Our study investigates the relation between the clinical cause of death, a history of cancer, and the autopsy rate by linking the NLCS to nationwide databases: the cancer registry, the Dutch Nationwide Pathology Databank (PALGA), the population registry, and the cause of death registry. The cause of death registry uses death certificates that are completed by physicians, usually within a few hours after a patient dies and before an autopsy is performed. To our knowledge, this linkage between clinical COD and the autopsy rate has not been investigated before. As in most European countries, permission for a clinical autopsy needs to be consented to by the relatives. In the Netherlands, this is done orally. This presumably results in more reluctance compared to countries in which no consent is needed, or autopsies are obligatory, especially in the older age categories. Consequently, in the Netherlands, the autopsy rate is among the lowest in Europe [6]. In a national study encompassing all clinical autopsies in the Netherlands, the autopsy rate in the age category 60–79 declined from just below 10% to approximately 3.9% from 1991 to 2015. In addition, the autopsy rate varied between different age categories, i.e., an average autopsy rate of 8.06% in the age category 60–64 years and 1.12% in 90–94 years. Lastly, a difference in autopsy rate according to sex could be explained by the age difference at the time of death. Our study shows a similar decreasing autopsy rate with older age, as shown in Table 1. More than half of all participants died from 1991 to 2009, mostly between the ages of 65 and 84 years. Contrarily, in all age categories, the autopsy rate was higher in males.

The results show a varying autopsy rate with different CODs, as shown in Table 2. Some considerations can be made when looking at the ICD codes that constitute the BELDO list, as shown in Tables 2 and 3. The autopsy rate in different CODs is derived from the NLCS, which is a population aged 55–70 at baseline in 1986, with a follow-up of 23 years. Although most deaths in the Netherlands occur in these age groups, these findings cannot be extrapolated to all patients as the COD distribution varies with age.

The most important consideration for relatives to give permission for an autopsy is the wish to learn about the cause of death [18]. The highest autopsy rate was observed in COD related to the digestive system (16.9%), followed by infectious and parasitic diseases (14.3%). Infectious and parasitic diseases can develop quite fast and are unpredictable, but as a CODs, they are rather rare in the Netherlands. This might explain the relatively high autopsy rate. One would expect this number to have increased even more in the face of the COVID-19 pandemic, but this is outside the time frame of this study. One could argue diseases of the digestive system may cause vague symptoms, which might lead to an unexpected and/or unexplained demise, therefore increasing the “need to know” of relatives and physicians.

Next, the autopsy rate was lowest in mental and behavioral diseases (0.8%) and diseases of the nervous system and the sense organs (4.0%). Of all the deaths in the “mental and behavioral diseases” group, 83.6% consisted of “unspecified dementia,” which was rated number 7 in the list of most common causes of death in 2000 in the Netherlands [32]. As patients with dementia are more prone to demise at home or in a nursing home, this might lead to a difference in autopsy rate, as shown by Lindstrom [3]. In addition, due to the long process of the disease, next of kin and physicians might be less inclined to refer to an autopsy [18]. A similar explanation is applicable to Alzheimer’s and Parkinson’s diseases in the group “diseases of the nervous system and sense organs.” An important reason for not requesting or permitting an autopsy is the assumption that the cause of death is already known [18]. This might be a feasible explanation for the low autopsy rate in deaths due to dementia, Parkinson’s disease, and Alzheimer’s disease. For the sake of completeness, there was one death due to an unspecified perinatal disease of the digestive tract, without an autopsy, which could either be a coding error or a very late death because of a congenital abnormality.

Our results show that the autopsy rate was positively correlated with the number of contributing causes of death (Table 4). This suggests physicians are more likely to request an autopsy when confronted with complex cases. However, due to technical and/or legal limits, death certificates are mostly completed before the conclusions of a postmortem become available. Despite improvements in clinical healthcare and technical advances in the last decades, a significant amount of major and minor discrepancies between clinical diagnoses and autopsy findings still remain [7, 20-22, 24, 33]. Major discrepancies are findings associated with the COD, where prior knowledge ante mortem might have changed patient management and survival in some cases. A study in the Netherlands showed major discrepancies in 16% of the autopsies in 2012/2013 [19]. Thus, autopsies continue to provide invaluable information for medical education and quality assurance [1]. Autopsies in particular have also been used as a measure for the accuracy of death certificates in general populations [34, 35] and in selected groups of diseases [36]. Therefore, some authors suggested that death certificates should be completed or amended utilizing data gained during autopsy [37]. Death certificates are the main source for mortality statistics and, as an indicator, contribute greatly to detecting trends in (inter)national healthcare [38]. As physicians are required to complete the death certificate, they play an important role in mortality statistics, and therefore indirectly, in the distribution of resources in healthcare and research.

In our study, the autopsy rate was affected by a diagnosis of cancer, most dramatically in deaths within 31 days after a diagnosis of cancer (Table 5). This increase in the first month could be explained by a sudden unset and/or rapid increase of the cancer, which may lead to unanswered questions for physicians and relatives. In the months and years thereafter, the cancer and possible cause of death would be known, which could lead to a decreased interest in autopsies, up to the stabilization after some 15 years.

The effect of completing death certificates without autopsy results, in regard to the incidence of cancer, is inconsistent. A study from 1997 conducted in Sweden suggested that the incomplete postmortem information due to the decline of autopsies was associated with a difference in the registered incidence of cancer [3]. However, in another study published in 2015 in Switzerland [39], the total registered incidence of cancers was not affected by the lower autopsy rate, perhaps due to advances in modern diagnostic tools as suggested by the authors. Another explanation for the contrasting results of both studies might be methodological and structural differences in the organization of the cancer registries within the two healthcare systems. In our study, a diagnosis on days 0–1 most likely means the cancer was detected as an incidental finding, i.e., during the autopsy, and was thereafter recorded in the cancer registry. Alternatively, the cancer was identified during a medical procedure such as surgery, after which the patient died, and the diagnosis was confirmed during an autopsy. In other words, the cancer was presumably undiagnosed before passing away in most of these cases. This probably explains the significantly higher autopsy rate of 78.0% on days 0–1. As there are only 269 autopsies with a diagnosis of cancer on day 0–1 in a study group with almost 25,000 patients with cancer, a possible effect of a decreasing autopsy rate on the cancer incidence is limited. Blokker et al. [40] speculated that the lower autopsy rate in older patients might be correlated to an increased number of deaths due to cancer. This differs from the findings presented here, as our average autopsy rate in cancer patients was slightly higher than in patients without cancer, even after excluding the “0–1 days” group. Our results suggest that the lower autopsy rate in older patients is more likely due to death in cases of dementia, as discussed above.

In our study, the linkage with excerpts from the PALGA-database was used to investigate whether an autopsy was performed. Not being able to see the full autopsy report in PALGA is therefore a limitation. Access to this data, perhaps in comparison with the cause of death registry by the CBS, may provide additional interesting insights.

The relevance of autopsies has been described in numerous publications over the years. Although major discrepancies between autopsies and clinical diagnoses remain [19,20,21,22,23,24,25], a steady worldwide decline of autopsies has been observed [3,4,5,6]. Therefore, it is the opinion of the authors that medical healthcare in general, as well as individuals, would benefit from an increase in postmortem investigations, among which autopsies. This increase can only be effectuated in close collaboration with clinicians and should be a solution for a problem, not the mere goal.