[Comment] Tumor debulking in combination with chemotherapy in multiorgan metastatic colorectal cancer: the ORCHESTRA randomized clinical trial
Abstract
Importance Local therapy, including surgery, radiation, and ablation, is increasingly used in patients with multiorgan metastatic colorectal cancer (mCRC). However, prospective evidence for a survival benefit of tumor debulking is lacking. Objective To investigate whether tumor debulking added to palliative chemotherapy improves survival of patients with multiorgan mCRC. Design, Setting, and Participants This investigator-initiated, open-label, multicenter, randomized clinical trial enrolled patients with multiorgan mCRC between May 2013 and May 2023. The last date of follow-up was April 4, 2024. Patients were enrolled in 27 hospitals in the Netherlands and 1 in the UK. Adult patients with multiorgan mCRC were considered eligible if more than 80% tumor debulking was deemed feasible by resection, radiotherapy, and/or thermal ablation prior to starting first-line palliative chemotherapy. Interventions After achieving objective tumor response or stable disease after 3 cycles of capecitabine and oxaliplatin or 4 cycles of 5-fluorouracil and oxaliplatin with or without bevacizumab, patients were randomized 1:1 to receive chemotherapy alone (standard care group) or tumor debulking followed by chemotherapy. Main Outcomes and Measures The primary end point was overall survival. Secondary end points included progression-free survival and serious adverse events. These outcomes were analyzed in the intention-to-treat population, applicable from randomization. A prespecified interim analysis performed after the initial 100 participants were enrolled revealed that the trial was both safe and feasible to proceed. Results A total of 382 of 454 enrolled patients were randomized: 192 in the chemotherapy alone group (133[69%] male) and 190 in the chemotherapy plus tumor debulking group (127[67%] male). The median age was 64 years in both groups. After a median follow-up of 32.3 months, median overall survival in the chemotherapy alone group was 27.5 months vs 30.0 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.88 [95% CI, 0.70-1.10]; P=0.26). Median progression-free survival in the chemotherapy alone group was 10.4 months vs 10.5 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.83 [95% CI, 0.67-1.02]; P=0.08). More patients in the chemotherapy plus tumor debulking vs chemotherapy alone group had any serious adverse events (101 [53%] vs. 74[39%]; P=0.006). Conclusions and Relevance Tumor debulking in addition to first-line palliative systemic treatment failed to improve overall survival compared with systemic treatment alone for patients with multiorgan mCRC and should not be considered standard care.
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BibTeX
@article{rongxin2026comment,
title = {{[Comment] Tumor debulking in combination with chemotherapy in multiorgan metastatic colorectal cancer: the ORCHESTRA randomized clinical trial}},
author = {Zhang Rongxin},
journal = {结直肠肛门外科},
year = {2026},
month = aug,
doi = {10.19668/j.cnki.issn1674-0491.2026.04.013},
url = {https://doi.org/10.19668/j.cnki.issn1674-0491.2026.04.013},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - [Comment] Tumor debulking in combination with chemotherapy in multiorgan metastatic colorectal cancer: the ORCHESTRA randomized clinical trial
AU - Zhang Rongxin
PY - 2026
DA - 2026/08/01
JO - 结直肠肛门外科
DO - 10.19668/j.cnki.issn1674-0491.2026.04.013
UR - https://doi.org/10.19668/j.cnki.issn1674-0491.2026.04.013
AB - Importance Local therapy, including surgery, radiation, and ablation, is increasingly used in patients with multiorgan metastatic colorectal cancer (mCRC). However, prospective evidence for a survival benefit of tumor debulking is lacking. Objective To investigate whether tumor debulking added to palliative chemotherapy improves survival of patients with multiorgan mCRC. Design, Setting, and Participants This investigator-initiated, open-label, multicenter, randomized clinical trial enrolled patients with multiorgan mCRC between May 2013 and May 2023. The last date of follow-up was April 4, 2024. Patients were enrolled in 27 hospitals in the Netherlands and 1 in the UK. Adult patients with multiorgan mCRC were considered eligible if more than 80% tumor debulking was deemed feasible by resection, radiotherapy, and/or thermal ablation prior to starting first-line palliative chemotherapy. Interventions After achieving objective tumor response or stable disease after 3 cycles of capecitabine and oxaliplatin or 4 cycles of 5-fluorouracil and oxaliplatin with or without bevacizumab, patients were randomized 1:1 to receive chemotherapy alone (standard care group) or tumor debulking followed by chemotherapy. Main Outcomes and Measures The primary end point was overall survival. Secondary end points included progression-free survival and serious adverse events. These outcomes were analyzed in the intention-to-treat population, applicable from randomization. A prespecified interim analysis performed after the initial 100 participants were enrolled revealed that the trial was both safe and feasible to proceed. Results A total of 382 of 454 enrolled patients were randomized: 192 in the chemotherapy alone group (133[69%] male) and 190 in the chemotherapy plus tumor debulking group (127[67%] male). The median age was 64 years in both groups. After a median follow-up of 32.3 months, median overall survival in the chemotherapy alone group was 27.5 months vs 30.0 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.88 [95% CI, 0.70-1.10]; P=0.26). Median progression-free survival in the chemotherapy alone group was 10.4 months vs 10.5 months in the chemotherapy plus tumor debulking group (adjusted hazard ratio, 0.83 [95% CI, 0.67-1.02]; P=0.08). More patients in the chemotherapy plus tumor debulking vs chemotherapy alone group had any serious adverse events (101 [53%] vs. 74[39%]; P=0.006). Conclusions and Relevance Tumor debulking in addition to first-line palliative systemic treatment failed to improve overall survival compared with systemic treatment alone for patients with multiorgan mCRC and should not be considered standard care.
SN - 1674-0491
ER -