The goals of AS include:
- To avoid or delay the costs of treatment without compromising cancer cure
- To be compliant with screening guidelines
- Needs to be based on the rationale that initial assessment is accurate and that monitoring is accurate and identifies sub-clinical progression at a time that initial treatment options are still available and curative
AS entails prostate-specific antigen (PSA) testing at 3-6-month intervals, digital rectal examination (DRE) at 6-12-month intervals, and repeat biopsy at 12-24 months. More recently, the use of multiparametric MRI and genomic profiling has been added to initial risk assessment and to allow for targeted biopsy. Active treatment should be considered for any grade, volume or change in both.
Dr. Carroll then presented the UCSF AS experience. This includes 1778 men, with 1499 patients having at least 2 or more biopsies. The mean age was 62.5 years, with a median PSA of 6.37, and a median follow-up of 62 months. The median time to rebiopsy classification was 25 months. Of the 59% of men who had a change upward in grade or volume, only 27% had a change that was moderate to large. Overall, this cohort had 96% overall survival, 98% metastases-free survival. And 99% of prostate cancer-specific survival.
Dr. Carroll moved on to describe the outcome of men who underwent a delayed radical prostatectomy (Figure 1).
Figure 1 – Results of delayed radical prostatectomy in the AS UCSF cohort
The next topic discussed was the impact of new technology. The NCCN guidelines recommend the use of genomic testing as follows (Table 1). However, genomic classifiers entail several concerns:
- How does the tumor heterogeneity affect the results of genetic biomarkers?
- Do all patients benefit from it? Specifically, which low and favorable-intermediate risk patients?
- Are these cost-effective?
- What are the long-term outcomes?
Table 1 – 2019 NCCN recommendation on genetic testing in prostate cancer patients:
Other important biomarkers include:
- PSA density – this has been shown to be a better predictor of treatment and reclassification than PSA, with a PSA density of above 0.15 posing the greatest risk factor
- PTEN staining
- Multiparametric MRI – an increase in the PIRADS score has been associated with biopsy upgrade (p=0.02). PIRADS increase from 1-3 to 4 or 5 was associated with 37% risk of biopsy upgrade at 5 years, and 49% at 7 years in patients on AS. Conversely, PIRADS 1-3 lesions that remained 1-3 had an 8% risk of biopsy upgrade at 5 years, and 12% at 7 years
- Pattern 4 histologic subtype staining
The current controversies in AS include the appropriate indication for patients – very low, low-risk disease only? Low CAPRA score? Are patients with Gleason 3 + 4 candidates for AS? Is it safe in African-American men? And are younger men appropriate candidates?
AS in men with Gleason 3 + 4 is a controversial topic. Data have shown that those with a single core of Gleason 3 + 4 demonstrated no increased risk of progression or BCR. There is no definite contraindication to include these patients in AS, however, caution should be exercised when the following are present:
- High PSA density
- PIRADS 5 on multi-parametric MRI
- Adverse genomic results
- Larger number of biopsy cores positive at diagnosis
- Cribriform (expansile) histology – It has been shown that Gleason type 4 has several subtypes, that are not typically reported, but have a huge impact on outcomes (Figure 2). The cribriform and stromal reaction is associated with higher genomic scores and the risk of extracapsular extension is higher.
Figure 2 – Gleason grade 4 subtypes:
When assessing data regarding young patients, the 3- and 5-year upgrade-free survival rate is better for younger patients (73% and 55% vs. 64% and 48%, respectively, p<0.01). Younger patients are more likely to receive subsequent treatment with radical prostatectomy vs. radiotherapy (26% vs. 7%). Multivariable regression models have shown that age ≤60 is associated with freedom from biopsy upgrade (hazard ration [HR] 1.48, 95% confidence interval [CI] 1.21-1.82), and biopsy progression (HR 1.32, 95% CI 1.11-1.57)1. No significant association was found between younger age and time to treatment of biochemical recurrence (BCR) following delayed radical prostatectomy. Figure 3 summarizes the indications and proper criteria for AS.
Figure 3 – Active surveillance indications:
Some important disruptors need to be mentioned as well. These include new technology that is used to decrease the detection of low-risk disease, refined biomarkers and the option of focal therapy.
Dr. Carroll summarized his talk stating that AS appears safe in well-selected patients. Patients with Gleason 3 + 4 can be candidates for AS. The newly introduced technology appears to make AS safer/acceptable, but better validation is necessary. AS needs to be made less burdensome and the biopsy rates need to be decreased. Efforts should focus on reducing over-detection. Lastly, in the near future, AS will be challenged by various modalities of focal therapy.
Presented by: Peter Carroll, MC, MPH, Professor and Chair, Ken and Donna Derr-Chevron Distinguished Professorship in Urology, Taube Family Distinguished Professor in Urology, Department of Urology, University of California San Fransisco, San Francisco, California
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, USA, Twitter: @GoldbergHanan at the 39th Congress of the Société Internationale d'Urologie, SIU 2019, #SIUWorld #SIU2019, October 17-20, 2019, Athens, Greece
Reference:
1. Leapman MS, Cowan JE, Nguyen HG, et al. Active Surveillance in Younger Men With Prostate Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2017; 35(17): 1898-904.