Present and future cancer staging with the eighth edition of the AJCC Cancer Staging Manual

It has been more than one year since the American Joint Committee on Cancer (AJCC) published the eighth edition of the AJCC Cancer Staging Manual. The final pieces are in place for implementation of this edition on January 1, 2018.

During this prolonged window of transition from the seventh to the eighth edition, many logistical tasks have been accomplished, allowing clinicians, hospitals, software vendors, and tumor registrars additional time to prepare for a more complex manual than necessary for previous tumor/node/metastasis (TNM)-based manuals. This implementation period has also allowed time to correct errata and provide important updates to clinicians.

Updates in breast cancer staging

One of the most significant updates is in breast cancer staging. The eighth edition moves to “prognostic staging” for breast cancer with inclusion of tumor grade, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status as key elements used to define stage. Prognostic staging was included in the 2016 publication, but with an additional year of clinical data and more than 340,000 breast cancer patients identified in the National Cancer Data Base, prognostic staging was separated into two schemata: clinical prognostic staging and pathological prognostic staging.

As therapy becomes more individualized, opportunities for neoadjuvant therapy have increased. The Alliance for Clinical Trials in Oncology ALTERNATE trial (ALTernate approaches for Clinical Stage II or III Estrogen Receptor positive breast cancer NeoAdjuvant TrEatment, Trial A011106) is an example of the expansion of neoadjuvant therapy to include endocrine therapy, with additional systemic treatment in select cases dictated by response. Clinical prognostic staging was added to provide an accurate staging option, assigned prior to treatment, for patients treated with neoadjuvant therapy. This methodology takes into consideration the anticipated impact of current and emerging neoadjuvant therapies.

Nonetheless, response to therapy remains an important criterion for survival and—due to the complexities of treatment and a logarithmic expansion of outcomes dictated by degree of response—a specific staging scheme incorporating response for breast cancer patients treated with neoadjuvant therapy remains regrettably absent. It is the hope and expectation of the AJCC that as additional data mature, a specific staging scheme for patients receiving neoadjuvant therapy will become a reality for patients and clinicians.

Moving beyond anatomic variables

As tumor subtypes, targeted therapy, and personalized medicine become more defined, staging will require more than anatomic variables. To maintain staging relevance, biomarkers and genomic assays need to be incorporated. Most importantly, tumor response to therapy and survival outcomes are critical to defining prognosis and stage, underlining the importance of consistent, correct application of cancer staging for present and future applications. This new staging paradigm also heavily relies on the assumption that survival, and thus stage, are achieved not based on preclinical variables alone but through patient and clinician compliance with treatment guidelines. Without therapy for aggressive tumor phenotypes, stage becomes inaccurate.

Second printing planned

Other important updates to the print version of the eighth edition include clarification of histologic codes, which form an important foundation for data collection by the tumor registrars and for the AJCC to monitor longitudinal trends in cancer, efficacy of treatment, and quality of care. The formal position of the eighth edition editorial board was to promulgate the World Health Organization (WHO) histologic classification cancers.

Despite this conceptually accurate and contemporary approach, multiple exceptions in the registrar community precluded an opportunity to stage hundreds of thousands of cancer patients. Although accurate data collection is a paramount goal of the AJCC, inclusion of all cancer patients for staging is of equal importance. A comprehensive review of histology codes outside of the WHO classification was performed to include histologic categories of many patients with unstageable cancers.

In view of the aggregate magnitude of updates and clarifications and the ongoing demand for the printed staging manual, the AJCC, in partnership with Springer, will proceed with a second printing of the eighth edition, which will include, among several upgrades, corrected errata, breast cancer classification tables, updated histologic codes, and clarifications in staging definitions.

This new version also will be available in an electronic format. A mechanism will be in place for all individuals and practices that have already purchased the eighth edition to obtain updates without incurring additional expense. More information is available at the AJCC website.

As January 1 approaches, accurate entry of stage and the collection of a new set of clinical data will be critical to developing future revisions and updates for cancer staging. It is incumbent upon all clinicians to stage the patient and define prognosis. Likewise, it is imperative that clinicians and tumor registrars monitor outcome and collect accurate and complete information for a diverse disease with an expanding array of treatment options. Staging with the eighth edition will more accurately determine the patient’s prognosis and will help to generate information for the next iteration as treatment and prognosticators continue to evolve.

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