Combined impact of primary tumor molecular profile and location in the relapse pattern of early-stage, microsatellite stable colorectal cancer.

3603 Background: The primary tumor location (PTL) and the genetic profile of colorectal cancer (CRC) impact the risk, localization and timing of metastases. We investigated the PTL-specific impact of genomic alterations in a large cohort of patients (pts) with localized, MSS CRC through the automatic data mining of radiology reports and comprehensive genome profiling (CGP). Methods: Eligible CRC cases consisted of consecutive early-stage primary tumor samples from pts seen at a single institution (Memorial Sloan Kettering, MSK). All tumors were MSS, without pathogenic POLE mutations, and diagnosed after Jan 1st 2015, when MSK-IMPACT testing was standard in the clinic. MSK-IMPACT sequencing provided CGP of 341-505 genes. All pts underwent at least 1 surveillance scan at MSK comprising at least chest, abdomen and pelvis, had a minimum follow-up (FUP) of 1 year and developed metastatic disease at least 6 months after initial diagnosis. Time to metastasis (TTM) for each anatomic site was retrieved from radiology reports using validated natural language processing methods. TTM was defined for each organ as the interval from the diagnosis until the first radiologic evidence of metastasis or last scan. TTMs and OS were modeled with univariate cox regression, using competitive risk of death for TTMs. FDR was used to account for multiple comparisons, with a threshold of <0.1. Results: The final cohort comprised 1442 pts, with a median FUP of 42.3 months (IQR 39.5-44.5) and a median number of 6 scans (IQR 4-10) per pt. The PTL was right colon, left colon and rectum in 305, 498 and 639 pts. Expected PTL-specific metastatic patterns were observed, comprising higher risk of peritoneal metastases for right-sided PTL (HR=1.41, p=0.050) and higher risk of lung metastases for rectal tumors (HR=1.45; p=0.004); rectal cancer had the highest risk of metastatic relapse (HR=1.42, p<0.001). The impact of genetic alterations on the risk of developing metastatic disease varied by PTL and the metastatic site. Ten, eight and one pathway-metastatic site significant associations were observed, respectively, in the left-sided, right-sided and rectal PTL cohorts; the most relevant are reported in the table. Conclusions: The metastatic patterns and prognostic stratification of pts with early-stage MSS CRC are affected by the interplay of PTL and genetic profile. Genomic alterations are less impactful on outcomes of pts with rectal cancers. Table: see text