Impact of Surgery on Oligometastatic Pancreatic Cancer: Current Status and Future Perspectives

Abstract

Pancreatic cancer is one of the most difficult human malignancies to treat. Surgery is generally contraindicated in advanced pancreatic cancer, even with one distant metastatic lesion [1]. However, recent advancements in the treatment of pancreatic cancer may change therapeutic concepts and strategies, even for metastatic pancreatic cancer. Even in cases of advanced pancreatic cancer, we occasionally see unexpectedly positive benefits of anticancer therapy in daily clinical practice. In such cases, surgical resection might result in long-term survival or even a complete cure. Oligometastasis is considered an intermediate state between localized and polymetastatic disease [2]. Currently, the best treatment for oligometastasis in pancreatic cancer, despite being widely discussed, remains controversial. There are several clinical questions regarding oligometastasis in pancreatic cancer. First, what is the definition of oligometastasis in pancreatic cancer? Second, does surgery play a significant role in the multidisciplinary treatment, even in patients with oligometastasis? Third, what is an appropriate biomarker to predict efficacy of treatment and determine surgical indications in oligometastatic pancreatic cancer?In this review, we present an update on the current status of surgery in the multidisciplinary treatment of oligometastatic pancreatic cancer, and discuss future perspectives.

Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor

“…In contrast to the above reported malignancies (colorectal, neuroendocrine, and gastric cancers), oligometastatic PDAC is generally considered a contraindication to surgical resection, even if a few visible metastatic lesions are limited to one organ and are easily resected. Twelve literature reviews on the subject carried out since the 2017 [155,157,158,[167][168][169][170][171][172][173][174][175] reported data from 38 articles overall. After considering the results of each of the 38 articles reported by the twelve reviews, excluding articles reporting duplicate (6) or non-topic (1) results, and considering the presence of two reviews, one article based on data from the Surveillance, Epidemiology and End Results program and another from the National Cancer database (2010-2015), we estimated that approximately 1400 patients with liver-only oligometastases undergoing a simultaneous resection of the primary tumor and metastatic disease were reported overall.…”

“…Due to the variety of criteria used to choose a surgical treatment, the variety of chemotherapy treatments used by different authors, and the variety of intervals between diagnosis and surgical resection, the twelve reviews reached different conclusions. Two were in favor of surgical resection due to its additional survival benefit in the medium term [167,171], one was largely inconclusive due to its limited study population and the heterogeneity of inclusion criteria among studies [173]; two interpreted the positive results of surgery as surrogate markers of favorable tumor biology, as appropriate tumor selection remains a challenge [155,172]; four were in favor of surgery only after an adequate response to NAT [157,158,168,170], even more so if this was associated with adjuvant chemotherapy [168], but also expressed their concern about patient selection and the timing of surgery [157]; and finally, three were in favor of surgery but underlined the difficulty in defining the appropriate time for surgery and chemotherapy [169] and the difficulty in selecting patients due to the inadequate selection capacity of the available biomarkers [174,175]. Seven further articles on the topic have recently been published.…”

“…Four reported improved survival after NAT and surgical resection [153,161,177,178]. Both the results of the twelve reviews [155,157,158,[167][168][169][170][171][172][173][174][175] and of the seven recently published articles [153,161,162,171,[175][176][177][178] are influenced by a selection bias due to the variety of criteria with which surgical resection patients were selected, as demonstrated by Table 5 [153,159,160,166,171,[178][179][180][181][182][183][184][185][186][187][188][189]] and Macfie's Table 3 [152]. Pathologically confirmed metastasis to an extrahepatic site identified at surgical exploration excluded.…”

“…Finally, the oncological criterion was based on a satisfactory morphological and/or biological response to NAT and was considered by only 26.1% of the articles. Considering 38 articles on the topic (31 included in the 12 reviews [155,157,158,[167][168][169][170][171][172][173][174][175], after excluding duplicate or non-topic publications, and 7 recent articles not included in the reviews [153,161,162,171,[175][176][177][178]), adequate data on NAT (useful/not useful), the interval between diagnosis and surgical resection after NAT (so called immortal time [154]), CA 19-9, and the oncological criteria used to propose synchronous surgical resection were reported by 21, 7, 23, and 14 articles. Of the 21 articles reporting data on NAT, almost all published after 2015, 76.2% reported satisfactory results, while it was considered useless by 14.3% and its effect was not specified by 9.5%.…”

“…Peritoneal metastasis is generally considered a systemic metastasis that contraindicates surgical resection, while peritoneal oligometastatic disease has rarely been discussed and established. Sho et al [175] reviewed seven articles reporting the results of 67 patients undergoing a resection of oligometastatic peritoneal PDAC. Studies up to 2010 reported an OS from the initiation of treatment ranging from 5.3 to 12.9 months, while it has ranged between 19.4 and 32.5 months in more recent studies.…”