Inadequate Lymph Node Resections in Colorectal Cancer Surgery

Abstract & Commentary

Synopsis: Most authorities agree that the minimal number of lymph nodes resected in primary colorectal cancer surgery is 12. This allows adequate evaluation and more accurate staging. In an examination of SEER data for colorectal cancer patients without known distant metastases during the years 1988 through 2001, the median number of nodes resected was 9, and in only 37% was the standard of 12 nodes achieved. Age, tumor site, and geographic location were statistically important factors accounting for some of the variability. The implications of inadequate lymph node resection are considerable with regard to clinical trial validity and overall clinical outcome.

Source: Baxter NN, et al. J Natl Cancer Inst. 2005;97:219-225.

Lymph node status is the strongest predictor of long-term outcome in patients with colorectal cancer who are without demonstrable distant metastatic disease. It would stand to reason that the number of lymph nodes resected would correlate with the accuracy of surgical staging. Accordingly, both the International Union Against Cancer and the American Joint Committee on Cancer have recommended the evaluation of at least 12 lymph nodes for adequate staging, and this has become a standard.1,2

Baxter and colleagues from the universities of Minnesota and Michigan used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program to determine the proportion of colorectal cancer patients in the United States for whom surgical resection met this standard of 12 resected lymph nodes. Within the SEER registry between the period of 1988 to 2001, 116,995 colorectal cancer patients underwent radical surgery without prior neoadjuvant radiation. For the entire population, the median number of lymph nodes removed was 9 and in only 37% of patients was the standard of 12 met. The proportion of patients receiving adequate lymph node evaluation increased from 32% in 1988 to 44% in 2001, a significant trend (P < 0.001). Older patients (> 70 years) were less likely to receive adequate lymph node evaluation than younger patients and similarly, those with left sided or rectal cancers were less likely than those with right sided lesions to have adequate node sampling. Geographic location within the United States was also a source of significant variability. For the 11 SEER reporting centers, the range in success at resecting 12 lymph nodes varied from 33% to 53%. Thus, as recent as 2001, the majority of patients with colorectal cancer received inadequate lymph node evaluation. The association of demographic factors such as patient age and geographic location was interpreted by the investigators to suggest that local surgical and pathology practice patterns may affect the adequacy of lymph node evaluation for colorectal cancer patients.

Comment by William B. Ershler, MD

This report highlights the importance of adequate lymph node evaluation for optimal management of colorectal cancer patients. In a multivariate analysis, after adjusting for confounders, younger patients, patients with right-sided colon cancer, patients with Stage II or III disease, and patients with poorly differentiated tumors were statistically more likely to receive adequate lymph node evaluation than older patients, those with left sided lesions, those with Stage I disease, or those with well, or moderately well, differentiated tumors (P < 0.01 for all variables). Nonetheless, even under the most optimal of these conditions, a large share of the patients receive inadequate lymph node assessment.

Before commenting on the reasons for this, it is important to examine the rationale for setting the standard at 12 nodes. An inadequate lymph node evaluation is associated with worse outcome in terms of tumor recurrence and patient survival.3-6 This may be because patients who are inaccurately identified with Stage II disease may not receive adjuvant therapy. In fact, some have suggested that patients deemed lymph node negative (Stage II) on the basis of a low number of retrieved negative nodes should be considered at high risk for tumor recurrence and considered candidates for adjuvant therapy.5 Furthermore, it is possible that the retrieval of a small number of nodes is an indication of suboptimal surgical technique and that in itself may place the patient at higher risk for recurrence.

An additional concern relates to clinical trials. As a result of a developing consensus regarding the adequacy of surgical staging and the ultimate influence of accurate staging on outcome, some authors have recommended that node-negative patients with fewer than 12 lymph nodes examined be routinely excluded from surgical or adjuvant therapy trials.4

An explanation for why there is such a high rate of inadequate lymph node sampling is complex. Variability in the actual number of nodes available and other patient factors such as obesity (which hinders node identification) no doubt explains some of the finding. Yet, the geographic variability, the effect of patient age and the site of tumor (left vs right) are harder to explain but suggest that modifiable procedural factors may be involved. Indeed, within single institutions, educational programs targeted at both surgeons and pathologists have been successful. For example, Smith and colleagues reported7 such an effort that resulted in a greater than doubling of the number of resected nodes (from 8 to 18) for Stage II colorectal cancer patients and the increased rate was sustained even 30 months after the program.

Thus, the majority of colorectal cancer patients in the United States receive inadequate surgical/pathological staging on the basis of too few evaluable lymph nodes. In order to improve treatment outcomes and the validity of clinical trial findings, this inadequacy needs to be corrected.

References

1. Sobin L, et al. Cancer. 2001:92;452.

2. Wittekind CH, et al. In: TNM-Classification of Malignant Tumors. Springer Press:New York, NY. 1997:64-67.

3. Swanson RS, et al. Am Surg Oncol. 2003;10:65-71.

4. Le Voyer TE, et al. J Clin Oncol. 2003;10:65-71.

5. Prandi M, et al. Ann Surg. 2002;235:458-463.

6. Tepper JE, et al. J Clin Oncol. 2001;19:157-163.

7. Smith AJ, et al. J Cancer Educ. 2003;18:81-86.

William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.