A Practice-Challenging Result in Liver Metastases: Is Chemotherapy Needed After Surgery?
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Long-term results of postoperative preventive (adjuvant) chemotherapy for colorectal cancer liver metastases have been reported. JCOG0603 shows that, although it delays recurrence, it does not prolong life.
Why Does This Matter?
Colorectal cancer is one of the world's most common cancers, and in a substantial proportion of patients it spreads to the liver (metastasizes). For patients with liver metastases, the gold-standard treatment is surgical removal of the tumor, if possible (hepatectomy). However, the greatest concern after surgery is recurrence. To reduce this risk, we oncologists have tended for years to give postoperative adjuvant, preventive chemotherapy.
However, the question, “Are we doing the right thing by giving every patient chemotherapy?” had long been debated. Unnecessary chemotherapy exposes patients to toxic side effects and reduces their quality of life. The Japanese study whose long-term findings were published on January 21, 2026 in JCO, JCOG0603, now provides a very clear and surprising answer.
Study Design: Who Was Studied, and How?
This was a randomized, controlled Phase II/III study involving patients with colorectal cancer that had metastasized to the liver but whose tumors had been completely removed surgically.
- Group 1 (Surgery + Chemotherapy): Patients who received 12 cycles of mFOLFOX6 chemotherapy after liver surgery (151 patients).
- Group 2 (Surgery Alone): Patients followed without any treatment after surgery (149 patients).
The study's primary endpoint was to measure the time without disease recurrence (DFS). Its secondary and most critical objective was to determine how long patients lived, or overall survival (OS).
Results: A Statistical Paradox
The findings revealed a paradox frequently encountered in oncology: chemotherapy delayed the return of the disease but did not make patients live longer.
Interpretation: Chemotherapy provided a 9.2% advantage in reducing recurrence risk.
KEY FINDING: Patients who underwent surgery alone lived numerically longer, although the difference was not statistically significant!
Why Did This Happen? An In-Depth Analysis
It may seem surprising that a longer disease-free period did not translate into longer survival and even showed a tendency toward shorter survival. The study authors and experts attribute this to several main factors:
| Factor | Explanation |
|---|---|
| 1. Toxicity and Chemotherapy Fatigue | Preventive chemotherapy takes a toll on patients' bodies. When the disease recurs, these patients may be unable to tolerate new, effective treatments. |
| 2. The Opportunity for Treatment After Recurrence | Patients in the surgery-only group responded better to stronger medicines at recurrence because they had not previously received chemotherapy and were treatment-naive. |
| 3. Invisible Liver Damage | Chemotherapy, especially oxaliplatin, can cause fatty changes in liver tissue or disrupt its structure. This may have led to small recurrences being missed on follow-up CT scans. |
The JCOG0603 study once again reminds us of the oncology principle that more treatment does not always mean a better outcome . For a patient whose liver metastases have been removed surgically, rather than reflexively starting intensive chemotherapy immediately, we see that watchful waiting can also be extremely safe and may even be more favorable for survival.
This study tells us: There is no standard treatment; there is individualized treatment. If a patient's tumor has been removed surgically, close monitoring with intervention only if recurrence occurs, rather than burdening the patient with chemotherapy side effects, preserves quality of life without putting overall survival at risk.
In the future, we will use more sensitive technologies such as liquid biopsy (ctDNA) to determine which patients definitely need chemotherapy. Until then, we should be much more selective when deciding on postoperative chemotherapy.
- Kanemitsu Y, et al. Randomized Phase II/III Trial Comparing Hepatectomy Followed by mFOLFOX6 With Hepatectomy Alone for Liver Metastasis From Colorectal Cancer: Long-Term Results of JCOG0603. J Clin Oncol. 2026 Jan 21. doi: 10.1200/JCO-25-01231.
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