High dose versus conventional dose in external beam radiotherapy of prostate cancer: a meta-analysis of long-term follow-up

Abstract

Purpose: To assess the efficacy and toxicity between high-dose radiotherapy (HDRT) and conventional-dose radiotherapy (CDRT) by collecting randomized controlled trials of long-term follow-ups.

Methods: Unrestricted by language, we searched Ovid MEDLINE, Ovid EMBASE, Cochrane Library, Science Citation Index (Web of Science) and ClinicalTrials.gov for the following end points: biochemical failure (BF), overall survival (OS), prostate cancer-specific survival (PCSS) and side effects. The meta-analysis was performed by using Review Manager 5.2 and Stata version 12.0 software packages. Results were expressed as the odds ratio (OR) with the corresponding 95 % confidence interval (CI).

Results: Six randomized controlled trials, with a total population of 2,822, were eligible. In terms of 10-year efficacy relative to CDRT, the HDRT was associated with almost an equivalent OS (73.4 vs. 74.3 %, OR 1.05, 95 % CI 0.86-1.28; p = 0.64) and PCSS (90.7 vs. 91.6 %, OR 1.11, 95 % CI 0.83-1.49; p = 0.47), but a significant decrease in the BF (34.0 vs. 24.7 %, OR 0.61, 95 % CI 0.51-0.74; p < 0.00001). In terms of toxicity, HDRT significantly increased the late Grade 2 or higher (G ≥ 2) gastrointestinal toxicity (28.0 vs. 18.6 %, OR 1.72, 95 % CI 1.42-2.08; p < 0.00001) and late G ≥ 2 genitourinary (GU) toxicity (22.6 vs. 19.5 %, OR 1.24, 95 % CI 1.01-1.52; p = 0.04). In the subgroup analysis, trials with or without androgen deprivation therapy both had a significant decrease in the BF at 10 years. With regard to quality of life, there was no significant difference between HDRT and CDRT (p > 0.05).

Conclusion: This was the first meta-analysis of trials with long-term follow-up to indicate that HDRT is superior to CDRT in terms of preventing BF in localized prostate cancer patients. However, this advantage did not translate into an improvement in OS and PCSS. This was also the first meta-analysis to suggest that the HDRT in three-dimensional conformal radiotherapy (3D-CRT) significantly increases the late G ≥ 2 GU toxicity. Thus, the dose escalation in 3D-CRT should be discreetly used in the treatment of prostate cancer due to the increase in late toxicities.

Fig. 1

Trial selection flowchart

Fig. 2

Meta-analysis regarding BF at 10 years

Fig. 3

Meta-analysis regarding OS at 10 years

Fig. 4

Meta-analysis regarding PCSS at 10 years

Fig. 5

Meta-analysis regarding GI toxicity

Fig. 6

Meta-analysis regarding GU toxicity

Fig. 7

Subgroup analysis regarding BF with or without ADT

Fig. 8

Funnel plot of publication on bias in the meta-analysis