QS142 - Treatment Strategies for Neuroendocrine Neoplasms of the Anal Canal – an Analysis of the National Cancer Database

Purpose/Background: Neuroendocrine neoplasms (NEN) are a heterogenous group of tumors that rarely occur in the anal canal. Given their rarity, outcomes for patients with anal NEN have not been thoroughly investigated. The optimal treatment strategy, including the role of neoadjuvant therapy, is not known. This study aimed to assess outcomes of anal NEN according to treatment strategy and surgical technique using the National Cancer Database (NCDB).

Methods/Interventions: A retrospective cohort analysis of patients with a diagnosis of NEN in the NCDB from 2004-2020 was performed. Treatment strategies (upfront surgery, surgery after neoadjuvant chemotherapy, chemotherapy alone) and type of surgery (local excision (LE) vs abdominoperineal resection (APR)) were compared using descriptive statistics. Overall survival (OS) was compared using the Kaplan-Meier method according to treatment strategy and type of surgery. A receiver operating characteristics (ROC) curve was used to estimate the cutoff tumor size associated with worse OS.

Results/Outcomes: 500 patients (55.6% male; mean age 61.2 years) were included. Neuroendocrine carcinomas represented 73.6% of cases, followed by carcinoid tumors (24.8%). Most patients had upfront surgery (63.1%), 31.3% only received chemotherapy and 5.7% had surgery after neoadjuvant therapy. Among patients undergoing surgery, LE was the most common approach (78.3%) followed by APR (21.7%). 30- and 90-day mortality rates were low (1.7% and 5.1%, respectively). At a mean follow-up of 40 months, 65.1% of patients had died. Patients with carcinoid tumors were more likely to have upfront surgery (40.6%, p< 0.001), while neuroendocrine carcinomas were more often treated with neoadjuvant therapy followed by surgery or chemotherapy alone (81%, 94%, p< 0.001). Upfront surgery involved LE more than APR (83.3% vs 16.7%, p< 0.001). Compared to patients treated with neoadjuvant therapy, patients who had upfront surgery had smaller tumors (18 mm [IQR 6-30] vs 35 mm [IQR 24.3-78.8], p< 0.001) of lower grade (G1: 26.1% vs 0%; G2: 13.0% vs 0%; G3: 60.8% vs 100%, p< 0.001). Charlson Deyo score, age, and 30- and 90-day mortality were not significantly associated with treatment strategy. Patients with low grade (G1-G2) NEN were significantly more likely to undergo LE compared to high-grade (G3) NEN (G1-G2: 43.9% vs 9.1%; G3: 56.1% vs 90.9%, p=0.002). Compared to APR, patients undergoing LE had smaller tumors (15 mm [IQR 6.0-24.3] vs 32 mm [IQR 25-52.3], p< 0.001). APR was significantly more associated with R0 resection compared to LE (80.8% vs 54.8%, p< 0.001). There was a significant trend to treat neuroendocrine carcinomas with APR compared to carcinoid tumors (74.5% vs 25.5%, p=0.013). ROC curve analysis revealed 12mm was the tumor size cutoff signifying worse OS when treated with LE (AUC 0.761). Patients receiving only chemotherapy had shorter OS than did patients receiving neoadjuvant therapy followed by surgery or upfront surgery (15.2 vs 39.2 vs 89.4 months, p< 0.001).

Conclusion/Discussion: Our findings show that anal NEN of small size, low grade, and with carcinoid histology are more likely to be treated with upfront surgery, often LE, without neoadjuvant therapy. Given the lack of guidelines for these rare neoplasms, treatment according to these pathologic criteria is justified until better prospective data is available. While upfront LE may be standard treatment, APR and neoadjuvant therapy may have a role in select patients with large (>12 mm), G3 tumors, and neuroendocrine carcinomas in order to achieve R0 resection and improve survival.