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Predictors of disease recurrence after curative surgery for nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNENs): a systematic review and meta-analysis

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Abstract

Purpose

Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs.

Methods

Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival.

Results

Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15–26%). Study quality (Odds ratio, OR 0.94, P = 0.016) and G3-PanNENs rate (OR 2.18, P = 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P < 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P < 0.001, G1 versus G3 HR 2.57, P < 0.001), microvascular (HR 1.25, P = 0.046) and perineural (HR 1.29, P = 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P = 0.253) and status of resection margins (R0 versus R1, P = 0.173) did not show any significant relationship with NF-PanNENs recurrence.

Conclusion

Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.

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Availability of data and material

All the data generated or analysed during this study are included in the manuscript or in the supplementary material.

Code availability

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Acknowledgements

The authors are grateful to Gioja Bianca Costanza Fund for supporting the PhD Scholarship of Dr. Valentina Andreasi and the Research Fellowship of Dr. Francesca Muffatti. The Authors are also grateful to the Fondazione Umberto Veronesi for supporting the Reserach Fellowship of Dr. Giovanni Guarneri. Authors thank the ERN EURACAN initiative.

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Author notes

  1. V. Andreasi and C. Ricci shares the first authorship.

  2. R. Casadei and M. Falconi shares the senior authorship.

Authors and Affiliations

  1. Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Hospital Neuroendocrine Tumor Group (ENETS Center of Excellence), IRCCS San Raffaele Scientific Institute, Milan, Italy

    V. Andreasi, S. Partelli, G. Guarneri, F. Muffatti, S. Crippa & M. Falconi

  2. Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy

    V. Andreasi, S. Partelli, S. Crippa & M. Falconi

  3. Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy

    C. Ricci, C. Ingaldi & R. Casadei

  4. Department of Internal Medicine and Surgery (DIMEC), S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy

    C. Ricci, C. Ingaldi & R. Casadei

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Contributions

Study concept and design: VA, CR, SP, RC, MF. Data collection: VA, GG, SP. Analysis of the data: CR, VA, GG, CI. Interpretation of the data: VA, CR, SP, GG, CI, FM, SC, RC, MF. Drafting the manuscript: VA, CR, SP, GG. Critical revision of the manuscript: all the authors.

Corresponding author

Correspondence to S. Partelli.

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This meta-analysis is based on published studies performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.

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Andreasi, V., Ricci, C., Partelli, S. et al. Predictors of disease recurrence after curative surgery for nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNENs): a systematic review and meta-analysis. J Endocrinol Invest 45, 705–718 (2022). https://doi.org/10.1007/s40618-021-01705-2

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