Transforming the diagnosis and treatment pathway for prostate cancer

Traditionally, prostate cancer diagnosis has been based on screening for raised levels of prostate-specific antigen (PSA) and biopsy. But PSA levels are not a reliable indicator of disease, leading to many unnecessary biopsies, over-diagnosis and missed cases of cancer.

Advances in MRI in the 2000s provided an opportunity to address these serious shortcomings. In a series of landmark studies led by Professor Emberton, UCL researchers and their international collaborators have shown that use of MRI can markedly and safely reduce the numbers of men needing biopsy.

Most notably, the PROMIS trial showed that MRI was a more accurate indicator of the absence of clinically significant disease than a gold standard test - serial biopsies every 5 mm across the entire prostate [1]. An MRI-based triage test in men with elevated PSA levels could allow an estimated 27% of men avoid a biopsy and lead to the diagnosis of 5% fewer cases of clinically insignificant disease. Furthermore, if subsequent biopsies were guided by MRI, 18% more cases of clinically significant disease could be detected.

MRI adds considerable complexity to the initial stages of the prostate cancer diagnostic pathway. Nevertheless, health economic analyses suggest that a reduction in the numbers of unnecessary biopsies and less treatment of clinically insignificant disease would make the overall pathway cost-effective [2].

Furthermore, the results of the recent large-scale PRECISION trial suggested that a combination of MRI and targeted biopsy is significantly better at identifying clinically significant cancer than standard biopsies [3]. The MRI approach also cut the number of men undergoing biopsy by 28%.

The ability to identify the precise location of prostate tumours also opens the way to more localised treatments, just as mastectomies have largely given way to lumpectomy in breast cancer. This has multiple potential benefits - not least fewer distressing side effects, incontinence and impotence, associated with more radical treatments.

A range of methods have been developed to eliminate cancerous tissue. One highly successful approach for low-risk cancers, vascular-targeted photodynamic therapy, involves the infusion of a laser-activated cytotoxic compound, padeliporfin. Following a successful phase III international trial involving 47 centres [4], the treatment (trade name Tookad) was approved by the European Medicines Agency in 2017.

Recently, Professor Emberton and colleagues have begun a new programme of work to refine further the diagnostic pathway for prostate cancer. Funded through the MRC's stratified medicine initiative, the re-IMAGINE study will combine MRI with deep phenotyping of 1000 men with early-stage prostate cancer, including blood tests and urine tests to identify circulating DNA or metabolic markers of cancer. The results should provide a more detailed picture of individual tumours, and potentially identify markers that provide a reliable guide to the presence of clinically significant disease, without recourse to biopsy.

1. Ahmed HU et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389(10071):815-822.
2. Faria R et al. Optimising the diagnosis of prostate cancer in the era of multiparametric magnetic resonance imaging: A cost-effectiveness analysis based on the prostate MR imaging study (PROMIS). Eur Urol. 2018;73(1):23-30.
3. Kasivisvanathan V et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378(19):1767-1777.
4. Azzouzi AR et al. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 2017;18(2):181-191.