Epidemiología de las metástasis hepáticas colorrectales resecadas y uso de la quimioterapia perioperatoria: un estudio prospectivo de cohorte sobre el impacto de la secuenciación de última generación y el perfil de mutaciones en una población real.

Colorectal liver metastasis (CRLM) selected for surgery is increasingly influenced by mutation-profiling yet scarcely described outside clinical trials. The aim of this study was to investigate impact of mutation-testing in routine care on management of CRLM. Analysis of a population-derived cohort study matched with the Cancer Registry of Norway. Clinicopathological, mutational, and survival data were analysed across time-intervals.

The study included 3022 patients with primary colorectal cancer; 777 (25.8%) developed CRLM (synchronous n = 560; 72.1% and metachronous n = 217; 27.9%; liver-only n = 376; 48.4%). Hepatectomy-rate was 24.6% (n = 191/777), and highest for metachronous presentation (33.6%). No time-difference in sex, age, number or size of CRLM lesions was found. Patients having hepatectomy were younger than patients without (median 65 vs. 72 yrs).

Females were less likely to undergo hepatectomy compared to males (20.6% vs 27.4%). Mutation-analysis increased over time, with KRAS-mutation (30.4%), BRAF-mutation (12.9%) and MSI+ (4.3%) across all tested in most recent time-period. Mutated KRAS (n = 55) was most common mutation, with KRASG12D and KRASG12V most frequent subtypes. PIK3CA occurred in 15 (11%) patients.

No mutation was found in 44 (31%) of tested CRLMs. Neoadjuvant chemotherapy increased (from 38% to 60%; P = 0.018), with more synchronous CRLM resected (from 46% to 65%; P = 0.039). The most recent time-period was associated with inferior survival. Resection-rates of CRLM were stable but selection factors varied over time.

Increased use of mutation-testing was associated with increased use of neoadjuvant chemotherapy, increased resection for bilobar and synchronous CRLM, and with temporal reduced recurrence-free and overall survival.