KRAS Mutations Linked to Aggressive Tumors, Poor Survival in Cholangiocarcinoma

A review of studies on mass-forming cholangiocarcinoma shows that KRAS-mutated (mKRAS) cancers are associated with aggressive tumor growth and shortened survival, according to findings that appeared last week in the European Journal of Surgical Oncology.

Testing for this mutation could guide treatment, wrote investigators from Humanitas University in Milan, Italy. This aligns with recent recommendations at the Cholangiocarcinoma Foundation annual meeting in Salt Lake City, Utah, where speakers emphasized the need to hunt down mutations so that patients could enroll in clinical trials and, possibly, gain access to targeted therapies.

The Milan team honed in on mKRAS in trying to understand the poor prognosis for mass-forming cholangiocarcinoma, which has dismal survival rates. Patients who have unresectable tumors have a life expectancy of just 24 months; even when surgery occurs, the 5-year survival rate is 25% to 35%, mostly due to cancer recurrence.

The team examined 8 studies that included 604 patients whose tumors were resected. Of these patients, 23% had mKRAS cancers. Presence of the mutation was linked to poor outcomes:

• Overall survival (OS) at 1 year was lower for those with mKRAS, with an odds ratio (OR) of 3.45 (95% CI, 1.85-6.42; P < .001), compared with those with wild-type KRAS.
• OS at 3 years was worse, with an OR of 4.82 for mKRAS (95% CI, 2.63-8.84; P <.001), compared with wild-type KRAS.
• At 5 years, OS in mKRAS tumors had an OR of 10.60 (95% CI, 3.12-36.03; P < .001), compared with wild-type KRAS.

The review also examined how survival rates were affected by the completeness of the surgical resection (R1 vs R0), the pathological lymph node rate, whether patients had a single or multiple tumors, and the perineural invasion rate. Investigators found that the pooled R1 resection rate was 18% for mKRAS and 23% for wild-type KRAS, but the OR did not reach significance. The pooled pathological lymph node rate was 23% for mKRAS and 17% for wild-type KRAS, but the OR did not reach significance.

By contrast, the pooled rate for multiple tumors was 55% in mKRAS vs 19% in wild-type KRAS, with an OR rate of 5.38 (95% CI, 1.76-16.48; P = .003), and the pooled rate for perineural invasion was 77% vs 31%, with an OR of 6.59 (95% CI, 2.13-20.37; P = .001).

Investigators concluded that not only was the mKRAS rate high in mass-forming cholangiocarcinoma, but that it was “strongly associated with a shortened survival and higher tumoral aggressiveness.”

Testing for KRAS mutations in this type of cholangiocarcinoma, they wrote, “could be a valuable adjunct in opening a scenario to new treatments and improving prognosis of patients.”

Reference

Procopio F, Branciforte B, Nappo G, Di Tommaso L, Lleo A, Torzilli G. Meta-analysis on prognostic value of KRAS mutation in resected mass-forming cholangiocarcinoma. Eur J Surg Oncol. Published online March 17, 2022. https://doi.org/10.1016/j.ejso.2022.03.005