Abstract
Transrectal, ultrasonography-guided prostate biopsy often fails to disclose the severity of underlying pathologic findings for prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy may improve the characterization of prostate pathologic results, but few studies have examined its use for the decision to enter active surveillance. To evaluate whether confirmatory biopsy findings by MRI guidance are associated with the risk of pathologic disease upgrading among patients with prostate cancer during active surveillance. This retrospective cohort study used prospectively obtained registry data from 332 men with prostate cancer of Gleason grade group (GG) 2 or lower who were referred for active surveillance at a large academic medical center from January 1, 2009, through December 31, 2017. All confirmatory and follow-up biopsies were performed using MRI guidance with an MRI-ultrasonography fusion device. Patients underwent repeated MRI-guided biopsies every 12 to 24 months. At follow-up sessions, in addition to obtaining systematic samples, lesions seen on MRI were targeted and foci of low-grade prostate cancer were obtained again using tracking technology. Active surveillance was terminated with detection of at least GG3 disease or receipt of treatment. The primary outcome was upgrading to at least GG3 disease during active surveillance. Secondary outcomes were the associations of MRI lesion grade, prostate-specific antigen (PSA) level, PSA density, and biopsy method (targeted, systematic, or tracked) with the primary outcome. Of 332 patients (mean [SD] age, 62.8 [7.6] years), 39 (11.7%) upgraded to at least GG3 disease during follow-up. The incidence of upgrading was 7.9% (9 of 114) when the confirmatory biopsy finding was normal, 11.4% (20 of 175) when the finding showed GG1 disease, and 23.3% (10 of 43) when the finding was GG2 disease (P = .03). Men with GG2 disease were almost 8 times more likely to upgrade during surveillance compared with those with normal findings but only among those with low PSA density (hazard ratio [HR], 7.82; 95% CI, 2.29-26.68). A PSA density of at least 0.15 ng/mL/mL was associated with increased risk of upgrading among patients with normal findings (HR, 7.21; 95% CI, 1.98-26.24) or GG1 disease (HR, 2.86; 95% CI, 1.16 to 7.03) on confirmatory biopsy. A total of 46% of pathologic disease upgrades would have been missed if only the targeted biopsy was performed and 65% of disease upgrades were detected only with tracked biopsy. The findings suggest that confirmatory biopsy with MRI guidance is significantly associated with future disease upgrading of prostate cancer, especially when combined with PSA density, and should be considered as an appropriate entry point for active surveillance. Systematic and targeted biopsies were additive in detection of clinically significant cancers. Repeated biopsy at sites at which findings were previously abnormal (tracking biopsy) facilitated detection of cancers not suitable for continued active surveillance.
Highlights
Active surveillance is currently the most rapidly growing management strategy for men with prostate cancer.[1,2,3,4] The goal of active surveillance is to defer treatment for men with prostate tumors unlikely to cause mortality, thereby preventing the morbidity that active intervention often entails
Men with GG2 disease were almost 8 times more likely to upgrade during surveillance compared with those with normal findings but only among those with low prostatespecific antigen (PSA) density
A PSA density of at least 0.15 ng/mL/mL was associated with increased risk of upgrading among patients with normal findings (HR, 7.21; 95% CI, 1.98-26.24) or Gleason score of or lower (GG1) disease (HR, 2.86; 95% CI, 1.16 to 7.03) on confirmatory biopsy
Summary
Active surveillance is currently the most rapidly growing management strategy for men with prostate cancer.[1,2,3,4] The goal of active surveillance is to defer treatment for men with prostate tumors unlikely to cause mortality, thereby preventing the morbidity that active intervention often entails. Enrollment in the early active surveillance programs was primarily based on the biopsy findings of low-risk cancers, and discontinuing active surveillance was mainly based on a subsequent biopsy finding indicating increased risk.[5] The strategy has been largely successful; few compliant individuals have experienced metastatic disease during active surveillance, and at present, most men who receive a diagnosis of with low-risk prostate cancer are treated expectantly.[4,6]. Histologic upgrading of prostate cancer beyond the low-risk disease found initially has been reported in 30% of men during the first year of follow-up.[7] Early disease upgrading likely indicates that the initial biopsy findings were inaccurate, which diminishes the efficiency of active surveillance and raises concern about the propriety of active surveillance. Accurate characterization of prostate pathologic findings from the start of active surveillance (and throughout follow-up) would be desirable
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