Prognostic significance of neoadjuvant gemcitabine and S-1 chemotherapy with or without concurrent radiation in patients with resectable and borderline resectable pancreatic cancer: A post hoc analysis of 2 phase II trials.

BACKGROUND

It is important to clarify which neoadjuvant therapy yields a better prognosis for patients with resectable or borderline resectable pancreatic cancer: chemotherapy or chemoradiotherapy.

METHOD: We have performed 2 multicenter phase II trials to evaluate the prognostic significance of preoperative therapy: in the first, we examined preoperative chemoradiotherapy, gemcitabine and S-1 with concurrent radiation (n = 63), and in the second we examined preoperative chemotherapy with gemcitabine and S-1 (n = 46). We tried to examine the additive prognostic impact of radiation therapy by analyzing the results of different phase II trials using the same chemotherapy agents. In addition, we performed propensity score matching to minimize the patient bias in each group and reanalyzed the prognostic significance of preoperative radiation therapy.

RESULTS

CA19-9 values and tumor size reduction percentage were significantly higher in the gemcitabine and S-1 with concurrent radiation group than in the gemcitabine and S-1 group. The 5-year overall survival rate in the gemcitabine and S-1 with concurrent radiation group was 40.8% and the progression-free survival rate was 32.7%, both significantly better than in the gemcitabine and S-1 group (25.2%, P = .043, and 20.3%, P = .022, respectively). The incidence of local recurrence with gemcitabine and S-1 with concurrent radiation was significantly lower than with gemcitabine and S-1 only (P < .001), but the incidence of distant recurrence did not differ between the 2 groups (P = .369), indicating that the better survival with gemcitabine and S-1 with concurrent radiation might arise from a powerful local antitumor effect of radiation. The number of severe adverse events and surgical complications did not differ significantly between the 2 groups. After propensity score matching, patients in the gemcitabine and S-1 with concurrent radiation group (n = 39) still showed significantly better overall survival and progression-free survival (P = .007, .018) with lower incidence of local recurrence (P = .002).

CONCLUSION

Although this study was a retrospective post hoc analysis of 2 phase II trials, which represents a major limitation, neoadjuvant chemotherapy with concurrent radiotherapy possibly improve survival compared with chemotherapy alone by suppressing local recurrence through a powerful local antitumor effect of radiation.