Prostate cancer is the second most frequently diagnosed cancer in men and the sixth leading cause of cancer-related death among men [1]. Each year, there are more than 1,100,000 new cases of the disease, and more than 300,000 deaths occur due to prostate cancer worldwide. The disease is more common among older men, with a median age at diagnosis around age above 60 years [2]. Given that the disease is often asymptomatic in its early stages, its diagnosis is usually based on abnormal prostate-specific antigen (PSA) levels followed by a transrectal ultrasound-guided biopsy, digital rectal exam, or both [3]. CT is a widely used modality in both the diagnosis and follow-up of nearly all malignancies, but it has only a limited role in the imaging of prostate cancer owing to its poor soft-tissue contrast resolution, which does not allow precise distinction of the internal or external anatomy of the prostate. The major role of CT in patients with prostate cancer is for the detection of bony involvement and nodal staging; however, CT only detects the enlargement of involved nodes, which is a late finding in patients with prostate cancer [4]. Figure 1 shows CT images of prostate cancer.

A CT image of metastatic prostate cancer with lymph node extension can be seen in Figure 2.

However, due to the poverty in Africa [5], diseases that do not immediately threaten people’s well-being are often neglected and underdiagnosed, which implies that prostate cancer is often diagnosed late. According to a study conducted by Le Roux et al. in South Africa, 66% of the Zulu population of KwaZulu-Natal presented with either radiological evidence of metastasis or serum PSA levels of more than 100 ng/ml, and only 81 out of a possible 625 cases of prostate cancer were diagnosed early [6]. Seraphin et al. also reported that only 23.6% of prostate cancer cases were diagnosed at stages I and II in sub-Saharan Africa, and the

late diagnosis of the disease in this part of the world comes with consequences such as higher rates of disease-related morbidity and mortality [7]. Also, the prevalence of prostate cancer in sub-Saharan Africa is constantly increasing. According to Ogunbiyi, prostate cancer, which affects up to 11% of the men in Nigeria, is the most common form of cancer among men in that country [8]. This steady increase in the prevalence of the condition is also accompanied by increments in the rates of disease-related morbidity and mortality. The 2013 Institute for Health Metrics and Evaluation (IHME) study further reported increasing disability-adjusted life years (DALYs) and mortality from prostate cancer, with an estimated 61% and 83% increase in DALYs and deaths from prostate cancer, respectively between 1990 and 2013 [9] [10]. In sub-Saharan Africa (SSA) alone, IHME estimated that DALYs from prostate cancer increased from 100,200 in 1990 to 219,700 in 2010, and the number of deaths also increased from 5600 to 12,300 over the same period [11] [12]. With such a huge disease burden and risk of death, it is important to identify factors indicative of prostate cancer aggressivity and a poor prognosis (usually the patient’s demise). Gann identified age, African-American ethnicity, and a contributive family history as risk factors for prostate cancer [13]. Furthermore, Lietzmann and Rohrmann reported that the only firmly established non-modifiable risk factors for the condition are age, race, and a contributive family history. They also reported that the frequent consumption of dairy products and meat also enhances the development of prostate cancer and that smoking and obesity are positively correlated with prostate cancer-related mortality [14]. However, there is a paucity of studies on the risk factors and determinants of a poor prognosis of the disease in sub-Saharan Africa.

This is a retrospective study that was carried out from 2015 to 2020 at the Centre medico-chirugical d’urologie in Douala, Cameroon. We included 203 patients who had prostate cancer diagnosed via histopathology after either prostate biopsy or transurethral prostate resection (TURP) and excluded all patients with incomplete clinical records. The indications for a prostate biopsy in our study were serum PSA level >4 ng/ml and/or abnormal findings during a digital rectal examination (DRE). The data collected from the clinical records of our study participants included each patient’s age, profession, year of diagnosis, body mass index (BMI), method of positive diagnosis employed, family history of prostate cancer, clinical presentation (including digital rectal examination findings), complications of the disease (including hip fractures, lymphoedema, and paraplegia), serum prostate-specific antigen (PSA) level, transrectal ultrasound (TRUS) findings (including the prostate volume and the presence of an abnormal prostatic echostructure), hemoglobin level, initial Gleason score, presence or absence of metastases, site of metastasis, histological grade, initial treatment (including radiotherapy, gosereline (zoladex) 10.8 mg, triptoreline (decapeptyl) 11.25 mg, laparoscopic prostatectomy, pulpectomy, watchful waiting, and surveillance), second treatment (including radiotherapy, docetaxel (Taxotere), abiraterone acetate (abirat), gosereline, and triptoreline), third treatment (including decetaxel, abiraterone acetate, gosereline, and tripitoreline), total follow-up duration, and outcome (survival/death). After the diagnosis was made and the initial treatment was administered, all the patients were followed up monthly. During the monthly follow-up visits, the patients were examined and certain parameters (including the patient’s weight, height, blood pressure, pulse, BMI, and hemoglobin level) were measured for follow-up. Every after three months, patients’ serum PSA levels were measured as well. Normally, the PSA levels were expected to decrease; however, if they stayed constant or increased, the patients concerned were given a second treatment, and even a third if the PSA levels did not decrease. To facilitate data analyses, we classified participants’ professions into four main categories. Those in the first category were skilled workers such as engineers, doctors, teachers, lawyers, magistrates, and technicians. Those in the second category were the unskilled workers such as traders, bricklayers, and drivers. Those in the third category were retired people and those in the fourth category were law enforcement officers, mainly police officers and soldiers.DRE findings were considered remarkable if the examiner felt indurations and/or nodules on the prostate gland on palpation. In our study, an abnormal echostructure was defined as the presence of hyperechoic, hypoechoic, or mixed ultrasonic patterns in certain regions of the prostate gland [15], especially the peripheries of the gland, as it has been established that prostate cancer is located in the peripheries of the gland in up to 70% of cases [16]. According to the WHO classification, A BMI of <18.5 kg/m² was considered underweight, 18.5 - 24.9 kg/m² was considered normal weight, 25 - 29.9 kg/m² was considered overweight, and ≥30 kg/m² was considered obesity (30 - 34.9 kg/m² was considered class I obesity, 35 - 39.9 kg/m² was considered class II obesity, and ≥40 kg/m² was considered morbid obesity) [17]. According to the WHO’s definition of anemia [18], participants with hemoglobin levels of less than 13 g/dl were considered anemic. The volume of each participant’s prostate gland was measured via TRUS, bearing in mind that the normal average volume in men of this age groupis 38 ml [19]. The tumors were classified using the Gleason and International Society of Urological Pathology (ISUP) grading systems, which are presented in Figure 3.

In this study, it was not possible to ascertain the tumor aggressivity in all the study participants since not all of them underwent surgery. So, the criteria for aggressivity in this study were the presence of metastases, serum PSA >50 ng/ml, and a Gleason score of ≥8, and patients who fulfilled these three criteria were considered to have aggressive prostate cancer. Biopsy was performed using a biopsy gun with the patients in the lateral decubitus position and under local anesthesia (using 2% Xylocaine). These biopsy samples were placed in formol inside little containers and transported immediately to the laboratory for histopathological analyses. In this study, histopathology was performed only for patients who underwent laparoscopic prostatectomy. All study participants received 500 mg of ciprofloxacin twice daily two days before and three days after a

biopsy.

All study data were entered into Microsoft excel 2007 and exported to Epi Info 7 for analysis. Continuous data were presented using the mean value and standard deviation for variables with normally distributed data and the median and interquartile range for variables with skewed data distributions. Categorical data were presented as frequencies and percentages. The Mann-Whitney U test and Student’s t-test were used to compare continuous data for skewed and normally distributed variables, respectively, while the chi-square test was used to compare proportions between categorical variables. Kaplan-Meier survival analyses were performed to determine the five-year overall survival of our study participants. P-values of ≤0.05 were considered statistically significant. This study was approved by the institutional review board of the Faculty of Medicine and Pharmaceutical Sciences of the University of Douala and the ethics committee of the Centre medico-chirugicale d’urologie, Douala, Cameroon. The requirement for informed consent was waived due to the retrospective study design.

In this study, we included 203 patients aged 41 years to 85 years who had prostate cancer diagnosed via histopathology after either prostate biopsy or laparoscopic prostatectomy. The mean age of our study participants was 64.76 ± 7.48 years. The most predominant age group was the 61 - 70 years age group, which accounted for 49.26% of our study participants, while the least common age groups were the 40 - 50 years and >80 years age groups, which each accounted for 1.97% of our study participants. The vast majority of our study participants (95.07%) did not declare having a family history of prostate cancer. More than half of our study participants were diagnosed in 2017 and 2018 (26.11% and 26.60%, respectively). The samples for histopathology were obtained through a prostate biopsy in 75.86% of our study participants and through TURP in 24.14% of them. The follow-up durations of our study participants ranged from 132 days to 2385 days with a median value of 951 [623 - 1278] days. The general information of our study participants is presented in Table 1.

*TURP = Transurethral resection of the prostate.

Regarding the initial clinical presentations of the study participants, 16.75% of them were asymptomatic, 61.58% had lower urinary tract symptoms, and 21.67% had acute urinary retention. A majority of our study participants (96.55%) had no complications; however, 1.97% of them had paraplegia, 0.49% had hip fractures, and 0.99% had lymphoedema. DRE findings were remarkable in 43.35% of study participants and unremarkable in 56.65% of study participants. The BMIs of the study participants ranged from 18.4 kg/m² to 42.4 kg/m² with a mean value of 26.98 ± 3.91 kg/m². Participants’ PSA levels ranged from 4.28 ng/ml to 8832 ng/ml with a median value of 44.20 [16.80 - 169.30]. Participants’ hemoglobin levels ranged from 6.3 g/dl to 17.0 g/dl with a mean value of 12.43 ± 2.26 g/dl. According to the participants’ hemoglobin levels, 49.26% of them were anemic. Per our definition of aggressive prostate cancer (the presence of metastases PLUS serum PSA >50 ng/ml PLUS Gleason score ≥8), 17.73% of our study participants had an aggressive form of the disease. The prostate volume on ultrasound ranged from 17 ml to 450 ml with a median value of 59 [43 - 80] ml. An abnormal echostructure was found in 29.06% of our study participants. The clinical, biological, and imaging profiles of the study participants are shown in Table 2.

The Gleason scores of our participants ranged from 6 to 9. The Gleason scores of our participants ranged from 6 to 9. The most common score was 6 (3+3), which accounted for 34.98% of our study participants, while the least common score was 8 (5+3), which accounted for 1.97% of our study participants. Sixty-four (33.51%) of our study participants had metastases while 127 (66.49%) of them did not. Of the 64 patients with metastases, 8 (12.5%) had metastases in the bones only, 24 (37.5%) had metastases in the ganglions only, 30 (46.88%) had metastases in the bones and ganglions, and 1 (0.52%) each had metastases in the liver and lungs. The histological classifications for 114 (patients who underwent laparoscopic prostatectomy) out of our 203 participants were available. The most common histological grade was pT2bN0M0, which was found in 13.16% of those with available histological grades. The Gleason scores and histopathological grades of our study participants are presented in Table 3.

The initialtreatment of the patients was radiotherapy in 5.91%, gosereline 10.8 mg in 20.69%, triptoreline 11.25 mg in 10.34%, laparoscopic prostatectomy in 56.16%, pulpectomy in 5.42%, watchful waiting in 0.99%, and surveillance in 0.45% of our study participants. Out of the 203 participants that received initial treatment, 37.93% received a second treatment. Of these, 49.35% underwent radiotherapy, 11.69% received docetaxel, 25.97% received abiraterone acetate, 9.1% received gosereline, and 3.90% received triptoreline. Twenty-four (31.17%) of the 77 patients who received a second treatment went on to receive a third. Of these 24, 16.67% received decetaxel, 4.17% received abiraterone acetate, 54.17% received gosereline, and 25% received tripitoreline. Thirty-three (16.26%) of our study participants died during the follow-up period. The follow-up period varied from 132 days to 2385 days, with a median duration of 951 [623 - 1278] days.

*Others include: pT1aNOM0, pT1cNxMx, pT3aNxMx, pT2cNxMx, pT1cN0M0, pT2bNxMx, pT2bN1M0, pT3bN0M0, pT1aN0M0, pT2cN1M0, and pT1G1NxMx.

The details of the treatment, follow-up, and outcomes of the study participants can be seen in Table 4.

Concerning the factors associated with prostate cancer aggressivity, there was no significant difference between the mean age of the patients with aggressive cancer and that of patients with non-aggressive cancer (odds ratio undefined, p-value 0.70). We found significant associations between certain professions (unskilled labor; odds ratio 2.10; 95% confidence interval [0.95 - 4.66]; p-value 0.05), the presence of paraplegia (odds ratio undefined, p-value < 0.001), the presence of lymphoedema (odds ratio undefined, p-value: 0.03), a remarkable DRE (odds ratio undefined, p-value < 0.001), anemia (odds ratio 16.41; 95% confidence interval [4.84 - 55.71], p-value < 0.001), large (volume > 50 ml) prostate glands (odds ratio 5.18; 95% confidence interval [1.92 - 13.97], p-value < 0.001), and abnormal prostate echostructures on transrectal ultrasound (odds ratio 0.18; 95% confidence interval [0.08 - 0.38], p-value < 0.001), and the presence of aggressive prostate cancer. The factors associated with prostate cancer aggressivity are presented in Table 5.

*LUTS = Lower Urinary Tract Symptoms.

Regarding the factors associated with patients’ outcomes, there was no significant association between the mean age and participants’ outcomes (odds ratio undefined, p-value 0.45). We found significant associations between the presence or absence of lymphoedema (odds ratio undefined, p-value: 0.02), DRE findings (odds ratio undefined, p-value < 0.001), the presence or absence of anemia (odds ratio 0.02; 95% confidence interval [0.003 - 0.16], p-value < 0.001), the volume of the prostate gland (odds ratio 0.28; 95% confidence interval [0.11 - 0.72], p-value 0.004), the prostatic echostructure (odds ratio 8.56; 95% confidence interval [3.74 - 19.61], p-value < 0.001), and the type of cancer (aggressive or non-aggressive: odds ratio 0.04; 95% confidence interval [0.02 - 0.11], p-value < 0.001) and patients’ outcomes (survival or demise). The factors associated with patients’ outcomes are presented in Table 6.

We aimed to identify factors indicative of prostate cancer aggressivity and a poor prognosis in patients with the condition. In this retrospective study, we included 203 patients with a mean age of 64.76 ± 7.48 years, which is similar to the 68 years reported by Fofana et al. in the Ivory Coast in 2017 [20]. This similarity in the mean age can be explained by the fact that both studies were carried out in sub-Saharan African countries. Also, the samples were representative of the population of patients with prostate cancer in both cases. In our study, 4.93 of the participants declared having a family history of prostate cancer. This is lower than the 15% reported by Steinberg et al. [21]. This difference can be accounted for by the fact that Steinberg et al. carried out their study in the United States, a country where public awareness of the disease is much higher and the disease is often diagnosed much earlier than it is in Cameroon. In our resource-limited setting, many cases of this disease currently go undiagnosed, and deaths due to prostate cancer are often blamed either on witchcraft or natural causes since the age of onset of the condition often coincides with the life expectancy for men in this part of the world. Increasing the rate of diagnosis of this condition in Cameroon will undoubtedly increase the proportion of people who report a contributive family history. We found that the presence of LUTS (61.58%) was the most common clinical presentation of the disease. This is in line with the findings of Merriel et al. in 2018 [22]. The presence of these symptoms is probably because the condition is often diagnosed at an advanced stage in this part of the globe. Studies conducted in the developed world report that early-stage prostate cancer is usually asymptomatic [23]. One of the main barriers to the early diagnosis of prostate cancer in Cameroon is that due to the low socioeconomic level of people in the country, routine checkups are not a common practice. Also, due to societal stereotypes and homophobia, people tend to shun digital rectal examinations, which are vital in the clinical diagnosis of the condition. Thus, much work needs to be done to sensitize people (especially men above the age of 50 years) and convince them to go for routine prostate examinations that will certainly increase the rate of diagnosis of the condition and also enable the condition to be diagnosed earlier. All our study participants had serum PSA levels of more than 4 ng/ml, which is in line with previous studies that recommend prostate biopsy and histopathology for patients with serum PSA levels of more than 4 ng/ml [24]. Although serum PSA at this cutoff has been reported to have a low sensitivity (20.5%), its high specificity (93.6%) makes this marker an asset in the diagnosis of the condition [25]. In our study, 49.26% of the participants were anemic. This is in line with the findings of previous studies that identify anemia as one of the features of advanced prostate cancer [26] [27]. The origin of prostate cancer-associated anemia is often multifactorial, with factors such as bone marrow metastases that lead to decreased hematopoiesis, radiotherapy that reduces bone marrow productivity, androgen deprivation therapy that takes a toll on erythropoiesis, and the chronic inflammatory state associated with the condition itself [26] [28]. We found that 17.73% of the participants had an aggressive form of the disease. This percentage is similar to the 15% reported by Ballentine Carter [29]. This similarity is probably because both studies were carried out in people of the same age group. This high prevalence of aggressive forms of the disease is undesirable as these forms are often associated with a poor prognosis. Hence, more efforts need to be put in to ensure that the condition is diagnosed early enough in our context. The median prostate volume in our study was 59 [43 - 80] ml, which is greater than the mean volume of 35.03 ± 17.41 ml in men aged 60 - 70 years reported by Zhang et al. in China [30]. This difference is mainly because Zhang et al. carried out a community-based study in which they included 1000 volunteers, irrespective of the state of health of their prostate glands, while we included 203 patients who had already been diagnosed with prostate cancer.

We found that 29.06% of our study participants had abnormal prostate echostructures indicative of prostate cancer during TRUS. This is much lower than the 50.87% reported by Maricic et al. in Croatia in 2010 [31]. This difference is probably because, in the developed world where resources are more available, TRUS is usually not plain but enhanced. Ultrasound techniques such as contrast-enhanced sonography using continuous harmonic imaging and intermittent harmonic imaging, as well as continuous color and power Doppler [32], are more efficient than plain ultrasonography. With such enhancements that are not often available in our resource-limited setting, the sensitivity of ultrasonography in the diagnosis of prostate cancer will definitely be higher. In this study, 16.26% of the participants died during the follow-up period. This is lower than the 21% reported by Braga et al. in Brazil in 2021 [33]. This difference can be accounted for by the fact that the average age of their study participants (70.5 years) was higher than that in our study and their study participants were followed up over a longer period (13 years, from 2002 to 2015) compared to our patients who were followed up for a median duration of 951 days (2.6 years).

In this study, we identified certain factors that were significantly associated with prostate cancer aggressivity. The practice of professions that require unskilled labor was one of these factors. This is probably because these people (site laborers, gasoline station attendants, iron scrab collectors, etc.) have high professional exposure to the culprit carcinogens. This finding is corroborated by those of Sauvé et al., who reported that gasoline station attendants and textile processing workers had higher exposure to high-grade prostate cancer in Canada [34]. We also found that paraplegia was associated with prostate cancer aggressivity, as corroborated by R M Jameson [35]. This paraplegia is due to metastatic spinal cord compression, which is considered a serious complication of prostate cancer that only occurs in aggressive forms of the disease [36]. We also identified factors that were associated with both aggressive disease and patients’ outcomes (survival or death). These factors include the presence of lymphoedema, abnormal DRE findings, anemia, enlarged prostate glands (prostate volume > 50 ml), and abnormal prostatic echostructures. Lymphoedema in prostate cancer is usually due to the presence of lymph node metastases that cause the lymph nodes to swell and block the flow of lymph and is often indicative of advanced-stage prostate cancer that has a poor prognosis [37]. Anemia is often associated with advanced prostate cancer and a poor prognosis. As mentioned earlier, anemia in men with advanced prostate cancer may be caused by several factors, including androgen deprivation, nutritional decline, bone marrow infiltration, treatment-related toxicity, and a chronic inflammatory state [26]. In our study, since the patients presented with anemia right from the onset, it was most probably due to bone marrow infiltration by metastases and the ensuing osteolysis that resulted in the attenuation of erythropoiesis and, hence, anemia. Abnormal DRE findings were also associated with cancer aggressivity and mortality. It has been well established that a DRE is an essential part of the assessment that can independently predict prostate cancer in the setting of a normal PSA level [38]; however, our findings indicate that this factor, in addition to its diagnostic value, may be useful in determining the prognosis of the condition in Cameroonian patients. We found that enlarged prostate glands (volume > 50 ml) were associated with both aggressivity and the disease prognosis. This is in line with the findings of Freedland et al. who suggested in their study thatprostate size may be an important prognostic variable that should be evaluated for use preoperatively and postoperatively to predict biochemical progression [39]. Lastly, we found that abnormal TRUS findings were associated with the aggressivity of the disease and patients’ outcomes. To the best of our knowledge, ultrasonography is currently considered a diagnostic tool, and some studies report that it may be considered only as a diagnostic complement to serum PSA levels and DRE findings [40]. Although multiparametric MRI (mpMRI) of the prostate has been identified as a test that could mitigate prostate cancer diagnostic errors [41], its high cost and relative unavailability make it impracticable in this part of the world. As such, ultrasonography remains the modality of choice in resource-limited settings. Moreover, the findings of our study indicate that it can also be of prognostic value in Cameroonian patients. Taken together, the findings of our study indicate that even with the resources available to health care providers in our resource-limited setting, more could be done by the relevant stakeholders to diagnose prostate cancer early and prevent precarious outcomes of the condition.

However, this study has its limitations. Firstly, the retrospective study design comes with recall bias, which has a negative effect on the findings of the study. This study design also means that no causal relationship could be ascertained between the exposure and outcome variables. Secondly, all the participants of this study were recruited from the same facility, which means that the findings are not quite representative of the entire Cameroonian population. We recommend that more prospective multi-center studies be carried on this topic out to further investigate our findings.

The late diagnosis of prostate cancer is a major public health problem in Cameroon because of the complications and poor prognosis of the disease at an advanced stage. More efforts should be made to ensure the early diagnosis of the condition and improve patient outcomes. Also, there are certain clinical, biological, and imaging factors that are associated with prostate cancer aggressivity and a poor prognosis, whose identification could help guide clinicians in making therapeutic choices for their patients.

The authors thank Health Search Association for critically reviewing the manuscript.

The data analyzed in this study are available from the corresponding author upon reasonable request.

Ethical approval was obtained from the institutional review board of the Faculty of Medicine and Pharmaceutical Sciences and the ethics committee of the Centre medico-chirugicale d’urologie in Douala, Cameroon. The requirement for informed consent was waived due to the retrospective nature of the study.

The authors did not receive any funding for this study.

The authors have no conflicting interests to declare.

Kamadjou, C., Wadeu, A.K., Kuitche, J., Mbassi, A., Kamga, J. and Angwafo, F. (2022) Prostate Cancer: Risk Factors and Outcome Indicators. Surgical Science, 13, 381-400. https://doi.org/10.4236/ss.2022.138047