Neuroendocrine tumours (NETs) presenting as metastatic cancer of unknown primary site (CUP) are suspected to confer poorer prognosis compared to metastatic NETs of known primary site. We performed a retrospective, single centre study to determine the prognostic indicators in CUP-NETs compared to metastatic small intestinal NET (SiNET), before and after adjusting for factors known to affect overall survival. Subjects were selected from a departmental database of 1050 NET patients discussed by the Oxford neuroendocrine service between 2011 and 2019. Inclusion criteria were histologically proven NET with radiological evidence of metastatic disease at diagnosis. Survival time began from the date of histological diagnosis until the last known follow-up. The primary end-point was death. Patients were divided into 3 cohorts: 1) CUP-NET, no primary identified; 2) likely SiNET, radiological evidence of mesenteric/SiNET, and 3) histologically confirmed SiNET. Cox proportional hazards models were constructed to compare unadjusted and adjusted hazard ratios (HR) for age, tumour differentiation [well vs. poor], grade and primary tumour resection [likely SiNET and SiNET] between each group: 233/1050 (21%) patients with metastatic NET (median follow-up of 22.5 months [95% CI 16−29, IQR 9−55]) were identified including 52/1050 (5%) CUP-NET, 66/1050 (6%) likely SiNET and 105/1050 (10%) SiNET. Unadjusted mean (standard error) overall survival data were 19 (2.4), 64 (5.8) and 102 (5.6) months respectively (P<0.02). Table 1 reports the unadjusted and adjusted HR for overall survival between each group. In conclusion, CUP-NET confers a poorer prognosis compared to metastatic SiNET. However, this difference is largely driven by patient age, tumour grade and differentiation.
|Groups||Unadjusted HR (95% CI)||Adjusted HR (95% CI)|
|CUP-NET to likely SiNET||3.1 (1.5−6.3)||0.8 (0.3−2.1)|
|CUP-NET to SiNET||6.5 (3.3−13.0)||1.8 (0.6−5.6)|
|Likely SiNET to SiNET||2.5 (1.4−5.7)||1.6 (0.2−13.8)|