P0027 - Squamous Cell Carcinoma of the Extrahepatic Bile Ducts: A National Cancer Database Analysis of a Rare Cholangiocarcinoma Histologic Variant

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Jad Mitri, MD

St. Elizabeth's Medical Center
Boston, MA

Jad Mitri, MD¹, Elena Panettieri, MD², Eduardo Vega, MD²
¹St. Elizabeth's Medical Center, Boston, MA; ²Saint Elizabeth's Medical Center, Boston, MA

Introduction: Squamous cell carcinoma (SCC) is a rare subtype of cholangiocarcinoma with limited previous literature. The aimed was to describe demographics, tumor characteristics, and survival outcomes in a cohort of 102 cases of SCC variant of extrahepatic cholangiocarcinoma (EHCC).

Methods: National Cancer Database was queried for patients with a diagnosis of EHCC, SCC and adenocarcinoma (AC) types between 2004-2018. Tumor primary site was determined through International Classification of Diseases 10 (ICD-10) codes C24.0-24.9.
Patient (age, race, sex, Charlson-Deyo comorbidity score), tumor (grade, tumor size, metastatic sites, therapeutic approach, margin positivity) and survival characteristics were analyzed and compared between SCC and AC. We used Chi-square and Mann-Whitney U test to study differences between categorical and continuous variables, respectively.
Patients who underwent surgery were selected for a survival analysis (logRank) and a Cox multivariate analysis after adjusting for relevant confounders. The level of statistical significance was set at p=0.05.

Results: 41,229 patients with EHCC were included: AC n=41,127 (99.76%) and SCC N=102(0.24%). SCC had a significantly larger median tumor size and more Grade 3 poorly or undifferentiated tumors (table 1). Median survival was 5.06 months for all SCC patients versus AC 11.07 months(p< 0.001). (Figure 1)
In a Cox multivariate analysis for overall survival (OS), tumor size (HR=1.001; 95%CI [1.001-1.002], p=0.000), positive resection margins (HR=1.875; 95%CI[1.761-1.995], p=0.000), age (HR=1.009; 95%CI [1.007-1.012], p=0.000), Charlson-Deyo score (HR=1.3; 95%CI[1.14-1.483], p=0.000), tumor grade (HR=1.671; 95%CI[1.536-1.817], p=0.000) and radiation therapy (HR=1.236; 95%CI[1.164-1.313], p=0.000) were positively associated with decreased survival for surgically managed cholangiocarcinoma. Chemotherapy had a favorable impact on survival (HR 0.687; 95%CI [0.65-0.725], p=0.000). While SCC group had a higher tumor size and grade, no difference in survival was found between SCC and AC patients treated surgically (HR=0.794; 95%CI= [0.439; 1.435], p =0,445).

Discussion: SCC is a rare histologic variant of EHCC with worse OS than AC. Surgery when indicated improves survival in EHCC, including SCC. Due to the low frequency of the SCC variant, more research is needed to better characterize this rare histologic type. We recommend an extensive workup for alternative primary sites when encountering SCC variant of EHCC given the paucity of cases.

Figure: Figure 1- Survival of patients with extrahepatic bile duct cholangiocarcinoma by histology

	Adenocarcinoma^^ n= 41 127	Squamous cell carcinoma^^^ n= 102	p value

Age, years **	71 (62-79)	71 (57-81)	0.641
Sex, male	22591 (55)	44 (43)	0.011
Race, ^			0.001
Asian	1906 (4.6)	13 (12.7%)
Black	3643 (8.9)	17 (16.7)
Hispanic	3345 (8.1)	4 (3.9)
Other	537 (1.3)	0 (0)
White	31276 (76)	67 (65.7%)
Unknown	420 (1)	1 (1)
Tumor size, in millimeters **	66 (41-95)	76.5 (62-115)	0.019
Primary site
Extrahepatic bile duct (C24.0)	17569 (42.7)	61 (59.8)	0.000
Ampulla of Vater (C24.1)	19263 (46.8)	23 (22.5)
Overlapping sites of biliary tract (C24.8)	378 (0.9)	0 (0)
Biliary tract, unspecified (C24.9)	3917 (9.5)	18 (17.6)
Grade, ^
Grade 1	2789 (7.4)	1 (1.1)	0.008
Grade 2	11461 (30.4)	20 (22)
Grade 3 or undifferentiated	8535 (22.6)	30 (33)
Unknown	18342 (44.5)	49 (48)
Charlson-Deyo Score, ^
0	27890 (67.8)	82 (80.4)	0.026
1	8953 (21.8)	17 (16.7)
2	2543 (6.2)	1 (1)
3	1741 (4.2)	2 (2)
Metastatic site ^
Bone	609 (2.2)	2 (2.7)	0.756
Liver	4032 (14.8)	16 (21.3)	0.422
Brain	59 (0.2)	0 (0)	0.815
Lung	1163 (4.3)	4 (5.3)	0.703
Lymph nodes	342 (3.5)	2 (6.9)	0.466
Other sites	510 (5.3)	1 (3.4)	0.883
Resection margins: ^
Negative	16167 (86.8)	16 (76.2)	0.185
Positive	2455 (13.2)	5 (23.8)
Treatment modality ^
Surgery only	9915 (25)	15 (16)	0.000
Chemotherapy only	5326 (13.4)	22 (23.4)
Radiation only	722 (1.8)	4 (4.3)
Surgery and chemotherapy	5013 (12.6)	5 (5.3)
Surgery and radiation	267 (0.7)	2 (2.1)
Surgery, chemotherapy, and radiation	4313 (10.9)	2 (2.1)
Chemotherapy and Radiation	1768 (4.5)	10 (10.6)
No surgical or medical management	12404 (31.2)	34 (36.2)
Survival, months ***	11.07 [10.85-11.29]	5.06 [3.95-6.17]	< 0.001 *

Table: Table 1 - Demographics, Tumor Characteristics And Survival Data Compared In Extrahepatic Duct Cholangiocarcinoma By Histology

Footnotes:
* calculated using log rank (Mantel-Cox)
**values: Median (25th-75th percentile)
*** values: Median[95% confidence interval]
^ values: number of patients (frequency %)
^^ ICD-O-3 (International Classification of Disease for Oncology, third edition) codes : 8140-8149, 8160-8162, 8190-8221, 8260-8337, 8350-8551, 8570-8576, 8940-8941
^^^ ICD-O-3 codes: 8070-8071

Disclosures:

Jad Mitri indicated no relevant financial relationships.

Elena Panettieri indicated no relevant financial relationships.

Eduardo Vega indicated no relevant financial relationships.

Jad Mitri, MD¹, Elena Panettieri, MD², Eduardo Vega, MD². P0027 - Squamous Cell Carcinoma of the Extrahepatic Bile Ducts: A National Cancer Database Analysis of a Rare Cholangiocarcinoma Histologic Variant, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.