Prostate cancer: A focus on diagnosis

 

As part of Prostate Cancer Awareness Month, we are taking a look at the latest developments and clinical trials surrounding prostate cancer diagnosis. Prostate cancer deaths have recently overtaken those of breast cancer in the UK for the first time on record. While breast cancer deaths have been falling for decades, prostate cancer deaths have increased over the same period.1 The reasons for this are varied, and largely relate to the increasing age of the UK population – prostate cancer is primarily a disease of older men, with a peak in diagnoses at ages 65–69 years.2 Early stage prostate cancer has few symptoms, and when symptoms do arise, they are mostly linked to the frequency and problems with urination, which can affect older men more generally.1

Improved detection of prostate cancer could help to reverse the increase in mortality, but only if these methods can distinguish aggressive, life-threatening prostate cancer from indolent disease (a cancer that is so slow growing, it is unlikely to cause harm to the individual over the period of a lifetime). One of the main issues facing healthcare professionals treating patients with prostate cancer is the lack of a standard diagnostic technique that can determine whether a man’s prostate cancer is aggressive and requires invasive treatment. Surgery and radiotherapy to the prostate can have significant long-term side effects such as loss of control of urination and loss of sexual function,3 so it is vital that men with clinically unimportant disease are not given invasive treatments.

A number high-profile clinical trials in prostate cancer have started to report results, and these could significantly change the way that prostate cancer is diagnosed and managed. The PROMIS trial investigated two different diagnostic techniques in men who had an elevated prostate-specific antigen (PSA) reading. PSA is a protein produced exclusively by the prostate, and while it is used as a blood test marker for prostate cancer, a man will have elevated PSA for a number of other reasons, including injury to the prostate, a urinary tract infection, or enlargement of the prostate. As such, it is a blunt tool for detecting prostate cancer, and many of the men who are sent for biopsy will not have prostate cancer, placing great importance on the sensitivity of the next step in the diagnostic pathway.4

In current clinical practice, elevated PSA is a trigger for a transrectal ultrasound biopsy (TRUS), a technique that is blind to the location of the cancer within the prostate, and therefore a random sampling of cells within the gland. This means that men with clinically unimportant disease are subjected to unnecessary biopsy, and there is over diagnosis of clinically unimportant disease and under-diagnosis of clinically important prostate cancer (over 50% of these are missed). PROMIS compared TRUS to another diagnostic technique called multi-parametric magnetic resonance imaging (mpMRI), which does not involve biopsy, and set out to find whether mpMRI might improve diagnosis and allow men to avoid unnecessary biopsy.5

The results of the PROMIS trial showed that mpMRI was around twice as good as TRUS at detecting prostate cancer, picking up 90% of clinically important prostate cancers. Rolling out mpMRI as standard clinical practice is estimated to allow 27% of men with suspected prostate cancer to avoid a biopsy, and lead to 5% fewer clinically insignificant cancers being diagnosed.5

The CAP trial, one of the largest prostate cancer studies ever conducted, involving more than 400,000 men ages 50–69 years and 600 GP practices has recently published results. The researchers were assessing the effectiveness of one-off PSA screening in detecting prostate cancer and followed up patients for 10 years. The trial found that PSA is a poor marker for early prostate cancer, with no significant different in prostate cancer mortality among patients who received PSA screening versus those who did not, and there was an increase in the number of low-risk prostate cancers detected. These results support the decision by national authorities not to offer a prostate cancer screening programme based on PSA, and highlight the need for an alternative means of detecting early stage prostate cancer.6

 

References

1.       BBC News. Prostate cancer deaths overtake those from breast cancer. Available at: http://www.bbc.co.uk/news/health-42890405 Accessed: March 2018.

2.       Prostate Cancer UK. Are you at risk? Available at: https://prostatecanceruk.org/prostate-information/are-you-at-risk Accessed: March 2018.

3.       Cancer Research UK. Surgery to remove your prostate gland. Available at: http://www.cancerresearchuk.org/about-cancer/prostate-cancer/treatment/surgery/surgery-remove-your-prostate-gland Accessed: March 2018.

4.       BBC Radio 4. Inside Health: Prostate cancer. Broadcast 4 January 2017. Available at: http://www.bbc.co.uk/programmes/b086s7jr Accessed: March 2018.

5.       Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;10071:815–22.

6.       Martin RM, Donovan JL, Turner EL, et al; CAP Trial Group. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: The CAP randomized clinical trial. JAMA. 2018;319:883–95.