Neoadjuvant Chemoradiotherapy Does Not Improve HRQOL in Esophageal Cancer

In results from the phase III CROSS trial reported in theJournal of Clinical Oncology,¹neoadjuvant chemoradiotherapy (nCRT) failed to lower postoperative health-related quality of life (HRQOL) compared with surgery alone for patients with esophageal or junctional cancer.

Cancer-specific 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 prior to treatment initiation and at 3, 6, 9, and 12 months postsurgery. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were predefined primary endpoints.

“Although HRQOL declined immediately after nCRT, no effect of nCRT according to CROSS was apparent on postoperative short-term HRQOL compared with surgery alone,” first author Bo Jan Noordman, MD, Department of Surgery, Erasmus MC—University Medical Center, and coauthors wrote. “In addition to the earlier described improvement in long-term overall and disease-free survival, these results support the view that nCRT according to this effective regimen should be regarded as a standard of care for patients with locally advanced resectable esophageal or esophagogastric junctional cancer.”

Scores for PF, EA, global QOL (GQOL), fatigue, and emotional problems (EM) deteriorated 1 week after nCRT, but most eventually returned to baseline levels. Only PF and fatigue scores remained low 1 year after surgery.

A total of 363 patients were included in this analysis. From March 2004 to 2008, patients with clinically resectable, clinical stage T1N1M0 or T2-3N0-1M0 cancer of the esophagus or esophagogastric junction enrolled in CROSS at 8 participating medical centers in the Netherlands. Patients were randomly assigned to surgery plus nCRT (n = 180) or surgery alone (n = 188).²

Patients in the nCRT group were treated with weekly administration of 5 cycles of IV carboplatin (AUC 2 mg/mL per minute) and 50 mg/m2 of paclitaxel for 23 days along with 41.4 Gy of concurrent radiotherapy administered in 23 fractions of 1.8 Gy on 5 days per week, followed by surgery.

Of 171 patients who received any nCRT, 162 (95%) completed the entire treatment regimen.

After a median follow-up for surviving patients of 84.1 months (range, 61.1-116.8; IQR, 70.7-96.6), median overall survival was 48.6 months (95% CI, 32.1-65.1) in the neoadjuvant chemoradiotherapy plus surgery group and 24.0 months (14.2-33.7) in the surgery alone group (HR, 0.68; 95% CI, 0.53-0.88;P= .003).

Cohen’s d (CD) effect sizes were calculated to give an indication of the clinical relevance of effects and to enable standardized comparison between results from different outcome variables.

Baseline PF levels and all changes over time were comparable between groups. PF declined at 3 months postsurgery (—18;P<.001; CD, —1.00; 95% CI, &ndash;1.14 to &ndash;0.86) but improved from 3 to 6 months (+5;P<.001; CD, 0.30; 95% CI, 0.18-0.41). Improvement in PF continued after that point, but the results were no longer considered statistically significant and baseline levels were not reached during follow-up.

Investigators found no statistically significant differences in EA at baseline and changes over time were comparable between the nCRT and surgery groups. EA declined at 3 months in both groups (+8;P<.001; CD, 0.32; 95% CI, 0.15-0.50), but improved from 3 to 6 months (—9;P<.001; CD, —0.32; 95% CI, &ndash;0.44 to &ndash;0.20) and from 6 to 9 months (+5;P= .001; CD, —0.22; 95% CI, &ndash;0.34 to &ndash;0.09). EA levels returned to baseline by 6 months (P= .98) and plateaued. Investigators found no further improvement after 12 months of follow-up compared with baseline levels (P= .01).

GQOL and EM scores declined by 3 months. GQOL scores returned to baseline by 9 months and EM scores did so by 6 months. FA scores had a similar drop at 3 months but improved from 3 to 6 months (—8;P<.001; CD, —0.34; 95% CI, &ndash;0.46 to &ndash;0.22) and remained stable from 6 to 9 months (P= .04) and from 9 to 12 months (P = .58). However, fatigue scores did not return to baseline levels (+10;P<.001; CD, 0.52; 95% CI, 0.38-0.65).

References:

1. Noordman BJ, Verdam MGE, Lagarde SM, et al. Effect of neoadjuvant chemoradiotherapy on health-related quality of life in esophageal or junctional cancer: results from the randomized CROSS trial.J Clin Oncol.
2. Shaprio J, van Lanscot JB, Hulshof, MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;16(9):1090-1098.doi: 10.1016/S1470-2045(15)00040-6.