Survival Data
Whether patients with MEN1 have premature death with shortened survival is controversial in some previous studies.78,88,101,129,465 In 2 studies88,101 the survival of patients with MEN1 did not differ from that of unaffected individuals; however, 3 other studies78,129,465 concluded that MEN1 patients had premature death with shortened survival. In one of the latter studies,129 the mean age at death of female MEN1 patients was 47 years and of male patients was 55 years, which was significantly younger than the age at death of Dutch control non-MEN1 female patients (75.6 yr, p = 0.032), or of control non-MEN1 male patients (70.1 yr, p = 0.001). A second series reporting premature death78 was a large, retrospective study of 228 MEN1 patients from the Mayo Clinic whose mean age at diagnosis of MEN1 was similar to that of our 106 NIH MEN1/ZES patients (39.2 vs 38.3 yr, respectively). In that study78 the expected survival at 20 years from age of diagnosis of the MEN1 for a matched control group was 80%, compared with 64% for their MEN1 patients, which was significantly less (p < 0.001) than their controls. The survival of their MEN1 patients is similar to the overall survival of our 106 MEN1/ZES patients prospectively followed, which was 67.5% at 20 years from diagnosis, suggesting that our patients also had a premature death.
However, in the current prospective study a number of results suggest that these patients are living longer than reported in many previous series. First, during the long follow-up (mean, 15.5 yr from MEN1 diagnosis; 24.5 yr from MEN1 onset), 23% of the 106 NIH MEN1/ZES patients died, which is comparable to the 28% ± 3% reported in 12 of the general MEN1 series in the literature that reported mortality percentages (1386 patients, see Table 12). However, the deaths in the NIH MEN1/ZES patients occurred over more than twice as long a follow-up period as the follow-up period reported in the literature cases (15.5 [NIH] vs 7.7 ± 1.0 yr from diagnosis of MEN1, n = 6 series]. Similarly for the 227 MEN1/PET deceased patients from the pooled literature, whose data came from 108 separate reports, they represented 18.8% ± 1.9% (data: 36 reports) of the total MEN1 patients being followed in these reports. However, similar to the 12 general MEN1 literature series, the percentage of patients that died in the pooled literature series occurred over less than half of the follow-up time (6.9 ± 1.3 yr) of the NIH series.
Second, if one compares the data from different series, the mean age at death of MEN1 patients varies markedly. In our 106 NIH MEN1/ZES patients, the mean age of patients who died was 55.1 ± 2.8 years. This age is older than that reported in a number of series in the literature, with mean ages of death of 31.7 years,15 43.3,444 45.1,254 47,88 50.3,46,57 50.9,465 and 51 years.129 However, it is similar to the ages reported in other studies, which have reported mean ages of death of 53.2 years,54 55 years, males/47 years, females,129 60,448 and 55 years.88
Third, in terms of survival calculated using the Kaplan-Meier method, the 106 NIH MEN1/ZES patients had a much better overall survival at 5, 10, 20, and 30 years postdiagnosis than the 227 pooled MEN1/PET literature patients (at 5 yr, 97.3% vs 60%, respectively; at 10 yr, 89% vs 21%; at 20 yr, 67.5% vs 5%; at 30 yr, 55% vs 0; p < 0.01). Similarly the NIH MEN1/ZES patients’ survival was significantly better than the average of 22 series in the literature,54,57,78,94,106,153,166,181,217,233,276,289,303,311,367,424,425,440,481,482 which had mean 5- and 10-year survival rates of 89% ± 1.9% and 78% ± 3.6%, respectively, compared to 97% (95% CI, 92%–100%) and 89% (95% CI, 81%–94%) (p < 0.05), respectively, in the NIH MEN1/ZES patients. If a similar comparison is made for just the MEN1/ZES patients, the survival of the NIH MEN1/ZES patients was also significantly better (p < 0.05) that that of 10 series of MEN1/ZES patients in the literature,54,106,166,181,217,276,303,311,367,424,440,481,482 which reported mean 5- and 10-year overall survival rates of 88% ± 2.9% and 80% ± 4.2%, respectively, compared to 97% (95% CI, 92%–100%) and 89% (95% CI, 81%–94%), respectively, for the NIH MEN1/ZES patients.