Comparative Analysis of Biopsy Upgrading in Four Prostate Cancer Active Surveillance Cohorts

Abstract

Background Active surveillance (AS) is increasingly accepted for managing low-risk prostate cancer, yet there is no consensus about implementation. The lack of consensus is due in part to uncertainty about risks of disease progression, which have not been systematically compared or integrated across AS studies with variable surveillance protocols and dropout to treatment. Objective To (1) compare risks of upgrading from Gleason score (GS) ≤6 to ≥7 across AS studies after accounting for differences in surveillance intervals and competing treatments and (2) evaluate tradeoffs of more vs less frequent biopsies. Design Joint statistical model of longitudinal prostate-specific antigen (PSA) levels and risks of biopsy upgrading. Setting Johns Hopkins University (JHU), Canary Prostate Active Surveillance Study (PASS), University of California San Francisco (UCSF), and University of Toronto (UT) AS studies. Patients 2,576 men aged 40–79 years diagnosed with GS ≤6 and clinical stage ≤T2 prostate cancer enrolled in 1995–2014. Measurements PSA levels and biopsy GS. Results After accounting for variable surveillance intervals and competing treatment, estimated risks of biopsy upgrading in PASS and UT were similar, but UCSF was higher and JHU lower. All cohorts produced a delay of 3–5 months in detecting upgrading under biennial biopsies starting after a first confirmatory biopsy relative to annual biopsies. Limitations The model does not account for possible biopsy GS misclassification. Conclusions Men in different AS studies exhibit different risks of biopsy upgrading after accounting for variable surveillance protocols and competing treatments. Nonetheless, despite these differences, the consequences of more versus less frequent biopsies appear to be similar across cohorts. Biennial biopsies appear to be an acceptable alternative to annual biopsies. Funding Source National Cancer Institute and others.

Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts

“…The delay between underlying upgrade and curative treatment depended on the biopsy frequency. Delay distributions were relatively comparable across all cohorts . The median delay ranged from 0.9 years under annual schedules to 4.1 to 4.4 years under biopsies every 5 years.…”

“…There are several challenges involved in using existing data for comparing AS protocols. First, patient populations may vary in underlying risk . Second, there is limited information on downstream outcomes, such as metastases and deaths, because of the low risk of progression and lengthy follow‐up needed to accumulate an adequate number of events.…”

The global burden of sepsis: barriers and potential solutions

“…Many guidelines and research studies have focused on bundled care [ 36 , 37 ], which can be challenging for clinicians who are unable to administer all features of a bundle. It is often difficult or impossible to discern which features of a bundled management approach are most effective—and cost-effective—in reducing sepsis morbidity and mortality [ 38 , 39 ].…”

Active surveillance for prostate and thyroid cancers: evolution in clinical paradigms and lessons learned

“…The Movember Foundation has started the Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative to develop a global database of active surveillance cohorts to help develop a global consensus on the selection criteria and active surveillance protocol. 67 Inoue and colleagues have attempted to provide some guidance regarding the optimal frequency of biopsy sampling 68 . Using data from the Canary Prostate Active Surveillance Study and studies conducted at Johns Hopkins, UCSF, and the University of Toronto, these researchers modelled the trade-offs associated with different biopsy sampling schedules used to detect disease progression.…”