No validated clinical tools currently exist to standardize the frequency of biopsies for men on active surveillance (AS) and clinicians often tailor surveillance based on tumor characteristics and patient factors. Multi-parametric MRI and genomic testing have been proposed to aid in tailoring surveillance intensity, however this remains to be determined. We aimed to determine predictors of biopsy upgrading at specific time points to understand which men may be safely monitored with less intensive surveillance.
Men with clinically low risk disease enrolled on AS between 2000-2016 were included. The genomic tests used were the Genomic Prostate Score, Decipher and Prolaris. A genomic score greater than the mean plus 1 standard deviation of the cohort were classified as “high” and a score less than or equal to the mean plus 1 standard deviation were classified as “low”. Upgrading was defined as grade group 2 or higher on subsequent biopsy. PSA kinetics was calculated using a linear mixed-effects model for log of PSA, adjusted for clinical characteristics. Multivariable Cox proportional hazards regression models were used to identify factors associated with risk of upgrade at first surveillance biopsy and at 3, 5 and 10 years.
1,303 men were included with a median PSA density of 0.13 ng/ml2 (IQR 0.09-0.18). 1,169 (90%) men were grade group 1. 257 (62%) had a PI-RADS 4-5 lesion. 70 (13%) of men stratified as “high” risk on genomic testing. Upgrade-free survival at 3, 5 and 10 years were 73%, 53% and 27% respectively. The risk of upgrade at first surveillance biopsy was associated with PSA density (hazard ratio [HR] 2.761, 95% confidence interval [CI] 1.895-4.023), and “high” genomic score (HR 1.867, 95% CI 1.025-3.401) on multivariable analysis after adjustments. Independent variables associated with risk of upgrade at first surveillance biopsy and at 3, 5 and 10 years on multivariable analysis after adjustments are shown (see table).
| Independent variables | Upgrade at first surveillance biopsy HR (95% CI) |
Upgrade at 3 Years HR (95% CI) |
Upgrade at 5 Years HR (95% CI) |
Upgrade at 10 Years HR (95% CI) |
| % cores positive | 1.18 (1.04-1.36) | 1.13 (1.02-1.26) | 1.17 (1.01-1.35) | NS |
| PSA density (log) | 2.76 (1.90-4.02 | 2.03 (1.46-2.82) | 2.29 (1.48-3.53) | NS |
| Gleason 3+4 vs 3+3 | 0.45 (0.24-0.87) | NS | NS | NS |
| “High” genomic score | 1.87 (1.03-3.40) | 2.10 (1.22-3.61) | NS | NS |
| PSA kinetics | NS | 1.14 (1.03-1.27) | 1.40 (1.15-1.70) | 1.63 (1.04-2.55) |
Our findings suggest that genomic score and PSA density are risk factors for upgrading within 3 years of commencing AS, however PSA kinetics is associated with longer-term risk of upgrade. When used in tandem, genomic scores may identify a subset of men who could potentially have less intensive surveillance.