Current strategies for monitoring men with localised prostate cancer lack a strong evidence base: observational longitudinal study

Abstract

BACKGROUND: The UK National Institute for Health and Clinical Excellence (NICE) guidance recommends conservative management of men with 'low-risk' localised prostate cancer, monitoring the disease using prostate-specific antigen (PSA) kinetics and re-biopsy. However, there is little evidence of the changes in PSA level that should alert to the need for clinical re-assessment. METHODS: This study compares the alerts resulting from PSA kinetics and a novel longitudinal reference range approach, which incorporates age-related changes, during the monitoring of 408 men with localised prostate cancer. Men were monitored by regular PSA tests over a mean of 2.9 years, recording when a man's PSA doubling time fell below 2 years, PSA velocity exceeded 2 ng ml -1 per year, or when his upper 10% reference range was exceeded. RESULTS: Prostate-specific antigen doubling time and PSA velocity alerted a high proportion of men initially but became unresponsive to changes with successive tests. Calculating doubling time using recent PSA measurements reduced the decline in response. The reference range method maintained responsiveness to changes in PSA level throughout the monitoring. CONCLUSION: The increasing unresponsiveness of PSA kinetics is a consequence of the underlying regression model. Novel methods are needed for evaluation in cohorts currently being managed by monitoring. Meanwhile, the NICE guidance should be cautious.

Systematic Review and Meta-analysis of Factors Determining Change to Radical Treatment in Active Surveillance for Localized Prostate Cancer

“…Higher baseline PSA and T stage were associated with a higher rate of change to radical treatment. PSA changes (including PSADT and PSAv) also led to many changes in treatment, although evidence of the validity of PSA as a measure of disease progression is lacking [45][46][47][48]. There was no evidence that any PSA eligibility criteria, frequency of PSA testing, or adoption of PSA triggers for treatment change were associated with rate of treatment change among studies, and only weak evidence that less mature studies had a higher rate of change.…”

Associations of Folate, Vitamin B12, Homocysteine, and Folate-Pathway Polymorphisms with Prostate-Specific Antigen Velocity in Men with Localized Prostate Cancer

“…We chose the five most recent PSA measurements because these provide a balance between sensitivity to upturns in velocity and insensitivity to random fluctuations (11). In sensitivity analyses, we determined whether results were similar if PSAV was derived from the four most recent PSA measurements (PSAV four ) and from all available (men with a minimum of five) PSA measurements (PSAV all ).…”

PSA‐detected prostate cancer and the potential for dedifferentiation—estimating the proportion capable of progression

“…Using a biostatistical approach, we estimated that a proportion of the prostate cancer is capable of dedifferentiation in the preclinical phase. Confirmation of these findings could come from the active monitoring arm of the ongoing ProtecT study 23…”