However, such associations have been tested in men with very low-risk prostate cancer using stringent inclusion criteria – whether active surveillance can be applied to young men of more expansive criteria has not been rigorously assessed. At the Active Surveillance vs Focal Therapy in Prostate Cancer session, Dr. Bandini from Milan and colleagues reported results from their single-center series whereby young men were enrolled in active surveillance regardless of the extent of biopsy involvement. They hypothesized that active surveillance can be safely applied to all younger men with low-risk prostate cancer regardless of the extent of cancer involvement at biopsy.
For this study, the authors evaluated 296 men with low-risk prostate cancer according to D’Amico risk grouping (PSA<10ng/ml, cT stage ≤T2a, GS 6) enrolled in an active surveillance protocol (2012-2018) at a single, tertiary referral center. Age at diagnosis was dichotomized as ≤60yr vs >60 yrs. Kaplan-Meier analyses examined the unadjusted effect of younger age on the outcomes of biopsy-based Gleason upgrade. Univariable and multivariable Cox-regression analyses tested the association between younger age and risk of progression during active surveillance. The authors also analyzed the pathological outcomes of patients who underwent radical prostatectomy upon progression according to age categories. Patients with either Gleason score ≥4+3 or pN1 or pathological stage ≥pT3 were considered as harboring unfavorable pathological characteristics.
Among these 296 patients included in the study, 95 (32.1%) were ≤ 60 years of age. There were no statistically significant differences between younger and older patients for PSA (5.7 vs 6.2ng/ml, p=0.2), PSA density (0.1 vs. 0.1ng/ml/cc, p=0.5), cT2a (3.2 vs. 6.5%, p=0.4), and use of MRI during active surveillance (55.8 vs. 55.2%, p=0.9). Overall, 45 (47.4%) men ≤ 60 years of age and 76 (37.8%) patients > 60 years of age-progressed during active surveillance. Unadjusted progression-free rates at 2 years of follow-up were 29.9 vs. 30.2% for younger vs. older patients, respectively (p=0.54).
On multivariable analyses, younger age was not associated with increased risk of progression (HR 1.27; 95%CI: 0.71-2.31). Finally, RP was performed in 30 (66.7%) younger men and 36 (47%) older men. Pathological evaluation of radical prostatectomy patients showed significantly worse adverse characteristics older (51%) compared to younger (24.2%) men (p=0.03), confirming prior studies.
Part of improving PSA screening justification is not over treating men that may not benefit from treatment. As such, placing younger men on active surveillance, regardless of the extent of biopsy involvement, appears to be safe based on this evaluation of patients at San Raffaele. Further validation of these findings will be important.
The authors concluded that even when applying less stringent criteria for inclusion in active surveillance, younger age was not associated with increased risk of progression or with more adverse pathological characteristics at radical prostatectomy after active surveillance. Young patients are those who may gain the highest benefit from an active surveillance approach without being exposed to increased risk of progression or misclassification.
Presented by: Marco Bandini, MD, IRCCS Ospedale San Raffaele, Division of Oncology, Unit of Urology, Milan, Italy
Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia, Twitter: @zklaassen_md at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.
References:
1. 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.