Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial

Abstract

To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and MethodsPatients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and -Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24). ResultsA total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen's d: 20.93, P , .001; 0.47, P , .001; 20.84, P , .001; 1.45, P , .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen's d: 21.00, 0.33, 20.47, 20.34, and 0.33, respectively; all P , .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen's d: 0.52 and 20.53, respectively; both P , .001). ConclusionAlthough HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study-regimen can be regarded as a standard of care.

Patients' preferences for treatment after neoadjuvant chemoradiotherapy for oesophageal cancer

“…This phenomenon has been described to a lesser extent in patients with prostate cancer 16,33 . The high postoperative morbidity and mortality rates associated with oesophagectomy, and the lasting impact of such surgery on patients' HRQoL likely underlie the substantial loss of life expectancy that patients are willing to trade off 3,11,12 . For clinicians, who tend to focus on long-term survival outcomes, it is important to realize that patients and physicians may differ in their trade-offs between different treatment options 15 -17,25,34,35 . The present findings may help patients and clinicians choose between active surveillance and oesophagectomy.…”

“…Relevant attributes that might influence the choice of oesophagectomy versus active surveillance after nCRT and the attribute levels were chosen based on information in the literature, and consensus discussion with two upper gastrointestinal surgeons and five patients who underwent nCRT followed by surgical resection. Attributes were 5‐year overall survival, short‐term HRQoL (3 months after treatment), long‐term HRQoL (more than 1 year after treatment), the risk that oesophagectomy is still necessary, and the average number of surveillance examinations per year involving endoscopy and PET–CT necessary for 5 years of follow‐up after treatment ( Table ).…”

Changes in gut hormones, glycaemic response and symptoms after oesophagectomy

“…The CROSS study established a modern benchmark, achieving a 47 per cent 5‐year survival rate among patients with locally advanced disease treated with multimodal therapy. With such welcome advances with respect to oncological outcome, there is increasingly a focus on functional recovery and health‐related quality of life (HR‐QoL) in survivorship, as the attritional impact of oesophagectomy is widely appreciated.…”

Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial)

“…Neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection improves long‐term survival compared with surgery alone, but may be associated with deterioration of HRQoL during and after treatment. None of the previous RCTs or meta‐analyses have been able to show any statistically significant survival difference between nCT and nCRT, making HRQoL outcomes even more important with regard to choice of neoadjuvant treatment.…”