Repeated centralized multidisciplinary team assessment of resectability, clinical behavior, and outcomes in 1086 Finnish metastatic colorectal cancer patients (RAXO): A nationwide prospective intervention study

Abstract

Background: Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice.

Methods: A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival.

Findings: In 2012-2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80·4 months in R0/1-resected (HR 0·15; CI_95% 0·12-0·19), 39·1 months in R2-resected/LAT (0·39; 0·29-0·53) patients, and 20·8 months in patients treated with "systemic therapy alone" (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively.

Interpretation: Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later.

Funding: The funders had no role in the study design, analysis, and interpretation of the data or writing of this report.

Keywords: Colorectal cancer; Conversion; Metastatic; Multidisciplinary; Multisite metastases; Resectability; Resection.

Fig. 1

Study design, patient flow, and intervention with resectability assessment at tertiary MDT in the RAXO study.

Fig. 2

Upfront resectable (panel A & C) and borderline (panel B & D) in the resectability assessment at central tertiary MDT compared with upfront resectability in the local assessment according by whom the assessment was done before treatment initiation and inclusion to the RAXO-study.

Fig. 3

Upfront resectability, conversion and resection rates and outcomes, and reasons why a curative intent resection was not undertaken. Data are shown for single-site (n = 586) and multisite (n = 500) metastases with intact or removed primary tumor. Procedures are divided into R0/1-resection, and R2-resection and/or Local Ablative Therapy (LAT).

Fig. 4

Overall survival (OS) and 5-year OS rate (panel A), with 12-months landmark (panel B), and progression-free survival (PFS) and 5-year PFS rate (panel C). Data shown from mCRC diagnosis in R0/1-resected, R2-resected or LAT, systemic therapy only, and best supportive care (BSC) groups. Hazard ratio (HR) and 95% confidence interval (CI) with systemic therapy used as reference group.

Fig. 5

Median OS from mCRC diagnosis. Data shown for upfront resectable and converted resectable with chemotherapy and/or biologics, according to R0/1-resection, R2-resection and/or local ablative therapy (LAT), upfront or converted resectable treated with “systemic therapy alone” versus borderline still unresectable or never resectable that were treated with “systemic therapy alone”.

Fig. 6

Metastatic sites. Frequency as curve and numbers of the 23 most common metastatic sites at baseline and during disease trajectory (presented to 60+ months) in panel A (color- and number-coded in order from most to least frequent). Appearance of metastases at 9 specific sites during the first 60 months of follow-up when 99% of eventual metastases had appeared (proportion of metastases appearing) in panel B (color and number-coded as in A panel).