A first step towards a global nomogram to predict disease progression for men on active surveillance

Background: Signs of disease progression (28%) and conversion to active treatment without evidence of disease progression (13%) are the main reasons for discontinuation of active surveillance (AS) in men with localised prostate cancer (PCa). We aimed to develop a nomogram to predict disease progression in these patients. Methods: As a first step in the development of a nomogram, using data from Movembers' GAP3 Consortium (n=14,380), we assessed heterogeneity between centres in terms of risk of disease progression. We started with assessment of baseline hazards for disease progression based on grouping of centres according to follow-up protocols [high: yearly; intermediate: ~2 yearly; and low: at year 1, 4 & 7 (i.e., PRIAS)]. We conducted cause-specific random effect Cox proportional hazards regression to estimate risk of disease progression by centre in each group. Results: Disease progression rates varied substantially between centres [median hazard ratio (MHR): 2.5]. After adjustment for various clinical factors (age, year of diagnosis, Gleason grade group, number of positive cores and PSA), substantial heterogeneity in disease progression remained between centres. Conclusions: When combining worldwide data on AS, we noted unexplained differences of disease progression rate even after adjustment for various clinical factors. This suggests that when developing a global nomogram, local adjustments for differences in risk of disease progression and competing outcomes such as conversion to active treatment need to be considered.