Stage 4 neuroendocrine pancreatic cancer life expectancy

Pancreatic cancer is relatively rare, with approximately 13 new cases and 12 deaths per 100,000 population per year in the United States [1]. Overall survival prognosis is exceptionally poor, with only approximately 8% of patients surviving 5 years post-diagnosis [1]. Unlike in many other forms of cancer, there do not appear to have been significant improvements in survival over the past few decades [1].

However, the outcome statistics are dominated by exocrine adenocarcinomas, which account for approximately 90% of cases [2]. While patients with this histological type often have median survival times of less than 1 year [2], prognoses for those with the less common pancreatic neuroendocrine tumors (PNETs) appear to be significantly better [2], [3], [4], [5]. For example, the 2008 study of Yao et al. reported a median survival time of 5 years from diagnosis [3].

The seminal work of Fesinmeyer et al. [2] together with further research by others [3], [4], [5], [6], [7] identified various risk factors related to survival in PNETs. Their results, however, were limited to relatively short-term survival probabilities (up to 5 years post-diagnosis) and were stratified by only one or two risk factors at a time, which has only limited utility in providing accurate prognoses for individual patients. For example, Keutgen et al. [8], [9] reported univariate survival curves and medians based on age, grade, location, and other factors, but did not provide results specific to any two factors or a combination of factors.

More recent studies have investigated recurrence and survival based on revised WHO 2010 and 2017 diagnostic criteria and various clinical markers [10], [11], [12], [13], [14], [15]. Insufficient time has passed, however, to investigate long-term survival based on refined clinical characteristics (such as Ki67 proliferative index, mitosis rate, lymph node ratio, p53 and rb1) [11].

Further, none of these works contained either life expectancies (the total average survival time) or conditional figures (e.g., for those who survive 1 year post-diagnosis). That is, to our knowledge, there have been no studies that specifically computed life expectancies with comparison to the general population. Nor have there been any studies reporting the subsequent survival of PNET patients who had already survived 1 or 5 years post-diagnosis.

The present study updates and expands on previous work, especially Keutgen et al. [8], [9] by developing a multivariate prediction model that simultaneously accounts for patient age and sex, cancer stage, tumor grade and histology, and surgical treatment status. Using this model, we examine trends in survival over time, controlling for these factors. Primarily, we use the model to obtain current life expectancy (i.e. mean survival time) estimates from the time of diagnosis, and also conditional life expectancy estimates for 1- and 5-year survivors. The latter may be particularly relevant and helpful to patients who have survived the initial treatment and are then naturally concerned about their future prospects. Finally, we compare our results to normal figures for the US general population, to highlight to what extent survival in functional and non-functional PNET is diminished.

Data source and cohort selection

The Surveillance, Epidemiology, and End Results (SEER) database, managed and maintained by the National Cancer Institute (NCI), is the largest source of information on cancer incidence and survival in the United States. The registries that provide patient information for SEER represent approximately 28% of the US population (based on the 2010 census). We queried the 2015 edition of the SEER database which includes over 8.2 million cases diagnosed between 1973 and 2013 in the United States [16].

Patient characteristics

Characteristics of the 5287 PNET cases are presented in Table 1. The mean age at diagnosis was 58 years and 54% were male. The large majority of cases (95%) were non-functioning histological types. Some 54% of all cases were diagnosed as distant stage and surgery was performed in 52% overall. Tumor grade was missing in 56% of cases, but amongst those with known grade the majority were well-differentiated grade I.

Because non-functioning histologies made up the large majority of cases, the

Discussion

As would be expected, we found PNET to be associated with reduced life expectancy, with an overall empirical median survival time of 4.1 years from diagnosis. Though this is considerably lower than the median survival time for persons of similar age and sex in US the general population, it is roughly 8 times longer than the 6-month median survival time for the more common pancreatic adenocarcinomas.

The present study indicates that survival prognosis varies dramatically according to patient

Limitations

The use of SEER's localized, regional, distant (LRD) staging classification is crude by comparison with the more refined AJCC staging systems based on TNM, and more recent WHO 2010 and 2017 divisions (PNET G1, G2, NEC). We chose to work with the simpler LRD system for three reasons. Firstly, it was much more complete (i.e., only 5% missing cf. AJCC 45% cf. no data in SEER using WHO 2017). Secondly, it allowed for a consistent staging classification, which is important when assessing trends in

Conclusion

Life expectancies of patients with pancreatic neuroendocrine tumors are generally lower than general population figures, but even in the worst cases their prognoses remain significantly better than that of patients with the more common pancreatic adenocarcinomas. In some very favorable cases, the life expectancy is near-normal, especially amongst 1- and 5-year survivors. These results underscore the importance of early detection and treatment in improving outcomes overall.

Funding

None.

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgements

None.

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