Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials

Doppenberg, D.; Dam, J.L. van; Han, Y.; Bonsing, B.A.; Busch, O.R.; Festen, S.; ... ; Dutch Pancreatic Canc Grp (2023)

Article / Letter to editor

In two RCTs, comparing neoadjuvant chemoradiotherapy (CRT) with upfront surgery in patients with resectable and borderline resectable pancreatic cancers, CRT was associated with better survival. There was no difference in treatment effect between patients with a baseline CA19-9 level higher or lower than 500 units/ml, meaning that neoadjuvant CRT should not be withheld because of a low CA19-9 concentration.Background Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. Methods In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. Results Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). Conclusion Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.

• All authors: Doppenberg, D.; Dam, J.L. van; Han, Y.; Bonsing, B.A.; Busch, O.R.; Festen, S.; Harst, E. van der; Hingh, I.H. de; Homs, M.Y.; Kwon, W.; Lee, M.; Lips, D.J.; Meijer, V.E. de; Molenaar, I.Q.; Nuyttens, J.J.; Patijn, G.A.; Roessel, S. van; Schelling, G.P. van der; Suker, M.; Versteijne, E.; Vos-Geelen, J. de; Wilmink, J.W.; Eijck, C.H.J. van; Tienhoven, G. van; Jang, J.Y.; Besselink, M.G.; Koerkamp, B.G.; Dutch Pancreatic Canc Grp
• Date: 2023-07-13
• Journal: British Journal of Surgery
• Volume: 110
• Issue: 10
• Pages: 1374 - 1380
• DOI: doi:10.1093/bjs/znad210
• Link: https://academic.oup.com/bjs/article/110/10/1374/7223793