PCa is more aggressive among men of African descent, probably due to delayed diagnosis and treatment, poor cancer awareness and low level of cancer screening programmes. Some environmental and genetic factors have also been implicated.
Nigeria and South Africa combined, have the highest cumulative risk incidence of PCa in Africa. A comparative study between the two countries found that 50% of participants, presented with locally advanced disease and 65.9% and 34.1% of Nigerian and South African men, respectively, with metastatic disease.
In 2018, the highest mortality rates as a result of PCa were recorded in Caribbean (29.3 per 100 000 population) followed by Southern Africa (24.4 per 100 000 population), followed by the and Middle Africa (24.2 per 100 000 population). The risk of mortality increases with age, and about 55% of all deaths occur >65-years.
Screening and diagnosis
The Council for Medical Schemes (CMS) recently updated their PCa prescribed minimum benefit (PMB) guideline. The CMS recommends medically informed patient-based screening as PMB level of care in males with a life expectancy of more than 10 years based on the following criteria:
- From the age of 40 in Black African patients and in those with a positive family history of PCa and/or breast cancer in a first-degree relative
- From the age of 45 years in all other males
- Patients with a history of lower urinary tract symptoms and/or clinical suspicion of PCa regardless of age group.
Prostate biopsy is the cornerstone of diagnosis
PCa is usually suspected based on the findings of a digital rectal examination (DRE), and/or elevated prostate-specific antigen (PSA) level (see Table 1). Diagnosis should be confirmed based on the findings of a prostate biopsy.
Most PCas are located in the peripheral zone and may be detected by DRE when the volume is >0.2ml. In about 18% of cases, PCa is detected by suspect DRE alone, irrespective of PSA level. A suspect DRE in patients with a PSA level <2ng/ml has a positive predictive value of 5%-30%.
The CMS recommends that a risk-adapted strategy, which is based on initial PSA level and DRE results, should be offered with follow-up intervals of two years.
PSA levels between 4.0ng/ml to 10.0ng/ml have poor specificity. Sign, symptoms, and biopsy results should be taken into consideration when making a diagnosis. A prostate biopsy is the cornerstone of PCa diagnosis. A lymph node biopsy is recommended if there is any suspicion on any imaging modality shows involvement of lymph nodes, recommends the guideline.
Risk stratification for PCa
Risk stratification, both at the time of diagnosis and at subsequent decision points, is an important part of planning the most appropriate treatment and assessing potential outcomes. PSA, clinical stage (see Table 2) and histological Gleason Score (see Table 3) are the mainstay of risk stratification and are important for selecting initial treatment in men with newly diagnosed PCa.
Table 3: Gleason score
Imaging radiology for diagnostic workup, staging and risk assessment
Perineal and/or trans-rectal ultrasound-guided biopsy remains the standard of care for baseline biopsy. In biopsy naïve patients and patients with prior negative biopsies, magnetic resonance imaging (MRI) targeted biopsies substantially improve the detection of PCa.
If not done pre-biopsy, MRI is recommended as PMB level of care for local imaging of intermediate and high risk PCa and not for low risk cases. A bone scan is indicated in patients who present with high-risk features and symptoms of having bone metastases, and generally not recommended in patients with a new diagnosis of low-risk PCa with PSA <10ng/ml, Gleason score<8 and no bone pain.
Management of PCa
Low-risk, localised disease
The CMS recommends deferred treatment in patients with localised disease (low risk, stage, and volume). Deferred treatment can be watchful waiting (conservative management of patients deemed unsuitable for curative treatment from the outset, recommended, in men with life-expectancy of <5- to 10-years and existing severe medical condition) or active surveillance (patients remain under close surveillance through structured surveillance programmes with regular follow-ups [See Table 4]).
Deferred treatment is not recommended in patient with intermediate and high risk localised disease (any PCa with T stage >T2, Gleason score ≥7 and PSA >10ng/ml) or in patients who are candidate for active treatment but choose to defer treatment.
Table 4: Active surveillance: patient characteristics
Radical prostatectomy is recommended when the cancer is believed to be confined to the prostate gland. The goal is to eradicate all cancer, while whenever possible, preserving continence and potency. An estimation of life expectancy is paramount in counselling a patient about surgery particularly for those who have an average life expectancy ≤10 years.
Radiotherapy can be administered in two forms:
- External beam radiotherapy (EBRT): directing the radiation from outside the body into the area of the tumour. All types (RT, 3D conformal RT and intensity modulated RT) of monotherapy radiation techniques are recommended as PMB level of care.
- Brachytherapy: placing a small source of radiation inside the body close to or within the area where the cancer is located. Two types of brachytherapy are available: permanent low-dose rate (LDR) and temporary high-dose rate. It should be noted that brachytherapy (with the exception of high dose brachytherapy) is now accepted as a PMB level of care and is reimbursable in line with regulation 8 for all qualifying patients. LDR can used as monotherapy in early disease for selected patients or combined with external beam radiotherapy in intermediate-/high-risk patients with localised disease (see Table 5). Short course neoadjuvant androgen deprivation therapy (ADT) prior to brachytherapy may reduce the volume of the prostate making. Treatment for an average of three months with ADT generally decreases the size of the prostate by about 30% with an acceptable level of toxicity.
Table 5: Patient selection for LDR
Intermediate and high-risk localised disease
The CMS underscores the importance of patient selection for EBRT taking risks and benefits into consideration (see Table 6). Generally, patients with previous obstructive bowel disease or diabetes are not good candidates for EBRT due to increased risk of complications. This risk-benefit ratio is higher for patients with localised disease than for patients with locally advanced disease.
Furthermore, the authors point out that although EBRT can be used for localised disease, brachytherapy has higher predicted probability of maintaining erectile function as compared to EBRT.
Table 6: Patient consideration for EBRT
Neoadjuvant or adjuvant hormonal therapy
Primary ADT has been the standard of care for over 50 years. There is no level 1 evidence in favour of a specific type of ADT, neither for orchiectomy nor for a luteinizing hormone-releasing hormone or gonadotropin-releasing hormone (GNRH) analogue or antagonist. The exception is patients with impending spinal cord compression for whom either a bilateral orchidectomy or LHRH antagonists are the preferred options.
The use of neoadjuvant ADT and chemotherapy either alone or in combination before radical prostatectomy is generally safe and feasible while reducing prostate volume and tumour burden. However, at present, pathologic complete response rates are low and no long-term survival benefit has been observed with the addition of neoadjuvant therapies over surgery alone.
The following hormonal therapies are not recommended as PMB level of care:
- Combined androgen blockade (only low level of evidence for the use of GNRH agonists with anti-androgens)
- Oestrogen (early studies evaluated oral diethylstilboestrol at several doses. Due to severe side-effects, especially thromboembolic complications, even at lower doses these drugs are not considered as standard first-line treatment).
Cassim N, et al. Prostate cancer age-standardised incidence increase between 2006 and 2016 in Gauteng Province, South Africa: A laboratory data-based analysis. S Afr Med J, 2020.
Ahmed RO, et al. A comparison of clinicopathologic features of prostate cancer between Nigerian and South African Black men. African Journal of Urology, 2022.
Taitt HE. Global Trends and Prostate Cancer: A Review of Incidence, Detection, and Mortality as Influenced by Race, Ethnicity, and Geographic Location. Am J Mens Health, 2018.
Council for Medical Schemes. PMB benefit guideline: Prostate Cancer. 30 September 2021 v1. https://www.medicalschemes.co.za/download/3566/genitourinary/24567/pmb-benefit-guideline-prostrate-cancer.pdf