Patterns of Care and Outcomes in Management of Localized High Grade Neuroendocrine Carcinoma of the Anal Canal

Purpose: High-grade neuroendocrine carcinoma (NEC) of the anal canal is an extremely rare disease entity with limited clinical data to guide treatment decisions. Given the aggressive nature of the disease, most cases are diagnosed at an advanced stage, however a subset of patients will present with localized disease. To better characterize management approaches and subsequent outcomes in the localized setting, we analyzed the national cancer database (NCDB).

Methodology: We queried the NCDB for patients diagnosed with localized high grade neuroendocrine carcinoma of the anus (including patients with grade 3 neuroendocrine carcinoma and small cell histology). Patients with metastatic, regional, or unknown stage were excluded, as were patients with low, intermediate, and unknown tumor grade. Receipt of chemotherapy within 30 days of receiving radiotherapy was defined as concurrent chemoradiotherapy (CRT). Univariable and multivariable analyses identified characteristics predictive of OS. Survival was calculated using Kaplan Meier method. Multivariable logistic regression was performed to identify clinicopathologic variables associated with treatment and histology (small cell vs other high grade NEC).

Results: Ultimately 59,537 patients with cancer of the anal canal were identified, of which 100 patients met inclusion criteria of localized high grade NEC (n=47 were coded as small cell). Median age was 53 years old and 31% were male and 69% were female with the following T stage breakdown: T1=19 patients, T2=27 patients, T3=3 patients, T4=5 patients and unknown T stage=44 patients. Regarding management, 85% of patients (n=85) received radiation to the primary (76% of patient received radiation to primary and regional lymph nodes and 24% received radiation to primary alone), with 89% (n=76) of patients in this subset receiving chemotherapy. Of the patients receiving chemotherapy and radiation, 70% (n=53) received concurrent CRT. A total of 49% (n=49) of patients underwent surgery [local excision: n=38 (78%) vs abdominoperineal resection: n=9 (22%)], of which 76% (n=37) received adjuvant radiation and 82% (n=40) received adjuvant chemotherapy.

Median radiation dose to the primary was 54Gy (IQR: 45-59.4Gy) and median dose to the regional lymph nodes was 45Gy (IQR: 44.75-54Gy). On multivariable analysis, concurrent CRT receipt (OR: 0.11, 95% CI: 0.19-0.59) was associated with improved OS. At a median follow-up of 15.8 months, median OS was 28 months and 18 months (p=0.01) and 3-year OS rates were 40% and 22% in those treated with and without concurrent CRT respectively. Concurrent CRT receipt was associated with small cell histology (OR: 3.95, 95% CI: 1.11-14.1, p=0.03) and omission of nodal radiation (OR: 6.10, 95% CI: 1.10-33.90 p=0.04) on logistic regression.

Conclusions: In the largest series of localized high grade NEC of the anal canal known to date, patients were most commonly managed with concurrent CRT. Patients receiving concurrent CRT had improved OS compared to those who did not.

References: