The prevalence of prostate cancer in Pakistan: A systematic review and meta-analysis

Background Prostate cancer is a significant public health issue, ranking as the second most common cancer and the fifth leading cause of cancer-related deaths in men. In Pakistan, the prevalence of prostate cancer varies significantly across published articles. This study aimed to determine the pooled prevalence of prostate cancer and its associated risk factors in Pakistan. Methods MEDLINE (via PubMed), Web of Science, Google Scholar, and local databases were searched from inception until March 2023, using key search terms related to the prevalence of prostate cancer. We considered a random-effects meta-analysis to derive the pooled prevalence and relative risks with 95% CIs. Two investigators independently screened articles and performed data extraction and risk of bias analysis. We also conducted meta-regression analysis and stratification to investigate heterogeneity. This study protocol was registered at PROSPERO, number CRD42022376061. Results Our meta-analysis incorporated 11 articles with a total sample size of 184,384. The overall pooled prevalence of prostate cancer was 5.20% (95% CI: 3.72–6.90%), with substantial heterogeneity among estimates (I2 = 98.5%). The 95% prediction interval of prostate cancer was ranged from 1.74%–10.35%. Subgroup meta-analysis revealed that the highest pooled prevalence of prostate cancer was in Khyber Pakhtunkhwa (8.29%; 95% CI: 6.13–10.74%, n = 1), followed by Punjab (8.09%; 95% CI:7.36–8.86%, n = 3), while the lowest was found in Sindh (3.30%; 95% CI: 2.37–4.38%, n = 5). From 2000 to 2010 to 2011–2023, the prevalence of prostate cancer increased significantly from 3.88% (95% CI: 2.72–5.23%) to 5.80% (95% CI: 3.76–8.24%). Conclusions Our meta-analysis provides essential insights into the prevalence of prostate cancer in Pakistan, highlighting the need for continued research and interventions to address this pressing health issue.


Introduction
Cancer is a primary reason of death globally, accounting for over 10 million deaths in 2020, or roughly one in every six deaths * Corresponding author.The University of Haripur, KP, Pakistan.** Corresponding author.Postdoc EIAS Lab, Prince Sultan University, Saudi Arabia.
Contents lists available at ScienceDirect [1-5].Prostate cancer is the most prevalent cancer among men and the second leading cause of cancer mortality after skin cancer [6].
Worldwide, an estimated 1,414,259 new cases and 375,304 deaths were linked to prostate cancer in 2020 [6].The prevalence of prostate cancer varies across different countries, with higher rates found in Eastern countries.In 2020, over 1.4 million new cases and 381,000 deaths were reported due to prostate cancer, making it the most commonly diagnosed cancer among men.By 2030, the number of new cases and deaths will increase significantly [7].Prostate cancer is a primary health concern and a significant economic burden.According to a study, the global financial cost of prostate cancer was estimated to be approximately $12.1 billion in 2010 [8].The cost of treatment, loss of productivity, and other indirect costs associated with prostate cancer can devastate families and communities.As age increases, there is a correlation between the prevalence and mortality of prostate cancer worldwide, with an average age of 66 years at diagnosis [9].It is worth noting that African-American men have higher incidence rates compared to white men, with 158.3 new cases per 100,000 men, and their mortality rates are about twice as high as those of White men [10].Some Asian countries, such as Israel, Lebanon, Kuwait, the United Arab Emirates, Qatar, Oman, and Japan, have a higher incidence of prostate cancer.The incidence rate of prostate cancer is 10.5 in Eastern Asia, 11.2 in Southeast Asia, and 4.5 in South Central Asia, with rising mortality rates [11,12].Prostate cancer is among the top ten most common cancers and the third most widespread genitourinary cancer among males in Pakistan [13].The prevalence of prostate cancer significantly varies in the published articles.There is no country-wide survey to estimate the overall prevalence of prostate cancer in the Pakistani community.As Pakistan is a developing country, Pakistan's healthcare system faces several challenges [14,15], such as insufficient funding, inadequate infrastructure, a shortage of healthcare professionals, and inequitable distribution of resources.This study aims to systematically find, quantify, and summarise the available data on the prevalence of prostate cancer in Pakistan.This study aims to bridge this knowledge gap and provide valuable information for policymakers and physicians to plan better and prevent prostate cancer in Pakistan.

Methods
The PRISMA guidelines (attached in supplementary file S1) were followed for this systematic review and meta-analysis [16], and the protocol is included in the supplemental file in Table 1.In November 2022, it was registered with PROSPERO (with registration no.CRD42022376061).
Search Strategy.In this study, the PRISMA guidelines [16] were followed.To find information about the prevalence of prostate cancer in Pakistan, the following electronic databases were used: PubMed, Google Scholar, and Web of Science.We used a keyword procedure to match the search phrases to the Medical Subject Heading.Moreover, to combine and separate the search strings, boolean operators such as OR and AND were used.We used (prevalence) AND (prostate OR cancer OR prostate cancer OR PCa) AND (Pakistan OR Pakistani) to find essential articles.The prevalence of prostate cancer in Pakistan was mentioned in articles published between 2000 and 2023.
Criteria for inclusion.The study included peer-reviewed journal publications on the prevalence of prostate cancer in Pakistan.The articles were all original research publications in English that provided essential data on the study population, diagnostic processes, and the prevalence of prostate cancer in different locations around Pakistan.
Criteria for Exclusion.This study excluded articles that did not provide data on the prevalence of prostate cancer, had an unknown sample size, or had case-control studies.
Data Extraction.The authors of this study created a collaborative data extraction form in Microsoft Excel, which comprised the first author's name, year of publication, study design, sample size, overall prostate cancer prevalence, setting, province, gender, working year, and diagnosis method.To ensure accuracy and consistency, the reliability of the extracted data was thoroughly reviewed, and any inconsistencies were resolved through detailed discussion among the authors.Additionally, the eliminated data files were rigorously scrutinized for accuracy.
Quality Assessment.The JBI Critical Appraisal Checklist for Studies [17] was used by two authors (S.A. and F.H.) to assess the risk of bias in selected research independently.Each investigation was assigned a quality score between 0 and 9, which was used to determine the probability of bias.Studies with a score of 1-3 were considered to have a higher likelihood of bias, those with a score of 4-6 had a medium possibility of bias, and those with a score of 7-9 had a low chance of bias.
Analysis.We utilized the statistical software R (version 4.2.1) for all of our analyses, with a statistically significant P value of 0.05 being determined for the statistical pooling of prostate cancer prevalence in Pakistan.We employed Der Simonian-Laird models with random effects [18,19] and tested for statistical heterogeneity using the Cochrane Q-statistic and I 2 , where I 2 greater than 50% defined heterogeneity [20,21].We displayed the pooled results with 95% confidence intervals (CIs) and a forest plot.We computed the prediction interval to find the range in which the pooled effect deviates from the mean.Initially, we conducted visual and statistical analyses of publication bias using funnel plots and the Egger regression and Beggs tests [22,23].Subgroup analysis was utilized in cases of significant heterogeneity to identify potential sources of heterogeneity.Various extracted variables, such as species (province, setting, and time), were used for subgroup meta-analyses.
Furthermore, meta-regression analysis was performed to explore heterogeneity further and determine the relationship between prostate cancer prevalence and study characteristics.The meta-regression included publication year, sample size, and investigation year.To better understand the impact of each study on the overall prevalence estimates, sensitivity analyses were conducted by systematically removing each study and re-analyzing the data.This helped to identify any potential outliers or sources of bias that may be driving the overall estimates.Furthermore, to assess the degree of agreement between the investigators, the Kappa statistic [24] was used to measure inter-rater reliability.
S. Akhtar et al.

Result
Fig. 1 depicts the adherence to the PRISMA guidelines for article selection, with 301 studies identified-301 from database searches and ten from reference lists.Following deduplication (n = 131) and careful screening of the titles and abstracts of 180 articles, 156 studies were removed.The full text of the remaining 24 studies was examined to assess their eligibility for inclusion, and those that did not meet the inclusion criteria were excluded.Ultimately, eleven articles were selected for analysis.The inter-rater agreement for study selection was deemed good (Kappa = 0.79, p = 0.01).

Discussion
Prostate cancer is a significant health concern in Pakistan.According to the Pakistan National Cancer Registry, prostate cancer is the second most common cancer among men in the country [36].Therefore, we performed this systematic review and meta-analysis to provide a pooled estimate of prostate cancer in Pakistan.This meta-analysis is based on data published between 2000 and 2023.The study utilized data from 11 distinct data sets with 184,384 prostate cancers from geographically varied Pakistani populations.Our study aims to give helpful information about prostate cancer to the health authorities of Pakistan so that something can be done to prevent deadly diseases like prostate cancer.The overall prevalence of prostate cancer was 5.20%, which shows the prevalence of prostate cancer in Pakistan.The findings of this meta-analysis are almost consistent with the study conducted in Iran, at 6.3% [37] and lower than in the studies conducted in Nigeria, at 8.8% [38].This disparity may be attributable to variations in research techniques, sample size, social, environmental, and genetic factors, and the universal definition of prostate cancer.
Subgroup meta-analysis by study location revealed that the pooled prevalence of prostate cancer was highest in Khyber Pakhtunkhwa (8.29%), followed by Punjab (8.09%), and lowest in Sindh (3.3%).The disparity in the prevalence of prostate cancer in different provinces may be due to socioeconomic and sociocultural differences between populations, variations in screening methods, or there may be no higher research on prostate cancer in those areas.Subgroup meta-analysis by setting revealed that the prevalence of prostate cancer was significantly higher in Urban areas than in Rural areas.This study also found that the prevalence of prostate cancer has increased over time, with the prevalence being 3.88% from 2000 to 2010, while the prevalence from 2011 to 2023 was 5.80%.
The following are some of the limitations of our study: seven studies had a medium risk of bias, while four had a low risk of bias.Second, the results are based on data from only three provinces.They lack data from two populous regions, Baluchistan and Azad Kashmir, limiting generalization to the entire country.Third, it is limited to peer-reviewed studies, which may result in publication bias.Additionally, high heterogeneity was detected in the analysis, which is common in meta-analyses of prevalence data.Finally, our    study only included peer-reviewed studies and excluded grey literature.In this study, despite limitations, our transparent approach involved publishing a study protocol and utilizing scientific and statistical methods, including subgroup and meta-regression analyses, to account for potential influencing variables in our estimate.

Conclusion
This study examines the prevalence of prostate cancer in the male Pakistani population from 2000 to 2023.According to this study, the pooled prostate cancer prevalence in Pakistan was 5.20%.However, it differed significantly by geographical subgroup, with Khyber Pakhtunkhwa having the highest rate and Sindh having the lowest.A nationwide cancer registry must be established.

Fig. 2 .
Fig. 2. Forest plot of the pooled prevalence of prostate cancer in Pakistan.

Fig. 4 .
Fig. 4. Sensitivity analysis of the prevalence of prostate cancer in Pakistan.
General characteristics of the included articles.

Table 2
describes the results of overall and subgroup meta-analyses of prostate cancer patients in Pakistan.The included studies reported a range of prevalence estimates for prostate cancer in Pakistan, from 2.2% to 9.4%.The random-effects total pooled estimated

Table 2
Meta-analysis estimates of prostate cancer in Pakistan.

Table 3
Univariate meta-regression analysis of prostate cancer.