Prostate cancer (PCa) is one of the most common malignancies affecting men and remains a leading cause of cancer-related mortality worldwide. In 2020, it accounted for approximately 25% of all male cancers, ranking second after lung cancer [1]. In the Democratic Republic of the Congo (DRC), PCa also occupies the second position (14%), just behind Kaposi’s sarcoma (14.5%) [2].

The management of PCa is based on a multimodal approach that combines local and systemic therapies, tailored according to tumor stage, prostate-specific antigen (PSA) level, ISUP grade, patient age, life expectancy, and comorbidities. Its hormone-sensitive nature, first demonstrated by Huggins in 1949, underscores the pivotal role of androgens (testosterone and dihydrotestosterone) in tumor progression. Suppressing their production or blocking their action effectively slows disease progression.

First-generation hormone therapy (FGHT), whether used alone or in combination with anti-androgens, remains the standard treatment for advanced and metastatic disease. Its efficacy can be enhanced by the addition of next-generation hormone therapy (NGHT) or chemotherapy [3].

Approximately 80% to 90% of patients initially respond favorably to FGHT, with improvements in pain control, a PSA reduction of ≥50%, radiologic stability or regression, and an overall improvement in quality of life [4][5]. However, this response is typically transient, lasting on average between 12 to 18 months before the onset of castration resistance (CR) [6].

In our context, limited access to healthcare and low socioeconomic conditions often result in delayed diagnosis, frequently at the advanced or metastatic stage. Consequently, FGHT remains the most commonly used therapeutic approach. This study aims to evaluate the rate of favorable response to FGHT, as well as the timeframe and factors associated with the development of CR in our context.

This study is the first in our context to evaluate the positive response rate to first-generation hormone therapy (FGHT1) in 258 patients with prostate cancer (PCa), as well as the factors and timing associated with castration resistance (CR). Diagnosis predominantly of PCa occurred in patients in their fifties, with the highest frequency in the 70 - 79 age group (50%), a mean age of 70.7 years, and extremes ranging from 53 to 94 years. These results align with several studies reporting a mean age between the sixth and seventh decades of life [7]-[12]. In our context, Moningo observed a similar predominance in the 70 - 79 age group (39.4%), with a mean age of 69.4 years [7], whereas Ngandu TJ in Mbuji-Mayi reported a younger mean age of 59.1 years, ranging from 57 to 60 years [8] (Table 9).

Table 9. Mean age of CaP according to authors.

Dysuria (64.7%), followed by nocturia (47.3%) and pollakiuria (43.8%), were the most frequent reasons for consultation. These findings are consistent with the literature but show some variation. Moningo etal. reported obstructive symptoms in 72.5% of cases and irritative symptoms in 33.5% [7]. In Algeria, Belabed Zaket A. observed a high frequency of pollakiuria (45%) but a lower rate of dysuria (31%) [13]. While in Kinshasa, Punga reported nocturia as the dominant symptom in 52.4% of cases [14].

Regarding tumor characteristics, stages cT3 - cT4 (62.4%) and ISUP grades 4 - 5 (50.8%) was the most frequent. Metastatic disease was present in 38.9% of patients, predominantly affecting the bone, followed by locally advanced forms (29.6%) and high-risk forms (26.1%). Low- or intermediate-risk tumors were less common with high-risk, locally advanced, and metastatic prostate cancers collectively accounted for 94.6% of cases. These results are in line with Moningo etal., who reported a predominance of metastatic CaP (47.1%) and high-risk CaP (25.5%) [7]. Other authors report similar findings [9][11][13]. The high frequency of bone metastases is consistent with the natural osteotropism of prostate cancer.

Therapeutically, LHRH analogues (82.6%), most often combined with bicalutamide (72.9%), were the main treatment modality. Orchidectomy was performed in 19% of patients. While abiraterone (58.9%) was reserved for patient’s resistant to FGHT. TURP was performed in 50% of patients for significant prostatic obstruction, while radical prostatectomy (RP) was rare (2.7%). These observations align with Moningo etal., who reported high use of LHRH analogues (95%) and orchidectomy in 23% of cases [7]. Overall, androgen deprivation therapy, whether medical or surgical, remains the cornerstone of treatment in our context, reflecting the often advanced stage at diagnosis [15][16].

Following initiation of first-generation hormone therapy (FGHT), 82.1% of patients in our cohort demonstrated a positive response, defined as a ≥50% reduction in PSA, often accompanied by clinical or radiological improvement. These results are consistent with the literature. For instance, Seront E., at the Saint-Luc University Clinics in Brussels, reported a response rate of 80% - 90% for ADT, with improvement in pain, PSA reduction, radiological stabilization, and better quality of life [4]. Similarly, Namiki M. in Japan emphasized that hormone therapy remains the treatment of choice for advanced PCa, achieving efficacy exceeding 90% [16]. In the United States, Raghavan D. documented an initial response rate of 60% - 70% for surgical or medical castration in hormone-sensitive cases [17].

A PSA reduction of 50% or more (PSA50) after starting HTG1 is a reliable biological indicator of favorable response [18][19]. Clinical trials such as SWOG 9346, CHAARTED, and LATITUDE demonstrated a significant association between this response and better overall survival [20]-[22]. Although the 2023-2024 European guidelines do not consider PSA50 as the sole criterion, for response evaluation, its clinical and prognostic significance is well recognized [23].

The median time to CR was 18 months (range 6 - 30 months). Resistance can emerge within the first months of therapy, with the incidence increasing from 8.5% at 1 month to 17.4% at 5 years. Similar observations have been reported elsewhere: Hellerstedt B.A. etal. in Michigan and Diaz M. etal. in Florida documented median progression-free survival (PFS) of 12 - 30 months following treatment initiation [24][25]. In Kinshasa, Moningo reported a CR rate of 43.1% with a median PFS of 17 months [7]. Our relatively low early resistance rate (8.5%) is consistent with estimates of primary resistance, which range from 10% to 30% (Table 10).

Table 10. Castration resistance rates over time.

The probability of CR was significantly higher in patients with baseline PSA ≥ 100 ng/mL, SGOT ≥ 38 UI/L, and advanced tumor stage cT3 - cT4. Both bivariate and multivariate analyses confirmed these variables as independent risk factors. Patients with high initial PSA levels showed a resistance incidence of 20.5 cases per 100 person-months, compared to 7.2 for those with low PSA. Similarly, elevated SGOT was associated with a higher risk of CR (RRa = 1.82; p = 0.024).

The presence of metastases at diagnosis increased crude risk nearly ninefold and remained significant after adjustment (RRa = 2.83; p = 0.014). High ISUP score (3 - 5), cT3 - cT4 stage, and high or very high risk according to D’Amico/NCCN/Stampede classification also increased resistance risk. These clinical, biological, and radiological factors are therefore essential for assessing the likelihood of CR in PCa treatment.

Moningo etal. used similar parameters to evaluate CR, demonstrating that elevated PSA levels, Gleason 8 - 10 (ISUP 4 - 5), high progression risk, presence of metastases, and advanced clinical stage (cT3 - cT4) are strongly associated with increased risk of CR [7], consistent with other studies [9][31].

In our cohort, the median overall survival (OS) was 28 months (range: 13 to 60.5 months), comparable to that reported by Moningo in Kinshasa (30 months) and Kurt İnci in Türkiye (30.44 months) [7][32]. In contrast, Morgan in the United Kingdom observed a longer OS of 48.2 months, whereas Hellerstedt in the United States reported a shorter OS ranging from 8 to 16 months [24][33]. B. Sine at Aristide Le Dantec Hospital of Dakar, found a median survival of 14 months [34].

Survival rates in our study were relatively high: 97.3% at 3 months, 93.4% at 1 year, and 84.5% at 5 years, closely aligning with those reported in other studies [7][9]. Conversely, Bolla in France documented a markedly lower 5-year survival rate of 30% among patients with castration-resistant prostate cancer (CR), highlighting the poor prognosis associated with advanced disease [35].

Prostate cancer (PCa) is a major public health issue in our region. It mainly affects patients aged 70 to 79 years, often with diagnosis occurring at an advanced stage. First-generation hormonal therapy (FGHT) shows notable efficacy, with 82.1% positive responses. The clinical response evolves progressively, allowing many patients to remain hormone-naïve at five years. HTG1 therefore remains a relevant therapeutic option in our context of resource-limited settings.

The DAS confirms the presence of data.

This study, the first of its kind in our context, has several limitations. Its monocentric and retrospective design led to the loss of certain relevant data, thereby limiting the generalizability of the results. Additionally, the low socio-economic status of many patients restricted access to complementary paraclinical investigations, which may have influenced the assessment of progression-free and overall survival.

This study is the first in our region to evaluate the positive response rate to first-generation hormone therapy. It confirms the results of a previous study titled (“Evolution of androgenic deprivation in treatment of prostate cancer in Kinshasa”) regarding the timing and factors associated with castration resistance. Furthermore, it provides a foundation for future research exploring the combined use of first- and new-generation hormone therapies.

DieudonnéMolambaMoningo: Study design and supervision.SergeMbiyaNsumba: Research, data collection, and manuscript writing.BienvenueMassambaLebwaze: Pathological analysis.NkodilaAliocha: Statistical analysis.Otherauthors: Critical review, comments, and suggestions.

This research did not receive any specific grant, financial support, or funding for publication costs.