Because the liver is the most frequent site of disease recurrence in patients with advanced pancreatic carcinoma, reducing the incidence of liver metastases may be an effective way of decreasing the likelihood of recurrence and, thus, improving the prognosis of these patients. Unfortunately, only a few studies focusing on the treatment of PCLM have been published. Most of these studies reported single-institution experiences with a wide variety of pancreatic tumor types distributed over a small number of patients.8, 9, 24–27
For instance, during our review of the literature, we identified only 6 studies on PCLM treated by diverse treatment modalities that included more than 10 patients. To our knowledge, the current study is the largest study regarding PCLM performed to date, and the first to investigate prognostic factors for multimodality treatment of this disease.
PCLM has a poor prognosis, with a median survival of ≤6 months.10
In the current study, median survival was 4.73 months and the 1-year overall survival rate was 18.3%. These results are similar to, and in some cases, better than, the findings reported by previous studies. The improvement in our results over those of other researchers may be explained by the fact that our institution employed a multimodality treatment for PCLM.
In the present study, we confirmed several prognostic variables previously identified in advanced pancreatic cancer, such as performance status, ascites, weight loss, and elevated CA19-9 levels.9,28–32
In addition, we also evaluated the effects of treatments on prognosis.
Surgery, whether curative or palliative, is still considered a controversial treatment method for patients with PCLM.33, 34
Gleisner et al.8
reported the treatment outcome of 22 patients with PCLM who underwent simultaneous hepatic and pancreatic resection. In their analysis, the median size of the largest hepatic lesion was 0.6 cm, and in our study, it was 3.3 cm. Accordingly, in Gleisner et al.’s study the median survival after diagnosis of liver metastasis was 5.9 months while it was only 4.7 months in our study. However, the researchers concluded that “even in well selected patients with low-volume metastatic liver disease, simultaneous resection of periampullary or pancreatic carcinoma with synchronous liver metastases did not result in long-term survival in the overwhelming majority of patients.”8
Recently, Müller et al.9
reported 136 cases of advanced pancreatic adenocarcinoma, 71 of which were PCLM, treated by bypass procedures alone. Their multivariate analysis found that American Society of Anesthesiologists score, presence of liver metastasis, pain, CA19-9 level, and CEA level were independent predictors of poor survival. Although an aggressive treatment strategy, such as surgery, may prolong the survival of a select subgroup of these patients, its exact role in the treatment of PCLM requires further evaluation.
Patients who received gemcitabine-based chemotherapy benefited in this series, with a median survival of 5.7 months. However, it must be remembered that patients who received chemotherapy were a select group with better general performance and endurance capacity. Compared with the TACE group, the overall response rate of patients receiving systemic chemotherapy was obvious insignificant. However, we found that the efficacy of TACE was closely associated with the number of treatments received: no remarkable improvement in survival was observed in patients with PCLM who underwent TACE only once.
Because PCLM is an incurable disease, we used only palliative treatment modalities. EBRT of the primary tumor was combined with chemotherapy. In a recent study, Hazard et al.35
found that radiation therapy was associated with improved survival compared with cancer-directed surgery without radiation in 1267 patients with pancreatic adenocarcinoma. HIFU ablation is a noninvasive treatment modality for localized tumors. An ultrasound beam can be focused as it passes through soft tissue, which enables the use of an external ultrasound energy source to induce thermal ablation of a tumor at a depth through the intact skin.36
Unfortunately, we did not find a significant difference in survival between patients treated with EBRT and HIFU, which might be partly due to our small sample population. They should be studied in randomized controlled trials.
It is noteworthy that CHM was determined an important prognostic factor in our analysis. Fu et al.37
previously reported that the QYHJ decoction can inhibit pancreatic cancer cells from proliferating, as well as reverse multidrug resistance expression, when administered in combination with gemcitabine, thereby inhibiting tumor growth both in vitro and in vivo. In our study, we calculated a median survival of 5.4 months and 1-year survival rate of 21.9% for the CHM group, compared with a median survival of 3.9 months and 1-year survival rate of 4.8% for the non-CHM group (P
< .001) ().
In this study, the number of treatment approaches used was found to remarkably affect overall survival during the follow-up period. For instance, patients who were treated 3 or more approaches (including chemotherapy, EBRT, CHM, and HIFU) had a longer median survival time than patients treated with 2 or only 1 approach (median survival: 6.0 vs. 4.5 vs. 2.7 months) (P < .001;). Patients in the ≥3-treatment group had a 1-year survival rate of 26% compared with 10% for those in the 2-treatment group and 4% for those in the 1-treatment group. These findings are of particular interest and are worth of further study.
Certainly, there are several limitations to the present study. Although the clinical data were prospectively collected, the study and analysis are retrospective and therefore subject to an inherent selection bias. The patients with TACE had larger primary tumors and a greater number of hepatic lesions than the medically or surgically treated patients. This is likely because our therapeutic model calls for palliative management and usually recommends TACE for patients with unresectable PCLM. Moreover, CHM is a common complementary therapy in our department, but the course of treatment is always individualized to the patient determined by a given doctor because procedural norms have not yet to be established. Owing to the few and restricted formal protocols available at our institutions, some therapeutic schedules were individualized on an ad hoc basis. Therefore, caution is warranted when interpreting these results; a randomized controlled trial of multimodality treatments using these specific techniques is currently warranted.
In conclusion, to our knowledge, this is the first large study concerning the prognostic factors of patients with PCLM receiving multimodality treatment. KPS, weight loss, ascites and elevated CA19-9 at diagnosis were independent factors indicating a poor prognosis. Chemotherapy and CHM were found to be protective factors. Overall, we conclude that multimodality treatment is well tolerated and may be effective in prolonging the survival of patients with PCLM.