The American Joint Committee on Cancer (AJCC) recently released the eighth edition of the AJCC Cancer Staging Manual. This edition incorporates significant changes in a manual that is now approximately 1,000 pages in length. The AJCC member organizations worked together to devise a comprehensive format revision to provide consistency throughout an expanded list of chapters, and new organ sites have been added to the text, as well. Several chapters introduce additional non-anatomic prognostic variables into staging schemes to increase the relevancy of the stage with regard to prognosis and defining optimal therapy.
New implementation postponed
Coordinating the implementation for a new staging system is critically important to ensure that all partners in patient care and cancer data collection are working in synchrony. Implementation was originally scheduled for January 1, 2017. However, to ensure that the cancer care community has the necessary infrastructure in place to successfully implement the new standards, compliance with the eighth edition cancer staging system has been delayed until January 1, 2018. The decision to delay implementation resulted from discussions between the AJCC Executive Committee, the National Cancer Institute, Centers for Disease Control and Prevention, the College of American Pathologists, the National Comprehensive Cancer Network, the National Cancer Database, and the Commission on Cancer.
The time extension will allow all partners to develop and update protocols and guidelines and for software vendors to develop, test, and deploy their products in time for the data collection and implementation of the eighth edition. Clinicians will continue to use the most recent information for patient care, including scientific content in the latest manual.
Rationale for changes in the manual
The eighth edition attempts to more fully synthesize stage groupings with relevant variables identified from multiple data sets based on registries and clinical trials. For example, after reviewing hundreds of publications, the Breast Expert Panel decided to include estrogen receptor and progesterone receptor status, HER-2 status, and grade into the creation of a prognostic stage, combined with traditional tumor, node, and metastases (TNM) variables as defined in Anatomic Stage. Information from multi-gene panels was incorporated for patients with T1-2N0M0, ER-positive, HER2-negative tumors. With these eight variables (T, N, M, grade, ER, PR, HER-2, and multi-gene panel score), the complexity of staging increased, creating several hundred possible combinations. Other noteworthy changes included the elimination of lobular carcinoma in situ as a breast cancer diagnosis.
As a consequence of including biomarkers in the staging of breast cancer, more than 40 percent of patients with stage I–III disease were reclassified into a different stage than if seventh edition criteria had been applied, with a nearly equal split between those patients who were up-staged (20.0 percent) and down-staged (20.6 percent). Maintaining consistent definitions of in situ and distant metastatic disease with other organ sites, stage reassignment was excluded for patients with stage 0 and stage IV disease.
Within the remaining stage groupings, 9.8 percent of patients were reassigned more than one stage higher or lower than according to seventh edition criteria. These stage changes reflect the significant impact of prognostic variables that clinicians have long recognized as important in determining prognosis and therapy. Although this model provides a much more robust categorization of stage, it is essential to recognize that the derivation of these survival figures and stage assignments assumes that patients and clinicians follow treatment guidelines. As an example, a patient with a T2N1M0, Grade 3, ER-positive, PR-positive, HER2-positive breast cancer is assigned to Stage IB, as the survival with proper treatment for such a patient is similar to that of smaller and node-negative cancers. However, without appropriate treatment, including chemotherapy, pertuzumab, trastuzumab, endocrine therapy, surgery, and radiation therapy, this patient would be at high risk of cancer-related mortality.
Accommodating diverse resources
The AJCC remains committed to serving cancer patients throughout the world. Many geographic regions lack the resources needed to define the aforementioned variables. In this case, anatomic stage will continue to be used in the absence of biomarkers. In contrast, in developed countries where biomarkers are routinely used and available, it will be expected that physicians and registrars alike will be committed to using prognostic stage with complete entry of all prognostic variables as stipulated in respective chapters.
As the complexity of staging increases beyond the traditional TNM work laid out in the previous editions of the AJCC Cancer Staging Manual, staging calculators and electronic health record software will be necessary to achieve accurate and consistent implementation of stage into the patient’s care. In addition, careful and complete entry of staging variables will help provide critical information to develop future staging algorithms, likely to consist of rolling updates; to reflect advancing knowledge and improvements in patient care; and to show progress and establish priorities in cancer control and prevention.