To date, little is known about the feasibility and survival outcome of patients who undergo surgery for synchronously hepatic metastasized PDACs. To the best of our knowledge, this is the first study to compare survival of patients after extended surgery for synchronous hepatic metastases (M1surg) to patients with localized disease (M0).
Taking the revised 8th edition TNM staging system into account with inclusion of lymphatic, perineural, and venous infiltration, our data demonstrated that patients with isolated synchronous hepatic metastases showed a similar overall survival in multivariate analysis compared to patients with localized disease (Group M1surg vs. M0). Length of hospitalization, morbidity and mortality rates did not show any statistical difference between the two groups.
Improved survival outcome by curative surgery, especially in regard to long-term outcome, has never been adequately studied in patients with limited and isolated synchronous hepatic metastases of PDAC. To date, surgery in these cases is not recommended in any current guideline. Therefore, this treatment strategy is only applied in highly selected patients (11, 12). However, for colorectal liver metastases, surgery remains the gold standard of care. Moreover, it has been proven to be oncologically beneficial, to prolong survival, and to improve the quality of life (13, 14). Furthermore, surgical therapy is also widely accepted for hepatic metastases of pancreatic neuroendocrine tumors (15). In PDAC with oligometastatic disease, however, only limited evidence is available.
It is clear that the decision for a surgical approach is made after subjective reflection of the surgeon. To date, pancreatic resections with synchronous metastasectomies of the liver are rarely performed only in high-volume centers with adequate experience (16). Thus, to date, only case reports and a limited number of larger case series exist. In previous literature, patients with surgically resected synchronously metastasized PDACs were mostly correlated to patients who were treated in palliative intent (16–20).
In two recent studies, a larger number of patients with synchronously hepatic metastasized PDACs were analyzed (16, 18). Six European pancreatic centers retrospectively reported on 69 patients diagnosed with synchronously hepatic metastasized PDACs, who received simultaneous pancreatic and liver resections (18). Patients treated in palliative intent served as a control group. A significant benefit for survival was achieved for patients undergoing this extensive surgical approach with tolerable rates of morbidity and mortality compared to patients who only received an exploration (14.5 vs. 7.5 months respectively; p < 0.001). In a large single-center study from Heidelberg, analogous
results were reported (16). No study compared the survival outcome after synchronously oligometastatic resection to patients with localized PDACs (M0). Our results clearly showed for the first time a survival benefit after surgery for M1 PDACs, as survival outcome was similar in patients with localized disease (M0).
However, our study has several limitations including different applied adjuvant treatment regimes. FOLFIRNOX for a multimodal treatment setting was applied in 22.8% of all M1surg and only 8.1% of all M0 patients. An intensified gemcitabine/cisplatin based adjuvant radiochemotherapy was again only administered in M1surg patients. Presumably, this might have influenced the benefit in survival outcome in M1surg patients. Considering the limited number of patients in group M1surg with FOLFIRINOX as a multimodal treatment concept, further studies are warranted to analyze the oncological benefit of this interdisciplinary therapeutic approach and foremost the setting of multimodality (9, 21).