UroToday

(UroToday.com) The 2024 South Central AUA annual meeting included a session on prostate cancer, featuring a presentation by Dr. Lisly Chery discussing active surveillance for intermediate-risk prostate cancer. Dr. Chery notes that it is quite clear that Gleason Grade Group 3-5 prostate cancer requires treatment, and that Gleason Grade Group 1 prostate cancer should be managed with active surveillance.

However, what is less clear is how we should be managing Gleason Grade Group 2 and whether active surveillance is reasonable for these patients. Notably, every major cancer organization says to consider active surveillance for select patients with intermediate-risk disease, including:

American Urological Association
American Society for Radiation Oncology
National Comprehensive Cancer Network (NCCN)
European Association of Urology
American Society of Clinical Oncology

The ProtecT trial¹ recently reported 15-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. This trial included 1,643 men, of which 24.1% were intermediate risk disease and 9.6% were high-risk disease. Among all patients, the prostate cancer mortality rate was:

Monitoring: 3.1%
Surgery: 2.2%
Radiation: 2.9%

The following shows the prostate cancer-specific survival Kaplan-Meier curves stratified by treatment approach: prostate cancer specific survival Kaplan-Meier curves stratified by treatment approach
When assessing prostate cancer deaths according to Gleason Grade Group, there was no difference between prostatectomy versus active monitoring or radiotherapy versus active monitoring for Gleason Grade Group 2 and 3 patients:
Moreover, death from any cause in the cohort occurred in 21.7% of patients. Metastases rates by treatment group are as follows:

Monitoring: 9.4%
Surgery: 4.7%
Radiation: 5.0%

Finally, the difference in the rate of metastasis at 10 years did not result in a mortality difference at 15 years. The NCCN defines favorable intermediate-risk prostate cancer as having all of the following criteria:

1 intermediate risk feature
Grade Group 1 or 2 disease
<50% of the biopsy cores positive for prostate cancer (ie. <6 of 12 cores)

Dr. Chery then discussed two studies that show the importance of the amount of Gleason pattern 4 disease. Kir et al.² previously assessed the clinical significance of observing <6% of Gleason pattern 4 tissue in biopsies of Gleason Score 7 prostate cancer. This study found that Gleason pattern 4 comprising 26-49% of the specimen, Gleason Score 4+3, and percentage of total core tissue scored as positive were significant and independent predictors of PSA failure after radical prostatectomy:

In another study, Sauter et al.³ assessed the clinical relevance of the fractions of Gleason patterns among prostatectomy specimens from 12,823 consecutive patients and of 2,971 matched preoperative biopsies. There was a continuous increase in the risk of PSA recurrence with an increasing percentage of Gleason 4 fractions with small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups: $continuous increase in the risk of PSA recurrence with increasing percentage of Gleason 4 fractions with small differences in outcome at clinically important thresholds$
Thus, based on the aforementioned studies, the amount of Gleason pattern 4 matters.

Dr. Chery concluded his presentation discussing active surveillance for intermediate-risk prostate cancer with the following take-home points:

Active surveillance is an option for select men with favorable intermediate-risk prostate cancer
This recommendation is supported by all cancer societies and data from randomized control trials
The amount of Gleason pattern 4 (<5%) on biopsy can be predictive of favorable pathology and outcomes

Presented by: Lisly Chery, MD, Urologic Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 South Central American Urological Association (AUA) Annual Meeting, Colorado Springs, CO, Wed, Oct 30 – Sat, Nov 2, 2024.

References:

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