Compliance Rates with the Prostate Cancer Research International Active Surveillance (PRIAS) Protocol and Disease Reclassification in Noncompliers.

BACKGROUND

Men with prostate cancer on active surveillance (AS) are advised to follow strict follow-up schedules and switch to definitive treatment on risk reclassification. However, some men might not adhere to these strict protocols.

OBJECTIVE

To determine the number of noncompliers and disease reclassification rates in men not complying with the follow-up protocol of the Prostate Cancer Research International Active Surveillance (PRIAS) study.

DESIGN, SETTING, AND PARTICIPANTS: A total of 4547 men with low-risk prostate cancer were included and prospectively followed on AS. Men were regularly examined using prostate-specific antigen (PSA), digital rectal examination, and repeat biopsies, and were advised to switch to definitive treatment on disease reclassification (>cT2c, Gleason score > 3+3, >2 cores positive, or PSA doubling time [PSA-DT] 0-3 yr).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Rates of men not complying with follow-up visits or a recommendation to discontinue AS are reported. Biopsy outcome (Gleason ≥7 or >2 cores positive) was compared between compliers and noncompliers using Cox proportional hazards analysis.

RESULTS AND LIMITATIONS

The compliance rate for PSA visits was 91%. By contrast, the compliance rate for standard repeat biopsies decreased over time (81%, 60%, 53%, and 33% at 1, 4, 7, and 10 yr after diagnosis, respectively). Yearly repeat biopsies in men with faster rising PSA (PSA-DT 3-10 yr) was low at <30%, although these men had higher upgrading rates at repeat biopsy (25-30% vs 16%). PSA-DT of 0-3 yr was the most common recommendation for discontinuation, but 71% continued on AS. Men with PSA-DT of 0-3 yr were at higher risk of upgrading on repeat biopsy (hazard ratio 2.02, 95% confidence interval 1.36-3.00) compared to men without fast rising PSA.

CONCLUSION

Some men and their physicians do not comply with AS follow-up protocols. In particular, yearly repeat biopsies in men with fast rising PSA are often ignored, as is the recommendation to discontinue AS because of very fast rising PSA. Although these men are at greater risk of higher Gleason scores on repeat biopsy, the majority still exhibit favorable tumor characteristics. Fast rising PSA should therefore not trigger a recommendation to receive active treatment, but should rather serve as a criterion for stricter follow-up. In addition, we should aim to find ways of safely reducing the number of biopsies to increase adherence to AS protocols.

PATIENT SUMMARY

We looked at compliance with an active surveillance protocol for low-risk prostate cancer in a large active surveillance study. We observed reluctance to undergo yearly biopsies because of fast rising prostate-specific antigen, despite a higher risk of disease progression. Further research should aim to safely reduce the number of repeat biopsies in men on active surveillance to increase protocol adherence.