Low-risk prostate cancer (LRPC) has been increasingly managed using active surveillance (AS) over the past decade. According to the Surveillance, Epidemiology, and End Results (SEER) database, the increase in usage of AS in low-risk prostate cancer increased from 14.5% to 42.1% between 2010 and 2015.1 If a patient and health care provider choose to follow a more conservative approach with AS, there are various protocols that have been used. 

Protocols can vary considerably between centers, with interval biopsies ranging from every 1 to 5 years. This heterogeneity, along with a more recent shift in AS preference, has led to a lack of long-term outcomes for different AS protocols. Key outcomes to consider when evaluating an AS protocol include time to progression of LRPC, development of metastases, mortality, and quality-adjusted life-years (QALYs). 

A research group led by Lange and colleagues published a study in 2019 using modeling of 4 North American patient cohorts to simulate potential long-term outcomes of varying AS protocols.2 The cohorts included patients from the multi-institutional Canary Prostate Active Surveillance Study (PASS), University of California at San Francisco (UCSF), Johns Hopkins University (JHU), and the University of Toronto (UT). The models were built using data from the Scandinavian Prostate Cancer Group 4 (SPCG-4) trial. 

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The study evaluated men initially diagnosed with Gleason score 6 (GS6) with “upgrading”, defined as the first point at which a biopsy would detect grade progression to a GS of at least 7. Both fixed and tailored biopsy schedules were analyzed. The authors calculated the time spent in AS before treatment, the delay between upgrade and treatment, LYs, QALYs, and net cumulative probabilities of metastasis and prostate cancer death at 10 years and 20 years. 

Compared with watchful waiting (WW), AS biopsies reduced the risk of metastases and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively. AS biopsies every 5 years also reduced the risk of metastases and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. 

There were no significant improvements in these risks when comparing annual/biennial schedules to biopsies every 3 years to 4 years. There was minimal difference in LYs (range, 0.04-0.16) and QALYs (range, -0.02 to 0.09) between the 1-year and 5-year AS biopsy cohorts. 

Compared with a biennial AS biopsy schedule, tailored schedules that reduced biopsy frequency to 5 years based on quartile of risk increased the 20-year risk of metastasis and death by only 0.1% to 0.5% and 0.2% to 0.6%, respectively. Similarly, LYs (<0.04) and QALYs (<0.01) were minimally reduced as well. Therefore, tailored schedules with risk stratification can lower the biopsy burden for patients without sacrificing a significant clinical benefit in the long term. 

The authors concluded that increasing AS biopsy frequency decreased metastases and death when compared to WW, although there were only minimal improvements seen in LYs and QALYs when comparing annual biopsy schedules to biopsies performed every 5 years. 

In addition, the authors determined that according to their results, an AS protocol in “low-risk” men (with GS </= 6) with biopsies every 3 to 4 years appears reasonable compared with annual biopsies. The authors did note that their study was based on modeling, therefore, this should be considered when evaluating the overall study. It will be interesting to see if the results from this study, coupled with new data, continue to shift more patients towards AS in the future. 

Disclosure: Some of the authors disclosed financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the original study.

References

  1. Mahal BA, Butler S, Franco I, et al. Use of active surveillance or watchful waiting for low-risk prostate cancer and management trends across risk groups in the United States, 2010-2015. JAMA. 2019;321(7):704-706.
  2. Lange JM et al. Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts [published online October 22, 2019]. Cancer. doi: 10.1002/cncr.32557