MRI-Targeted, Systematic, and Combined Biopsy for Prostate Cancer Diagnosis

Abstract

Background: The use of 12-core systematic prostate biopsy is associated with diagnostic inaccuracy that contributes to both overdiagnosis and underdiagnosis of prostate cancer. Biopsies performed with magnetic resonance imaging (MRI) targeting may reduce the misclassification of prostate cancer in men with MRI-visible lesions.

Methods: Men with MRI-visible prostate lesions underwent both MRI-targeted and systematic biopsy. The primary outcome was cancer detection according to grade group (i.e., a clustering of Gleason grades). Grade group 1 refers to clinically insignificant disease; grade group 2 or higher, cancer with favorable intermediate risk or worse; and grade group 3 or higher, cancer with unfavorable 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.

Results: A total of 2103 men underwent both biopsy methods; cancer was diagnosed in 1312 (62.4%) by a combination of the two methods (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%).

Conclusions: 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 tumors. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy. (Funded by the National Institutes of Health and others; Trio Study ClinicalTrials.gov number, NCT00102544.).

Figure 1.. Enrollment and Outcomes.

All 2103 men who were included in the primary analysis underwent two methods of prostate biopsy: one that targeted lesions with the use of magnetic resonance imaging (MRI) and one that systematically removed 12 biopsy cores with ultrasonographic guidance (systematic biopsy). Rates of cancer detection by each of these methods and in combination (combined biopsy) were included in the primary analysis. Among the patients in whom prostate cancer was diagnosed, various treatment options were offered, including active surveillance, prostatectomy, external-beam radiation, and focal therapy. Among the patients who underwent radical prostatectomy, the investigators correlated the initial biopsy findings with the cancer grade group as determined on whole-mount histopathological analysis after surgery.

Figure 2.. Prostate Cancer Detection According to Biopsy Method.

Shown are the total numbers and percentages of cancers that were detected by systematic biopsy, MRI-targeted biopsy, and a combination of the two methods in each of the five grade groups among the 2103 patients who were included in the primary analysis. The difference in the rates of cancer detection between systematic biopsy and MRI-targeted biopsy were significant for grade group 1 (P<0.001), group 3 (P = 0.004), group 4 (P<0.001), and group 5 (P = 0.003). A P value of less than 0.01 was considered to indicate statistical significance after the use of the Bonferroni correction to account for the five primary grade groups. MRI-targeted biopsy led to the detection of significantly more cancers than systematic biopsy in groups 3, 4, and 5. Systematic biopsy led to the detection of significantly more cancers than MRI-targeted biopsy in group 1. Also shown are the numbers and percentages of patients who received an upgraded diagnosis on the basis of the biopsy method that was used. When cancer detection rates were clustered in grade group 2 or higher or in grade group 3 or higher, MRI-targeted biopsy showed a higher rate of cancer detection than systematic biopsy. Newly detected cancers in grade group 1 were seen with the combination of all biopsy methods but were most pronounced with the use of systematic biopsy alone. In the combined-biopsy group, a new diagnosis of grade group 1 cancer (in 105 patients [5.0%]) was defined as the total number of grade group 1 cancer diagnoses on combined biopsy (in 394 patients) minus all grade group 1 diagnoses on targeted biopsy alone (in 289 patients). Details regarding the statistical analysis are provided in the Supplementary Appendix.

Figure 3.. Cross-Tabulation of Highest Grade Group Detected by Biopsy Method.

Shown are the numbers and percentages of the 2103 men who were included in the primary analysis in whom no prostate cancer was diagnosed or in whom prostate cancer was diagnosed (grade groups 1 through 5) on systematic biopsy or MRI-targeted biopsy. The areas that are shaded in gray indicate the men in whom systematic biopsy and targeted biopsy detected cancer of the same grade group. The areas that are shaded in blue indicate the men who were found to have a cancer in a higher grade group on MRI-targeted biopsy, and the areas that are shaded in green indicate the men who were found to have cancer in a higher grade group on systematic biopsy.

Figure 4.. Downgrading and Upgrading of Cancer Grade Group after Whole-Mount Histopathological Analysis, According to Biopsy Method.

Among the 404 men who underwent radical prostatectomy, shown are the numbers and percentages of those in whom the grade group of prostate cancer was downgraded or upgraded after whole-mount histopathological analysis of surgical specimens according to the biopsy method that was used. The areas that are shaded in blue indicate the downgrading of events from biopsy to whole-mount analysis, and the areas shaded in red indicate the upgrading of events. Darker colors represent more extreme levels of downgrading or upgrading. The lowest percentage of upgrading events was seen with combined biopsy (14.4%) and the highest with systematic biopsy (41.6%). Differences in rates of upgrading between systematic and MRI-targeted biopsy were significant for upgrading of any grade group (P = 0.002), upgrading to grade group 2 or higher (P<0.001), and upgrading to grade group 3 or higher (P<0.001). The differences in rates of downgrading were not significant for any grouping. A P value of less than 0.006 was considered to indicate statistical significance with the use of the Bonferroni correction to account for the eight secondary outcomes. Results of the statistical analyses are shown in Table S5.