American Joint Committee on Cancer

New edition of thyroid cancer staging system shows better prediction of survival

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The eighth edition of the American Joint Committee on Cancer/tumor node metastasis staging system for differentiated thyroid cancer was a better predictor of overall and disease-specific survival than the seventh edition of the staging system regardless of cancer subtype, according to data published in Thyroid.

Evert F.S. van Velsen

“This study shows that in a European population of patients with differentiated thyroid cancer harboring a large subset of follicular thyroid cancer patients, applying the AJCC/TNM eighth edition leads to reclassification of 36% of the patients into a lower stage,” Evert F.S. van Velsen, MD, MSc, a PhD student and internist in training at the Academic Center for Thyroid Diseases in the department of internal medicine at Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues wrote. “Furthermore, using this eighth edition, there is no significant difference between papillary thyroid cancer and follicular thyroid cancer anymore regarding survival rates per stage, implying that AJCC/TNM stage is a good predictor for both differentiated thyroid cancer subtypes.”

The researchers evaluated retrospective data from 792 patients (79% with papillary thyroid cancer and 21% with follicular thyroid cancer) who were diagnosed and/or treated at the Erasmus Medical Center in Rotterdam from 2002 to April 2016. Researchers categorized patients according to the seventh edition of the American Joint Committee on Cancer/tumor node metastasis (AJCC/TNM) staging system and then reclassified them using the eighth edition, which was introduced in clinical practice in January.

After a median follow-up of 86 months, 106 patients (13%) had died, 54% from differentiated thyroid cancer. Patients with follicular thyroid cancer were older (P < .001) and had a higher mortality rate (P < .001).

Researchers classified disease stage using both the seventh and eighth editions of the staging systems. Based on the seventh edition, 431 patients (54%) were classified as stage I, 82 (10%) as stage II, 96 (12%) as stage III and 183 (23%) as stage IV. Based on the eighth edition, 282 patients (36%) — 49% with follicular thyroid cancer and 32% with papillary thyroid cancer — were reclassified into a lower stage. The number of patients diagnosed as stage I increased from 431 with the seventh edition to 575 with the eighth edition; similarly, the number of patients diagnosed as stage II increased from 82 to 129. The numbers of patients diagnosed with stage III and stage IV disease decreased from 96 to 30 and 183 to 58, respectively. Researchers found similar patterns when they separately evaluated patients with papillary and follicular thyroid cancer.

To further analyze the reclassification patterns, the researchers classified patients using the eighth edition classification system with the seventh edition’s age cutoff. They found that 271 patients (34%) were still reclassified into a lower stage, but fewer were reclassified to stage I and more were reclassified into stages II and III.

Regardless of stage at diagnosis, patients with papillary thyroid cancer had higher 10-year overall and disease-specific survival compared with patients with follicular thyroid cancer (P < .001) using both editions of the classification system. Stage at diagnosis was related to overall and disease-specific survival for differentiated thyroid cancer as well as papillary and follicular thyroid cancer separately using either edition of the classification system (P < .001). However, the eighth edition showed a better distinction between the stages for survival and a worse prognosis for patients with stage II (10-year disease-specific survival = 100% with the seventh edition vs. 85% with the eighth edition), stage III (96% vs. 46%) and stage IV (59% vs. 28%) thyroid cancer. Researchers observed the same pattern when evaluating papillary and follicular thyroid cancer separately.

“The eighth edition performs well regardless if your patient has papillary or follicular thyroid cancer,” van Velsen told Endocrine Today. “This important information can be used in counseling patients upon diagnosis.” – by Tina DiMarcantonio-Brown

Revised Classification for Head and Neck CSCC

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The latest staging criteria for cutaneous squamous cell carcinoma (CSCC) from the American Joint Committee on Cancer (AJCC) improves the previous version in stratifying risk of disease-related outcomes, suggests a study published in December.

Using the AJCC Cancer Staging Manual, 8th edition (AJCC 8) tumor classification, which is specific to CSCCs of the head and neck, 17.8% of the cohort was classified in the high tumor categories (T3 and T4), and those accounted for 70.4% of poor outcomes in the overall cohort.

 By comparison, using the 7th edition (AJCC 7), just 0.7% of tumors were T3 or T4, and they accounted for only 16.9% of poor outcomes, according to the results published in JAMA Dermatology.

That suggests that the upper categories of AJCC 8 have a strong ability to stratify tumors with significant risk of disease-related poor outcomes, said the study’s senior author, Chrysalyne Schmults, MD, director of the Dermatologic Surgery Center at Brigham and Women’s Hospital in Boston.

“The biggest improvement with AJCC 8 is that there’s been a large expansion of cases that now qualify to be T3, and this has made it such that T3 and T4 now capture a lot more of the poor outcomes.”

T3 in particular is capturing most of the poor outcomes because T4 is still quite restrictive, according to Schmults, although between the two systems, they are capturing 71% of nodal metastases and 85% of deaths due to CSCC.

Using AJCC 7 criteria, the majority of poor outcomes occur in patients with tumors classified as T2, which is actually a large, heterogeneous group in terms of outcomes, she said.

 “There is a subset of people who are doing poorly — in T2 under AJCC 7 — but they are mixed in with all these people who are doing well. It becomes impossible to pull them out of that larger group and decide, for example, who needs staging of their lymph nodes, who needs adjuvant treatment after surgery, or who would be good candidates for clinical trials.”

Staging Evolution

Most CSCCs have a favorable prognosis. Estimates previously published by Schmults and colleagues suggest a risk of 3.0% for local recurrence, 4.0% for nodal metastasis, and 1.5% for death.

Staging is pivotal to helping separate the rare, high-risk cases from the low-risk majority, she explained.

The AJCC 7 criteria, introduced in 2010, represented an improvement over the previous edition, which had grouped all non-melanoma skin cancers together and used just a limited set of staging factors including tumor diameter and bone and intracranial invasion. AJCC 7 included, for the first time, risk factors including tumor thickness greater than 2 mm, perineural invasion, Clark level of IV or higher, and poorly differentiated histology.

However, studies began to show that AJCC 7 was not adequately stratifying disease-related outcomes.

In a retrospective cohort study published in JAMA Dermatology in 2013, Schmults and colleagues reviewed 256 primary high-risk CSCCs and found that outcomes for AJCC tumor stages T2-T4 were “statistically indistinguishable,” since less than 2% of the cohort qualified as stage T3 or T4; thus 83% of nodal metastases and 92% of deaths from CSCC occurred in cases classified as T2.

As part of that study, the team proposed an alternative CSCC staging system to more precisely identify the small number of cases at high risk of metastasis and death. That system incorporates risk factors including poor differentiation, perineural invasion, tumor diameter ≥2 cm, and invasion beyond subcutaneous fat.

Using the alternative system, the tumors classified as T2b (i.e., having two to three of those risk factors present) or T3 (all four risk factors or bone invasion) comprised 19% of tumors and accounted for 72% of nodal metastases and 83% of deaths from CSCC, according to the published report.

In a subsequent study published in 2014 in the Journal of Clinical Oncology, Schmults and colleagues compared AJCC 7, the International Union Against Cancer (UICC) staging system, and a modified version of their own previously published alternative system in a larger cohort of patients (N = 1,818). Results suggested that the alternative system offered better prognostic discrimination versus AJCC 7 and UICC, leading the authors to call for further population-based validation.

 Subsequently, the team sought to validate the CSCC staging system released in AJCC 8, which is specific to CSCC tumors of the head and neck, since it was developed in conjunction with AJCC’s head and neck cancer committee.

“The head and neck surgical community — they grapple with the worst of these cases — and they really felt like, for their purposes, they needed something,” said Schmults, who also participated in development of the AJCC 8 staging system.

The new staging criteria, which were implemented in clinical practice starting in January 2017 and were set to be implemented by tumor registrars as of January 2018, includes changes based on findings related to independent prognostic factors in CSCC that have become available since AJCC 7, Schmults said.

Notably, T2 is now restricted to tumors that are at least 2 cm yet less than 4 cm in largest dimension with no risk factors, while the T3 definition was expanded to encompass tumors at least 4 cm in largest dimension or at least one risk factor. Risk factors for T3 upstaging in AJCC 8 include deep invasion, perineural invasion, and minor bone invasion, while poorly differentiated histologic features was dropped as a risk factor for upstaging.

Schmults said that although she is pleased with the improved performance of AJCC 8 in this most recent cohort study, more changes will be needed. In particular, the cohort study of AJCC 8 demonstrated a considerable overlap between T2 and T3 categories in terms of the 10-year cumulative incidence of local recurrence, nodal metastasis, and disease-specific death.

Together, T2 and T3 comprised about 23% of squamous cell cancers in this study. “If we suddenly started doing lymph node staging or offering treatment beyond surgery to 23% of squamous cell patients, we would be overtreating. We know that probably only around 5% to 10% of those people would ever really need or benefit from that.”

Nevertheless, she said she was hopeful that AJCC 8 will make an impact in the community and possibly allow for population-based registry tracking through the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute to validate and refine CSCC tumor classification.

“I hope that we can come to some kind of standardization across the country in reporting clinical tumor diameter and other prognostic factors on SCC pathology reports, so that whether SEER is able to do it or not, then at least on institutional levels, people would be able to use AJCC 8 staging and track SCC outcomes better,” she said.

Since the current staging system applies to head and neck CSCCs, “I think it will be up to clinicians and researchers how to stage everybody else. I think a lot of people are going to end up using [AJCC 8 head and neck staging] for those non-head and neck CSCCs, rather than continuing to use AJCC 7, which had a lot of trouble.”