CUA 2017: Optimizing Active Surveillance for Prostate Cancer

Toronto, Ontario (UroToday.com) Dr. Stacy Loeb gave an excellent talk on the challenges and optimization of active surveillance (AS) in prostate cancer.  Historically the vast majority of low risk patients received radical treatment, leading to unnecessary side effects. This has started to change, but even nowadays, in academic centers in the USA AS is utilized in 17% of cases, compared to 8% in community centers. 

Indeed in the past the percentage of patients with low risk disease that were observed and not actively treated was around 10% in 2004-2006. This has been rising steadily to 40-49% in 2011-2013.1 Canadian data has shown a similar rise from 11% in 2002 to 21% in 2010.2 There has also been a rise in the usage of AS for intermediate risk patients, based on PSA and Gleason score.

In Sweden, 91% of very low risk patients and 74% of low risk patient during 2011-2014 have been treated with AS.3 The proposed reasons for higher AS in Sweden vs. USA might be due to cultural differences and equal access healthcare system in Sweden.

Dr. Loeb continued and described some of the challenges in the implementation of AS.

Challenge 1 – barriers to uptake in patients and physicians. “Cancer” is an emotional laden term but Gleason 6 has limited metastatic potential. There have been proposal to remove the term “cancer” and new grade groups have been adopted reclassifying Gleason 6-10 to grade 1-5. Additionally, the biopsy itself is a barrier to some patients. There is significantly lower uptake of AS in men who have had complications on previous biopsies.

When looking at specific barriers for physicians, some have had very minimal exposure to AS during their training. There is also the issue of financial incentives. As opposed to the USA, in Europe, there is no fee for service system, thus making the uptake of AS to be exponentially higher than in the USA. Physicians are also worried about liability and missing the opportunity to treat a cancer that might progress later on. 

Long term data has actually shown that there is a 94%-99.9% prostate cancer specific survival at 15 years of AS, with patients 9-24 times more likely to die from other causes.4,5 In-fact, most guidelines today (ASCO, CCO, ASTRO, SUO, AUA, NCCN) recommend AS for low risk patients. It may even be offered to select patients with low volume, intermediate risk disease.

Challenge 2 – risk of upfront misclassification. It is important to remember that PSA, clinical stage and standard biopsy result in substantial rates of misclassification (>1/3). There is substantial biologic heterogeneity within broad risk groups, and therefore there is a large potential role for imaging and biomarkers to refine selection. There is substantial evidence that MRI is useful to confirm eligibility for AS and the NICE guidelines have recommend performing MRI at AS initiation. There are also a considerable number of genomic tests today, available for risk stratification. These include Oncotype, Prolaris, and Decipher. However, a recently Canadian published health technology assessment has declared that there is no  evidence on clinical outcomes of patients whose treatment was informed by Prolaris.6

Challenge 3 – monitoring protocols. There has been difficulty creating the ideal monitoring protocol. PSA changes had only shown an area under the curve (AUC) of 0.59 (similar to a coin toss) for biopsy reclassification. Biopsy based AS protocol presents significant risks and patient burden. Therefore, MRI has been incorporated into the protocol in most centers. Additional markers such as the prostate health index (phi), approved for prostate cancer detection by the FDA in 2012, are also considered.

Dr. Loeb concluded and summarized that there has been increasing use of AS worldwide, but there are persistent barriers to uptake for patients and physicians. AS is now guideline recommended for very low risk patients with greater risk of death from other causes. Future improvement with greater personalization and integration of non-invasive tests should be performed. 

Presented By: Stacy Loeb, MD, New York University, New York, NY

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre  Twitter: @GoldbergHanan at the  at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada

References:
1. Cooperberg, M. R. & Carroll, P. Trends in management for patients with localized prostate cancer, 1990-2013. JAMA 314, 80–82 (2015).

2. Richard, P. O. et al. The uptake of active surveillance for the management of prostate cancer: A population-based analysis. Can. Urol. Assoc. J. 10, 333–338 (2016).

3. Loeb, S. et al. Uptake of active surveillance for very-low-risk prostate cancer in sweden. JAMA Oncol. (2016).

4. Klotz, L. et al. Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients With Prostate Cancer. J. Clin. Oncol. 33, 272–277 (2014).

5. Tosoian, J. J. et al. Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J. Clin. Oncol. 33, 3379–3385 (2015).

6. G., B., R.H., B., S., K.-R., A.V., L. & S., P. Ontario health technology assessment series: Prolaris cell cycle progression test for localized prostate cancer: A health technology assessment. Ont. Health Technol. Assess. Ser. 17, 1–75 (2017).
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