MRI/Ultrasound Fusion Biopsy Versus Standard 12-Core Biopsy

Prostate biopsy effectively samples < 1% of the prostate and many men undergo multiple repeat biopsies during their lifetimes.¹ Recently, numerous studies have examined the use of multiparametric MRI (mpMRI) of the prostate as a standalone technology as well as targeted biopsies using MRI-US fusion.² This review summarizes two studies demonstrating the potential that targeted biopsies hold in limiting the diagnosis of insignificant disease while still detecting significant cancer.

Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Significantly Upgrades Prostate Cancer Versus Systematic 12-core Transrectal Ultrasound Biopsy

Siddiqui MM, Rais-Bahrami S, Truong H, et al. Eur Urol. 2013;64:713–719. doi: 10.1016/j.eururo.2013.05.059.

There are several ways to perform MRI-guided prostate biopsies, which include direct MRI-guided biopsy, MRI-US fusion, and cognitive coregistration. The current study was designed to assess whether MRI-US fusion results in a more accurate biopsy than standard 12-core transrectal ultrasound (TRUS) biopsy. From 2007 to 2012, 582 patients (including 89 patients on AS and 320 with prior negative biopsy results) were enrolled in a prospective trial at the National Institutes of Health. All men underwent 3T mpMRI prior to prostate biopsy, which were reviewed by two experienced genitourinary radiologists.

All participants then underwent a standard 12-core TRUS-guided biopsy (blinded to the MRI results), with the addition of at least two additional cores using MRI-US fusion for each lesion identified on MRI. The mean number of targeted biopsies per patient was 5.7 versus 12 cores with standard biopsy. Positive biopsy results were classified as clinically significant, high grade (Gleason ≥ 4 + 3), or clinically insignificant, low-grade disease (Gleason ≤ 3 +4).

Among men with prostate cancer detected on 12-core prostate biopsy, performing the targeted biopsies resulted in Gleason upgrading in 81 (32%) cases. Targeted biopsies resulted in 43 (22%) additional cases of Gleason ≤ 3 + 4 prostate cancer and 38 (67%) additional cases of clinically significant prostate cancer.

Conversely, compared with targeted biopsy, 12-core biopsy resulted in Gleason score upgrading in 67 (26%) cases. Adding 12-core biopsy to the targeted biopsy resulted in 60 (36%) additional cases of Gleason ≤ 3 + 4 prostate cancer and 7 (8%) additional cases of clinically significant prostate cancer. Overall, 17 patients with high-grade disease would have been labeled as cancer free based on standard 12-core biopsy results alone.

On multivariable analysis, significant predictors of Gleason score upgrading on targeted prostate biopsy were smaller prostate volume (odds ratio [OR] 0.84; 95% confidence interval [CI], 0.74–0.93; P = .005), higher PSA level (OR 1.03; 95% CI, 1.01–1.05; P = .004), more lesions on MRI (OR 1.4; 95% CI, 1.2–1.8; P = .0005), and higher MRI suspicion score (OR 1.7; 95% CI, 1.02–3.0; P = .04).

A limitation of the study is that the two biopsy modalities were compared with each other, unlike other studies using template mapping biopsy or radical prostatectomy specimens as the gold standard. In addition, the study population was heterogeneous and a substantial proportion had previous negative prostate biopsy results. Consequently, more data are needed to evaluate the incremental value of this technique among biopsy-naive patients. Finally, men with no visible lesions on MRI were excluded from the study, and all targeting was done using a fusion platform so the generalizability of these results to alternate techniques, such as cognitive fusion, is unknown. Nonetheless, this study adds to increasing evidence that suspicious lesions on multiparametric MRI increase the risk of high-grade disease, and that fusion biopsy can enhance its detection.

Comparison of MR/Ultrasound Fusion-Guided Biopsy With Ultrasound-Guided Biopsy for the Diagnosis of Prostate Cancer

Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. JAMA. 2015;313:390–397. doi: 10.1001/jama.2014.17942.

This article is an extension of the aforementioned study by Siddiqui and colleagues (Eur Urol. 2013;64:713–719). The goal of this study was to assess targeted versus standard biopsy, and the two approaches combined, for the diagnosis of intermediate- to high-risk prostate cancer. Using the previously described imaging and prostate biopsy protocol, 1215 men were prospectively evaluated for study inclusion with 3T mpMRI. After excluding 181 men with no lesions on MRI and 31 with prior treatment for prostate cancer, the analysis ultimately included 1003 men who all underwent both targeted and standard prostate biopsy.

Biopsy results were classified as low-risk (Gleason 6, or Gleason 3 + 4 with < 50% cancerous involvement of any core and < 33% of standard biopsy cores positive for cancer). Intermediate-risk disease was defined as higher-volume Gleason 3 + 4 disease, and any Gleason ≥ 4 + 3 was considered high risk.

Overall, 690 (69%) patients demonstrated concordance between the two biopsy strategies for the presence of low- or high-risk cancer. Although a similar absolute number of cancers were diagnosed by targeted biopsy (461) and standard biopsy (469), targeted biopsy alone diagnosed 30% more high-risk disease compared with standard biopsy (P < .001). Meanwhile, targeted biopsy alone detected 17% fewer low-risk cancers than standard biopsy (P = .002).

Combining targeted and standard biopsy led to the diagnosis of 103 (22%) additional cases, but the vast majority (83%) were Gleason 6 or low-volume Gleason 3 + 4, and only 5% were classified as high-risk. The authors estimated that 200 men would need to undergo standard biopsy in addition to targeted biopsy to find one case of high-risk prostate cancer. Meanwhile, 17 extra low-risk cancers would be detected per each additional high-risk cancer diagnosed.

Subset analysis was performed in 170 patients who underwent radical prostatectomy to compare biopsy results with whole-gland pathology. This subset included 17 men whose cancer was detected on standard biopsy alone and 20 men whose cancer was found only in the targeted biopsy. Intermediate- to high-risk cancer was found at prostatectomy in 3 (18%) versus 12 (60%) of these men, respectively. Overall, the sensitivity of targeted-only biopsy was 77% compared with 53% for standard biopsy when compared with final prostatectomy pathology. Specificity was similar for both techniques (68% vs 66%). On receiver operating characteristic analysis, targeted biopsy outperformed both standard biopsy (area under the operating curve [AUC] 0.73 vs 0.59; P = .005) and the combined technique (AUC 0.73 vs 0.67; P = .04).

Finally, the authors performed a subgroup analysis of 196 biopsy-naive patients who had similar targeted biopsy risk distribution compared with the repeat biopsy group (P = .52). The risk distribution at standard biopsy was higher for biopsy-naive patients, and was not significantly different from targeted biopsy. The addition of standard biopsy to targeted biopsy led to upgrading to intermediate risk in 11 (5.6%) and to high risk in 7 (3.6%) patients.

A significant limitation of this study is that the majority of patients had previous biopsies, so additional validation is necessary in a larger population of men without prior biopsy. Similar to their earlier study, patients with no visible lesions on MRI were excluded from the study, so it is not possible to compare the results of biopsy for these patients.

Overall, improvements in prostate cancer detection protocols are needed to decrease the detection of clinically insignificant disease while maximizing early detection of potentially life-threatening disease. These studies highlight how targeted fusion biopsies can help reduce the detection of clinically insignificant disease while increasing the efficiency of detection of high-risk prostate cancer.