Ep 134 – Prostate cancer

One in six UK males will be diagnosed with prostate cancer in their lifetime. In the UK prostate cancer is the most common male cancer, with over 55,000 new cases diagnosed every year. There has been much discussion in the media recently regarding whether men under the age of 50 should have access to prostate-specific antigen (PSA) testing, particularly if they have a strong family history of prostate cancer. In this episode, Dr Roger Henderson takes a look at prostate cancer, including guidance on screening, investigations and treatment.

Key take-home points

• The three main risk factors for prostate cancer are increasing age, ethnic origin and genetic predisposition, with age being the most important. However, around 25% of cases occur in men below the age of 65.
• Prostate cancer mortality is strongly related to age, with the highest mortality rates in older men.
• Prostate cancer is most common in black males, then white males and least common in Asian males, and the risk of developing prostate cancer is increased in men with a positive family history of prostate cancer.
• Overweight and obese men with prostate cancer are at an increased risk of disease recurrence, treatment-related adverse effects, obesity-related comorbidities, earlier progression and development of metastatic disease, and higher all-cause and prostate cancer-specific mortality.
• The Faculty of Sexual and Reproductive Healthcare guidance advises there is no evidence of a causal relationship between vasectomy and cancer of the prostate.
• No organised screening programme for prostate cancer exists in the UK although there is an NHS Prostate Cancer Risk Management Programme that aims to provide information in in primary care to help asymptomatic men aged 50 and over decide whether or not to have a PSA test.
• PSA testing may be combined with digital rectal examination (DRE) as part of screening, since approximately 25% of men diagnosed with prostate cancer have a normal PSA.
• The upper level of normal for PSA level varies according to age. The PSA test is not diagnostic and PSA levels may also vary with race.
• A prostate biopsy should not be offered just on the basis of serum PSA level alone and a negative prostate biopsy does not exclude a diagnosis of prostate cancer, especially if there is significant clinical suspicion, or if a PSA result is persistently elevated or rising.
• If there is a negative biopsy but an elevated PSA, then very close follow-up with DRE and further PSA should be performed – ideally within 6 months of the negative biopsy.
• A combined MRI-targeted and systematic biopsy approach improves the detection of clinically significant prostate cancer.
• Prostate biopsies find fewer than half of the clinically significant prostate cancers that MRI scans miss.
• Most men with prostate cancer are asymptomatic at presentation, and initial suspicion is only raised following screening with PSA testing and DRE.
• There is significant crossover in symptoms between prostate cancer and benign conditions affecting the prostate such as benign prostatic hypertrophy and prostatitis, making it very challenging to distinguish between them on the basis of symptoms.
• Prostate cancer can be divided into non-metastatic and metastatic.
• The Gleason and TNM (tumour, node, metastasis) methods are the approved scoring systems.
• NICE now recommends risk stratification for all people with newly diagnosed localised or locally advanced prostate cancer.
• NICE guidance says that for localised and locally advanced prostate cancer, the three treatment options should be active surveillance, radical prostatectomy and radical radiotherapy.
• Evidence does not show a difference in the number of deaths from prostate cancer among people offered active surveillance, prostatectomy or radical radiotherapy, but there is good evidence that both prostatectomy and radiotherapy reduce disease progression compared with active surveillance.
• Both prostatectomy and radiotherapy reduce the rate of development of distant metastases compared with active surveillance.
• Of men with PSA-detected prostate cancer, 45% are candidates for deferred management.
• The surgical treatment of prostate cancer consists of radical prostatectomy. Laparoscopic radical prostatectomy is indicated for localised prostate cancer with no evidence of spread beyond the prostate gland or distant metastases.
• Radiotherapy is an important and valid alternative to surgery as the sole form of curative therapy and the ProtecT trial found no difference between radical prostatectomy and external beam radiotherapy for all oncological outcomes.
• Androgen deprivation treatment reduces the effects of testosterone and other androgens, thus inhibiting the progression of prostate cancer. The main treatments used are luteinising hormone-releasing hormone (LHRH) agonists and anti-androgens.
• LHRH agonists such as goserelin and leuprorelin induce castrate levels of testosterone within 4 weeks.
• Anti-androgens cause apoptosis and inhibition of prostate cancer growth with two classes available – steroidal (such as cyproterone acetate) and non-steroidal (such as bicalutamide).
• Prostate cancer is often curable, with overall survival depending on the initial stage of disease at the time of diagnosis.

Key references

1. Cancer Research UK. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer.
2. Merriel SWD, et al. Adv Ther. 2018;35(9):1285-1294. doi: 10.1007/s12325-018-0766-1.
3. European Association of Urology. https://uroweb.org/guidelines/prostate-cancer/chapter/epidemiology-and-aetiology.
4. Public Health England. 2016. https://www.gov.uk/guidance/prostate-cancer-risk-management-programme-overview.
5. NICE. 2023. https://www.nice.org.uk/guidance/NG12/.
6. NICE. 2021. https://www.nice.org.uk/guidance/ng131.
7. Hamdy FC, et al. N Engl J Med. 2016;375(15):1415-1424. doi: 10.1056/NEJMoa1606220.
8. Albertsen PC, et al. JAMA. 2005;293(17):2095-2101. doi: 10.1001/jama.293.17.2095.