In some malignancies, such as colorectal, kidney and lung cancers, there is growing body of evidence that a metastasectomy can improve survival outcomes of selected patients[4-7, 12-14]. For colorectal cancers and kidney cancers, surgical metastasectomy is the treatment of choice in the National Comprehensive Cancer Network (NCCN) guidelines. In non-small-cell lung cancer, Gomez et al. showed local consolidative therapy with radiotherapy or surgery improved both PFS and OS of OM cases. In colorectal cancer, Kobayashi et al. proposed synchronous resection of localized peritoneal metastasis improved survival outocomes.
In PDAC with distant metastases, Tachezy M et al. suggested a survival benefit for undergoing simultaneous pancreas and liver resection. Several prior studies have revealed that the resection of lung and liver metastases prolong prognosis in PDAC[15-17]. Kandel et al. considered oligometastasis can be defined as the status of two or fewer metastatic tumors. Demanakis et al. reported that oligometastasis could be defined as four or fewer metastatic tumors. They insist that patients with limited metastatic status have a chance to get a good prognosis by metastasectomy, even for PDACs.
Another standard requirement of oligometastases is a low level of serum tumor markers. Although we defined the optimal cut-off value of preoperative serum CA19-9 as 2000 U/ml, it does not appropriately work for Lewis antigen-negative patients. Luo et al. proposed that CEA and CA125 can be applied as biomarkers in patients with no CA19-9 secretion from PDACs. Wei et al. proposed that tumor makers' criteria was at least a 50% reduction of serum CA125 or CEA levels if the patient had a normal CA19-9 level before conversion chemotherapy. Basically, we need other rules for theses patients.
Our analyses revealed that four or fewer liver metastases have a good prognosis. This is the same cut-off number as previous retrospective reports[9, 15, 20]. As for peritoneal metastases, some studies mentioned that only localized peritoneal metastasis can be included in oligometastases and can be treated[21, 22]. It implies that peritoneal metastasis basically has a poor prognosis, and incomplete metastasectomy does not affect the survival outcomes. In colorectal cancers, synchronous resection of localized peritoneal metastasis improved survival outcomes, while the diffuse or larger size (> 20 mm) peritoneal metastases were independent poor prognostic factors. Staging laparoscopy of PDAC cases sometimes reveals unsuspected peritoneal dissemination, as Karabicak et al. reported (19%). At that time, it is still unkown peritoneum metastases removal affects the patient's survival or not.
The period when we examined it is long, and there is the change of the standard treatment, too, and chemotherapy varies in this examination. With evolution of the chemotherapy, a recent case tends to have a good prognosis. However, as for the prognostic difference by OM, the developing front of the chemotherapy is more remarkable. It may be said that the situation of tumor determines OM than contents of the treatment intervention.
Treatment of OM cases of PDAC is still controversial. The current study suggests that patients with OM status could benefit from systematic chemotherapy. This may be an important finding that should however be verified with a larger cohort of patients. Non-OM patients with sufficient performance status should not be denied the opportunity to receive chemotherapy at this time. Since the study population does not include patients who underwent metastasectomy, we could not make any recommendation on whether or not to consider metastasectomy for PDAC. This issue could be solved from the viewpoint of conversion surgery, for which only responders to the chemotherapy are usually considered eligible.
Our study has some limitations. First, patient selection bias can exist because of the retrospective nature of the study. Most of subjects in this cohort had relatively good performance status enough to received palliative or probe laparotomy without postoperative complications. Secondly, we did not evaluate metastases outside of the liver and peritoneal surface because of the small number of such cases. Thirdly, we did not evaluated the case that a bypass does not need with distant metastasis diagnosed without laparotomy. Fouthly, considerations for Lewis antigen-negative patients have not been made at this time. Unlike the case with other types of cancer, we have not discussed on relevance of metastasectomy. This is in part attributable to the particular poor prognosis of PDAC, but metastasectomy could still be an issue for future debate, pending improvements in systemic treatment.
In conclusion, PDAC OM cases can be identified by limited visible metastatic sites with moderately low serum CA19-9.