In a study reported in the Journal of Clinical Oncology, Pritesh S. Karia, MPH, and Chrysalyne D. Schmults, MD, MSCE, of Brigham and Women’s Hospital, Boston, and colleagues compared Brigham and Women’s Hospital, American Joint Committee on Cancer (AJCC), and International Union Against Cancer (UICC) tumor staging systems for cutaneous squamous cell carcinoma.¹ They found that Brigham and Women’s staging offered advantages over the conventional staging systems.

Study Details

The study involved analysis of 1,818 primary tumors diagnosed from 2000 to 2009 at Brigham and Women’s Hospital. Poor outcomes, including local recurrence, nodal metastasis, and disease-specific death, were analyzed by AJCC, UICC, and Brigham and Women’s T stage with regard to distinctiveness (outcome differences between stages), homogeneity (outcome similarity within stages), and monotonicity (outcome worsening with increasing stage).

Brigham and Women’s staging system is as follows: T1 = 0 high-risk factors, T2a = 1 high-risk factor, T2b = 2 to 3 high-risk factors, and T3 = ≥ 4 high-risk factors; high-risk factors include tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, and tumor invasion beyond fat, excluding bone invasion, which automatically upgrades tumors to stage T3.

Patients had a median age of 71 years at diagnosis, 98% were white, 53% were male, 14% were immunosuppressed, 73% had 1 tumor and 21% had 2 to 4 tumors, 85% had tumors < 2 cm in diameter, 66% had well-differentiated tumors, 90% had tumors that did not invade subcutaneous fat or deeper structures, and 4% had perineural invasion. Median follow-up was 50 months.

Poor Outcomes by Stage

For local recurrence, 10-year cumulative incidence (95% confidence interval [CI]) was 0.7% (0%–1%), 8% (5%–10%), 67% (21%–94%), and 67% (21%–94%) for AJCC T1 to T4 stages; 2% (1%–2%), 7% (4%–12%), 16% (8%–30%), and 67% (21%–94%) for UICC T1 to T4 stages; and 0.6% (0%–1%), 5% (3%–8%), 21% (13%–27%), and 67% (30%–90%) for Brigham and Women’s T1, T2a, T2b, and T3 stages.

For nodal metastasis, 10-year cumulative incidence (95% CI) was 0.1% (0%–1%), 6% (4%–9%), 67% (21%–94%), and 67% (21%–94%) for AJCC stages; 1% (0%–2%), 3% (1%–7%), 21% (11%–35%), and 67% (21%–94%) for UICC stages; and 0.1% (0%–0.4%), 3% (1%–5%), 21% (13%–27%), and 67% (30%–90%) for Brigham and Women’s stages.

For disease-specific death, 10-year cumulative incidence (95% CI) was no events, 6% (4%–9%), 100% (44%–100%), and 100% (44%–100%) for AJCC stages; 0.3% (0%–1%), 3% (1%–6%), 14% (6%–27%), and 100% (44%–100%) for UICC stages; and no events, 1% (0%–3%), 10% (6%–19%), and 100% (61%–100%) for Brigham and Women’s stages.

For overall death, 10-year cumulative incidence (95% CI) was 32% (29%–34%), 37% (32%–41%), 100% (44%–100%), and 100% (44%–100%) for AJCC stages; 33% (31%–35%), 31% (24%–38%), 49% (35%–63%), and 100% (44%–100%) for UICC stages; and 32% (30%–35%), 32% (28%–37%), 51% (41%–58%), and 100% (61%–100%) for Brigham and Women’s stages.

Distinctiveness

With regard to distinctiveness, 95% CIs overlapped for AJCC and UICC T3 and T4 stages for all endpoints, as did all four UICC stages for overall death, indicating that AJCC and UICC T3 and T4 are not distinct. Brigham and Women’s T stages had slight overlap of 95% CIs for overall death but no overlap for any other endpoint, indicating good distinctiveness of all four stages for local recurrence, nodal metastasis, and disease-specific death.

Homogeneity

Homogeneity was evaluated by comparing the proportion of poor outcomes (local recurrence, nodal metastasis, disease-specific death) occurring in low T stages. Overall 86% (95% CI = 77%–91%) of poor outcomes were in AJCC T1 and T2 cases, 70% (95% CI = 61%–79%) were in UICC T1 and T2 cases, and 40% (95% CI = 30%–49%) were in Brigham and Women’s T1 and T2a cases, with 66% of the poor outcomes being local recurrence in the Brigham and Women’s staging.

The nonoverlapping 95% CIs indicate that the Brigham and Women’s system had a significantly lower proportion of poor outcomes in low T stages compared with AJCC and UICC systems, suggesting a higher degree of homogeneity.

Monotonicity

Monotonicity was evaluated by comparing the proportion of poor outcomes occurring in high T stages. Overall, 14% (95% CI = 9%–23%) of poor outcomes occurred in AJCC T3 and T4 cases and 30% (95% CI = 21%–39%) in UICC T3 and T4 cases. By comparison, 60% (95% CI = 50%–69%) of poor outcomes occurred in Brigham and Women’s T2b and T3, including 70% of cases of nodal metastasis and 83% of disease-specific deaths.

Stage Changes

Of 112 tumors that were downstaged from AJCC T2 to Brigham and Women’s T1, there were only two local recurrences and one nodal metastasis. In 56 tumors downstaged from UICC stage T2/T3 to Brigham and Women’s T1/T2a, there was only one local recurrence. In 20 tumors downstaged from UICC T3 to Brigham and Women’s T2b, there were four local recurrences, six nodal metastases, and three disease-specific deaths.

In 86 cases that were upstaged from AJCC T1/T2 to Brigham and Women’s T2b/T3, there were 18 local recurrences, 18 nodal metastases, and 9 disease-specific deaths. In 66 cases upstaged from UICC T1/T2 to Brigham and Women’s T2b, there were 14 local recurrences, 12 nodal metastases, and 6 disease-specific deaths.

The investigators concluded, “[Brigham and Women’s Hospital] staging offers improved distinctiveness, homogeneity, and monotonicity over AJCC and UICC staging. Population-based validation is needed.”

They noted that the Brigham and Women’s system consolidated poor outcomes in the two highest stages: “Although these two stages make up only 5% of the cohort, they account for the majority (60%) of poor outcomes… Thus, [Brigham and Women’s] T2b and T3 tumors make up a high-risk subset of [cutaneous squamous cell carcinoma] worthy of further study regarding staging and adjuvant therapy.”

Dr. Schmults is the corresponding author for the Journal of Clinical Oncology article. ■

Disclosure: The study authors reported no potential conflicts of interest.

Reference

1. Karia PS, Jambusaria-Pahlajani A, Harrington DP, et al: Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women’s Hospital tumor staging for cutaneous squamous cell carcinoma. J Clin Oncol. December 23, 2013 (early release online).