Combination Prostate Biopsy Can Overestimate Gleason Grade Compared with Surgical Pathology

Recently a group at the National Cancer Institute determined that combination prostate biopsy (standard systematic biopsy plus multiparametric MRI–ultrasound fusion biopsy) improves concordance with final surgical pathology. In The New England Journal of Medicine, they also reported a reduction in upgrade rates with combination biopsy—higher Gleason grade (GG) on surgical pathology than on biopsy pathology.

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However, the downgrade rate in that study contradicted the results of previous research. To address the conflict, Adam S. Feldman, MD, MPH, of the Department of Urology at Massachusetts General Hospital, Alice Yu, MD, MPH, of the H. Lee Moffitt Cancer Center, and colleagues conducted their own evaluation of concordance, upgrade and downgrade. In Urologic Oncology, they report combination prostate biopsy often overestimates GG compared with surgical pathology.

Study Methods

The researchers retrospectively studied 173 men who underwent multiparametric MRI followed by targeted and 12-core systematic combination biopsy between April 2014 and August 2018 and were treated with radical prostatectomy (RP).

Concordance

Surgical pathology was concordant (the GG matched) with 45% of systematic biopsies, 47% of targeted biopsies, and 57% of combination biopsies. In multivariate analysis, combination biopsy was the best predictor of GG on RP:

• Vs. systematic—RR, 1.27; P=0.001
• Vs. targeted—RR, 1.21; P=0.002

Upgrade

The risk of upgrade on surgical pathology (higher GG than on biopsy) was significantly lower with combination biopsy:

• Vs. systematic—RR, 0.57; P<0.001
• Vs. targeted—RR, 0.67; P<0.001

Details of upgrading:

• Systematic—Of 89 patients with GG ≤1 on biopsy, 5% had high-risk disease (GG≥4) on RP, and 64% had intermediate-risk disease (GG2–3)
• Targeted—Of 75 patients with GG ≤1 on biopsy, 4% had high-disease on RP, and 59% had intermediate-risk disease
• Combination—Among 56 patients with GG ≤1 on biopsy, the chance of missing high-risk disease was reduced to 1.8%, and the chance of missing intermediate-risk disease was 50%

Downgrade

The risk of a downgrade on surgical pathology (lower GG than on biopsy) was significantly increased with combination biopsy:

• Vs. systematic—RR, 1.93; P<0.001
• Vs. targeted—RR, 1.26; P<0.01

Specific results after combination biopsy:

• 45% of 31 patients were downgraded from high-risk to intermediate-risk disease on RP
• 46% of 26 patients were downgraded from unfavorable intermediate-risk disease (GG3) to favorable intermediate-risk disease (GG2)
• Two patients were downgraded from GG2 to GG1; however, both had tertiary score of 4

Concordance, upgrade and downgrade rates were similar when systematic biopsy alone was compared with targeted biopsy alone.

Clinical Implications

Confirming a number of previous studies, these findings show that adding fusion biopsy to traditional systematic biopsy improves the concordance of biopsy results with final surgical pathology. This is important to know when counseling patients about their management options.

Still, it's important to note the high chance that combination biopsy overestimates GG, which can lead to overtreatment of what might actually be a less aggressive disease. For example, misclassifying intermediate-risk disease as high-risk could lead to more aggressive surgery, including more extensive pelvic lymph node dissection or avoidance of a nerve-sparing approach, both of which can increase postoperative morbidity.

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