Starting in January, physicians and tumor registrars will classify cancers using an updated system published in the sixth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. Such revisions are made every 5 or 6 years by cancer-site-specific task forces that determine whether new knowledge dictates changes to the system.
The system, called TNM for tumor, node, metastasis, is used by more than 1400 cancer programs accredited by the Commission on Cancer of the American College of Surgeons and is also used by the International Union Against Cancer (UICC).
The system classifies tumors by their anatomic site, histology, and extent. The major determinants of stage, common to all sites, are size or local extension of the primary tumor (T), involvement of regional lymph nodes (N), and the presence or absence of distant metastasis (M), leading to classification into stages I through IV. Each site also has a unique set of clinical and pathologic factors that determine substage.
Because the system is considered "the universal language of cancer staging," any revision to the system is a learning experience for oncologists, pathologists, surgeons, and registrars around the world. Revisions will also change treatment indications for some patients.
The system that will take effect in January recognizes new technologies that sharpen the diagnoses of cancer. Imaging techniques, such as positron emission tomography and magnetic resonance imaging, are making possible more accurate clinical staging. And laboratory analyses such as immunohistochemistry and, in some cases, polymerase chain reaction (PCR) are being added to the traditional hematoxylin and eosin staining to improve pathological staging.
New techniques can detect a few isolated cancer cells but cannot determine their clinical significance. To account for this, the updated system will include the suffixes "i" (+ or -) for immunohistochemical and "mol" (+ or -) for PCR and other molecular assays to indicate whether micrometastases were detected by these methods in a patient who is otherwise considered node-negative.
These findings do not affect which stage of cancer a patient is assigned to. But in the future, when large data sets that include this information have been amassed, the data may help researchers determine whether the emerging techniques have any prognostic value.
For melanoma and breast and gastrointestinal cancers, an added feature is the suffix "sn," meaning that a sentinel node dissection was performed. In this procedurewhich is becoming standard practicethe lymph node at highest risk for metastasis is identified; if the sentinel node is cancer-free, the other nodes are likely to be as well.
In the future, the AJCC expects to incorporate findings from molecular markers and advanced imaging methods into the system, but this will require conclusive evidence that these data have reliable prognostic significance. To date, testicular cancer is the only site for which serum markers are included in the TNM system, but AJCC encourages physicians and registrars to collect data on other markers for future use.
"There was a lot of discussion about whether we should put estrogen and progesterone receptors into the TNM staging for breast cancer, and the decision was not to do thatbut we still want to collect the data," said AJCC chairman Frederick Greene, M.D., chairman of the department of surgery at the Carolinas Medical Center in Charlotte, N.C. "And we debated whether to include PSA for prostate cancer, but the task force felt there was not enough good data to decide where the cut point should be."
|
|
In breast cancer, "most of the changes have to do with how we stage the regional lymph nodes," Singletary said. Metastases to the supraclavicular nodes will once again be classified as regional (stage III) disease after being moved to the distant (stage IV) disease category in the fifth edition.
"The reason why thats so important is that in calling these patients stage IV, physicians tend to treat them only in a palliative mode," she said, "whereas we know that some of these patients can be long-term survivors with aggressive treatment." An M. D. Anderson study published in 2001 showed that 30% of patients in this group survived 10 years. By contrast, 10-year survival for breast cancer patients with distant metastasis is less than 4%.
Another change brings the AJCC system in line with the common practice among oncologists of using the number of affected lymph nodes to predict survival. The categories of one to three affected nodes, four to nine nodes, and 10 or more nodes are familiar to physicians treating breast cancer, but such categories have not been included in the TNM system until now.
A thorny issue for the breast cancer task force, Singletary said, was whether to include histologic grade in the staging system. Although histologic grade is believed to be an important prognostic factor, hard evidence is lacking. To confuse matters further, pathologists have not yet adopted a uniform system of grading. Singletary said the so-called Nottingham index has proven reliable and reproducible, and the adoption of Nottingham as a universal standard should put histologic grade on firmer footing. "Emerging data will undoubtedly support the incorporation of grade in the AJCC staging system in the near future," she and co-authors predicted in an article on the new breast cancer system in the Sept. 1, 2002 Journal of Clinical Oncology.
The task force on breast cancer made a decision on another controversial question: How large must a cluster of tumor cells in a lymph node be to put a patient into the node-positive category? In the new system, those between 0.2 mm and 2.0 mm will be counted as micrometastases (node-positive), while smaller ones will be noted as "isolated tumor cells" (node-negative).
"I think the oncology community is going to be happy that at least we have taken a stand on this," Singletary said. "In the past, some patients [with micrometastases] were treated as node- positive, some as node-negative."
In an editorial accompanying Singletarys article, Craig Bunnell, M.D., and Eric Winer, M.D., of the Dana-Farber Cancer Institute in Boston, pointed out that the changeswhich they characterize as a victory for the "splitters" over the "lumpers"will mean more work for both physicians and tumor registrars who have to learn a more complex system and additional nomenclature.
However, they wrote, "in our view, the effort and cost are likely to be worthwhile. ... In the short term, the new system may be beneficial to clinicians and their patients by better risk categorization and by acknowledging the uncertainty that exists in some situations. ...Ultimately, the new staging guidelines are an investment in the future. By better defining subgroups, we will have the tools to characterize the natural history of breast cancer to a degree never before possible."
For melanoma, a major change is the addition of ulceration (where the tumor breaks through the epidermis) as a factor in staging.
"Melanoma ulceration heralds such a high risk for metastasis that its presence upstages the prognosis of all such patients, compared with patients who have melanomas of equivalent thickness without ulceration," Charles Balch, M.D., and co-authors wrote in the August 15, 2001, Journal of Clinical Oncology. Balch, executive vice president and chief executive officer of the American Society of Clinical Oncology, Alexandria, Va., chaired the melanoma task force for AJCC. Survival rates for patients with ulcerated melanoma are closer to those of patients with non-ulcerated tumors in the next highest stage. So, for instance, melanomas coded T2b (ulcerated tumor between 1 and 2 mm thick) and T3a (non-ulcerated, 2 to 4 mm) are both classed as stage IIA.
An analysis by Greene and colleagues of data on 50,042 patients from the National Cancer Data Base led to a new system for stage III colon cancer that is incorporated into the new AJCC system. Stage III patients will be subdivided into IIIA, IIIB, and IIIC based on tumor invasion and lymph node involvement. An article by this group in the October 2002 Annals of Surgery shows that the new system stratifies stage III patients into three groups with 5-year survival rates of 60%, 42%, and 27%, respectively. While adjuvant chemotherapy is indicated for all these patients, the authors suggest that "stage IIIC patients may benefit from a more aggressive regimen than the current 5-fluorouracil-based therapy."
On November 21, Greene, Balch, and Singletary will hold a national teleconference with about 400 hospitals to discuss the new system.
In addition to regular updates of the TNM system, the AJCC has several initiatives under way to facilitate its use. One is a self-learning program on CD-ROM, expected to be available in 2003, which will teach physicians and medical students how to do staging. Another is the Collaborative Stage Project, which allows users to translate between TNM and two other staging systems: the extent-of-disease (EOD) and summary stage systems used by the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) program and by some state cancer registries.
"Were going to roll this out January 1, 2004," Greene said, "and for the first time, a registrar will be able to put in a certain stage, say TNM, and the extent-of-disease and summary stages will automatically be computed."
Also going into effect in 2004 are guidelines that AJCC created with the College of American Pathologists that will mandate the inclusion of the "T" and "N" stages in every pathology report done at participating hospitals.
"This will make it much easier for physicians to navigate through pathology reports," Greene said.
Because new discoveries and advances are made every year, the AJCC staging system is a perennial work in progress.
"Were already looking forward to the seventh edition," Greene said.
More information on cancer staging is available on the AJCC Web site, http://www.cancerstaging.org.
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |