MPM is a rare aggressive tumor, regarded as a universally fatal disease. Despite the regulatory actions and the reduction in using of asbestos, the annual number of MPM deaths remained substantial[9, 10, 24]. The elderly made up the majority of the patients, it has been shown that elderly patients have a poorer prognosis than adult patients[10, 11, 15]. Our study combined with SEER database to conduct an in-depth analysis of elderly MPM patients.
Among our study population, the number of male patients was higher than females, similar to the results of the previous studies, to explain such a gender difference, it has been proposed that compared with women, men have more occupational exposure to asbestos, thereby leading to a higher incidence in males[25, 26]. Different from previous studies, in our study, the elderly patients had a larger proportion of male than the adults group (58.80% vs 52.60%), while a multinational multi-center study published in 2011 suggested a prominent higher proportion of men aged 55 and below than patients over 55 (59% vs 41%)[27].The reason may be that all cases in this study were taken from the SEER database, which is only a collection of data from 18 regions in the U.S. mainland, there are some regional limitations to the results.
Due to the low incidence and the shortage of studies based on large sample cases in various regions, there are not many data on survival analysis of MPM patients, moreover, the results of different regional studies are inconsistent, but the general survival time without treatment is less than 1 year. Salo Sas et al[28]. reported a median survival of only 4 months for 90 MPM patients in Finland between 2000 and 2012. John T. Miura et al. suggested a median overall survival of 9 months[29], and V. de Pangher Manzini et al. showed an even longer survival of 13 months[16]. As for the survival comparison between elderly and adult patients, the elderly was found to be associated with a worse survival[12, 15]. However, Cao C, et al. had shown that there was no statistical difference of the survival time between male MPM patients older than 55 and younger than 55[27]. In this study, elderly patients showed shorter median survival time than adults (6 months vs 19 months), and the survival rate was significant lower than adults. Considering the reasons, maybe it’s because that the elderly generally has, compared with the adults, weaker health, more age-dependent physiological changes, as well as more complications, and tend to palliative treatment.
It was found that females with MPM generally had better outcomes than males, without considering age, time to diagnosis, and histology type[13, 27]. A 2018 case study showed that female patients had a higher 5-year survival rate than male (33% > 12%)[15]. Similarly, in this study, the median survival time of female MPM patients in the elderly group was 9 months, longer than male (5 months). Further analysis revealed that only 25.58% of elderly male patients underwent surgery, while 44.53% of female patients did, suggesting that females can receive more aggressive and effective treatment than males.
Several tumor-related studies suggested that married patients’ prognosis was better than singles because of earlier disease detection, better financial support and more health care resources[29–31]. Contrary to our expectation, in this study, the married patients had a shorter median survival time and slightly lower CSS than unmarried group. After further analysis, we found the majority of married patients were male (72.11%), and women accounted for most of the unmarried patients (61.34%) in our study. With this in consideration, we may explain why married patients’ prognosis was worse in our study.
Consistent with previous study, histology type[10, 21, 32] and differentiation grade[14] were found as independent prognostic factors for the elderly MPM patients. Patients with epithelioid type had the most favorable outcome, while those with biphasic and sarcomatoid type had the worse one (HR: 2.279; 3.913). The risk of CSD in moderately differentiated, poorly differentiated and undifferentiated patients was 0.978, 2.900 and 1.430 times higher than that in well differentiated patients, respectively.
At present, there is no matured TNM staging system for MPM. Yan et al. proposed a set of TNM staging system for diffuse malignant peritoneal mesothelioma in 2010 [33]. SEER database divide the patients into localized staging group, regional staging group and distant metastasis group. It was shown that 40–60% of MPM patients had distant metastasis at the time of detection[8, 10], consistent with our finding (50%). Our results showed that the 5-year CSS rates of the elderly MPM patients in localized, regional, and distant stage were 22.75%, 18.47% and 8.38%, respectively. Distant metastasis is independently associated with poor survival.
For treatment, the effect of radiotherapy for MPM patients is not clear. Silja A.S. Salo et al. showed that for patients who were treated with radiotherapy alone[22], the median survival time was 2 months and a 1-year CSS rate was 20%. Our study shows that patients who had radiotherapy or not (including unknown group) had the same median survival time for 6 months, the results showed that radiation therapy has no obvious effect on the prognosis of elderly MPM patients.
In this study, only 33.38% of all elderly MPM patients underwent surgery, consistent with Anish Thomas’ report in 2015 (32%) [12]. Surgery interventions have been proved to associate with better outcome[14]. We observed that the 5-year survival rate of the patients who underwent surgery were higher than that of those who didn’t (19.14% vs 8.76%). No surgery group had 1.733 times the CSD risk of surgery group, surgery was the treatment option to improve prognosis. But, elderly patients mostly have multiple and complex underlying diseases and tend to palliative treatment.
Chemotherapy is often combined with surgery to treat MPM, which can be delivered in the form of heated intraperitoneal chemotherapy (HIPEC). Nagata Y et al. found that cisplatin plus pemetrexed showed consistent efficacy with MPM[34], which can be recommended as first-line treatment for unresectable MPM. Yan et al. reported the median survival of 56 months for 372 patients who received HIPEC and 23 months for those who did not (P = 0. 049) [21]. However, some studies had shown that systemic chemotherapy had no positive effect on the prognosis of MPM patients[35]. In this study, patients receiving chemotherapy showed longer median survival time than those did not or unsure (13 months vs 10 months). About 44.21% elderly patients underwent chemotherapy, far more than surgery or radiotherapy. Multivariate analysis demonstrated that chemotherapy was independently associated with improved survival outcomes.
At present, cytoreductive surgery (CRS) combined with HIPEC as the first-line treatment of MPM has been proved to improve the prognosis of MPM patients[36–40]. A systematic review and meta-analysis showed patients receiving CRS and HIPEC had a median survival time of 29.5–100 months, much longer than that of untreated patients[41]. CRS surgery is suitable for patients below 75 years age without distant metastasis, and no contraindication signs of operation[42]. However, the elderly patients who can meet the above conditions are not many. In addition, Deepa Magge et al. found that there may be no benefit gained from CRS-HIPEC in the sarcomatoid type and biphasic groups, compared to those with epthelioid type[19]. Thus, more clinical studies on elderly MPM patients are necessary.