comprehensive genomic analyses of large sets of primary tumors, it could focus on matched pair analyses of primary tumors, LN metastases and distant metastases from the same patient. Randomized clinical trials of patients at high risk for LN metastases could assess the therapeutic benefits, if any, of regional LND (none v. any, limited v. extensive) in a variety of tumor types (e.g., bladder, kidney, prostate cancer). Implications of success: hundreds of thousands of surgical resections and radiation treatments of primary tumors are performed each year in the U.S. without clear indications whether therapy should also be directed specifically at the regional lymph nodes. If LND has no therapeutic benefit, the cost and morbidity of these procedures could be eliminated, and focus could be placed on the development of better noninvasive imaging to detect nodal metastases and optimal use of systemic rather than regional therapy for patients likely to have nodal metastases. Novel targeted therapeutics, which reduce the risk of LN mets, or block their ability to metastasize further, could greatly increase disease free survival rates for the common cancers.
| This question has not yet been evaluated by users |
Comments
