SYNCHRONOX is a multicenter cohort (retrospective then prospective) intending to include 550 patients with mid or low rectal adenocarcinoma (pMMR, T3-T4 and/or N+) and resectable synchronous liver metastases, treated upfront with at least two cycles of induction FOLFIRINOX chemotherapy. The primary objective is to determine, at 18 months, the R0 resection rate of both tumor sites (rectum and liver), while secondary objectives focus on 3 year overall and progression free survival, radiological and pathological responses, postoperative morbidity and mortality, and comparison of the different surgical strategies after FOLFIRINOX.

SYNCHRONOX is a multicenter, observational retrospective cohort followed by a prospective validation cohort designed to evaluate therapeutic pathways and oncologic outcomes in adults with mid- or low-rectal adenocarcinoma and resectable synchronous liver metastases who received induction FOLFIRINOX chemotherapy. The study aims to describe and compare real-world management strategies after induction FOLFIRINOX (simultaneous rectum and liver surgery, "classic" rectum-first, "reverse" liver-first, and adaptive sequencing) and to identify factors associated with achieving complete curative-intent treatment of both tumor sites.

Eligible patients are ≥18 years old with pMMR mid/low rectal adenocarcinoma staged cT3-T4 and/or N+, with synchronous liver metastases diagnosed within 3 months before or after the rectal cancer diagnosis, without extrahepatic metastases, and treated with at least two cycles of induction FOLFIRINOX. Liver disease is considered resectable when lesions are unilobar (no limit in number) or bilobar with up to 10 lesions, corresponding to class I (clearly resectable with a conventional hepatectomy of ≤4 segments leaving >40% remnant liver) or class II (potentially resectable, requiring complex/extended liver surgery and possibly two-stage strategies). Because this is a non-interventional study, all diagnostic work-up, chemotherapy, radiotherapy, surgical decisions, and follow-up are performed as part of routine care and remain at the discretion of local multidisciplinary tumor boards. The research does not mandate any additional clinical, laboratory, radiologic examinations, surgical procedures, or questionnaires.

The primary endpoint is the rate of curative-intent complete treatment (R0) of both tumor sites at 18 months after the start of induction FOLFIRINOX. For rectal cancer, R0 resection is defined as a distal margin ≥1 cm and a circumferential resection margin >1 mm. Organ preservation without surgery is also considered curative-intent when achieved after a clinical complete response and not followed by tumor regrowth within the first year. For liver metastases, curative-intent treatment requires R0 resection of all visible lesions (margin >1 mm) and/or local destruction by radiofrequency ablation.

Secondary objectives include overall survival and progression-free survival at 3 years from the start of FOLFIRINOX, R0 resection rates for the rectal primary and liver metastases separately, radiologic response assessment at both sites (ymrTRG for rectal MRI response and RECIST for liver lesions), pathologic tumor regression grading (Rödel score for rectal cancer and Blazer classification for liver metastases), clinical complete response rate of the rectal tumor, and 30-day postoperative morbidity and mortality after rectal and liver surgery (Dindo-Clavien classification). Data are collected in an electronic case report form (eCRF) from standard medical records for both retrospective and prospective cohorts, with planned comparative analyses between strategies using matching variables and propensity-score methods to limit indication bias. The retrospective cohort includes patients diagnosed between June 1, 2020 and June 1, 2025, and the prospective validation cohort includes patients diagnosed between June 1, 2025 and June 1, 2028, with an overall follow-up duration of 60 months.

Inclusion Criteria:

• Adult subjects aged 18 years and older
• Adenocarcinoma of the middle and/or lower rectum pMMR T3, T4, and/or N+
• Resectable synchronous liver metastases

Exclusion Criteria:

• Minor under the age of 18.
• Presence of extrahepatic metastases
• Induction chemotherapy with FOLFIRINOX of less than 2 courses

Patients with mid/lower rectal cancer with resectable synchronous liver metastases, treated with FOLFIRINOX induction chemotherapy