Management of asymptomatic sporadic non-functioning pancreatic neuroendocrine neoplasms no larger than 2 cm: interim analysis of prospective ASPEN trial

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One of the most controversial subjects in Neuroendocrine Neoplasms is the management of small non-functional (asymptomatic) pancreatic NETs (NF-PanNEN).  In the most general terms, surgery is not recommended in tumours less than 2cm.  Allowances are made for those who are functional (i.e. symptomatic with one of several syndrome possibilities) or where the tumour is threatening important vessels (i.e. pre-emptive surgery).  Normally watching and waiting is recommended.  I wrote more detail in an earlier blog – Pancreatic Neuroendocrine Tumours – to cut or not to cut

Some patients opt (or push for) a non-guideline surgery regardless and as one other patient advocate put it, “they will surgeon shop until they find one who will do it”. 

While the guidelines are just that (guidelines), decisions on surgery in such cases must be carefully considered given that pancreatic surgery can come with considerable morbidity and the risk of mortality is there. 

One of the issues is the lack of solid data to base such decisions on.  There is also no test available with sufficient sensitivity to indicate the likelihood of particular individuals remaining localised and manageable or going on to develop growth of the primary, locally advanced scenarios and distant metastases.  Work on molecular markers is not yet advanced but it is a work in progress.  It is likely these markers would help decision-making.  There are also some suggestions in the US that the guidelines should be amended to make the threshold less than 1cm. 

Thus why I was very interested to see the Management of asymptomatic sporadic non-functioning pancreatic neuroendocrine neoplasms no larger than 2 cm: interim analysis of prospective ASPEN trial which concludes “….. active surveillance is the preferred approach for sporadic, asymptomatic, NF-PanNENs no larger than 2 cm. An active surveillance strategy seems safe, but the measurable risk of distant metastases, as well as the presence of histological characteristics of aggressiveness in almost one-fifth of operated tumours, necessitates personalized management for lesions larger than 1 cm as well as for young patients and in the presence of measurable growth of the nodule. Moreover, surgery is always mandatory for small NF-PanNENs with a dilated MPD (author insert: main pancreatic duct). According to the protocol, the study will be concluded 1 year after the enrolment of the last patient. Nevertheless, as these preliminary results showed only a very low rate of patients with tumour growth after a median follow-up of 2 years, longer follow-up is probably needed for definitive conclusions to be reached.

I have cited the study output below – click the link in blue. 

Study citation

Stefano Partelli, Sara Massironi, Alessandro Zerbi, Patricia Niccoli, Wooil Kwon, Luca Landoni, Francesco Panzuto, Ales Tomazic, Alberto Bongiovanni, Gregory Kaltsas, Alain Sauvanet, Emilio Bertani, Vincenzo Mazzaferro, Martyn Caplin, Thomas Armstrong, Martin O Weickert, John Ramage, Eva Segelov, Giovanni Butturini, Stefan Staettner, Mauro Cives, Andrea Frilling, Carol Anne Moulton, Jin He, Florian Boesch, Andreas Selberheer, Orit Twito, Antonio Castaldi, Claudio G De Angelis, Sebastien Gaujoux, Katharina Holzer, Colin H Wilson, Hussein Almeamar, Emanuel Vigia, Francesca Muffatti, Martina Lucà, Andrea Lania, Jacques Ewald, Hongbeom Kim, Roberto Salvia, Maria Rinzivillo, Alojz Smid, Andrea Gardini, Marina Tsoli, Olivia Hentic, Samuele Colombo, Davide Citterio, Christos Toumpanakis, Emma Ramsey, Harpal S Randeva, Ray Srirajaskanthan, Daniel Croagh, Paolo Regi, Silvia Gasteiger, Pietro Invernizzi, Cristina Ridolfi, Marc Giovannini, Jin Young Jang, Claudio Bassi, Massimo Falconi, Management of asymptomatic sporadic non-functioning pancreatic neuroendocrine neoplasms no larger than 2 cm: interim analysis of prospective ASPEN trial, British Journal of Surgery, 2022;, znac267,


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