Although it is assumed that patients that embark on active surveillance are those with an indolent disease where the risk/benefit ratio seems to fall in favor of no radical intervention, it may not hold true in all cases, and multiple other factors should be considered. Active surveillance can lead to approximately 45-70% of men with favorable risk disease avoiding radical local therapy, with approximately 25-35% leaving the program due to pathologic upstaging.1,2 Additionally, a subset of patients who initially present with favorable risk disease will still go on to die from metastatic prostate cancer.2,3 Although the quality of life may be improved in patients undergoing active surveillance, there is no guarantee of that either, as there may be added stress in a patient, harboring known prostate cancer with a rising PSA. There may also eventually be greater financial toxicity in a patient undergoing active surveillance for many years, due to the cost of repeat prostate biopsies
As a result, the field has been implementing many interventional trials in the “active surveillance” setting. These trials may be ideal for patients with slightly higher risk of the low risk subsets, where adverse long-term outcomes from disease progression of prostate cancer may occur at a higher rate. Enrollment into a clinical trial for patients with favorable risk disease may also be welcome by patients who psychologically will not tolerate the idea of no active intervention. These types of trials may also be ideal for patients who desire low toxicity systemic intervention without the local side effects of either surgery or radiation. Finally, this setting may be ideal for the biologic study of novel agents or nutraceuticals, since the downside risk of a non-efficacious intervention is low, while important tissue and biomarker data can be acquired and analyzed.
The goal of these trials may not need to include the same primary endpoints as trials for patients with more advanced prostate cancer disease states. For example, regulatory agencies are unlikely to require overall survival benefit for patients undergoing intervention in the active surveillance setting. Prevention of patient progression to a potentially morbid and costly local therapy intervention may suffice for patients initially planning on active surveillance of prostate cancer.
Below I highlight select ongoing trials with interventions spanning a broad range, including exercise, dietary supplementation, low-risk medications, immunologic and even regulatory approved agents for more advanced prostate cancer with proven efficacy but acceptable toxicity profiles.
- Exercise (ERASE) – NCT03203460
- Exercise (ASX) – NCT02435472
- Low-fat diet and Fish Oil – NCT02176902
- Cholecalciferol supplement – NCT00887432
- Vitamin D and Omega-3 Fatty Acid – NCT03290417
- Aspirin and/or Vitamin D3 (PROVENT) – NCT03103152
- Metformin (MAST) – NCT01864096
- ProstAtak® Immunotherapy (ULYSSES) – NCT02768363
- Enzalutamide (ENACT) - NCT02799745
- Active Surveillance With or Without a 6 Months Apalutamide Treatment in Low Risk Prostate Cancer: A Phase II Randomized Multicenter Trial NCT03088124
- A Phase 2 Study of Apalutamide in Active Surveillance Patients - NCT02721979
Written by: Evan Yu, MD
- Tosoian JJ, Trock BJ, Landis P, et al. J Clin Oncol 2011; 29:2185-90.
- Klotz L, Vesprini D, Sethukavalan P, et al. J Clin Oncol 2015; 33:272-7.
- Musunuru HB, Klotz L, Vesprini D, et al. J Urol 2016; 196:1651-8.
Watch: Active Surveillance: Who is the Right Patient? - Matt Cooperberg