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. 2021 Jan 29:3:100049.
doi: 10.1016/j.lanepe.2021.100049. eCollection 2021 Apr.

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

Pia Osterlund  1   2   3 , Tapio Salminen  1 , Leena-Maija Soveri  2   4 , Raija Kallio  5 , Ilmo Kellokumpu  6 , Annamarja Lamminmäki  7 , Päivi Halonen  2 , Raija Ristamäki  8 , Eila Lantto  9   10 , Aki Uutela  11 , Emerik Osterlund  11   12 , Ali Ovissi  9 , Arno Nordin  11 , Eetu Heervä  8 , Kaisa Lehtomäki  1 , Jari Räsänen  13 , Maija Murashev  14 , Laura Aroviita  15 , Antti Jekunen  16 , Reneé Lindvall-Andersson  17 , Paul Nyandoto  18 , Juha Kononen  19 , Anna Lepistö  20 , Tuija Poussa  21 , Timo Muhonen  22 , Annika Ålgars  8 , Helena Isoniemi  11 ; Members of The RAXO study group are collaborators of this study and are listed in Appendix Table 4B
Affiliations

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

Pia Osterlund et al. Lancet Reg Health Eur. .

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; CI95% 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.

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Conflict of interest statement

All authors report institutional research funding from Eli Lilly, Merck KGaA, Roche Finland, Sanofi and unrestricted grants from Amgen and Servier, during the conduct of the study. PO, HI, LMS, PH, TS, AÅ, RR, EH, RK, AML, KL and TML report grants, personal fees or non-financial support from Abbvie, Amgen, Astra-Zeneca, Bayer, Celgene, Eli Lilly, Eisai, Erytech Pharma, Incyte, Fresenius, Jansen-Cilag, Merck, MSD, Nordic Drugs, Nutricia, Pierre-Fabre, Roche, Sanofi, Servier, Sobi or Varian.

Figures

Fig 1
Fig. 1
Study design, patient flow, and intervention with resectability assessment at tertiary MDT in the RAXO study.
Fig 2
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
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
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
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
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).
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