Locally Advanced Pancreatic Adenocarcinoma (LAPC)

At initial diagnosis, 30% of patients with pancreatic adenocarcinoma present with locally advanced tumour (LAPC).12The goals of treatment are to reduce symptoms and prolong life. Treatment recommendation depends on the patients performance status. Patients with poor performance status would not benefit from aggressive therapy. The following discussion is meant for patients with good performance status.

Chemotherapy versus Chemoradiotherapy

There are differing treatment recommendations. Both NCCN and ESMO guidelines recommend systemic chemotherapy alone, although NCCN does endorse chemoradiotherapy following a course of systemic chemotherapy in selected patients. PEBC, CCO prefers chemoradiotherapy whilst JPS lists chemoradiotherapy as an option.

The utility of adding radiotherapy to chemotherapy is debatable. Two chemoradiotherapy strategies have been employed: 1) upfront chemoradiotherapy and 2) chemoradiotherapy following chemotherapy.

Upfront Chemoradiotherapy

Two recent studies have evaluated the role of upfront chemoradiotherapy in this setting with differing conclusions. Both studies were however terminated early. ECOG 4201 compared gemcitabine alone versus gemcitabine with radiotherapy in patients with LAPC. Despite poor accrual and early termination, median OS of patients who received radiotherapy was longer (9.2 months vs 11.1 months, P = 0.017). This study however lacks statistical robustness as the confi dence interval of survival between the 2 arms overlap.13

The FFCD-SFRO study randomised 119 patients to receive either gemcitabine alone or intensive chemoradiotherapy with 5-FU plus cisplatin followed by maintenance gemcitabine. This study demonstrated a superior OS at 1 year for gemcitabine alone compared to chemoradiotherapy (53% vs 32%, HR = 0.54; 95% CI, 0.31 to 0.96; P = 0.006). This study was stopped early as interim analysis showed a lower survival rate in combination arm attributable to increased severe toxicities.14

Taken together, upfront chemoradiotherapy in patients with LAPC is controversial. Use of upfront chemoradiotherapy however, can be considered in selected cases, for example in patients with poor pain control.

Chemoradiotherapy Following Chemotherapy

The LAP 07 trial attempted to evaluate the additional benefi t of chemoradiotherapy after a course of chemotherapy. Preliminary analyses have been presented in abstract form. LAPC patients were first randomised to gemcitabine or gemcitabine plus erlotinib. Patients with controlled disease after 4 months of chemotherapy were then randomised to 2 additional months of chemotherapy or chemoradiotherapy amounting to 54 Gy and concurrent capecitabine. Administration of chemoradiotherapy in patients with LAPC controlled with induction chemotherapy was not superior to continuing chemotherapy alone in terms of overall survival. The OS was not signifi cantly different between the 2 arms (15.2 vs 16.5 months, P = 0.8). Even though the OS was not improved in the chemoradiotherapy arm, patients with non-progressive LAPC after 4 months of induction chemotherapy had a longer time without treatment in the chemoradiotherapy arm (159 vs 96 days, respectively, P = 0.05) with signifi cantly less local tumour progression (34% vs 65%, P <0.0001).15

Choice of Chemotherapy

Choice of chemotherapy used in patients with LAPC mirrors the options of systemic chemotherapy in the metastatic setting.

Recommendations for LAPC

1. Chemotherapy alone or fluoropyrimidine-based chemoradiotherapy are reasonable options.

2. Chemotherapy regimens recommended as per metastatic setting.

3. Upfront chemoradiotherapy can be considered for patients with poorly controlled pain from local disease.

4. Participation in clinical trials recommended if available.