FOIU 2018: Active Surveillance for Intermediate Risk Prostate Cancer - FOR

Tel-Aviv, Israel ( Larry Goldenberg, MD demonstrated his support for using active surveillance (AS) in intermediate-risk prostate cancer (IRPC). Goldenberg began his talk by stating that not all IRPC is the same. It is agreed by most, that unfavorable IRPC requires treatment.  Conversely, favorable IRPC require more stringent follow-up but deferred therapy is not dangerous. Ultimately, it comes down to a man’s risk threshold (his comfort zone).

It is agreed by most, that AS is generally underutilized, and patient selection is critical. Approximately 25-50% of patients will progress, usually in the first 3-5 years. Death due to PC on AS is in the range of 1-2.4%, and death due to non-PC reasons is 15-20 times more likely. Finally, the triggers for intervention are not clearly validated.

Next, Goldenberg discussed and elaborated on the factors against AS in IRPC. The main factor is the inability to accurately predict the biological behavior of cancer in a given individual (biology vs. histology). Additionally, for the physician, it is actually easier to not recommend AS, as if the disease progresses, the physician has done everything possible to treat the disease, and if the disease does not progress, the physician has totally cured the patient.

The “Achilles heel” of AS is the missed high-grade PC, and “today’s metastasis is yesterday’s organ-confined cancer”. An important issue to remember is that not all IRPC is the same, as figure 1 demonstrates. Gleason 3+4 is not the same as 4+3, and the percentage of pattern 4 makes a huge difference on disease biology and prognosis. According to the new updated NCCN guidelines, there is a clear distinction between:

  • Very low-risk disease (T1c, GGG1, 3 or fewer positive cores of 12 cores, 50% or less involved volume of each core, and PSA density <0.15 ng/ml)
  • Low-risk disease (PSA <10 ng/ml, Gleason Grade Group 1, T1/2a)
  • Favorable intermediate-risk disease – Major pattern grade 3 and less than 50% positive biopsy cores, with 1 intermediate risk factor, including T2b/c, Grade Group 2 or PSA 10-20
  • Unfavorable intermediate-risk disease - >1 intermediate risk factor, Grade group 3
  • High risk – PSA>10 ng/ml, Gleason score >7, T2C/3
Aside from the percentage of pattern 4 that varies in IRPC, there are other important factors, including:

  • - Scattered vs.clustered grade 4
  • - Continuous vs. discontinuous tumor involvement
  • - Cribriform/glomeruloid pattern vs. poorly formed/fused vs a mix
  • - Total tumor involvement of a core
There is a pathologist interobserver agreement of approximately 74% with the greatest discrepancy differentiating Gleason 3 and 4

Figure 1: Not all Gleason 7 is the same:
UroToday FOIU2018 Active Surveillance for intermediate Risk Prostate Cancer FOR
Goldenberg summarized his talk by stating that in most large AS cohorts, the majority of patients with Gleason 3+4 (80%) did not metastasize after 15 years of follow-up. It is critical to differentiate the biologically significant cases from the insignificant and to avoid the morbidity of treatment whenever possible. For this purpose, biomarkers and mpMRI need to be utilized.

Presented by: Larry Goldenberg, MD, Vancouver, Canada

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan  at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel

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