Background
The diagnostic pathway for prostate cancer usually involves an elevated serum prostate specific antigen test and a digital rectal examination combined with clinical history followed by a transrectal ultrasound-guided prostate biopsy (TRUS-biopsy).
In addition to the side-effects of TRUS-biopsy, including bleeding, pain, and infection, many men are found to either not have cancer at all or clinically insignificant cancers are identified.
Moreover, some clinically significant cancers are missed with TRUS-biopsy. Recently evidence has been accruing that the use of multi-parametric magnetic resonance imaging (mp-MRI) can enhance the detection of aggressive cancers and reduce over-detection and improve targeted biopsies.
It is also being investigated for use in active surveillance protocols and to aid focal treatments for prostate cancer.
Aim
To investigate whether mp-MRI can discriminate between men with and without clinically significant prostate cancer based on template prostate mapping biopsy (TPM-biopsy); to compare the accuracy of mp-MRI with TRUS; and to determine whether mp-MRI could be used as a triage test to avoid unnecessary TRUS-biopsy.
Methods
PROMIS was a prospective multi-centre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-biopsy against a reference test (TPM-biopsy).
Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy.
The conduct and reporting of each test was done blind to other test results. Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core length 6 mm or longer.
Sensitivity, specificity, positive and negative predictive values were calculated and compared between mp-MRI and TRUS biopsy using McNemar tests and odds ratios (ORs).
Ratios were presented as TRUS relative to mp-MRI so ratios greater than 1.0 favour TRUS and less than 1.0 favour mp-MRI.
Results
Between May 17, 2012, and November 9, 2015, 740 men were enrolled in the study across 11 centres. 576 underwent 1·5 Tesla mp-MRI followed by both TRUS-biopsy and TPM-biopsy.
On TPM-biopsy, 408 of 576 men (71%; 95% confidence interval (CI) 67%-75%) had cancer with 230 of 576 patients (40%; 95% CI 36%-44%) with clinically significant cancer.
For clinically significant cancer, mp-MRI was more sensitive (93%, 95% CI 88%–96%) than TRUS-biopsy (48%, 42%–55%; OR=0.52, p<0·0001) and had higher negative predictive value (89%, 95% CI 83%-94%) than TRUS-biopsy (74%, 95% CI 69%-78%; OR=0.34, p<0.0001).
However, mp-MRI was less specific (41%, 95% CI 36%-46% than TRUS (96%, 95% CI 94%–98%; OR=2.34; p<0·0001) and had lower positive predictive value: mp-MRI = 51% (95% CI 46%-56%) vs TRUS = 90% (95% CI 83%-94%; OR=8.2; p<0.0001).
The authors considered the implications of using mp-MRI by comparing the standard strategy of of TRUS-biopsy for all men to 2 alternative strategies using mp-MRI as a triage test with only men with a suspicious mp-MRI going on to either TRUS-biopsy or MRI-directed TRUS-biopsy (as the latter weren’t done in the study the authors assumed similar accuracy to TPM-biopsy). 27% (n=158) of men would avoid a primary biopsy under the triage scenarios.
In the ‘best-case’ scenario, using MRI-guided biopsy, there could be up to 5% more clinically insignificant cancers detected (121 out of 576; 21%) compared to TRUS-biopsy alone (90 out of 576; 16%) but 5% fewer cases (n=62, 11%) in the triage scenario with TRUS-biopsy following triage with mp-MRI (‘worst-case’ scenario).
In the ‘best case’ scenario, the correct diagnosis of clinically significant cancer might increase to 213 (37%) compared to standard TRUS-biopsy (n=111, 19%).
44 (5·9%) of 740 patients reported serious adverse events, including eight cases of sepsis.
Conclusion
The use of mp-MRI to triage men might allow 27% of patients avoid a primary biopsy and the diagnosis of 5% fewer clinically insignificant cancers.
If subsequent TRUS-biopsies were directed by mp-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. mp-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter.
mp-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer.
