At present, a man is judged to be at risk of harbouring prostate cancer if he has any of the following: a raised serum PSA level (present in the majority of cases), an abnormal digital rectal examination (DRE), a positive family history of prostate cancer or a specific ethnic risk profile.12The diagnostic pathway of
interest to this work relates to men with signs and symptoms that are suspicious of prostate cancer who have been referred for confirmatory diagnostic testing. In these men, prostate cancer, if present, is typically localised. Men with signs and symptoms of locally advanced cancer or metastatic cancer are often managed in a different manner with staging whole-body scans and the institution of systemic therapy with or without confirmatory prostate biopsy.
Men in whom there is diagnostic uncertainty are currently advised to have a transrectal ultrasound (TRUS)-guided prostate biopsy.13Men with a negative TRUS-guided biopsy result are advised to consider
multiparametric magnetic resonance imaging (mpMRI) (using T2- and diffusion-weighted imaging) to determine whether or not another biopsy is needed. Between 59,000 and 80,000 men have a TRUS-guided biopsy in the UK each year,14although this is likely to be an underestimate considering that three to four
TRUS-guided biopsies are usually carried out to diagnose one man with cancer.
Men diagnosed with localised prostate cancer in England are managed according to their risk of progression (Table 1). The risk of progression is assessed on the basis of their serum PSA concentration, Gleason score and clinical stage. PSA is a protein produced by the prostate gland; an elevated PSA level is a sign that cancer may be present. The Gleason pattern classifies prostate cells obtained in the TRUS-guided biopsy by level of differentiation, which is related to the degree of aggressiveness of prostate cancer. Cancer cells can be classified from Gleason grade 1 (well differentiated and lower risk) to Gleason grade 5 (poorly differentiated and higher risk).13The Gleason score is the sum of the grades of the two
most common types of cells. For example, if the man’s most common cells are Gleason grade 3 and Gleason grade 4, the Gleason pattern is 3+4=7. The clinical stage is assessed by the urologist by DRE
with or without imaging scans, although the majority of men diagnosed with prostate cancer also undergo pelvic and prostate magnetic resonance imaging (MRI) after the biopsy.
The 2014 National Institute for Health and Care Excellence (NICE) clinical guideline13recommends that
men with low-risk prostate cancer are offered active surveillance, as described inTable 2. Men with intermediate- or high-risk cancer should be offered active treatment. In men with intermediate-risk cancer, the 2014 NICE clinical guideline recommends RP or radical radiotherapy but considers active surveillance or high-dose-rate brachytherapy with external-beam radiotherapy as possible options. Men with high-risk cancer should be offered RP, radical radiotherapy or high-dose-rate brachytherapy with external-beam radiotherapy. Interestingly, the NICE guidance also recommends prostate MRI as a baseline test at the commencement of active surveillance. Under the current NICE guidance and clinical practice, therefore, almost all men who have a TRUS-guided biopsy are recommended to undergo MRI after biopsy.
TABLE 1 Risk groups for localised prostate cancer
Risk PSA level (ng/ml) Gleason score Stage
Low <10 AND ≤6 AND T1–T2a
Intermediate 10–20 OR 7 OR T2b
High >20 OR 8–10 OR ≥T2c
Notes
T1, the tumour is too small to be seen on a scan or felt during examination of the prostate; T2a, the tumour is in only half of one of the lobes of the prostate gland; T2b, the tumour is in more than half of one of the lobes; T2c, the tumour is in both lobes but is still inside the prostate gland; T3, the tumour has broken through the capsule of the prostate (locally advanced); and T4, the tumour has spread to other organs nearby.
Information drawn from NICE.13
INTRODUCTION
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The current clinical pathway and potential for imaging
Men undergo prostate biopsy in the absence of accurate imaging that can visualise a suspicious lesion, as ultrasonography is used to identify the prostate, not the suspect lesion. The result is that biopsies are taken‘blindly’from areas of the gland. Although protocols stipulate that the biopsies should sample certain regions in a fanlike manner, studies have shown that this is often not the case and that the biopsies are clustered.15This results in a random, rather than systematic, deployment of the needle. This approach
(Figure 1) contrasts markedly with that used for other cancers, in which the physician either visualises (e.g. using endoscopy) or images (e.g. using mammography) a suspect lesion in order to guide a biopsy needle to it.
The use of mpMRI prior to TRUS-guided biopsy could offer several important advantages:
l less overdiagnosis–in that fewer CNS prostate cancers are detected by avoiding unnecessary biopsy of men who do not have CS cancer
l less overtreatment–as fewer CNS prostate cancers are detected
l increased detection of CS prostate cancers–by directing biopsies to areas of the prostate that appear abnormal on mpMRI
l improved characterisation of individual cancers–as a result of more representative biopsy sampling
l reduced complications (including sepsis and bleeding)–as fewer men are biopsied and fewer biopsies are taken in men who are biopsied.
In addition, a revised diagnostic pathway based on the findings of the PROstate Magnetic resonance Imaging Study (PROMIS) also has the potential to offer a more cost-effective use of NHS resources. This is explored in the accompanying economic evaluation.