In a study that involved 2013 men with elevated prostate specific antigen, the use of both, magnetic resonance imaging (MRI)-targeted and 12-core systematic biopsies was more effective at detecting clinically significant prostate cancers than either biopsy method alone. The results are published on 5 March 2020 in The New England Journal of Medicine.
Currently, the transrectal, ultrasonographically guided, 12-core systematic biopsy is the most common method for the initial diagnosis and grading of prostate cancer. However, it is associated with missed cancer diagnoses and substantial grade misclassification at the time of biopsy. In addition, further upgrading or downgrading of the cancer diagnosis at the time of radical prostatectomy is common. One consequence of this diagnostic inaccuracy is overtreatment of patients with low-grade disease. Conversely, when aggressive disease is missed on biopsy, patients risk undertreatment.
Advances in prostate multiparametric MRI have allowed for MRI-targeted biopsies of suspicious imaging findings. Studies have shown that MRI-targeted biopsies result in a higher rate of detection of high-grade cancers than systematic biopsy. However, despite the improved detection of clinically significant cancers with MRI-targeted biopsies, debate persists about whether MRI-targeted biopsy should be used in place of systematic biopsy or in conjunction with it. Specifically, controversy exists regarding whether the systematic biopsy should still be performed and whether previous biopsy status should affect the type of biopsy method that is selected.
The Trio Study was a substudy of a larger clinical trial entitled Use of Tracking Devices to Locate Abnormalities During Invasive Procedures. In the substudy, the investigators assessed the use of MRI-targeted, systematic, or combined prostate biopsy in an attempt to define the most effective method for prostate cancer diagnosis.
The primary outcome was cancer detection according to grade group. Grade group 1 refers to clinically insignificant disease; grade group 2 or higher, cancer with favourable intermediate risk or worse; and grade group 3 or higher, cancer with unfavourable intermediate risk or worse. Among the men who underwent subsequent radical prostatectomy, upgrading and downgrading of grade group from biopsy to whole-mount histopathological analysis of surgical specimens were recorded. Secondary outcomes were the detection of cancers of grade group 2 or higher and grade group 3 or higher, cancer detection stratified by previous biopsy status, and grade reclassification between biopsy and radical prostatectomy.
A total of 2103 men underwent both biopsy methods. Cancer was diagnosed in 1312 (62.4%) by combined biopsy, and 404 (19.2%) underwent radical prostatectomy. Cancer detection rates on MRI-targeted biopsy were significantly lower than on systematic biopsy for grade group 1 cancers and significantly higher for grade groups 3 through 5 (p < 0.01 for all comparisons). Combined biopsy led to cancer diagnoses in 208 more men (9.9%) than with either method alone and to upgrading to a higher grade group in 458 men (21.8%). However, if only MRI-target biopsies had been performed, 8.8% of clinically significant cancers (grade group ≥3) would have been misclassified. Among the 404 men who underwent subsequent radical prostatectomy, combined biopsy was associated with the fewest upgrades to grade group 3 or higher on histopathological analysis of surgical specimens (3.5%), as compared with MRI-targeted biopsy (8.7%) and systematic biopsy (16.8%).
The authors concluded that among patients with MRI-visible lesions, combined biopsy led to more detection of all prostate cancers. However, MRI-targeted biopsy alone underestimated the histologic grade of some tumours. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy.
Collectively, the findings suggest that combined biopsy provides improved diagnostic accuracy over either systematic or MRI-targeted biopsy alone and better predicts the results of final histopathological analysis.
The study was supported by the US National Institutes of Health (NIH), the National Cancer Institute, Center for Cancer Research, NIH Clinical Center, and NIH Center for Interventional Oncology. Philips provided materials and technical support as part of a Cooperative Research and Development Agreement.
Ahdoot M, Wilbur AR, Reese SE, et al. MRI-Targeted, Systematic, and Combined Biopsy for Prostate Cancer Diagnosis. N Engl J Med 2020; 382:917-928. DOI: 10.1056/NEJMoa1910038