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Later Surgery for Advanced Pancreatic Cancer in Treatment Responders with Hepatic Lesions ?

Criteria for exclusion of patients from surgery for pancreatic cancer (ductal adenocarcinoma of the pancreas) include detection of distal metastases including those noted in the liver (also known as the hepatic organ).  However especially over the past decade, there have been a number of studies aimed at trying to discern whether liver lesions alone should rule out pancreatic cancer surgery for every patient – or might careful selection based on chemotherapy response or multimodal therapy possibly including hepatic surgery treatment yield access to surgery and possible survival advantage?

The outcomes of such studies have been mixed. For example, an article in the December 2007 issue of the journal Cancer by Johns Hopkins University researchers showed no advantage by including hepatic metastases in the greater scope of surgical targets in pancreatic cancer surgery, whereas in 2008 German authors presented a review of the medical literature in the journal Digestive Surgery which indicated that there might be such a survival advantage in select such patients with pancreatic cancer.

But 2016 produced at least four studies (including the article-under-review; with a link at the end of this blog entry) from international researchers (including one Johns Hopkins researcher) which address the issue of concomitant surgery of hepatic metastatic lesions along with more standard pancreatic cancer in select patients, or standard pancreatic cancer surgery under select circumstances (significant response to chemotherapy).

The article under review was authored by researchers from Vita-Salute University in Milan, Italy and from Università Politecnica delle Marche in Ancona, Italy. They published their results in the October 2016 issue of the European Journal of Surgical Oncology, the official journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. The authors retrospectively examined the outcomes at their two institutions of pancreatic cancer patients who had who had undergone chemotherapy for hepatic metastases without evidence of extra-hepatic metastases, and who had acceptable personal performance status. 127 patients were identified (76 male and 51 female), had been treated with chemotherapy, and followed with regular CA 19-9 levels.

After treatment, 19 of these patients demonstrated a complete or partial radiological response of their pancreatic cancer; each of these patients additionally showed major biochemical response defined as a significant reduction of CA 19-9 levels. On subsequent evaluation, seven patients were excluded from pancreatic cancer surgery due to further studies that located increased liver or peritoneal metastases, or in one case a significant rise of CA 19-9 levels after the chemotherapy had ended.  Laparotomy was performed on twelve patients with a full pancreaticoduodenectomy completed on 11 patients (one was found to have peritoneal metastases at surgery). In this sub-group of eleven patients with advanced pancreatic cancer who later underwent surgical resection, the median survival duration was 46 months as compared to 11 months for the patients with pancreatic cancer who were unable to undergo surgery (P< 0.0001).

This is a quite interesting study that begins to challenge existing orthodoxy in the context of the effectiveness of new chemotherapy regimens for the treatment of pancreatic cancer. The recent research concerning possible advantages of hepatic surgery or multimodal treatment for pancreatic cancer with hepatic metastases in select patients will be left for another time. But for now, perhaps it is enough to highlight this tentative conclusion that identifies significant-response-to-chemotherapy as a marker to possibly negate the absolute exclusion of pancreatic cancer patients with hepatic metastases for surgical resection. Obviously more research is needed, but this is an intriguing outcome worthy of further consideration, with accolades given from this vantage to the authors.

 

Article Under Review

 

Dale O’Brien, MD