September 15, 2011 — The commonly recommended practice of evaluating 12 or more lymph nodes in newly diagnosed colon cancer is of dubious value, according to the results of a new study published in the September 14 issue of JAMA, the Journal of the American Medical Association.
The study examined trends in lymph node evaluation for colon cancer since the late 1980s, using Surveillance, Epidemiology, and End Results (SEER) program data.
In 1988–1990, 34.6% of American patients had 12 or more lymph nodes evaluated. Twenty years later, the percentage had more than doubled; in 2006–2008, 73.6% of patients had that degree of nodal evaluation.
Despite this large increase in surgery, the proportion of node-positive cancers that were found did not change with time (40% in 1988–1990, 42% in 2006–2008; P = .53), report the authors, led by Helen Parsons, MPH, from the National Cancer Institute in Bethesda, Maryland.
In other words, many more nodes have been examined in recent years but the proportion that were positive — and therefore indicative of more advanced disease — has stayed the same for about 20 years.
The dramatic increase in lymph node retrieval over the 2 decades "likely results from the perception that examination of more nodes would result in better staging with subsequent improved survival from colorectal cancer," writes Sandra Wong, MD, from the University of Michigan Cancer Center in Ann Arbor, in an editorial that accompanies the study.
As the study indicates, retrieving and examining more nodes did not result in finding more positive nodes, "effectively debunking the notion that counting more nodes improved staging accuracy," she writes.
Survival Is Linked to Having More Nodes Examined
Interestingly, the study did find a significant association between lymph node count and survival.
Having more nodes examined was associated with a reduced 5-year hazard of death (adjusted hazard ratio for 30 to 39 nodes vs 1 to 8 nodes, 0.66; 95% confidence interval, 0.62 to 0.71; unadjusted 5-year mortality, 35.3%). This was true for both node-negative and node-positive cancers.
The protective association of having high numbers of nodes evaluated was especially pronounced in the node-negative cancers.
This curious finding has been reported before, notes Dr. Wong. But removing nodes that are known to be negative and thus without disease is not worthwhile, she writes.
What do these findings mean?
The authors suspect that "providers who evaluate more lymph nodes may provide some other unmeasured care, leading to better outcomes."
Dr. Wong explores a similar explanation. Perhaps having more lymph nodes removed and examined is a "proxy" for improved cancer care and is evidence of greater surgical and pathology skills, she suggests. However, a hospital-level analysis that accounted for such bias did not find a link between higher counts and survival (JAMA. 2007;298:2149-2154).
A "plausible and underappreciated explanation" is the tumor–host interaction, she says.
"Patients who mount a stronger immune response to their cancers may have larger lymph nodes present in regional nodal basins, making them easier to find by pathologists. These patients may have an improved prognosis irrespective of finding cancer in their lymph nodes," Dr. Wong writes.
The authors also explore this concept. "Tumor factors may stimulate lymph nodes to enlarge, reflecting immune system recognition of the tumor and more favorable survival outcomes," they write.
In the end, Dr. Wong says that, in general, quality indicators such as the removal of a target number of lymph nodes are fuzzy measures.
Finding, removing, and examining 12 or more lymph nodes in colon cancer is not a process "that by itself improves outcomes," concludes Dr. Wong, who adds that the study "further questions the utility of this practice."
No Data on Chemo
The investigators analyzed SEER data on 86,394 patients surgically treated for colon cancer.
The authors report that they categorized patients in 2 ways: 12 or more lymph nodes examined (yes/no), which is "generally considered an acceptable level of lymph node evaluation for determining nodal status based on several clinical guidelines"; and a series of smaller lymph node categories (0, 1 to 8, 9 to 11, 12 to 15, 15 to 19, 20 to 29, 30 to 39, and 40 or more).
The study did not indicate whether or not patients received chemotherapy. This is important because "one of the heralded benefits of improved staging is the ability to select patients for adjuvant chemotherapy," notes Dr. Wong.
However, Dr. Wong does not think that this takes too much away from the study and its findings for a number of reasons. Not all node-positive patients receive chemotherapy in practice, she explains. Also, clinical practice guidelines recommend chemotherapy for some node-negative patients.
The authors have disclosed no relevant financial relationships.
JAMA. 2011;306:1089-1097, 1139-1141. Abstract, Editorial
The study examined trends in lymph node evaluation for colon cancer since the late 1980s, using Surveillance, Epidemiology, and End Results (SEER) program data.
In 1988–1990, 34.6% of American patients had 12 or more lymph nodes evaluated. Twenty years later, the percentage had more than doubled; in 2006–2008, 73.6% of patients had that degree of nodal evaluation.
Despite this large increase in surgery, the proportion of node-positive cancers that were found did not change with time (40% in 1988–1990, 42% in 2006–2008; P = .53), report the authors, led by Helen Parsons, MPH, from the National Cancer Institute in Bethesda, Maryland.
In other words, many more nodes have been examined in recent years but the proportion that were positive — and therefore indicative of more advanced disease — has stayed the same for about 20 years.
The dramatic increase in lymph node retrieval over the 2 decades "likely results from the perception that examination of more nodes would result in better staging with subsequent improved survival from colorectal cancer," writes Sandra Wong, MD, from the University of Michigan Cancer Center in Ann Arbor, in an editorial that accompanies the study.
As the study indicates, retrieving and examining more nodes did not result in finding more positive nodes, "effectively debunking the notion that counting more nodes improved staging accuracy," she writes.
Survival Is Linked to Having More Nodes Examined
Interestingly, the study did find a significant association between lymph node count and survival.
Having more nodes examined was associated with a reduced 5-year hazard of death (adjusted hazard ratio for 30 to 39 nodes vs 1 to 8 nodes, 0.66; 95% confidence interval, 0.62 to 0.71; unadjusted 5-year mortality, 35.3%). This was true for both node-negative and node-positive cancers.
The protective association of having high numbers of nodes evaluated was especially pronounced in the node-negative cancers.
This curious finding has been reported before, notes Dr. Wong. But removing nodes that are known to be negative and thus without disease is not worthwhile, she writes.
What do these findings mean?
The authors suspect that "providers who evaluate more lymph nodes may provide some other unmeasured care, leading to better outcomes."
Dr. Wong explores a similar explanation. Perhaps having more lymph nodes removed and examined is a "proxy" for improved cancer care and is evidence of greater surgical and pathology skills, she suggests. However, a hospital-level analysis that accounted for such bias did not find a link between higher counts and survival (JAMA. 2007;298:2149-2154).
A "plausible and underappreciated explanation" is the tumor–host interaction, she says.
"Patients who mount a stronger immune response to their cancers may have larger lymph nodes present in regional nodal basins, making them easier to find by pathologists. These patients may have an improved prognosis irrespective of finding cancer in their lymph nodes," Dr. Wong writes.
The authors also explore this concept. "Tumor factors may stimulate lymph nodes to enlarge, reflecting immune system recognition of the tumor and more favorable survival outcomes," they write.
In the end, Dr. Wong says that, in general, quality indicators such as the removal of a target number of lymph nodes are fuzzy measures.
Finding, removing, and examining 12 or more lymph nodes in colon cancer is not a process "that by itself improves outcomes," concludes Dr. Wong, who adds that the study "further questions the utility of this practice."
No Data on Chemo
The investigators analyzed SEER data on 86,394 patients surgically treated for colon cancer.
The authors report that they categorized patients in 2 ways: 12 or more lymph nodes examined (yes/no), which is "generally considered an acceptable level of lymph node evaluation for determining nodal status based on several clinical guidelines"; and a series of smaller lymph node categories (0, 1 to 8, 9 to 11, 12 to 15, 15 to 19, 20 to 29, 30 to 39, and 40 or more).
The study did not indicate whether or not patients received chemotherapy. This is important because "one of the heralded benefits of improved staging is the ability to select patients for adjuvant chemotherapy," notes Dr. Wong.
However, Dr. Wong does not think that this takes too much away from the study and its findings for a number of reasons. Not all node-positive patients receive chemotherapy in practice, she explains. Also, clinical practice guidelines recommend chemotherapy for some node-negative patients.
The authors have disclosed no relevant financial relationships.
JAMA. 2011;306:1089-1097, 1139-1141. Abstract, Editorial
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