Watch and Wait Strategies in NET Patients: More than Expected.

Abstract

Neuroendocrine tumors of the gastroenteropancreatic (GEP-NET) system include sporadic and hereditary diseases which have been increasing in incidence recently [1]. In patients with resectable low grade well-differentiated neuroendocrine tumors (NET) surgery is the mainstay of therapy. However, the majority of patients present with unresectable disease, most frequently with liver metastases. In patients with low grade NET G1 (Ki67<2%) a watch-andwait (W&W) strategy can be recommended in patients with loco-regional lymph node metastases or in patients with liver metastases if the liver tumor burden is low. The current German and European guidelines consider the use of W&W as a safe approach in this patient population [2, 3]. However, absence of symptoms and radiological tumor progression are essential requirements, along with a welldifferentiated morphology and low grade as well as limited metastasis. The clearest evidence for an W&W approach in GEP-NET derives from the CLARINET trial, where a median progression-free survival (mPFS) of 18 months was achieved in the placebo group with tumor stability within 3-6 months prior to start of lanreotide [4]. Out of 103 patients in the placebo arm 60 patients experienced progression within 24 months. However, 43 patients demonstrated stable disease even after 2 years which confirms that a subgroup of patients has no need for therapy even in the long-term. Data on the current prevalence of patients with a W&W strategy are not available. In 2021, we surveyed NET patients in Germany, Austria and Switzerland to assess the medical care under the COVID-19 pandemic. The online survey (constructed by LimeSurvey software) was distributed via personal contact and by the patient organization NETZwerk NET e.V. In this process, 542 out of 684 NET patients completely answered all questions [5]. Of these, 68 (12.5%) patients indicated that they were followed by a W&W strategy. About half were between 41-60 years of age (n=36, 53.0%), 30 affected people were between 61-80 years (n=30, 44.1%). Most participants had a small bowel or pancreatic primary tumor with 25.0% (n=17) and 23.5% (n=16), respectively. 25% of the W&W group (n=17) self-reported a functional-active disease and 66.2% (n=45) displayed symptoms at the time of the survey. In most cases, the diagnosis required more than 12 months (n=30, 44.1%) and almost half of the participants have been living with the disease for more than 5 years (n=33, 48.5%). Present comorbidities were specified as follows: hypertension (44.5%, n=30), diabetes (19.1%, n=13), asthma/COPD (16.2%, n=11), chronic renal failure (13.2%, n=9), heart insufficiency (8.8%, n=6). Only one participant mentioned a chronic infection. Liver cirrhosis as comorbidity was not reported. All clinically available characteristics of the participants are listed in Table 1.