Precision Medicine in Active Surveillance for Prostate Cancer: Development of the Canary–Early Detection Research Network Active Surveillance Biopsy Risk Calculator

Abstract

BACKGROUND Men on active surveillance (AS) face repeated biopsies. Most biopsies will not show disease progression nor change management; such biopsies do not contribute to patient management, are potentially morbid, and costly. OBJECTIVE To use a contemporary AS prospective trial to develop a tool to predict AS biopsy outcomes. DESIGN, SETTING AND PARTICIPANTS Biopsies (median 2, range 2 to 9 per patient) from 859 men participating in the Canary Prostate Active Surveillance Study with Gleason grade 6 prostate cancer (median follow-up: 35.8 [range 3.0–148.7] months) were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression was used to predict progression, defined as Gleason score increase from ≤ 6 to ≥ 7 or increase in percent of cores positive for cancer from < 34% to ≥ 34%. 5-fold internal cross-validation was performed to evaluate the Area-Underneath-the-receiver-operating-characteristic-Curve (AUC). RESULTS AND LIMITATIONS Statistically significant risk factors for progression on biopsy were prostate-specific antigen (PSA), (odds ratio [OR] 1.045, 95% confidence interval [CI], 1.028 to 1.063), percent cores positive for cancer on most recent biopsy, (OR 1.401, 95% CI=1.301–1.508), and history of at least one prior negative biopsy (OR 0.524, 95% CI=0.417–0.659). A multivariable predictive model incorporating these factors, age, and number of months since last biopsy achieved an AUC of 72.4%. CONCLUSIONS A combination of readily-available clinical measures risk-stratify patients considering active surveillance prostate biopsy. Risk of progression or upgrading can be estimated and incorporated in clinical practice. PATIENT SUMMARY The Canary-EDRN Active Surveillance Biopsy Risk Calculator, an online tool, can be used to guide patient decision-making regarding follow-up prostate biopsy.

Is magnetic resonance imaging‐targeted biopsy a useful addition to systematic confirmatory biopsy in men on active surveillance for low‐risk prostate cancer? A systematic review and meta‐analysis

“…The upgraded proportion due to the TRUS‐guided biopsies was 20% (95% CI 16–25%; Table ), which is slightly higher than the ~15% in published reports at confirmatory assessment . Part of the upgrading could be influenced by the unblinded study design in two reports , favouring the TRUS‐guided biopsies.…”

A Decade of Active Surveillance in the PRIAS Study: An Update and Evaluation of the Criteria Used to Recommend a Switch to Active Treatment

“…Currently we individualize the biopsy frequency only based on the PSA DT; however, several other predictors of reclassification were specified (eg, PSA density, the number of positive biopsy cores, and time since last biopsy) [3,4,18,19]. Risk prediction models were already developed and should be validated and updated in several cohorts to prolong the time to next biopsy in men with a low risk of reclassification and increase the frequency in men with high risk [19]. In the future, these models can be supplemented by newly validated markers predictive of outcome [20].…”

Active surveillance for prostate cancer: current evidence and contemporary state of practice

“…Similarly, some studies have shown that patients with very-low-risk cancer have less frequent reclassification and improved pathologic outcomes compared to low-risk men, and measures of higher disease volume are predictive of short-term intervention/reclassification in multiple cohorts. 92–94 Whether this will translate to inferior long-term oncologic outcomes remains unknown.…”