Table 2.
Future directions on the management of locally advanced pancreatic cancer.
| Subject | Current Evidence | Future Directions |
|---|---|---|
| Chemotherapy | Promising results are reported for the use of FOLFIRINOX and gemcitabine-nab-paclitaxel as induction treatment of LAPC. It currently remains unknown which of the two regimen is superior as first-line treatment of LAPC. | The results of the ongoing NEOLAP study will assess the superiority of either FOLFIRINOX or gemcitabine-nab-paclitaxel as induction treatment for LAPC. |
| There currently is no consensus on the optimal duration of induction treatment of LAPC. Some centers advocate two months treatment duration, whereas other centers routinely treat patients for four months. This also accounts for the use of adjuvant chemotherapy after initial induction treatment | Future studies should also determine the optimal duration of induction chemotherapy and added value of adjuvant chemotherapy for LAPC after resection. | |
| Response evaluation | Current imaging modalities often underestimate the response of LAPC to induction chemotherapy, as they cannot distinguish fibrosis from vital tumor tissue. Biomarkers may aid in selecting patients with good overall response to chemotherapy but lack specificity. | New response evaluation criteria and/or imaging modalities are required to more accurately determine resectability after induction chemotherapy. |
| The added value of biomarkers to predict response to induction chemotherapy should be established in future studies. | ||
| Surgery | Current evidence on resection of LAPC after induction chemotherapy is promising, but randomized trials confirming the additional value of surgery after chemotherapy are lacking. | Future randomized trials should establish the added value of surgery compared with that of chemotherapy alone in LAPC. |
| Because of the lack of accuracy of current imaging modalities to predict resectability of LAPC, several centers advocate routine surgical exploration in patients with at least stable disease after induction chemotherapy. | The optimal selection criteria for surgical exploration of LAPC after induction chemotherapy should be established. | |
| Neoadjuvant radiotherapy | Some centers perform routine SBRT of LAPC prior to surgical exploration after induction chemotherapy to improve the chance of a radical resection, decrease local recurrence, and improve OS. The added value of this approach has not yet been determined. | The added value of SBRT prior to surgical exploration should be compared with that of chemotherapy alone in patients with LAPC undergoing surgical exploration after induction chemotherapy. |
| Ablative therapies | Local ablative therapies are considered in some centers in patients with persistent LAPC after induction chemotherapy. Randomized trials to determine the added value of ablative therapies to chemotherapy-alone are lacking. | The results of the currently ongoing PELICAN trial will assess the added value of RFA to chemotherapy-alone. |
| Currently there are no completed trials comparing multiple ablative modalities. Therefore, the superiority of either technique (IRE, RFA, SBRT) remains unknown. | The ongoing CROSSFIRE trial will determine the superiority of either IRE or SABR in patients with LAPC after induction chemotherapy. Future comparative studies are needed to determine the most effective local ablative treatment in LAPC. | |
| There is increasing evidence that local ablative therapies can induce a systemic anti-tumor response (i.e., abscopal effect). It is suggested to combine local treatment with immunotherapy to both increase local-and distant disease control | Future studies should focus on combining local ablative therapy with (systemic) immunotherapy. |
LAPC: locally advanced pancreatic cancer; IRE: irreversible electroporation; RFA: radiofrequency ablation; SBRT: stereotactic body radiation therapy; SABR: stereotactic ablative radiotherapy.