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Review

Challenges of Urologic Oncology in Low-to-Middle-Income Countries

by
Sami E. Majdalany
1,2,
Mohit Butaney
1,2,
Shane Tinsley
3,
Nicholas Corsi
3,
Sohrab Arora
2,
Craig G. Rogers
2 and
Firas Abdollah
1,2,*
1
VCORE—Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation, Henry Ford Hospital, Detroit, MI 48202, USA
2
Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI 48202, USA
3
School of Medicine, Wayne State University, Detroit, MI 48202, USA
*
Author to whom correspondence should be addressed.
Soc. Int. Urol. J. 2024, 5(5), 303-311; https://doi.org/10.3390/siuj5050049
Submission received: 23 June 2024 / Revised: 10 August 2024 / Accepted: 19 August 2024 / Published: 16 October 2024
Review Reports Versions Notes

Abstract

We performed a literature review to identify articles regarding the state of urological cancers in low-to-middle-income countries (LMICs). The challenges that LMICs face are multifactorial and can include poor health education, inadequate screening, as well as limited access to treatment options and trained urologists. Many of the gold standard treatments in high-income countries (HICs) are scarce in LMICs due to their poor socioeconomic status, leading to an advanced stage of disease at diagnosis and, ultimately, a higher mortality rate. These standards of care are vital components of oncological disease management; however, the current and sparse literature available from LMICs indicates that there are many obstacles delaying early diagnosis and management options in LMICs. In the era of evolving medical diagnosis and treatments, sufficient data must be gathered and understood in order to provide appropriate diagnostic and treatment options to curtail rising mortality rates and, therefore, help to alleviate the burden in LMICs.

1. Introduction

Of the 20 million new cases of cancer worldwide in 2022, 29.4% were prostate, 5.6% bladder, 4.4% kidney, 1.7% testis, and 0.79% penile cancer [1,2]. The associated death rates were as follows: 7.3%, 1.8%, 1.5%, 0.21%, and 0.28%, respectively [1,2]. Urologic cancers have increased globally, with the greatest rise in incidence and mortality seen in low-to-middle-income countries (LMICs). The expected rise in cancers can be attributed to low physical activity, high consumption of fatty and processed foods, and increased screening rates [3,4,5,6].
Currently, there are 24 low-income and 105 middle-income countries [7]. Despite the incidence of urologic cancers increasing universally, the mortality rate is higher in LMICs [4,7]. The causes are likely multifactorial, including patient, provider, and environmental factors [8,9,10]. Moreover, challenges also stem from knowledge and training deficits, diagnostic support, limited access to operative modalities, and access to disposable tools [8].
The objective of this review is to assess the factors influencing the diagnosis and treatment of urologic cancers in LMICs while demonstrating the necessity of investing in prevention and management strategies for those diseases in those regions.

2. Methods

Literature Search

In November 2022, a literature review using MEDLINE, PUBMED, and Google Scholar identified peer-reviewed publications assessing urologic oncology issues in LMICs. Based on our inclusion and exclusion criteria, we identified 67 articles.

3. Results

3.1. The Current State of Prostate Cancer in LMICs

3.1.1. Epidemiology of Incidence and Mortality

Over the last 20 years, there has been an increase in prostate cancer (PCa) cases in LMICs [9,11]. Universally, the incidence of PCa initially increased and then gradually decreased following the implementation of prostate-specific antigen (PSA) screening [4,5,6,12,13]. The use of PSA screening, including in LMICs, has been influenced by recommendations from internationally endorsed PCa screening guidelines, such as the United States Preventive Services Task Force (USPSTF). For instance, in Lebanon, PSA screening initially increased between 1994 and 2012 [14]. However, following the USPSTF recommendation against the use of PSA screening in 2012, only 29% of Lebanese providers were recommending screening in men aged ≥50 years [14,15]. This implies that changes in cancer screening guidelines in developed countries (i.e., the United States) can have significant repercussions in LMICs. This can have unintended consequences for patient populations that the guidelines were not developed to intentionally impact.
Indeed, variations in cancer screening also vary domestically and internationally among LMICs due to socioeconomic factors such as income. For example, Brazil is plagued with socioeconomic inequality, which may produce varying degrees of access to healthcare. This notion is supported by observations of higher PSA screening, resulting in greater PCa detection, in more affluent regions [16]. Limitations for more widespread screening would include costs and the availability of PSA testing in certain parts of the countries. This is corroborated by Lim et. al., which observed higher incidences of PCa in higher-income Asian countries compared to LMIC Asian countries.
Within the past five years, mortality rates have increased in LMICs [9,17]. The highest mortality rates were observed in regions such as Polynesia, Western Africa, Southern Africa, Middle Africa, and the Caribbean: Age-Standard Ratio (ASR) per 100,000: 18.8, 20.2, 22.0, 24.8, and 27.9, respectively [1]. Similar to incidence patterns, inter-regional variations both domestically and internationally in mortality rates were observed based on socioeconomic factors. More specifically, regions with higher socioeconomic status had more favorable cancer-specific mortality rates compared to lower socioeconomic areas [6,16,18]. Based on current evidence, it is reasonable to assume factors contributing to limited PCa screening and access to care could be driving the observed cancer-specific mortality rates in LMICs in contrast to HICs.

3.1.2. Treatment Options

According to the national and international PCa treatment guidelines, management recommendations are stratified based on the risk of disease progression [19,20]. Yet, in LMICs, treatment options may not be feasible due to scarce healthcare and/or patient resources [18,21,22]. As a result, adaptations to the treatment modalities are necessary. For instance, in LMICs, it has been reported that external beam radiation therapy (EBRT) hypofractionation could increase treatment capabilities from 249 to 485 courses [21]. Differences in technology and available resources may limit treatment accessibility. For example, HICs have a higher availability of radiation oncologists compared to LMICs, where there is often a shortage of trained professionals. Technology may also differ between HICs and LMICs for radiation treatments, such as Image-Guided Radiation Therapy (IGRT) and proton therapy in HICs, whereas LMIC technology has many centers that still rely on older linear accelerators, which are less precise in treatment [23,24].
Moreover, in terms of surgical intervention for PCa, due to limited access to advanced surgical technology (i.e., robotic surgery), it is typically performed using open-surgical techniques in LMICs [9]. With the late presentation of prostate cancer in LMICs, other treatment modalities should be explored, such as Androgen Deprivation Therapy (ADT), orchiectomy, and Novel Anti-Androgen Therapies and chemotherapy, if available. While ADT is a critical component of prostate cancer treatment, its accessibility and effective use in LMICs are hindered by economic, infrastructural, and social factors. Addressing these challenges requires a multi-faceted approach, including improving healthcare infrastructure, increasing awareness, and promoting education. Orchiectomy is a viable and effective treatment option for advanced prostate cancer, particularly in settings where other forms of ADT are not available or feasible. It offers a cost-effective and immediate method for reducing androgen levels.

3.2. The Current State of Bladder Cancer in LMICs

3.2.1. Incidence and Mortality

Bladder cancer (BCa) is the tenth most common cancer globally. The incidence and mortality rates are higher among males compared to their female counterparts [1,2]. BCa, similar to PCa, has higher incidence rates in developed countries (ASR in males is 20 per 100,000 per year, and ASR in females is 4.5 per 100,000 per year) compared to developing countries (ASR is 6 per 100,000 for males and 2 per 100,000 for females) [25,26]. Moreover, in an observational study, it was reported that the incidence of BCa is higher in developed nations (ASR: 12.76 per 100,000) compared to developing nations (ASR: 3.20 per 100,000) [27]. These differences in incidence between HICs and LMICs could stem from exposure to external risk factors. Further research is required to understand these phenomena.
Although the incidence of BCa is higher in developed countries, mortality rates are higher in LMICs. More specifically, the ASR per 100,000 for mortality in LMICs was 3.73 versus 2.39 in HICs [27]. The highest mortality rates were observed in Turkey and Egypt at 6.6 and 6.5 per 100,000, respectively [28]. The relatively elevated mortality rates in LMICs may be due to the fact that patients present more frequently with an advanced stage at diagnosis [29,30]. In LMICs, there have been several environmental factors associated with bladder cancer: industrial aromatic amines (rubbers and dyes), contaminated water sources (Arsenic, Schistosomiasis), Agricultural Pesticides, and tobacco. In LMICs, bladder cancer may be linked to the higher prevalence of smoking and the late presentation of hematuria. Efforts have been made by the Médecins Sans Frontières mobile clinics in Africa and Asia for the diagnosis of those presenting with hematuria. Currently, there is a lack of data investigating the incidence of advanced risk profiles at diagnosis in LMICs.

3.2.2. Treatment Options

In HICs, various treatment options (i.e., surgery, radiation therapy, chemotherapy, and/or immunotherapy) have aided in the decline of BCa mortality [30]. Though HICs present many modalities for BCa management, barriers to treatment options are challenging in LMICs [31]. These barriers include healthcare costs or the acquisition of healthcare resources required for treatment (i.e., intravesical therapy agents). For instance, a report from Lebanon showed that, from a private payer perspective, the annual cost per patient for treatment increased from $3114 in 2008 to $4135 in 2017 [32]. This reflects a 32% increase in healthcare costs [32]. As a result, with the current trajectory, the cost of treatment will severely impact those reliant on the healthcare system in Lebanon, which is able to cover only 20% of treatment costs, with the remaining amount burdening the patient [32]. Additionally, as aforementioned, data suggest that 50–90% of oncology patients in LMICs have limited access to treatment due to a shortage of equipment and trained personnel [33,34].

3.3. The Current State of Kidney Cancer in LMICs

3.3.1. Incidence and Mortality

Similarly, the incidence of kidney cancer (KCa) is higher in developed countries, where the ASR per 100,000 was 9.71 in HICs compared to 2.27 in LMICs [35]. It can be stipulated that the higher incidence of KCa in developed nations could stem from differences in lifestyle, environmental, and/or social risk factors that contribute to the development of KCa [36]. Conversely, patients in developing countries typically present with a more advanced disease at diagnosis, contributing to a higher mortality rate [37]. In developed countries, the likelihood of a patient being diagnosed with advanced KCa is lower due to intentional or incidental work-up for KCa, which is not always possible in LMICs due to limited access to care [37].
Regarding KCa mortality, ASR per 100,000 was 0.97 in LMICs versus 2.3 in HICs (where ASR is the weighted mean of age-specific mortality per 100,000 people) [2]. The MIR was the lowest in North America (0.25) and the highest in Africa (0.63). Overall, HICs have a lower MIR compared to LMICs, 0.37 and 0.50, respectively [2]. MIR is a population-based indicator for a specific cancer in a population, where the mortality rate is divided by the incidence [38]. Sung et al. also observed that MIR was lower in countries whose total expenditure on health had a higher gross domestic product percentage (R2 = 0.107 and p = 0.013) [2]. The availability of technology for screening, diagnostics, and treatments in these countries may also contribute to the decreased mortality rate compared to LMICs, whose mortality rate is higher compared to HICs [39]. A meta-analysis by Brand et al. investigating the barriers to cancer care determined that delays in presentation were due to limited access to care [39]. This delay was evident between low-income countries with a 6.5-month delay compared to upper-middle-income countries with a 1-month delay [39]. A recent study by Qu et al. categorized delays in care as poor health literacy, insufficient health service coordination, and limited diagnostic and treatment services [40].

3.3.2. Treatment Options

Treatments for renal cell carcinoma (RCC) depend on the stage of the disease, whether localized or metastatic. In localized RCC, there are three widely accepted approaches: radical nephrectomy, partial nephrectomy, and thermal ablation [41]. While robotic-assisted operations for radical and partial nephrectomies are now commonplace in the developed world (decreasing morbidity and hospital stays and improving quality of life), they are scarce in LMICs [42]. Since 2019, there have been 5582 Da Vinci Surgical Systems® installed across the globe. Of these, 63% were in the United States, and 17% were in Europe, and only 14% were in Asia, and the rest 6% were in other countries [43]. A recent study from Pakistan analyzed 119 patients (both male and female) who underwent Da Vinci robotic surgery and determined that patients had short hospital stays (a mean of 3 days) and minimal complications (17/119 patients) [43]. However, the authors noted that the cost of machine maintenance and the cost of surgery are major obstacles in an LMIC, where the gross domestic product per capita is $1188 and the cost of robotic surgery is $2156 [43,44]. Laparoscopic radical and partial nephrectomies are minimally invasive and more affordable than robotic options for LMICs. However, the constraints for these surgeries in LMICs include training expertise, resources, and healthcare constraints in accessing advanced surgical equipment.
Regarding treatments for metastatic RCC, a study by Bergerot et al. compared the trends in first (1 L), second (2 L), and third (3 L) line treatments in patients with metastatic RCC in a Brazilian health system to a previously studied cohort in the United States [45]. The authors noted substantial variability in chemotherapeutic use among different countries. Specifically, in 1 L, there was a higher use of Pazopanib in Brazil vs. the US (21.7% vs. 13.2%), and in 2 L, Everolimus was used more in Brazil vs. the United States (37.3% vs. 27.8%, respectively) [46]. This variation may reflect the lack of access to targeted treatments and/or physician education [45].

3.4. The Current State of Testes and Penile Cancer in LMICs

3.4.1. Incidence and Mortality

On a global scale, the incidence of testicular cancer has increased over several decades, while the incidence of penile cancer has been steady [47]. Although arising from different pathogenesis, the incidence rates of testicular and penile cancers are lower compared to other urologic oncological diseases. However, testicular cancers and penile malignancies occur at a disproportionately higher rate in LMICs [47]. Currently, the reasons behind the increase in testicular cancer are unclear, and the trends are being investigated. These trends illustrate a reverse pattern, with incidence being higher in HICs and mortality being higher in LMICs [48]. Higher mortality rates from testicular cancer are observed in LMICs and may be due to limited access to treatment options [48,49]. In an HIC, such as Norway, the incidence was 11.8/100,000 compared to India and Thailand, where the incidence was 0.5 and 0.4/100,000, respectively [50]. The mortality rate for southeast Asian countries was 0.3/100,000, compared to 0.2/100,000 for Northern Europe. Overall, according to GLOBOCAN 2020, the incidence in HICs was 37,131 compared to 10,245 in LMICs, and the mortality rates were 1783 and 2756, respectively [26].
In contrast, penile cancer is a rare malignancy, with its incidence rates being higher in LMICs compared to HICs, as calculated by GLOBOCAN 2020. In the United States, the incidence rate of this disease is 0.5/100,000, compared to 1.6/100,000 in India and 1.3/100,000 in Brazil [26]. The most common etiology of penile cancer is phimosis (and its related chronic infections) [51,52]. Similar to the incidence rate, the associated mortality rate illustrates a similar pattern per 100,000—higher in LMICs and lower in HICs—in the USA (0.13), India (0.72), and Brazil (0.42) [26].

3.4.2. Treatment Options

A timely diagnosis and treatment are crucial to patients with penile carcinoma, as it is highly aggressive. Unfortunately, patients in LMICs tend to receive care late, when the disease is at a more advanced stage [53,54]. Treatments usually involve surgery and/or chemotherapy. In regard to chemotherapy, the World Health Organization stated that there may be a limited supply of these agents available in Sub-Saharan Africa at any given time and that they are too expensive for the average citizen [50,55].
As with most carcinomas, management options for testicular cancers are based on staging. These treatment modalities begin with radical orchiectomy, and once pathology and stagging are confirmed, other treatments include AS, retroperitoneal lymph node dissection (RPLND), chemotherapy, or radiation [56,57]. A study in Asia showed a 5-year survival rate for primary mediastinal seminoma of 87% and for non-seminomatous mediastinal germ cell tumors (GCTs) of only 27% [58]. A study from India demonstrated a similarly unfavorable result: a 5-year survival rate for non-seminomatous mediastinal GCTs of 44.7% [59]. Compared to a single center study from China (an HIC), the 5-year survival for non-seminoma and seminoma was 54.1% and 100%, respectively [60]. In regards to treatment availability, a study from Brazil observed that only a low proportion of patients were being treated with first-line chemotherapy for salvage treatments, which was most likely attributed to the low socioeconomic support of the public health system [61].

4. Discussion

Barriers in LMICs

  • The current and future burden of urologic cancers in LMICs is an issue that must be recognized globally. As the world population continues to grow, this burden will only lead to a greater mortality incidence ratio in LMICs.
  • Although it is encouraging to see a few studies assessing the burden of cancers in LMICs, there continues to be sparse data investigating the reasons behind mortality rates of urologic oncological diseases in LMICs. Additionally, there are only a few randomized clinical trials (RCTs) in LMICs. For example, in South America and Asia, the incidence rate of penile cancer is 13.8% and 56.3%, respectively, but only two RCTs originated from these regions addressing the outcome of this disease [62]. This scarcity of RCTs may prevent patients from receiving potentially beneficial experimental treatments [62]. A study analyzing the difficulties of RCTs in LMICs has outlined potential barriers, such as enrollment issues, where patients in LMICs may be hesitant to participate due to unfamiliar terms (like “randomization”) or cultural resistance toward foreign documents [63,64,65]. These findings highlight the importance of physician-to-patient education when describing the potential benefits of RCTs. In order to facilitate education, Wong et al. suggest increasing the leadership role of physicians in LMICs to participate in RCTs [66]. In their analysis of RCTs in LMICs, from 454 publications, only 19% involved authors from an LMIC, and 17% had a first or corresponding author from an LMIC [66]. With this knowledge, it is imperative to broaden LMIC physician involvement in RCTs in order to increase patient education. Treatments are also evolving in HICs; precision and molecular medicine are now leading contenders in therapies. Currently, HICs have small sample sizes from ethnic groups within their cities. These small sample sizes make the development of precision medical treatments for other ethnicities who make up the majority of LMICs and who are non-white or Caucasian challenging. This again supports the need for increased representation of RCTs in LMICs.
In addition, there is a lack of research regarding the reasons for delayed presentation, which frequently leads to a more advanced stage at diagnosis. Regarding medical treatment and availability, a limitation in LMICs is access to a urologist. In Nigeria and Ghana, the ratio of urologists in a population is 1:3.8 million and 1:2.5 million, respectively [62]. This is a much lower availability for urologists when comparing ratios in the United States and the United Kingdom, which are 1:27,000 and 1:90,000, respectively [62]. This access to a trained urologist is a critical rate-limiting factor leading to delays in presentation. Despite the sparsity of data from LMICs, it is evident that there are disparities in access to healthcare. Initiatives tailored to the specific needs in each region, such as targeting risk factors (i.e., smoking rates in LMICs) or increasing patient education, can help affect incidence and mortality.
More recently, the COVID-19 pandemic significantly impacted healthcare systems worldwide, with particularly severe consequences, which led to delays in the presentation and management of urologic cancers. Factors of disruption included resource reallocation, suspension of screening programs, and diagnostic delays, as well as psychological impact; fear of contracting the virus in healthcare settings discouraged many patients from seeking timely medical attention, leading to a “wait-and-see” approach. In many hospital settings, urologic surgeries were triaged and systemic therapies delayed [67].

5. Conclusions

LMICs face significant challenges regarding the incidence and mortality of urological cancers. Increased use of imaging modalities or PSA screening saturation can lead to an increase in incidence. While delays in presentation to a healthcare provider decrease the early stage of diagnosis, limited access to resources may make access to top-notch therapies difficult, in turn leading to an increase in mortality. Overall, it is important to understand the issues facing LMICs; however, the lack of data from these countries must be addressed in order to make substantial changes. These changes must include patient empowerment, advances in techniques and technology, and simple practice changes.

Author Contributions

Conceptualization, S.E.M. and F.A.; methodology, S.E.M. and M.B.; resources, S.E.M., N.C. and S.A.; original draft preparation, S.E.M.; writing—review and editing, S.E.M., M.B. and S.T.; supervision, F.A. and C.G.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors have no conflicts of interest.

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MDPI and ACS Style

Majdalany, S.E.; Butaney, M.; Tinsley, S.; Corsi, N.; Arora, S.; Rogers, C.G.; Abdollah, F. Challenges of Urologic Oncology in Low-to-Middle-Income Countries. Soc. Int. Urol. J. 2024, 5, 303-311. https://doi.org/10.3390/siuj5050049

AMA Style

Majdalany SE, Butaney M, Tinsley S, Corsi N, Arora S, Rogers CG, Abdollah F. Challenges of Urologic Oncology in Low-to-Middle-Income Countries. Société Internationale d’Urologie Journal. 2024; 5(5):303-311. https://doi.org/10.3390/siuj5050049

Chicago/Turabian Style

Majdalany, Sami E., Mohit Butaney, Shane Tinsley, Nicholas Corsi, Sohrab Arora, Craig G. Rogers, and Firas Abdollah. 2024. "Challenges of Urologic Oncology in Low-to-Middle-Income Countries" Société Internationale d’Urologie Journal 5, no. 5: 303-311. https://doi.org/10.3390/siuj5050049

APA Style

Majdalany, S. E., Butaney, M., Tinsley, S., Corsi, N., Arora, S., Rogers, C. G., & Abdollah, F. (2024). Challenges of Urologic Oncology in Low-to-Middle-Income Countries. Société Internationale d’Urologie Journal, 5(5), 303-311. https://doi.org/10.3390/siuj5050049

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