The prostate cancer debate: pros & cons of screening and preventive drugs

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Prostate cancer is the most common cancer in men, with over 40,000 new cases diagnosed in the UK every year. There is intense debate over whether men should undergo regular prostate-specific antigen (PSA) testing, as outlined in our previous blog post, and clinical trials have come to opposing conclusions about whether PSA screening saves lives or causes unnecessary harm. On one hand, the European Randomized Study of Screening for Prostate Cancer (ERSPC) showed that routine PSA testing reduced the risk of dying from prostate cancer by around 20%, whereas the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial found that regular PSA screening did not lead to fewer prostate cancer deaths.

Could stratified screening reduce the risks of PSA testing?

Recent research published in BMC Medicine by Andrew Vickers and colleagues from Memorial Sloan Kettering Cancer Center found that if PSA testing was restricted based on age and baseline PSA levels, overdiagnosis could be substantially reduced. The pros and cons of restricted screening were also recently discussed by the lead investigators of the ERSPC and PLCO trials in a Q&A in Biome magazine. Fritz Schröder,DGU Kongress 2009 in Dresden. leading the ERSPC trial, cautions that stratified PSA screening based on PSA levels per se could lead to certain cancer types being missed:

Adjustment of PSA levels will always lead to the loss of aggressive cancers and is not a good option. No level of sensitivity can be identified which would optimize specificity”

Lead author of the PLCO trial Gerald Andriole indicates that risk stratification is necessary to decrease the risk of prostate cancer overdiagnosis, and highlights other ways in which screening could be made more personalized:

Andriole 2013 pic crop“I anticipate that the use of PSA-based screening will become more risk stratified with the use of other markers in addition to PSA, such as new serum and urinary markers.”

Andriole concludes that further improvements in detecting rapidly-progressing prostate cancer should identify those with slow-growing tumors, so these men can undergo active surveillance rather than aggressive overtreatment.

Looking to the future, Schröder outlines that:

Our hope is that additional tests such as the application of multi-parametric MRI testing will allow the selective exclusion of low risk men from the biopsy procedure and thereby reduce overdiagnosis”

Such tests are now under clinical development; a new clinical trial carried out in Australia recently showed that MRI-guided biopsy can significantly improve the diagnosis of life-threatening prostate cancer, thus helping to avoid the side-effects of unnecessary treatment in those unlikely to benefit. We look forward to further work on how PSA screening can be optimized with the concomitant use of techniques such as MRI to reduce the harms associated with screening.

Can aspirin cut prostate cancer risk?

In addition to the controversy surrounding prostate cancer screening, opinions differ on how best to prevent getting the disease in the first place. There have been many suggestions for how men can decrease their risk of developing prostate cancer – from eating more broccoli and avoiding vitamin E supplements to reducing stress and doing more exercise – but the evidence is not yet strong enough to make conclusive recommendations.

Wikipedia (Ragesoss)A systematic review and meta-analysis published in BMC Medicine by Yanqiong Liu and colleagues from Guangxi Medical University in China shows that taking aspirin is associated with reduced prostate cancer incidence and mortality, especially with advanced prostate cancer. These findings suggest that long-term aspirin use could be beneficial in preventing prostate cancer, and are in line with previous findings suggesting that aspirin could reduce the risk of dying from several types of cancer.

However, while these results are promising, it is important to take the potential harms of long-term aspirin use into account before recommendations about regular use can be made. Aspirin can cause stomach bleeding, nausea, breathing problems and allergic reactions in some people, and has been associated with hemorrhagic stroke in rare cases. An NHS review of the benefits and harms of aspirin use carried out in 2013 concluded that the drug should not be taken prophylactically until there is more evidence.

Liu and colleagues highlight that the optimal dose and frequency of aspirin to prevent prostate cancer are as yet unknown, and caution that:

[we need] to ensure that the associated prevention benefits of aspirin outweigh the potential side effects”

Together with recent insights on how we can reduce the harms associated with PSA screening, Liu and colleagues’ study highlights the importance of taking all the effects of interventions for prevention and detection into account before appropriate recommendations can be made. We look forward to further research showing how the potential harms associated with PSA screening can be reduced, and how best to decrease the risk of developing prostate cancer through prophylactic drugs and lifestyle choices.