Previously, AS was only used for very low-risk prostate cancer – this included men with tumor volume <0.5 cc, which was later increased to 1.3 mL if pT2 and Gleason <7. Even as recent as a decade ago, the probability of getting treated was ONLY based on the positive number (<3 – 5 -- >5). The most recent review in Nature 2016 1 suggests that most often AS is still used solely for (very) low risk disease: ISUP 1, few positive cores, and short length. The most ‘mature’ AS cohort is the Sunnybrook experience published by Klotz et al.2 in 2015, with 993 patients and a median follow-up of 6.4 years. In this cohort, 79% were low risk and 21% intermediate risk (3% PSA >10 ng/mL and Gleason 7); 60% of patients were still on AS at 15 years.
According to Dr. Mottet, there are several key factors excluding patients from AS: ductal carcinoma, sarcomatoid features, small cell carcinoma, extraprostatic extension, and lymphovascular invasion. Currently, there is conflicting data regarding age and AS - younger men are at lower risk of upgrading, whereas older age predicts biopsy reclassification. mpMRI of the prostate can also help with appropriate patient selection for AS, as mpMRI can better detect anterior lesions, predicts increased grading/staging, and allows subsequently targeted biopsies.
Candidacy among patients with intermediate-risk prostate cancer has become a hotly contested topic. Looking once again at the Sunnybrook experience, 213 intermediate risk and 732 low-risk cases (for comparison) were identified 3. Median follow-up was comparable between the groups (6.7 years for intermediate risk vs 6.5 years for low risk). Gleason 7 disease comprised 60% of the intermediate risk cohort. The 15-year metastasis-free, overall, cause-specific and treatment-free survival rates were inferior in the intermediate risk group: metastasis-free survival HR 3.14, 95%CI 1.51-6.53; 82% for intermediate risk vs 95% for low risk). Among 30 patients developing M+ disease, only two were initially Gleason 6. One of the take-home messages from this paper3 is that a PSA > 10 ng/ml (with no other adverse risk factors) had no impact on clinical outcomes.
One proposed method for stretching the indications for AS is to use PSA to better stratify patients; PSA kinetics alone is no longer considered. PSA density is often considered and a threshold has been debated: <0.2 (PRIAS) or <0.15 (JHH); the higher the threshold, the higher the risk of reclassification. Biomarkers, such as PCA3, TMPRSS2:ERG, DNA methylation, and PTEN loss have been considered for risk stratification, although these are not yet mainstream. The EAU guidelines suggest that we should be offering AS to all patients suitable for curative treatment but with low-risk prostate cancer. Second, clinicians should be performing an mpMRI prior to confirmatory biopsy.
Dr. Mottet concluded with several take-home messages:
- Very low-risk criteria for AS is mostly outdated; all low risk are eligible
- Intermediate risk: based on PSA only; when based on ISUP, GG possibly for the “limited” only (use with caution) – there is likely going to be an added benefit with mpMRI
- Biomarkers may help in the future
Presented by: Nicolas Mottet, MD, Ph.D., Head of the Urology Department, University Hospital, and Professor of Surgery, University Jean Monnet, Saint-Etienne, France.
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic
References:
- Bruinsma SM, Bangma CH, Carroll PR, et al. Active surveillance for prostate cancer: a narrative review of clinical guidelines. Nat Rev Urol 2016 Mar;13(3):151-167.
- Klotz L, Vesprini D, Sethukavalan P, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol 2015;33(3):272-277.
- Musunuru HB, Yamamoto T, Klotz L, et al. Active Surveillance for Intermediate Risk Prostate Cancer: Survival Outcomes in the Sunnybrook Experience. J Urol 2016 Dec;196(6):1651-1658.