EAU 2017: First repeated biopsy represents the most informative predictor of progression-free survival at 3 years follow-up in patients included in an active surveillance protocol for low-risk prostate cancer

London, England (UroToday.com) Active surveillance has become standard of care for low-volume, low-risk clinically localized prostate cancer. However, despite adequate assessment, approximately 20-30% of men placed on active surveillance will progress to needing intervention; a portion (approximately 1/3) of those are due to patient choice, but the rest are due to progression of disease. Being able to identify these patients at risk of progression is important for counseling and decision making. Additionally, by identify those not likely to progress, reduced frequency of biopsies may be considered.

In this study, the authors utilize their single-institution Active Surveillance experience to dentify the predictors of progression-free survival (PFS). Between 2009 and 2016, 235 consecutive patients affected by low-risk PCa, according to the PRIAS criteria (cT1/T2a; PSA<10 ng/ml; PSA density <0.2; Gleason score <7; <3 positive cores), were enrolled into active surveillance. This entailed repeated annual biopsies as part of the routine protocol.
  • In discussion with the presenter, confirmatory biopsy is not part of their protocol.
  • Indeed, this first biopsy is functionally their “confirmatory biopsy”


Outcome was tumor progression (defined as pathological upgrading to Gleason >6 or >2 positive cores at repeated yearly biopsies). Patients subsequently assessed at 3-years post initiation into AS – they were stratified based on progression risk. Univariable and multivariable logistic regression analyses were used to predict 3-year PFS. Covariates consisted of age, total PSA, clinical stage (cT) and number of positive cores at the time of enrolment as well as negative (no cancer) 1-year biopsy.
  • mpMRI was not utilized in surveillance due to the time frame. They are now beginning to introduce it into practice, but not as a routine prior to biopsies.

Patient demographics:

chart 12

Median follow-up was 19 months (1.5 years). Progression-free survival rates were 85%, 55%, and 40% at 1, 3 and 5 years, respectively.

Overall, 56 (23.8%) patients were progression-free at 3 years of follow-up. At univariable analyses, total PSA and negative 1-year biopsy were significant predictors of 3-year PFS (all p<0.05). Patients with negative biopsy at 1 year had a 3-year PFS of 75.8 vs. 29.0% in those with positive biopsy at 1-year. These results were confirmed at multivariable analyses, where a negative 1-year biopsy represented the only independent predictor of 3-year PFS (OR: 2.47; p=0.04). Full multivariable analysis shown below:

chart 12b

In this study, the 3-year PFS rate of 23.8% is very low. I suspect this is because of a serious flaw in their methodology. In most active surveillance programs, prior to being included in active surveillance, patients often undergo a confirmatory biopsy within 3-12 months to confirm no missed higher grade / higher volume disease – it is only after this is negative or consistent are the patients consider to be on AS.

In this study, the “first biopsy” is the confirmatory biopsy. Hence, it is only after this is negative or stable should patients be continued onto AS. As such, the outcomes of people with a positive “first biopsy” are contaminated by patients who were not AS candidates to begin with.

Until this flaw is addressed, the results are not reliable.

Speaker: S. Luzzago

Co-Author(s): Suardi N., Dell'Oglio P., Fossati N., Capitanio U., Gandaglia G., Zaffuto E., Mirone V., Bertini R., Damiano R., Freschi M., Gaboardi F., Montorsi F., Briganti A.

Institution(s):
1. Vita-Salute University San Raffaele, Dept. of Urology, Milan, Italy
2. "Federico II" University, Dept. of Urology, Naples, Italy
3. Vita-Salute University San Raffaele, Dept. of Pathology, Milan, Italy
4. Magna Graecia University, Dept. of Urology, Catanzaro, Italy

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the #EAU17 - March 24-28, 2017- London, England