Study Finds Adjuvant Therapy Beneficial for Distal Cholangiocarcinoma With Lymph Node Metastasis

Patients who undergo surgical resection for distal cholangiocarcinoma (DCC) often experience recurrence, even when surgical intervention was initially curative. Considering lymph node (LN) metastasis is the most common route of metastasis in DCC, a recent study aimed to characterize LN metastasis, recurrence, and predictors of metastasis in patients with DCC after surgical resection.

LN metastasis is widely acknowledged as a negative prognostic factor in DCC, which is 1 of 3 types of cholangiocarcinoma. Thus far, surgical resection is the only curative therapy for DCC, but the 5-year survival rate is only approximately 20% to 40%. DCC occurs below the confluence of the cystic duct and has higher rates of LN metastasis—a negative prognostic factor—than intrahepatic or perihilar cholangiocarcinoma.

The small retrospective study, published in the International Journal of Clinical Oncology, aimed to investigate the stations, patterns, and predictors of metastasis, as well as the effectiveness of LN dissection at each station and the effectiveness of adjuvant therapy after resection.

The study included 105 patients who underwent surgical resection for DCC, 93 of whom underwent subtotal stomach-preserving pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy.

The 12 remaining patients underwent extrahepatic bile duct resection. A total of 22 patients experienced complications post-surgery, which included pancreatic fistula, bile leakage, intra-abdominal abscess, bleeding, ileus, and pulmonary artery thrombosis.

A total of 26 patients (24.8%) had cancer cells at the hepatic ductal margin and 43 patients (41%) underwent adjuvant therapy after resection. In past studies, the authors note that postoperative adjuvant therapy has led to mixed outcomes regarding improvements in overall survival (OS) or recurrence-free survival (RFS). In this study, surgeons decided whether patients should undergo adjuvant therapy post-procedure, and patients with LN metastasis or positive bile duct margin status were more commonly given adjuvant therapy.

The liver, local sites, LNs, and peritoneum were the most common sites of recurrence (27.6%, 24.8%, 13.3%, and 4.8% of patients overall, respectively). Median OS was 42 months, and median RFS was 32 months. There were several independent risk factors for shorter OS: positive bile duct margin, LN metastasis, and serum carbohydrate antigen (CA) 19-9 levels greater than 37 U/mL. LN metastasis and positive bile duct margin status were independent risk factors for shorter RFS.

The median number of dissected lymph nodes was 23, and 16 patients (15.2%) had LN recurrence, while 6 patients (5.7%) had LN metastasis as the first recurrence. At surgery, the most common metastatic LN stations were Nos. 13, 12, 17, and 8 (32.7%, 19.2%, 9.6%, 6.6%, respectively). There were no 5-year survivors with metastasis in stations 8, 14, or 16, suggesting no effectiveness in dissecting those LNs.

Patients with LN metastasis who were given postoperative adjuvant therapy had significantly better OS and RFS than patients who did not undergo adjuvant therapy. However, the same benefit was not seen in patients with positive ductal margins or those with high serum CA 19-9 levels who underwent adjuvant therapy. Overall, the results suggest adjuvant therapy may improve prognosis in patients with LN metastasis. Further research might help determine whether neoadjuvant therapy for patients with DCC and negative prognostic factors might be effective.

Although the study was limited in its size and its retrospective nature, it suggests adjuvant therapy is associated with longer OS and RFS in certain patients. Studies with larger cohort sizes are warranted to confirm this benefit.

Reference

Kurahara H, Mataki Y, Idichi T, et al. Spread of lymph node metastasis and adjuvant therapy for distal cholangiocarcinoma. Int J Clin Oncol. Published online May 11, 2022. doi:10.1007/s10147-022-02175-z