Prognostic and predictive factors on overall survival and surgical outcomes in pancreatic neuroendocrine tumors: recent advances and controversies

ABSTRACT

Introduction: Recent advances in diagnostic modalities and therapeutic agents have raised the importance of prognostic factors in predicting overall survival, as well as predictive factors for surgical outcomes, in tailoring therapeutic strategies of patients with pancreatic neuroendocrine neoplasms (panNENs).

Areas covered: Numerous recent studies of panNEN patients report the prognostic values of a number of clinically related factors (clinical, laboratory, imaging, treatment-related factors), pathological factors (histological, classification, grading) and molecular factors on long-term survival. In addition, an increasing number of studies showed the usefulness of various factors, specifically biomarkers and molecular makers, in predicting recurrence and mortality related to surgical treatment. Recent findings (from the last 3 years) in each of these areas, as well as recent controversies, are reviewed.

Expert commentary: The clinical importance of prognostic and predictive factors for panNENs is markedly increased for both overall outcome and post resection, as a result of recent advances in all aspects of the diagnosis, management and treatment of panNENs. Despite the proven prognostic utility of routinely used tumor grading/classification and staging systems, further studies are required to establish these novel prognostic factors to support their routine clinical use.

KEYWORDS:

• Pancreatic neuroendocrine neoplasms
• prognostic factor
• biomarker
• molecular marker
• pathological factor
• surgical resection

Article highlights

• Numerous factors are leading to an increased need for prognostic/predictive factors in patients with panNENs

• These factors include: their increasing incidence, increasing incidental discovery of asymptomatic small tumors, the increased array of treatments for advanced disease, their variable courses, increasing insights into their pathogenesis and variable courses post-surgical treatments

• A number of factors have been identified that have prognostic/predictive for the overall survival or postsurgical disease course of patients with panNENs

• Prognostic factors identified for both survival and surgical outcomes include: clinically related factors (clinical, laboratory, imaging, treatment-related factors), pathological factors (histological, classification, grading) and molecular factors prognostic predictive factors in panNETs

• Particularly important in all studies is the recent classification/grading systems, although there is still a need for additional prognostic factors

• Molecular insights are generating numerous predictive/prognostic factors; however generally, similar to the many of the other prognostic factors reviewed here, their evaluations are still limited, and large, prospective studies are needed to identify which factors should be routinely used

• These advances have generated a number of controversies and new unanswered questions.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National institutes of Health intramural funds [grant number DK 053200-26].