Characteristics of study populations

Table 1 presents actuarial and demographic characteristics of the study cohorts. The study population included 301 astronauts and 117 cosmonauts. There were just under 7,300 person-yrs of accrued follow-up time for astronauts and 3,000 for cosmonauts, with an average length of follow-up of 24 yrs per astronaut and 25 yrs per cosmonaut. There were 53 astronaut deaths during the study period and 36 cosmonaut deaths. For astronauts, the most common category of cause of death overall comprised external causes (including aircraft, spacecraft, and automobile accidents), accounting for 38% of the 53 astronaut deaths to date. The next most frequent cause group was cancer, accounting for 30% of the deaths so far. Other and unknown natural causes and CVD were less frequent, each accounting for approximately 15% of deaths. Among cosmonauts, the most common cause of death was CVD, with 50% of cosmonauts dying of this cause. Cancer was the next most common with 28%. External causes were responsible for a smaller proportion of deaths among cosmonauts in comparison to astronauts, accounting for 17% of cosmonaut deaths.

Table 1 Astronaut and cosmonaut group characteristics. Full size table

Astronaut survival

Figure 1 shows the results of cumulative incidence (of mortality) and survival plots for US astronauts. The topmost plot shows cumulative incidence curves for each cause of death individually (by color) and for all causes combined (in black), computed using standard K-M methods with deaths due to competing causes treated as censored observations for each curve. The estimated probability of death by all-causes, computed here by adding the (naïve, K-M) estimates at each point, exceeds 1.7 at approximately 55 years. This is driven largely by the jump to 1.0 in the cumulative probability of death from cancer at that time. That the probability of death due to any one cause could reach 1.0, and that the sum of the probabilities of death due to each of the individual causes could exceed 1.0, indicate that bias is present in the naïve estimates of cause-specific survival probabilities.

Figure 1 Cumulative incidence and survival curves for specific causes of death among US astronauts, 1959–2018. The upper panel shows the cumulative incidence from multiple causes when computed from naïve K-M survival estimates. The four middle panels provide naïve K-M and properly computed competing risk survival curves by cause. The bottom panel shows cumulative incidence curves by cause derived from competing risk survival curves. Full size image

The four plots in the middle of the panel show each properly computed cause-specific survival curve (properly accounting for competing causes of death) overlaid with the corresponding naïve K-M curve. As expected, the survival curve estimated by naïve K-M in all cases tracks lower than that estimated by competing-risk curves. However, the degree to which the curves diverge varies by cause. External causes show almost no divergence between the two curves while the plots for cancer, CVD, and other natural causes show divergence starting at approximately 40–45 years of follow-up. Cancer shows the largest divergence, with the competing risk survival estimate of 53% at 55 years instead of the K-M estimate of 0%. For CVD the difference between the K-M and competing risks curves was 7% after 55 yrs of follow-up, while other natural causes had a difference of 18% at 55 yrs.

Table 2 gives the areas under the curves (AUCs) for the curves in the 4 cause-specific plots of Fig. 1. Just as the competing risk curves give more optimistic survival estimates than the K-M curves, the AUCs for the competing risk curves are greater than those of the corresponding K-M curves. In spite of some of the large differences in end-of-period survival noted above, the differences in AUC were slight: the naïve K-M AUCs were all within 2% of the competing risk AUCs and the largest difference was still less than 1 person-year. The smallest ratio (indicative of the largest difference) was for other natural and unknown causes, with a ratio of 0.985 and a difference of 0.81 person-years. The largest ratio (smallest difference in AUC) was in external causes, with a ratio of 0.999 and a difference of 0.06 person-years.

Table 2 AUCs, AUC differences, and AUC ratios by cause of death category for K-M and competing risk survival curves for astronauts. Full size table

The analyses in Fig. 1 and Table 2 have assumed that the three astronaut deaths due to unknown causes were due to other natural causes, rather than cancer, CVD, or external causes. We conducted separate analyses to examine the effect of adding those three deaths to the cancer or CVD category. When the three deaths from unknown causes were assumed to be cancer deaths, the survival estimate from the competing risk curve was 47% at 55 years, and the ratio of AUCs was reduced to 0.988. When instead we considered the unknown deaths to be from CVD, the competing-risk survival at 55 yrs was 80%, and the ratio of AUCs was 0.987. In both these scenarios, the survival for other natural causes increases to 75% at 55 yrs, and the ratio of AUCs increases slightly to 0.988.

The bottom-most plot in Fig. 1 shows all of the corrected cumulative incidence curves. As in the topmost plot, the black line is the sum of the individual cumulative incidence values at each point. In this plot the black line hits a maximum of 1.0 at approximately 55 yrs, demonstrating that the biases in the individual cause curves have indeed been corrected.

Cosmonaut survival

Figure 2 shows the same set of cumulative incidence and survival plots as in Fig. 1, in this case for cosmonauts. The all-cause cumulative incidence curve in the topmost plot shows no apparent bias in the cosmonaut cohort, as the curve does not exceed 1.0 at any point in the 55-yr follow-up. In the bottom-most plot, the all-cause cumulative incidence at 55 years of follow-up is 73%, compared to 90% in the original, biased version displayed in the top-most plot (black lines).

Figure 2 Cumulative incidence and survival curves for specific causes of death among Soviet and Russian cosmonauts, 1960–2017. The upper panel shows the cumulative incidence from multiple causes when computed from naïve K-M survival estimates. The four middle panels provide naïve K-M and properly computed competing risk survival curves by cause. The bottom panel shows cumulative incidence curves by cause derived from competing risk survival curves. Full size image

For both the other natural causes of death group and external causes of death group, the curves show almost no divergence across the follow-up period, with less than 1% difference in the curves for these two causes after 55 yrs of follow-up. However, there was approximately 3.5% divergence between the K-M and competing risks curves for cancer, and 14% divergence in the curves for CVD.

Table 3 contains the AUCs for the cause-specific survival curves of Fig. 2. Just as with astronauts, most K-M AUCs were within 1–2% of the competing risk AUCs with AUC differences of less than 1 person-year. The notable exception is CVD, where the K-M curve provided an AUC that was approximately 4% smaller than that of the competing risk curve. This equated to an AUC difference of 1.96 person-years.