Lymph Node Assessment: Quality, Not Quantity

Abstract

Adequate lymph node staging in gastrointestinal cancers is a key component of quality cancer care as staging has major prognostic relevance and potential implications for adjuvant therapy. What is controversial, however, is the exact method and the metrics that will optimize nodal staging. One issue that is frequently studied is the extent of lymphadenectomy. Extent of lymphadenectomy has been studied from the perspectives of the impact of the number of lymph nodes in a standard lymphadenectomy and the impact of extended versus standard lymphadenectomy. While most studies in the Western literature have not shown a significant benefit to extended lymphadenectomy for most disease sites, the converse is true for the number of lymph nodes. Myriad studies in most disease sites demonstrate that survival is significantly associated with lymph node number, particularly in node-negative disease. Sampling and stage migration are frequently cited as the primary mechanism for this relationship. This has translated into recommended minimums being codified in current guidelines for colorectal cancer (12 nodes), gastric cancer (16 nodes), and esophageal cancer (15 nodes) among others. More importantly, some of these thresholds have been adopted as quality metrics. However, it is important to recognize that the relationship between the number of lymph nodes evaluated and improved oncologic outcomes represents association, not causation. Several factors other than understaging may explain this association, including the presence of confounding variables related to patient factors and the patient-tumor immunologic response. The latter theory implies that the number of assessable lymph nodes may be related, at least in part, to tumor biology, and thus the absolute number of lymph nodes assessed may not always be a marker of quality. The current standard of 12 nodes for colorectal cancer is based largely on data from colon cancer and extrapolated to rectal cancer. However, the current paradigm of neoadjuvant chemoradiation for the treatment of rectal cancer complicates this issue because radiation is known to result in a decrease in the number of assessable lymph nodes. Currently, we do not fully understand the possible implications, or lack thereof, of this decreased nodal harvest. We have previously demonstrated that although the total number of nodes assessable is lower in rectal cancer patients who have undergone preoperative neoadjuvant chemoradiation, there is no clinical impact on nodal staging or oncologic outcome. In this issue of the Annals, de Campos-Lobato and colleagues present work that adds to our understanding of this issue. In their examination of 237 patients treated with long-course neoadjuvant chemoradiation for locally advanced rectal cancer (clinical stage II and III), they similarly found no significant association between number of nodes assessed (dichotomized as \12 vs.[12) and most oncologic outcomes, with the exception of local recurrence. However, they did find a significant association between final pathologic stage and number of lymph nodes assessed: more patients with a complete pathologic response had less than 12 nodes assessed (36 vs. 19 %). This supports the concept that the number of assessable lymph nodes reflects phenomena related to Dr. Baxter holds the Cancer Care Ontario Health Services Research. The Institute for Clinical Evaluative Sciences is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. The opinions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by the Institute for Clinical Evaluative Sciences or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred.