Maximal Tumor Debulking With Systemic Therapy Does Not Impact QoL in mCRC


While a notable difference in the occurrence of adverse events was seen between patients treated with maximal tumor debulking and standard systemic therapy vs systemic therapy alone, health-related quality-of-life and fatigue scales showed no substantial differences over time.

Colorectal cancer, medical illustration.3d illustration: © Anatomy Insider -

Colorectal cancer, medical illustration.3d illustration: © Anatomy Insider -

The addition of maximal tumor debulking to standard systemic therapy did not significantly impact the overall quality-of-life (QoL) for patients with metastatic colorectal cancer (mCRC) compared with systemic therapy alone, according to findings from a prespecified exploratory analysis of the ORCHESTRA trial (NCT01792934).1

Among the 300 patients randomized to the standard arm (n = 152) and intervention arm (n = 148), significant adverse events (AEs) were observed in 21% of patients vs 43% of patients, and the difference in the proportion of patients who encountered serious AEs between the study arms was statistically significant (P ≤.001).2

For the health-related quality of life (HRQol) analysis, there were no statistically or clinically relevant differences seen between study arms over time for all preselected HRQoL and fatigue scales. In the standard arm vs intervention arm, the overall mean differences in scores were -3.1 (95% CI, -6.21-0.04); global health status, -2.9 (95% CI, -7.81-1.97); physical functioning, -3.5 (95% CI, -7.45-0.40); emotional functioning, +1.0 (95% CI, -3.50-5.52); general fatigue, +0.9 (95% CI, -0.21-1.96); and physical fatigue, +0.8 (95% CI, -0.37-1.89).

“This could mean that the negative impact of complications on quality of life is temporary and eventually balances out with a decrease in tumor-related symptoms after treatment. Patients might also adapt their HRQoL perceptions during the course of their disease and treatment.” explained lead author Lotte Bakkerus, MD, Radboud Institute for Health Sciences, the Netherlands, in a press release.1

In the ongoing ORCHESTRA trial, investigators are assessing standard palliative chemotherapy alone vs palliative chemotherapy plus either surgery, ablative therapy, and/or radiotherapy to reduce tumor burden. A total of 300 patients were randomized to receive standard care or additional intervention.

Patients were eligible for enrollment if they have had clinical benefit after 3 or 4 cycles of first-line palliative systemic therapy with fluoropyrimidines and oxaliplatin with or without bevacizumab (Avastin). These patients then were randomized to receive maximal tumor debulking followed by systemic therapy vs systemic therapy alone. Patients must have had multiorgan mCRC, and 80% debulking was deemed feasible.2

To enroll in the study, patients were required to complete the EORTC QoL Questionnaire-Core 30 and the Multidimensional Fatigue Inventory questionnaire at prespecified time points during treatment. Results from a preplanned exploratory secondary end point of HRQoL from the ORCHESTRA trial were focused on in the study. This was measured using the EORTC QOL Questionnaire-Core 30 and the Multidimensional Fatigue Inventory questionnaire at pre-specified time points during treatment.

Additional findings from the 300 patients showed that across study arms, HRQoL after 1 year of treatment did not significantly differ from HRQoL at the time of randomization. In the intervention arm, patients had serious AEs twice as often as patients in the standard arm.

Further, in patients with multiorgan mCRC, the combination of maximal tumor debulking with palliative systemic therapy was significantly associated with more serious AEs which occurred because of local therapy. However, there was no difference in HRQoL vs palliative systemic therapy alone, showing a lack of association between the occurrence of serious AEs and impact on HRQoL.

“Given the considerable amount of complications from local treatment, we had expected to see a bigger impact on overall and persistent quality of life in the experimental group. The fact that local therapy associated serious [adverse] effects did not translate to a noticeable dip in the patients' perceived quality of life is quite intriguing and warrants further exploration. These results, including the risk of complications, should be taken into account in the consultation room in order to decide, together with the patient, what the right treatment choice is for each individual,” added Bakkerus, in a press release.1

1. More aggressive treatment doesn’t impact quality of life for metastatic colorectal cancer patients, according to new study in JNCCN. News release. National Comprehensive Cancer Center. October 12, 2023. Accessed October 16, 2023.
2. Bakkerus L, Buffart LM, Buffart TE, et al. Health-related quality of life in patients with metastatic colorectal cancer undergoing systemic therapy with or without maximal tumor debulking. J Natl Compr Canc Netw. 2023;21(10):1059-1066.e5. doi:10.6004/jnccn.2023.7050
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