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Contemporary approach to active surveillance for favorable risk prostate cancer |
Laurence Klotz()
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Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada |
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Abstract The approach to favorable risk prostate cancer known as “active surveillance” was first described explicitly in 2002. This was a report of 250 patients managed with a strategy of expectant management, with serial prostate-specific antigen and periodic biopsy, and radical intervention advised for patients who were re-classified as higher risk. This was initiated as a prospective clinical trial, complete with informed consent, beginning in 2007. Thus, there are now 20 years of experience with this approach, which has become widely adopted around the world. In this chapter, we will summarize the biological basis for active surveillance, review the experience to date of the Toronto and Hopkins groups which have reported 15-year outcomes, describe the current approach to active surveillance in patients with Gleason score 3 + 3 or selected patients with Gleason score 3 + 4 with a low percentage of Gleason pattern 4 who may also be candidates, enhanced by the use of magnetic resonance imaging, and forecast future directions.
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Received: 16 October 2018
Available online: 15 December 2018
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Corresponding Authors:
Laurence Klotz
E-mail: Laurence.klotz@sunnybrook.ca
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Pathway | Gleason score 3 | Gleason score 4 | EGF, EGFR [9] | No | Overexpressed | AKT, MAP2 kinase [8] | Expressed | Aberrant | HER2neu [9] | Expressed | Amplified | Insensitivity to growth inhibitory signals (cyclin D2, etc.) [10], [11], [12] | Expressed | Absent | Resisting apoptosis, BCL2 [13] | Negative | Strong expression | Absence of senescence, TMPRSS2-ERG [16], [17], [18] | ERG normal | Increased | VEGF, microvessel density, other pro-angiogenic factors [19], [20] | Low expression | Increased | PTEN [21] | Present in 90% | Deleted in 70%-90% | Markers of tissue invasion and metastasis [14], [15] | Normal | Overexpressed | Clinical evidence of metastasis/PCa mortality [23], [24] | Virtually absent | Present |
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Gleason score 3 vs. 4 and hallmarks of cancer.
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| Low-risk PCa | Intermediate risk | Tests | Other tests | 5-ARI | Cancer Care Ontario CUAJ 2015 [56] | AS preferred management | Active treatment; AS for selected patients | PSA 3-6 months DRE 1 yr selected pts | MRI when clinical and path findings discordant | May have a role | ASCO JCO 2016 [57] | Same [1] | Same | Same | Other tests remain investigational | No clear role | NICE 2016 [58] | Same | Radical treatment for “disease progression” [2] | PSA 3-4 months, monitor kinetics | MRI at enrollment | | AUA 2017 [59] | Same | AS for selected patients | Same | Same | |
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Summary of contemporary AS guidelines.
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Study | n | Median follow-up (year) | Freedom from treatment | bNED after deferred treatment | PCa mortality % | OS | UCSF [41] | 321 | 3.6 | 67% at 5 yr | 1 recurrence at 3 yr | 0 | 0 | University of Toronto [38] | 993 | 8.5 | 70% at 5 yr | 5-yr bNED: 47% | 5% at 15 yr | 10-yr OS: 68% | Multicentre PRIAS [41] | 2494 | 1.6 | 77% at 2 yr | No data | 0 | 4-yr OS: 87% | University of Miami [42] | 230 | 2.6 | 85.7% at 5 yr | No recurrences | 0 | No data | Johns Hopkins [43] | 1298 | 5 | 59% at 5 yr | 90.6% recurrence free at 2 yr | 0.1% at 15 yr | 15-yr OS: 69% | Royal Marsden [44] | 471 | 5.7 | 70% at 5 yr | 85% PSA-failure free at 5 yr | 2% at 8 yr | 9% at 8 yr |
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Results of mature active surveillance cohorts.
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