Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial

Abstract

Background As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored. Patients and Methods Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS–HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm. Results Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue [mean difference (MD) + 14, p = 0.001], loss of appetite (MD + 15, p = 0.003), hair loss (MD + 18, p < 0.001), and loss of taste (MD + 27, p < 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively. Conclusions In patients with resectable CPM randomized to perioperative systemic therapy or CRS–HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial’s previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.

Consensus Guideline for the Management of Colorectal Cancer with Peritoneal Metastases

“…In the phase II component of the CAIRO6 trial, half of the patients declined trial participation due to concerns about systemic therapy’s toxic effects and cancer becoming unresectable during neoadjuvant therapy. Despite this, all patients in the neoadjuvant arm proceeded to surgery, with comparable patient-reported outcomes between the study arms (perioperative systemic therapy with CRS-HIPEC and CRS-HIPEC alone) [37, 66]. Results of the phase III trial of CAIRO 6 are pending and may help address uncertainties surrounding upfront CRS.…”

ASO Author Reflections: Patient-Reported Outcomes of the CAIRO6 Phase II Trial

“…However, all of these (except loss of appetite) returned to baseline scores at 3 or 6 months after CRS/HIPEC. 4 As this is the first published comparison of PROs in this setting, the present study provides relevant insight into the burden of perioperative systemic therapy for patients with resectable CPM. The previously published CAIRO6 phase II trial report suggested that perioperative systemic therapy in this setting is feasible, well tolerated, and able to induce relevant response of CPM.…”

“…As part of the phase II trial, patient-reported outcomes (PROs) were compared between both treatment groups to evaluate the burden of perioperative systemic therapy in this setting. 4…”