Naturally, as active surveillance gains traction in the low-risk population, there is increased interest in expanding it to more men. However, the earlier experience with expanding active surveillance to intermediate risk GG2 PCa has hit significant limits, with caution now recommended for this population.2
In this study, the authors argue that data derived from a relatively homogenous Scandinavian European populations need to be cautiously applied and validated in a more diverse US population. To that effect, the authors utilized their own robust institutional radical prostatectomy (RP) database to validate the findings of Loeb et al. and explore racial variations not captured in that original paper.
Men with biopsy GG 1-2 PCa who underwent RP at their institution were identified. Men were then stratified by serial adjustments of increasing GG, clinical T-stage (cT), PSA, and % core involvement. Primary outcomes were RP GG score 3-5, pT3-4, pN+, or composite adverse surgical pathology (ASP), which was defined as any of the prior 3 adverse features.
748 patients met inclusion criteria (389 GG1, 359 GG2). The breakdown into NCCN and AUA/EAU low-risk criteria are seen below:
Men meeting strict active surveillance criteria per guidelines have a risk of ASP between 17-18%.
Expanding PSA to 15 increases risk of ASP to 21.3%:
This is a relatively modest increase in ASP, and is consistent with the Loeb data.
However, expanding PSA to >15 or including all GG2 patients would increase ASP to >22.5%, likely precluding them from safe active surveillance.
The authors then focused on the GG2 patients, in an effort to identify a subset of patients with similar ASP risk as the Loeb cohort. With further stratification of GG2 patients, only the cohort that fulfills all 3 of the following criteria had ASP outcomes similar to the Loeb cohort (21.4%): PSA<5, <17% core involvement (any GG) and % GG2 positive core involvement <50%.
In an analysis of racial variations, the authors focused only on African-American men. Interestingly, they found that for African-American men, PSA thresholds even for men with GG1 disease would have to be lowered to <= 5 to have similar ASP findings! This is consistent with prior reports that African-American men may harbor more aggressive disease, and active surveillance may need to be used more judiciously.
Lastly, when applying current active surveillance guidelines, 40% of active surveillance eligible men potentially harbor GG2 disease – a relatively high rate of upgrading on final RP pathology. In contrast, men with GG2 disease on biopsy rarely get a downgrade to GG1 on final pathology (<3% in the entire cohort). This suggests that men with GG2 on biopsy can be safely be assumed to GG2 on final RP pathology – but eligible men on active surveillance may harbor higher grade disease at significant rates, and should be monitored closely.
Presented by: James R. Mark, MD, Thomas Jefferson University, Sidney Kimmel Cancer Center, Department of Urology, Philadelphia, Pennsylvania, United States
Written by: Thenappan Chandrasekar, MD (Clinical Instructor, Thomas Jefferson University) (twitter: @tchandra_uromd, @TjuUrology) at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.
References:
1. Loeb S, Folkvaljon Y, Bratt O, Robinson D, Stattin P, Defining Intermediate-Risk Prostate Cancer Suitable for Active Surveillance, The Journal of Urology® (2018), doi: https:// doi.org/10.1016/j.juro.2018.09.042.
2. Chandrasekar T, Herrera-Caceres JO, Klotz L. Active surveillance in intermediate risk prostate cancer. Arch Esp Urol. 2019 Mar;72(2):157-166. English, Spanish.