Timing of curative treatment for prostate cancer: a systematic review

Abstract

Context: Delaying definitive therapy unfavourably affects outcomes in many malignancies. Diagnostic, psychological, and logistical reasons but also active surveillance (AS) strategies can lead to treatment delay, an increase in the interval between the diagnosis and treatment of prostate cancer (PCa).

Objective: To review and summarise the current literature on the impact of treatment delay on PCa oncologic outcomes.

Evidence acquisition: A comprehensive search of PubMed and Embase databases until 30 September 2012 was performed. Studies comparing pathologic, biochemical recurrence (BCR), and mortality outcomes between patients receiving direct and delayed curative treatment were included. Studies presenting single-arm results following AS were excluded.

Evidence synthesis: Seventeen studies were included: 13 on radical prostatectomy, 3 on radiation therapy, and 1 combined both. A total of 34 517 PCa patients receiving radical local therapy between 1981 and 2009 were described. Some studies included low-risk PCa only; others included a wider spectrum of disease. Four studies found a significant effect of treatment delay on outcomes in multivariate analysis. Two included low-risk patients only, but it was unknown whether AS was applied or repeat biopsy triggered active therapy during AS. The two other studies found a negative effect on BCR rates of 2.5-9 mo delay in higher risk patients (respectively defined as any with T ≥ 2b, prostate-specific antigen >10, Gleason score >6, >34-50% positive cores; or D'Amico intermediate risk-group). All studies were retrospective and nonrandomised. Reasons for delay were not always clear, and time-to-event analyses may be subject to bias.

Conclusions: Treatment delay of several months or even years does not appear to affect outcomes of men with low-risk PCa. Limited data suggest treatment delay may have an impact on men with non-low-risk PCa. Most AS protocols suggest a confirmatory biopsy to avoid delaying treatment in those who harbour higher risk disease that was initially misclassified.

Keywords: Active surveillance; Delay; Expectant management; Outcomes; Prostate cancer; Radiation therapy; Radical prostatectomy.

Fig. 1

Literature search and selection of studies for analysis flowchart.

Fig. 2

Schematic presentation of the disease course of low-, intermediate-, and high-risk disease against life expectancy and the effect of treatment delay (dashed arrows). A similar delay may result in missing the window of curability for higher risk disease.