Beyond Primary Tumor Location and RAS/BRAF Mutational Status as Prognostic Factor in Stage III Colon Cancer—Reply

703 Background: Primary tumor location of colon cancer (CC) is emerging as an important prognostic factor owing to distinct biological features. However, this factor still does not represent a prognostic parameter when deciding for adyuvant or palliative chemotherapy. In a meta-analysis of 66 studies including patients with all stages of disease, left-sided primary tumor location was associated with a significantly reduced risk of death and this was independent of other prognostic factors. Methods: We retrospectively included patients with stage II and III CC that underwent surgical resection between 2009 and 2014 HURyC. We performed a multivariate Cox model analysis to estimate if tumor location is an independent prognostic factor for overall survival (OS). The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes ( < 12 or ≥ 12), perforation, grade, use of adyuvant chemotherapy and age. A covariate was considered a confounder factor if the difference between the adjusted and unadjusted coefficient of chemotherapy varied > 10%. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (267 left sided and 297 right sided). The median follow-up of the entire cohort was 49 months. Globally, right sided CC was not significantly associated with better DFS or OS in comparison with left sided CC (HR: 0.74, p: 0.128; HR: 0.94, p: 0.75, respectively). By stages, stage II right sided CC seemed to show better DFS (HR: 0.45, p: 0.02), although no significant differences were found in OS (HR: 1.004, p: 0.98). Stage III right sided CC was not significantly associated with better DFS or OS in comparison with left sided CC (HR: 0.87, p: 0.585; HR: 0.66, p: 0.19, respectively). Conclusions: The multivariate analysis did not show significant differences in terms of prognostic relevance of primary tumor location in the adyuvant setting.

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Is primary tumor location an independent prognostic factor in stage IV colon cancer?

Journal of the Anus Rectum and Colon ◽

10.23922/jarc.2019-006 ◽

2019 ◽

Vol 3 (4) ◽

pp. 196-202

Author(s):

Sachio Yokoyama ◽

Hideo Baba

Keyword(s):

Colon Cancer ◽

Prognostic Factor ◽

Primary Tumor ◽

Stage Iv ◽

Tumor Location ◽

Independent Prognostic Factor ◽

Primary Tumor Location

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Association of prognostic value of primary tumor location in stage III colon cancer with RAS and BRAF mutational status.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3515 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3515-3515 ◽

Cited By ~ 3

Author(s):

Julien Taieb ◽

Hampig Raphael Kourie ◽

Jean-François Emile ◽

Karine Le Malicot ◽

Ralyath Balogoun ◽

...

Keyword(s):

Colon Cancer ◽

Primary Tumor ◽

Prognostic Value ◽

Disease Free Survival ◽

Tumor Location ◽

Stage Iii ◽

Metastatic Colon Cancer ◽

Tumor Site ◽

Anatomic Site ◽

Mutational Status

3515 Background: Recent data suggest that the anatomic site of colon primary tumor may be an important factor in the interpretation of molecular markers with clinical outcome in metastatic colon cancer (CC) patients (pts). We assessed here the prognostic value of primary location in fully resected stage III CC pts and its relationship to MSI, RAS and BRAF mutational status. Methods: Pts enrolled in the PETACC-8 trial were analyzed. We categorized tumor site as located proximal (left-sided) or distal (right-sided) to the splenic flexure. The association between tumor location and disease free survival (DFS), survival after relapse (SAR) and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, MSI, BRAF and RASmutation status. The outcome of pts receiving FOLFOX or FOLFOX and cetuximab in the adjuvant setting were also determined according to tumor site. Results: Among the 1869 pts with full molecular data available, 755 (40%) had a right-sided tumor, 164 (10%) were MSI, 942 (50%) were mutated for RAS and 212 (11%) were mutated for BRAF. Right-sided tumor was not prognostic for DFS in the whole population but was associated to a shorter SAR (HR: 1.54 [1.23 - 1.93], p = 0.001) and OS (HR: 1.25 [1.02 - 1.54], p = 0.03). Same results were observed for MSS and for MSI pts. However, when looking at pts mutated for RAS or BRAF(MUT) and those double wild type (DWT) for those mutations, we found that right-sided tumors, when compared to left-sided tumors, was associated with a worst DFS in DWT patients (HR:1.39[1.01-1.92], p = 0.04) and a better DFS in MUT patients (HR:0.77[0.63-0.95], p = 0.01). These results were found independently of the treatment received and no beneficial effect of cetuximab on DFS or OS was observed in left-sided tumors. Conclusions: In the whole study population of stage III CC pts, though right-sided tumor location influences OS as previously reported, it does not seem to influence DFS but only SAR, when disease becomes metastatic. Interestingly, sidedness seems to influence DFS when splitting the population in MUT or DWT for RAS and BRAF, with a worst DFS for right-sided tumors in DWT and a worst DFS for left-sided tumors in RAS or BRAF mutants. Clinical trial information: 2005-003463-23.

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