This was a retrospective descriptive and analytical study, from January 1, 2022 to August 31, 2023, of prostate cancer patients who had undergone bone scintigraphy with^99mTc-HMDP. It took place in the nuclear medicine department of Idrissa Pouye General Hospital (HOGIP) in Dakar. Operational since June 2009, it remains the only functional nuclear medicine department in Senegal. The nuclear medicine department at the Idrissa Pouye General Hospital was chosen as the setting for the study, since it is the only nuclear medicine department currently in operation in the whole of Senegal.

Whole-body scintigraphy (WBS) bone scans were performed using a dual-head SPECT gamma camera (Mediso Nucline TM Spirit DH-V type), 3 hours after intravenous injection of 8 MBq/kg (555 to 740 MBq) of ^99mTc-HMDP.

For the selection of patients, we opted for the most exhaustive sampling, taking into account all patients with prostate cancer who benefited from bone scintigraphy.

➢ Inclusion criteria

All patients with histologically confirmed prostate cancer and who underwent whole-body bone scintigraphy were included in the study. In addition, the Gleason score given by the pathologist and the PSA assay should be available at the same time, or one of them.

➢ Non-inclusion criteria

Not included in our study:

­ Patients who did not have both a Gleason score and/or a PSA assay, and those with incomplete medical records (socio-demographic and clinical data not provided),

­ Patients who have undergone bone scintigraphy for reasons other than prostate cancer extension.

➢ Dependent variable

The dependent variable of the study was the presence or absence of bone metastasis. It presented three modalities: yes for presence of metastasis, no for absence of metastasis, and doubtful (doubtful presence of metastasis).

➢ Independent variables

­ General data: age, weight, family history of cancer, duration of evolution,

­ PSA levels,

­ Histological and prognostic data: histological type, Gleason score,

­ Scintigraphic data:

*Indication for scintigraphy: initial extension workup, monitoring, biochemical recurrence, follow-up workup;

*The dose of^99mTc-HMDP administered;

*Contributory or non-contributory scintigraphy;

*Presence or absence of bone metastases;

*Single or multiple metastasis location(s);

*Topographies of metastatic bone lesions;

*Type of bone lesions (hyper-fixing, hypo-fixing, mixed);

*Quantification of bone damage using the SOLOWAY score.

­ To collect and process the data, we used:

*Patient bone scan records from the software database (InterViewXP/Médiso);

*Scintigraphy prescription forms and physical records (observation sheets) for each patient included;

­ Bone scan images during the study period were all visualized and analysed;

­ For each file, the data were transcribed onto a data processing form designed for the study. This form was tested and corrected on some twenty files.

Data were recorded and analysed using Excel and Epi Info (French version). Quantitative variables are expressed as averages, while qualitative variables are expressed as percentages.

Quantitative variables were compared using the Fisher test. A value of p < 0.05 was considered significant.

All ethical requirements relating to health research were respected. Patient data were treated confidentially and in strict compliance with medical secrecy. Data sheets were completed anonymously, using an identification code. Confidentiality of the data collected was ensured.

A total of 288 patients were enrolled, with a mean age of 68.37 years and a standard deviation of 7.79 years. The median age was 69 years, with extremes ranging from 43 to 88 years. The age range ]60 - 80] was the most frequent, accounting for 78.47% of patients (Figure 1).

In our study, 67 patients (23.26%) had a family history of cancer. Of these, 36 patients (53.73%) were first degree related, 19 patients (8.36%) were second

degree related and 12 patients (7.91%) were third degree related (Figure 2).

In our study, PSA levels were available in 221 patients, i.e. 76.73% of cases. Of these, 144 patients (65.61%) had a PSA level above 20 ng/ml and 39 patients (17.65%) had a PSA level between 10.1 and 19.9 ng/ml.

The figure below (Figure 3) shows the distribution by PSA level.

The duration of evolution of clinical signs in relation to histological confirmation was analysed in 248 patients, i.e. 86.11% of cases. The mean evolutionary time was 3.3 years, with extremes ranging from 1 month to 20 years. The most common duration was over 36 months, with a percentage of 29.44, followed by between 6 and 12 months.

The figure below (Figure 4) shows the distribution of evolution times.

The following table (Table 2) shows the relationship between the mCi activity of the radiopharmaceutical (^99mTc-HMDP) and patient weight.

In our study, the mean dose of radiotracer activity administered for the standard weight range [70 - 90 kg[ was 16.9 mCi, with extremes of 12.03 mCi and 20 mCi. Table 2 shows the distribution of injected activity by weight range.

PSA is an important biomarker for diagnosis and active surveillance, although it is not a specific marker for prostate cancer.

In our study, the mean PSA level was 97.6 ng/ml, with extreme values ranging from 0.006 ng/ml to 791.6 ng/ml, and a median of 31.17 ng/ml:

➢ Those with metastases on scintigraphy had a mean PSA level of 190.2 ng/ml, a median of 138.6 ng/ml and extremes of 0.006 to 791.6 ng/ml;

➢ Patients without metastases had a mean PSA level of 40.6 ng/ml, a median of 49.2 ng/ml and extremes of 0.006 to 243 ng/ml;

➢ For those with a doubtful scan, their mean PSA level was 81.5 ng/ml, with a median level of 29.6 ng/ml and extremes from 0.02 to 702 ng/ml (Table 5).

The SOLOWAY score was used to quantify metastatic bone lesions. Fifty-four (54) patients were grade I, including 11 solitary lesions. Thirty-three (33) patients,

or 37.93%, had a SOLOWAY score greater than or equal to II.

Table 6 shows the distribution of patients with bone metastases according to the SOLOWAY scintigraphy score.

The mean age of our patients was 68.37 years, with extremes ranging from 43 to 88 years. The [60 - 80] age group was the most affected, with 78.47% of patients. This result is comparable to that reported by B. Ndong et al. [9] , who in a study

of 45 patients found an average age of 66.71 years (extremes: 50; 80 years). Other studies carried out in Senegal had similar results, which corroborate our data [6] [10] . A study by Ndoye M et al. and Zaman M. U. et al. reported an average age of 71 years [11] [12] . Other studies from Asia [13] [14] and Europe [15] had also reported an increase in average age compared with our study. It is uncommon before the age of 50, but becomes more common between the ages of 60 and 70, particularly in developing countries. This trend can be explained by the lack of awareness of the disease and the absence of adequate screening programs. In addition, limited access to specialized care services poses a further challenge.

The presence of a family history of prostate cancer is an important factor to consider when assessing an individual's risk of developing the disease. In our study, we found that 23.26% of patients had a family history of prostate cancer. This suggests a genetic predisposition to the disease, and raises questions about the influence of hereditary susceptibility in the development of prostate cancer. Among patients with a family history, we observed different kinship relationships with family members with prostate cancer. Of the 67 patients concerned, 53.73% were 1st degree relatives, meaning that they were brothers or fathers of patients with the disease. This genetic proximity reinforces the hypothesis of hereditary transmission of prostate cancer susceptibility. What's more, 28.36% of patients were 2nd degree relatives, including uncles, nephews or grandfathers with the disease. These less direct kinship relationships, but still sharing a certain proportion of the genetic heritage, also suggest a genetic contribution to the incidence of prostate cancer. Finally, 17.91% of patients had 3rd degree relationships, encompassing cousins, great-grandfathers or first cousins with the disease. Although the genetic influence may be less marked in these cases, the presence of prostate cancer in these branches of the family still indicates a familial predisposition.

These findings underscore the importance of family history in assessing individual prostate cancer risk. Systematic collection of a family history of cancer, particularly prostate cancer, can help identify high-risk patients who may benefit from early detection and close surveillance. Furthermore, these data support the idea of a genetic component in prostate cancer susceptibility and encourage future research into the identification of specific genetic markers associated with this disease. It should be noted that our study has certain limitations, including a relatively small sample size and a specific population. Larger and more diversified studies are needed to confirm our observations and better understand the role of genetic factors in the development of prostate cancer [2] [16] - [22] .

In our series, the time from cancer diagnosis to bone scan varied considerably, from one month to twenty years. A significant proportion of patients (29.44%) had a time to progression of more than 36 months. Earlier studies, such as that by Diop et al. [23] , had also found delays ranging from six months to seven years.

The precise dates of onset of metastases and their duration of evolution are not known for our patients, as was mentioned in the research by Diop et al. [23] .

In our context, scintigraphic examinations are not performed on a regular basis due to the regular unavailability of radiopharmaceuticals and sometimes technical problems. Patients therefore do not benefit from regular follow-up scintigraphy, which could enable early detection of metastases, an essential element in optimal cancer management.

In summary, there are wide variations in the time between cancer diagnosis and bone scan, ranging from a few months to several years. Constraints related to the availability of scintigraphic examinations in our country, due to radiopharmaceutical and technical problems, result in irregular follow-up with scintigraphy, compromising early detection of metastases and adequate management of the cancerous disease.

In our series, the exclusive histological appearance observed was that of adenocarcinoma, in line with the findings reported by B. Ndong et al. [9] . However, other studies by L. Niang et al. [6] and M. Ndoye et al. [11] reported a case of sarcoma in their respective series. These observations indicate that sarcomas are rare, representing less than 1% of prostate tumours. Moreover, they tend to occur in subjects under 50 years of age.

In 70.13% of patients in our series, the Gleason score was obtained from prostate biopsies following an increase in PSA and/or an abnormal digital rectal examination. The Gleason score is a histopronostic indicator used to differentiate tumours according to their tumour architecture and to classify them according to grades of increasing malignancy.

In our study, 23.76% of patients (i.e. 46 patients) had a Gleason score of 6 (3 + 3), 43.07% of patients had a Gleason score of 7 (3 + 4 or 4 + 3), 27.23% of patients had a Gleason score of 8 (4 + 4), and 5.45% had a Gleason score of 9 (4 + 5 or 5 + 4). The Gleason score was subdivided into three groups: the group with a Gleason score less than or equal to 6, representing 24.26% of patients; the group with a Gleason score equal to 7, representing 43.07% of patients; and finally the group with a Gleason score greater than or equal to 8, representing 32.68% of patients.

According to the 2013 onco-urology guidelines [24] , high-risk prostate cancer is defined by a Gleason score greater than or equal to 8, or equal to 7 but with a predominance of grade 4 or 5, or by the presence of cancer on more than 50% of biopsies, or by positive biopsy lengths greater than 20%. Thus, in our study, 32.68% of patients (Gleason score ≥ 8) belonged to this high-risk cancer group. It should be noted that patients with a Gleason score equal to 7 (4 + 3) were also included in this high-risk cancer group due to the predominance of grade 4. Furthermore, several studies have shown that in 25% of cases, a Gleason score equal to 7 underestimated the true Gleason score of prostate cancer [25] .

This makes it difficult to classify cancers with a Gleason score equal to 7 between the intermediate-risk and high-risk groups. The low-risk group was represented in our series by 24.26% of patients (Gleason score ≤ 6). However, to define this group, all the parameters of D'Amico's classification are required [24] .

These results reveal a discordance with clinical stage and PSA levels, underlining a diagnostic delay in the detection of the disease in our countries. Anatomopathological analysis, on the other hand, reveals a large number of low-risk cancers. This may be explained by the lack of pathologists in our countries, such as Senegal, and by the fact that the pathologists available are not specialized in uropathology. In addition, access to immunohistochemical studies is limited.

In our study, there was no correlation between the activity of the radiopharmaceutical administered and patient weight, with a correlation coefficient r = 0.31. In principle, the activity to be administered to patients should be a function of their weight, i.e. 8 MBq of radiobiphosphonate per kg of patient weight, without exceeding 1000 MBq. Staff must be made more aware of the need to correlate radiopharmaceutical doses with weight. However, these doses were always in line with the standards of the French Society of Nuclear Medicine, the European Society of Nuclear Medicine and the American Society of Nuclear Medicine, which recommend 15 to 20 mCi for patients of standard weight (60 - 80 kg).

The majority of indications for bone scintigraphy in patients were related to the initial extension workup, accounting for 96.43% of cases. A limited number of cases (2.5%) were related to follow-up workup, while only 0.71% of cases were related to biochemical recurrence. A study by Punnen and colleagues [26] highlighted the importance of medical imaging in the management of cancer pathologies, noting almost 30% of biochemical recurrence in their sample. However, it should be noted that nuclear imaging in the management of cancer pathologies is not limited solely to extension assessment. The results obtained suggest that the lack of adequate nuclear imaging equipment in Senegal may explain these findings. Many authors have argued in favor of the use of 18F-FCholine PET/CT for the detection and localization of recurrences in patients with biochemical relapse [27] [28] [29] [30] [31] .

Other studies have demonstrated the importance of identifying recurrence sites by 68Ga-PSMA-11 PET/CT imaging, in order to propose loco-regional or systemic treatment. These studies have also revealed a higher positivity rate for 68Ga-PSMA-11 PET/CT imaging than for 18F-FCholine PET/CT [32] - [37] .

It is important to note that these results underline the need for an adequate nuclear imaging technical platform for better management of prostate cancer patients in Senegal. Advances in imaging techniques, such as the use of 68Ga-PSMA-11 PET/CT, may enable more accurate detection of recurrences and thus propose more targeted treatments. However, efforts must be made to improve access to these advanced imaging technologies in countries where they are not yet available.

Scintigraphy was contributed in 70.48% of cases (203 cases) in our study. In 29.51% (85 cases), the result was doubtful. Of the patients who underwent scintigraphy, 30.90% had a positive scan, while 39.58% had a negative scan. These results are consistent with those of the study by Ndong and colleagues, who also observed a similar positive scan rate of 33.33% in their study [9] . With the improvement of nuclear imaging equipment in Senegal, notably SPECT/CT and PET/CT, doubtful cases could be explored more precisely. The advantage of this is more appropriate patient management. Thanks to these technological advances, it becomes possible to refine diagnostic results and better assess the extent of the disease, which can lead to more informed therapeutic decisions and improved clinical outcomes. It is important to emphasize that improving the technical platform for nuclear imaging must be supported by ongoing investment in infrastructure and training of medical staff. This will optimize the use of these advanced imaging modalities and guarantee quality care for prostate cancer patients in Senegal.

In our sample, multiple metastatic lesions predominated, accounting for 87.35% of metastases. This observation is in line with the results of other studies, which also found a high prevalence of multiple metastatic lesions [9] [23] [38] . In our study, metastatic lesions were mainly located in the axial skeleton. These results are consistent with those reported in the literature [9] [23] [38] . Indeed, tumour cells tend to localize preferentially, though not exclusively, in the most richly vascularized regions of the skeleton, such as the hematopoietic bone marrow of the axial skeleton, and the upper extremities of the humerus, femur and tibia [39] [40] .

Furthermore, our study revealed that, in descending order, 52.43% of metastatic lesions were at the spinal level, 46.53% of metastatic lesions at the pelvic girdle level, 15.63% of metastatic lesions at the skull level, 12.50% at the thoracic girdle level, and 9.03% of metastatic lesions on the appendicular skeleton. These results are virtually identical to those reported by some authors in the literature [9] [23] [41] . These observations highlight the tendency of metastases to localize preferentially in specific skeletal regions such as the axial skeleton, which may have important implications for treatment planning and follow-up of patients with bone metastases.

The results of our study showed a predominance, if not exclusivity, of hyper-fixating bone lesions among metastases. This observation has also been highlighted by some authors in the literature [23] [38] . It is important to note that bone hyperfixation is suggestive of metastases, but is not specific, which can make differential diagnosis difficult [42] . Indeed, there may be confusion between metastases and benign pathologies that result in significant bone remodelling, particularly when osteoblastic hyperfixation foci are unique and/or located in particular anatomical regions (e.g. close to joints) [42] . This non-specificity of bone hyperfixation underlines the importance of a comprehensive diagnostic approach and the use of other imaging modalities to confirm or exclude the diagnosis of bone metastases. Additional investigations, such as biopsies or advanced imaging, may be required to establish an accurate diagnosis and differentiate metastatic lesions from benign pathologies. It is essential to take these considerations into account when interpreting imaging results and to consult other clinical data in order to arrive at an accurate diagnosis and propose appropriate management to patients a tainted with bone metastases.

Of the 288 patients with prostate cancer, those with metastases on scintigraphy had a mean PSA blood level of 190.2827 ng/ml and a median of 138.6 ng/ml with extremes of 0.006 to 791.6 ng/ml. Patients without metastases had a mean PSA blood level of 40.6 ng/ml and a median of 19.2 ng/ml, with extremes ranging from 0.006 to 243 ng/ml.

Already described in the literature, PSA blood levels correlate with the presence of metastases [9] . Jemal and colleagues showed that a PSA level above 10 ng/ml was indicative of localized prostate cancer; a level above 50 ng/ml was indicative of extra-prostatic involvement in 80% of cases; and a level above 100 ng/ml was indicative of systematic involvement.

The SOLOWAY score was used in our study to assess the quantity of metastatic bone lesions.

This quantification method revealed that around forty percent of patients with metastases (37.93%) had a poor prognosis, with a grade equal to or greater than II. This indicated that these patients either consulted late or had poor outpatient follow-up, as previously mentioned. This finding is also confirmed in the literature [9] [43] . For prostate cancer patients, mean and median PSA levels increased significantly with SOLOWAY score grades. This increasing relationship between SOLOWAY grades and PSA levels has already been described in the literature [44] [45] . These results underline the importance of the SOLOWAY score in assessing the prognosis and follow-up of patients with bone metastases in prostate cancer.

Using this quantification method, it is possible to identify high-risk patients and implement closer monitoring, which can have an impact on therapeutic decisions and improved clinical outcomes.

The results of our study lead us to formulate recommendations for the development of nuclear medicine in Senegal.

The results of this study highlight several important elements related to the diagnosis of prostate cancer, underlining the importance of an advanced diagnostic and therapeutic approach using nuclear medicine. In Senegal, it would be beneficial to consider capacity building in the field of nuclear medicine to better manage prostate cancer patients. As a first step, investment in nuclear medicine equipment, such as SPECT-CT and PET/CT, would be essential to enable accurate and reliable molecular imaging examinations. These tools would more effectively enable early cancer diagnosis, initial staging and treatment evaluation. Targeting the PSMA with PET tracers labelled with¹⁸ F or⁶⁸Ga would mark an important turning point in the early management and follow-up of cancerous disease.

The acquisition of SPECT-CT will reduce the number of lesions classified as doubtful by increasing the specificity of the examination. In fact, planar bone scintigraphy does not allow localization in 3D space, reducing the specificity of the examination. The arrival of^99mTc-PSMA will enable SPECT-CT to detect both bone and visceral lesions during the scintigraphic examination.

Finally, efforts should be made to raise awareness among the general public and healthcare professionals of the benefits of nuclear medicine in the management of prostate cancer. This would contribute to greater acceptance and adherence to these advanced techniques, as well as to earlier detection and more effective treatment of the disease.