Preoperative CAPOX-Bevacizumab Edges Ahead in Resectable Colorectal Liver Metastases
Perioperative chemotherapy remains central to the management of resectable colorectal liver metastases, yet the sequence of treatment has never been settled with real confidence. HiSCO-01 addressed that gap by comparing eight cycles of CAPOX plus bevacizumab given before surgery with the same regimen delivered after resection. The trial’s primary endpoint, treatment compliance rate, was built around a practical question every hepatobiliary team recognizes: can patients complete enough systemic therapy and still reach an R0 resection?
The answer leaned toward the preoperative strategy.
Among 81 enrolled patients, 76 were eligible for analysis. The treatment compliance rate reached 89.2% in the preoperative arm and 71.8% in the postoperative arm, a numerical difference that fell just short of conventional statistical significance with a p value of 0.06. Even without crossing that threshold, the direction of effect matters clinically. When chemotherapy is delivered before hepatectomy, the full planned regimen can be administered while the patient is still strongest, before surgical recovery, postoperative fatigue, adhesions, or complications interfere with treatment delivery.
Treatment Delivery Shaped the Trial Result More Than Toxicity
The trial did not show a major toxicity penalty for moving CAPOX-bevacizumab ahead of surgery. Grade 3 or higher chemotherapy-related adverse events occurred at similar rates in both groups, which is important because the hesitation around neoadjuvant treatment in resectable liver metastases often centers on fears of overtreatment, cumulative toxicity, or loss of operability. Those concerns were not borne out here.
In practical terms, preoperative treatment may act as a biologic and logistical filter. Systemic therapy can expose aggressive micrometastatic disease earlier, while also giving clinicians a window to assess tumor biology before committing to hepatectomy. Patients who tolerate and respond to preoperative therapy may be the very group most likely to benefit from definitive local treatment. Surgery after systemic therapy also avoids one of the most common failure points in perioperative oncology: the patient who is fit enough for resection but never recovers enough to resume chemotherapy afterward.
That sequence problem is not trivial. Once major abdominal surgery is completed, postoperative pain, infectious complications, delayed oral intake, and reduced performance status can all disrupt planned adjuvant therapy, especially in a treatment program that depends on eight cycles of CAPOX-bevacizumab.
Postoperative Safety Was Similar, Except for Biliary Fistula
Surgical complications were broadly comparable between the two arms, with one clear exception: biliary fistula occurred more often in the postoperative chemotherapy group. The trial summary does not supply the absolute fistula rate, so the safest reading is the one the data allow — a signal emerged, and it favored the preoperative arm.
For hepatobiliary surgeons, that finding deserves attention because bile leak and biliary fistula can prolong hospitalization, delay systemic therapy, and compound postoperative morbidity. A complication in this setting is not just a surgical event; it can interrupt the entire multimodal sequence. Even a modest increase in biliary leakage could reverberate through recovery and make it harder to keep patients on schedule for chemotherapy, which is one plausible reason the postoperative strategy lagged in treatment compliance.
Bevacizumab complicates perioperative planning because of its vascular effects, but this study did not show a broad safety collapse. The overall incidence of chemotherapy-related grade 3 or higher adverse events remained similar in both groups, suggesting that the regimen can be integrated around surgery with appropriate timing and multidisciplinary coordination.
Survival Signals Remained Comparable in This Phase II Trial
Long-term outcomes did not separate cleanly between the two sequences. The 3-year progression-free survival rate was 32.2% in the preoperative group and 38.5% in the postoperative group. Five-year overall survival was 60.5% with preoperative therapy and 57.2% with postoperative therapy. Those numbers do not establish superiority for either strategy, and the trial was not designed to answer a definitive survival question.
Still, the survival data are clinically useful because they reduce concern that delivering chemotherapy first somehow compromises the chance of durable control. The absence of a survival disadvantage, paired with better compliance in the preoperative arm, strengthens the argument that upfront systemic therapy is at least a credible alternative to postoperative delivery in carefully selected patients with resectable CRLM.
Why Preoperative Therapy May Fit the Biology of Resectable CRLM
The biology of colorectal liver metastases supports the logic of earlier systemic therapy. Micrometastatic disease often accompanies apparently resectable lesions, and surgery alone cannot address occult dissemination. Preoperative CAPOX-bevacizumab can begin that systemic control immediately, while the primary lesion is still in place and before surgical stress alters immune and inflammatory signaling. In a disease where recurrence risk remains substantial even after technically complete resection, treatment sequence is not a cosmetic choice; it is a way of deciding when to strike the microscopic disease burden.
Bevacizumab adds a second layer of rationale. By targeting tumor angiogenesis, it can suppress vascular support for metastatic deposits and may enhance the effectiveness of cytotoxic chemotherapy. CAPOX brings a familiar oxaliplatin-based backbone that fits existing guideline-based perioperative practice. The study therefore tested a regimen already grounded in standard oncology, not an experimental detour.
A Practical Message for Hepatobiliary Teams
The most actionable signal from HiSCO-01 is not a dramatic survival split. It is the better completion of the planned multimodal program when CAPOX-bevacizumab is delivered before surgery. For a patient with resectable colorectal liver metastases, the chance to receive at least six cycles and still proceed to R0 resection is a meaningful endpoint because it reflects both disease control and real-world feasibility.
This phase II study leaves several issues unresolved. The sample size was modest, the treatment compliance difference did not reach conventional statistical significance, and the survival estimates remain exploratory rather than practice-defining. Even so, the regimen was safely administered in both sequences, and the preoperative arm produced a numerically higher compliance rate with no clear toxicity penalty. Future confirmatory trials will need to determine whether that advantage translates into a reproducible benefit in recurrence control and whether specific surgical subgroups are more vulnerable to biliary complications when chemotherapy is delayed until after hepatectomy.