Differences in prostate tumor characteristics and survival among religious groups in Songkhla, Thailand

Worldwide, the overall burden of prostate cancer has increased substantially over the last three decades, with geographical variation in incidence and mortality [1‐3]. The highest incidence rates of prostate cancer are observed in Western, developed countries such as the United States (US), (age-standardized incidence rate (ASR): 98.2 prostate cancer cases per 100,000 person-years) [4]. This high incidence can be partially explained by the implementation of population-based screening programs using the prostate-specific antigen (PSA) test in the US population [5]. However, even Western developed countries that do not conduct population-based PSA screening have relatively high incidence rates of prostate cancer (e.g. Canada: 88.9 and the UK: 73.2 prostate cancer cases per 100,000 person-years) [4]. On the other hand, incidence rates of prostate cancer are relatively low in non-Western, less developed regions such as South-East Asia (ASR: 5.5 prostate cancer cases per 100,000 person-years) [4].

Despite these current lower rates in South-East Asia, the burden of disease is expected to increase in this region and other low and middle income countries worldwide [1, 2, 6‐8]. In Thailand, prostate cancer is the fourth most common diagnosed cancer and the fourth leading cause of cancer death among Thai men [4]. In southern Thailand, incidence and mortality rates of prostate cancer have increased significantly from 1990 to 2013 at an estimated annual percent change of 4.8 and 5.3% respectively [9]. In addition, prostate cancer rates are projected to continue increasing through 2030, doubling the rates observed in 2013 [9].

Unlike the lower incidence rates in Southeast Asia, prostate cancer mortality rates are relatively high (ASMR: 6.7 deaths per 100,000 person-years) [4]; the mortality-to-incidence ratio (MIR) in Thailand is 0.51, compared to more developed countries such as the US (MIR: 0.09) [9, 10]. The lower survival rates of prostate cancer in many Asian countries is consistent with the large proportion of prostate cancer diagnosed at advanced stages, mostly due by the lack of PSA screening [11, 12]. However, we cannot rule out other factors, such as genetics, access to care, and sociocultural characteristics of Asian populations that may influence disparities in prostate cancer outcomes not only between- but also within- countries [13].

Songkhla is a province in southern Thailand, located on the eastern side of the Malay Peninsula [14]. It has 16 districts with a population of 1.5 million inhabitants [15]. The composition of the population in Songkhla is unique because of the diversity in ethnic/religious groups [14]. Approximately, 25% of the people are Muslims and 75% Buddhists. There are documented health disparities between Buddhists and Muslims in Songkhla, Thailand. These differences are thought to be due, in part, to variability in lifestyle factors because of cultural differences between these groups [16, 17]; for example, studies have reported differences in risk of cancer at several sites, including prostate cancer, as well as differences in risk of other chronic diseases and risk factors, such as metabolic syndrome, cardiovascular diseases and diabetes [17‐19]. Prostate cancer incidence rates in Muslims are lower compared to Buddhists (ASR: 8.7 prostate cancer cases per 100,000 person-years in Buddhists vs < 5 in Muslims) [17]. However, to our knowledge, no studies have examined if these differences extend to differential cancer survival between these two religious groups. Therefore, the purpose of our study was to compare the prostate tumor characteristics and the survival time after diagnosis with prostate cancer between Buddhist and Muslim men in Songkhla, Thailand.

Of the 945 prostate cancer cases, 89.2% were Buddhists and the rest Muslims, with a median age at diagnosis of 74 (Interquartile range (IQR) = 67, 79) and 72 (IQR = 68, 77) respectively (Table 1). Of tumors with known grade at diagnosis the majority were moderately/poorly differentiated. Similarly, among tumors with known stage at diagnosis, the majority were distant. In addition, Muslims seem to have a slightly higher proportion of undifferentiated and distant tumors compared to Buddhists. On the other hand, the proportion of ungraded and unstaged tumors is slightly higher in Buddhists compared to Muslims. Furthermore, more than 80% of the cases have been diagnosed since the year 2000 when universal health coverage was introduced in Thailand. We observed no statistically significant differences by religious group for any of the variables examined (Table 1). Age at diagnosis did not differ across categories of stage, grade and year of diagnosis (p-values: 0.71, 0.08 and 0.57, respectively), and, as expected, higher grade and stage tumors were statistically significantly more likely to die (data not shown).

The overall median survival time after diagnosis of prostate cancer was 3.7 years (95%CI: 3.4, 4.2), and the overall 5-year survival probability was 40.6% (95%CI: 37.0, 44.2) (Fig. 1). Despite the small number of Muslim prostate cancer cases (n = 98), we found a borderline significant difference in prostate cancer survival between Buddhists and Muslims (log-rank test, p = 0.08). The median survival time was longer in Buddhists 3.8 years (95%CI: 3.4, 4.3) compared to Muslims 3.2 years (95%CI: 2.0, 4.4) (Fig. 2, and Table 2). Similarly, Buddhists have a higher 5-year survival probability of prostate cancer than Muslims, 41.3% (95%CI: 37.4, 45.0) vs 34.7% (95%CI: 23.8, 45.8), respectively (Table 2).

We next estimated differences in survival after diagnosis between religious groups. After adjustment for age at diagnosis, Muslim men were more likely to die of any cause post-diagnosis with prostate cancer compared to Buddhist men (HR: 1.31, 95%CI: 1.00, 1.72; p = 0.04). This finding was only slightly attenuated after further adjustment for stage and grade at diagnosis (HR: 1.27, 95%CI: 0.97, 1.67; p = 0.06). There was no evidence of statistically significant interactions between religious group and age (p = 0.64), grade (p = 0.22) or stage at diagnosis (p = 0.29). In addition, our multiple imputation analysis from 100 imputed datasets yielded similar results for the multivariable-adjusted Cox regression model, the estimated HR for death in Muslims vs Buddhists was 1.28 (95%CI: 0.97, 1.66). Furthermore, the overall stage distribution and by religious groups remain similar after multiple imputation (Additional file 1: Table S1).

Estimates from the overall median survival time (years) by period after partitioning follow-up time show that although overall, there are modest increases in the median survival time and 12-months, 2- and 5-years survival probabilities pre- and post- introduction of universal health access, these increases appear limited to Buddhist men. The 1-year survival probability increases from 77.9% in 1990–1999 to 83.6% in 2010–2014 in Buddhists. On the other hand, among Muslims the 1-year survival probability remained unchanged during 1990–1999: 75.0% and 2010–2014: 75.5% (Table 3). Finally, the three methods used to account for time (person-years, calendar time, and age) yielded similar results in both the age-adjusted and fully-adjusted models (Table 4).

We compared prostate cancer characteristics and survival after diagnosis between Muslim and Buddhist men in Songkhla, Thailand. We found that Muslim men had a higher risk of death after diagnosis of prostate cancer compared to Buddhists, finding which was not fully explained by differences in tumor characteristics at diagnosis. However, the large number of unstaged and ungraded tumors in both groups does not allow for complete adjustment for these factors even when imputation was used to attempt to assign stage and grade to those with missing information. Differences in the distribution of tumor characteristics among those with missing information by religious groups might still explain the observed survival differences.

Overall, the percent of people surviving five years after diagnosis of prostate cancer is lower in Thailand (40.6%) compared to more developed countries such as the US (98.9%). This is partially explained by the widespread use of PSA screening in the US. In Thailand, PSA is not used for screening purposes, although, it is part of the diagnostic workup in patients with suspected prostate cancer. Other factors such as sociocultural characteristics and genetics may explain the differences in prostate cancer outcomes. Importantly, differences in life expectancy between Thailand and more developed countries such as the US is unlikely to explain the difference in survival as the life expectancy in Thai males is close to the US males (72.0 vs 76.1 years) [15, 24].

Our findings are consistent with those from several published studies that suggest that Muslim populations have poorer cancer survival after diagnosis compared to other ethnic and religious groups [23, 25‐29]. In Songkhla, Thailand, lower survival rates for oral, breast and cervical cancer have been observed among Muslims compared to Buddhists [25]. Another study conducted in Asian populations found that breast cancer survival is higher among Indian (54%) and Chinese (49%) women compared to Malay women (45%), which is a predominantly Muslim population [26]. In addition, Malay women are more likely to be diagnosed at advanced stages of breast cancer than other ethnic/religious groups [27]. It should be noted that the Muslims in Songkhla, Thailand are predominantly of Malay descent. Similarly, a study conducted in Northern Israel found that Arab women are more likely to be diagnosed at advanced stage for breast cancer, and with more aggressive disease compared to their Jewish counterparts, likely due to differences in genetic susceptibility as well as socioeconomic factors [28]. In the US, a prostate cancer survival study found that risk of death after diagnosis of the disease is 40% higher among South Asian men compared to Whites [30].

It remains unclear why Muslims may experience poorer cancer outcomes. In Thailand, access to healthcare is relatively consistent across the country, and there are ongoing efforts to integrate Muslims in Songkhla into communities along with Buddhists. The Thai government has established policies for cultural assimilation of minority religious groups (e.g. promotion of Thai language and identity). However, there has been resistance to these policies, and cultural differences do persist. For example, some Muslims in southern Thailand speak Yawi (a Malay dialect) as their first language, creating barriers to communicating with healthcare providers who largely speak Thai [25]. In addition, cultural beliefs could be an important barrier for individuals to seek and/or receive healthcare [31]. This may cause delay in diagnosis and treatment for cancer. For example, one study found that Thai Muslims experienced delays in the time from diagnosis to treatment for oral cancer compared to Buddhists, which the authors concluded was likely due to differences in health attitudes, among Muslims in Thailand [32, 33]. Another study that evaluated knowledge and health belief attitudes for oral cancer among Thai Muslims found that they are more likely to use traditional medicine to prevent and treat oral cancer, even if diagnosis of oral cancer was confirmed in a hospital setting [33].

Several studies have reported that the perspectives of sickness and death among Muslims are different than other religious groups [34]. In some studies about health attitudes and knowledge, Muslims have reported a perception of sickness as a God’s proof of their faithfulness [35]. This belief may lead individuals to delay seeking medical care for their cancer, which may partially explain the poorer survival from prostate cancer among Muslim men in Songkhla. Anecdotal evidence from physicians practicing in Songkhla, Thailand suggests that Muslims may be less likely to accept treatment after a diagnosis with cancer, despite having equal access to high quality care. Supporting this, our findings have shown that survival has not improved among Muslims after the introduction of universal health care. Although, reports from a recent WHO report (CONCORD-3) show that prostate cancer survival in Thailand appear to increase by 10% from 1995 to 2014 [36]. In addition, the risk of death after prostate cancer diagnosis appear to increase in Muslims compared to Buddhists after the introduction of the universal healthcare access, e.g. 1990–1999 HR: 0.96, 95%CI: 0.21, 4.19; 2010–2014 HR: 1.52, 95%CI: 1.00, 2.30 (Additional file 1: Table S2). However, this increase is not statistically significant and the number of deaths were small for the earliest period. One possible concern is that if competing risks from other causes of death differ by religious group, this may bias our findings. However, studies comparing chronic disease risk factors between Muslims and Buddhists in Thailand have noted few differences in risk factor profiles by religion [18, 19] . Thus, competing risks seems unlikely to fully explain our findings. Further research is warranted to identify what factors may play a role in the increased risk of death among Muslim men diagnosed with prostate cancer in Thailand and whether similar disparities in cancer survival exist for other cancer sites or chronic conditions.

Muslim men had a higher risk of death after diagnosis of prostate cancer compared to Buddhist men. In contrast with Buddhists, prostate cancer survival has remained constant in Muslims even after the introduction of universal health care access. It is important to understand what risk factors may underlie the poorer survival observed in Muslims to design targeted interventions in both populations.