Abstract
Reports on the prognostic role of programmed death-ligand 1 (PD-L1) expression in rectal cancer are controversial. We investigated expression patterns and changes of PD-L1 in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Seventy-two patients diagnosed with rectal cancer and/or treated with fluorouracil-based neoadjuvant CRT at the Department of Internal Medicine III of the Paracelsus Medical University Salzburg (Austria) between January 2003 and October 2012 were included. PD-L1 scoring was performed according to the tumor proportion score (TPS), combined positive score (CPS), and immune cell score (IC). PD-L1 TPS prior to neoadjuvant CRT had a statistically significant impact on survival (median: ≤1%: 95.4 months (95% CI: 51.8—not reached) vs. >1%: not reached, p = 0.03, log-rank). Patients with a PD-L1 TPS ≤1% prior to and after CRT showed an inferior survival compared to all other patients (median: 56.7 months (95% CI: 51.4—not reached) vs. not reached, p = 0.005, log-rank). In multivariate analysis, PD-L1 TPS prior to neoadjuvant CRT (>1% vs. ≤1%, hazard ratio: 0.29 (95% CI: 0.11–0.76), p = 0.01) remained independently associated with survival. In conclusion, low PD-L1 TPS was associated with inferior survival in rectal cancer patients undergoing neoadjuvant CRT. A prospective validation of the prognostic value of PD-L1 expression in rectal cancer patients within a clinical trial is necessitated.
Highlights
The treatment of stage II-III rectal cancer usually consists of neoadjuvant capecitabine or 5-fluorouracil (5-FU)-based long-course chemoradiotherapy (CRT) followed by surgery [1,2]
By investigating three established programmed death-ligand 1 (PD-L1) scores in this retrospective analysis, we found a statistically significant survival benefit for rectal cancer patients with a higher PD-L1 tumor proportion score (TPS) (>1%) compared to patients with a PD-L1 TPS ≤1% prior to neoadjuvant CRT (Figure 3A)
Our findings of a positive prognostic value of higher PD-L1 TPS prior to neoadjuvant CRT are in line with the publication by Chen et al [21], while Chiang et al [19], Hecht et al [18], and Ogura et al [20] did not show a statistically significant association between PD-L1 TPS prior to neoadjuvant CRT and Overall survival (OS)
Summary
The treatment of stage II-III rectal cancer usually consists of neoadjuvant capecitabine or 5-fluorouracil (5-FU)-based long-course chemoradiotherapy (CRT) followed by surgery [1,2]. Despite the application of adjuvant chemotherapy, 32–43% of rectal cancer patients experience a disease relapse within the first six years [3]. Immune checkpoints, such as programmed death-ligand 1 (PD-L1), can be therapeutically targeted, which has led to dramatic clinical improvements in various tumor entities [4,5,6,7,8,9,10,11,12]. The aim of our retrospective single-center analysis was to evaluate PD-L1 expression patterns and time-dependent changes according to three established PD-L1 scores and the impact on clinical outcome in a well-defined rectal cancer cohort undergoing neoadjuvant CRT
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