Adjuvant Therapy Shows No Significant Benefits After Cholangiocarcinoma Resection

Even in cases when complete, curative resection is an option for cholangiocarcinoma (CCA), many patients relapse after surgery. Thus, many agents have been studied as potential adjuvant therapies after resection. But a recent retrospective study found that adjuvant therapy may not improve overall survival (OS) or progression-free survival (PFS) after CCA resection.

CCA, which occurs in the biliary system, has seen treatment advances in recent years, but the 5-year overall survival rate still ranges from 10% to 40%. Many cases are diagnosed when CCA is already advanced, and only 20% to 30% of cases are eligible for resection. Approximately two-thirds of those who undergo surgery relapse within 5 years.

While adjuvant therapy seems a potential solution to improve outcomes after surgery, past findings regarding chemotherapeutic agents, radiotherapy, or both for adjuvant therapy have been conflicting. The current study, published in the Journal of Yeungnam Medical Science, compared outcomes of surveillance versus adjuvant therapy after CCA resection with no residual tumor (R0 resection).

Out of 210 patients who underwent curative CCA surgery at Daegu Catholic University Medical Center in South Korea between January 2010 and December 2019, 154 eligible CCA patients who underwent R0 resection were included in the study. A total of 109 patients (70.8%) received adjuvant therapy, while 45 (29.2%) were only surveilled after R0 resection.

Patients in the surveillance group tended to be older than those in the adjuvant therapy group, and more patients in the adjuvant therapy had American Joint Committee on Cancer stage III disease versus the surveillance cohort (13.8% versus 2.2%). Most cases (96.8%) were adenocarcinomas. Tegafur-uracil was the most commonly used adjuvant therapy, followed by gemcitabine, and gemcitabine-cisplatin (37.6%, 25.7%, and 20.2%, respectively).

At a median follow-up duration of 899 days, there was no statistically significant difference in survival in the adjuvant therapy group versus the surveillance group. The 1-year, 3-year, and 5-year OS rates were 95.2%, 75.8%, and 69.3%, respectively in patients who received adjuvant therapy versus 92.8%, 75.9%, and 64.2% in those who did not. The 1-year, 3-year, and 5-year PFS rates were 88.2%, 67.3%, and 48.9%, respectively, in the surveillance group versus 70.3%, 45.4%, and 42.6%, respectively, in the adjuvant therapy cohort. Neither the OS nor PFS differences are statistically significant, although PFS was higher in the surveillance group.

Among adjuvant therapy regimens, tegafur-uracil group had the highest rates of OS and PFR compared to other regimens, but it still showed no OS or PFS benefit compared with surveillance. In the adjuvant therapy group, 72 out of 109 patients (66.1%) finished their therapeutic cycle, while 37 patients (33.9) did not finish their cycles. Recurrence, patient refusal, neutropenia, and loss to follow-up were all reasons for stoppage.

Having stage III CCA was a prognostic factor for OS (hazard ratio [HR], 10.81; 95% CI, 2.92-40.00; P < .001) and PFS (HR, 8.08; 95% CI, 2.80-23.32; P < 0.001) in a multivariate analysis. Patients with mild systemic diseases in addition to CCA or whose CCA was stage II had better PFS ([HR, 0.50; 95% CI, 0.31-0.81; P = .005] and [HR, 3.14; 95% CI, 1.25-7.89; P = .015], respectively). More research on why mild comorbidities led to favorable PFS in this study is warranted, the authors noted.

Notably, past studies have only found capecitabine adjuvant therapy to increase OS, but no patients in the current study were receiving capecitabine. Tegafur-uracil is similar to capecitabine, but it did not show statistically significant survival benefits in this study. The low rate of therapy completion in this cohort could also have impacted the lack of OS and PFS benefits.

Study limitations included its retrospective nature and differences between the AT and surveillance cohorts. Considering it was a single-center study, the generalizability is uncertain.

Even so, the findings suggest adjuvant therapy did not improve OS or PFS in patients who underwent R0 resection for CCA. But given the low rate of therapy adherence, more intervention to ensure adherence might help improve outcomes.

Reference

Jeong HT, Lee J, Jo HH, Kim HG, Han J. The effect and therapeutic compliance of adjuvant therapy in patients with cholangiocarcinoma after R0 resection: a retrospective study. J Yeungnam Med Sci. Published online May 26, 2022. doi:10.12701/jyms.2022.00213