Cancer Keys

Key points: 

• Men with a father or brother with prostate cancer are more than twice as likely to develop the disease when compared to men with no relatives affected. 
• Men are at an increased risk of prostate cancer if they have a sister or mother with breast or ovarian cancer.  
• BRCA1 and BRCA2 gene variants are associated with an increased risk of prostate cancer and more aggressive disease. 
• New guidance advises annual PSA screening from 40 years old for male carriers of a BRCA2 gene variant. An onward referral is recommended if the PSA is >3.0ng/mL.
• Currently it is not advised to carry out regular PSA screening for patients with a family history of prostate cancer or an underlying inherited cancer predisposition syndrome. 
• The decision to request a PSA test should be made on a case-by-case basis, with careful counselling on the risk of false positives or negatives and any potential onward investigations.  
• Refer to clinical genetics if a patient has a suspected inherited cancer pre-disposition syndrome.  

During reports of Sir Chris Hoy’s courageous disclosure of his metastatic prostate cancer diagnosis, it has been revealed that he has a family history or prostate cancer, with both his father and grandfather having the disease. News articles have been urging patients with a family history of prostate cancer to consult with their GP. 

Potential pitfalls: Should we routinely screen patients for prostate cancer if they are high-risk? 

• Current evidence suggests routinely screening patients with a high risk of prostate cancer does not help prevent deaths and may lead to unnecessary investigations and treatment.  
• Current guidance does not support regular PSA screening in patients with a family history or an underlying inherited cancer predisposition syndrome. This may change with BRCA2 gene variants in men as new evidence emerges. 
• Cancer Research UK outlines that asymptomatic men aged 50 and over can usually ask their GP for a PSA blood test if they wish. 
• Prostate Cancer UK suggests patients consider asking their GP for a PSA test from the age of 45 if they have a high risk of prostate cancer. 

The decision to request a PSA test should be made on a case-by-case basis with careful counselling regarding the risk of false positives or negatives and describing any potential onward investigations.  

When counselling a patient on PSA testing, consider what can falsely raise the result such as: 

• Vigorous exercise, such as cycling, within the last 48 hours. 
• Ejaculation in the last 48 hours. 
• Having had a urological procedure such as a prostate biopsy within the last 6 weeks. 
• Having had a UTI within the last 6 weeks.  
• Prostate cancer UK provides a list of what can falsely raise a PSA which can be used when counselling patients.  

Helpful hints: 

Ask about family history:

• Men with a father or brother with prostate cancer are more than twice as likely to develop the disease when compared to men with no relatives affected, and this risk is further increased if the relative was diagnosed under the age of 60. 
• 2 or more close relatives on the same side of the family with prostate cancer also increases the risk of developing the disease. 
• Due to the association with BRCA gene variants, prostate cancer risk is increased in men with a mother or sister diagnosed with breast or ovarian cancer.  

The United Kingdom Genetic Prostate Cancer Study has shown better survival rates in patients with a family history of prostate cancer, and this is believed to be due to greater awareness of the disease resulting in early diagnosis and treatment. However, the study identified correlations, rather than providing proof of an effect on early diagnosis. 

Genetics and prostate cancer:

• 5% to 10% of prostate cancers are linked to inherited gene variants. 
• Patients are around 2 to 5 times more likely to develop prostate cancer if they have a BRCA2 gene variant. 
• A BRCA1 gene variant also increases risk, however the exact level of risk is not clear. 
• Both BRCA1 or BRCA2 gene variants are associated with more aggressive forms of prostate cancer. 
• Patients with Lynch syndrome have an increased risk of developing prostate cancer. 

In primary care, consider the following factors for an underlying genetic diagnosis:

• Prostate cancer diagnosed below the age of 60. 
• Patients who present with more than one associated cancer (e.g. prostate, breast, ovarian, bowel and endometrial). 
• A patient with multiple close relatives with associated genetic cancers. 
• A patient of Ashkenazi Jewish heritage. 

When to consider a referral to secondary care or a clinical genetics service:

• A patient with a family history which suggests an inherited cancer pre-disposition syndrome. 
• A gene variant has already been identified in one of the patient’s relatives.  
• You can consider a referral for BRCA gene variant testing if a patient is 18 or older and has 1 or more Jewish grandparent.  
• When referring a patient to a genetics service, counsel them on the implications of identifying a gene variant and consider genetic counselling.  

NHS England genomics suggests the following management in primary care:

• Addressing lifestyle and risk factors. 
• Advising patients on red flag symptoms and early presentation. 
• Managing a patient’s anxiety. 
• Advising patients to re-present if their family history changes. 
• Advice on screening (if applicable).  

Practice takeaway: 

Prostate Cancer UK has a 30 second risk checker that patients can use to assess their risk of prostate cancer. This is a useful resource which outlines a patient’s risk, symptoms to look out for, and the likely next steps.