Prostate Radiotherapy for Metastatic Hormone-sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta-analysis

Abstract

Background Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC). Objective To systematically review trials of prostate radiotherapy. Design, setting, and participants Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known. We searched extensively for eligible trials and asked investigators when results would be available. We could then anticipate that a definitive meta-analysis of the effects of prostate radiotherapy was possible. We obtained prepublication, unpublished, and harmonised results from investigators. Intervention We included trials that randomised men to prostate radiotherapy and androgen deprivation therapy (ADT) or ADT only. Outcome measurements and statistical analysis Hazard ratios (HRs) for the effects of prostate radiotherapy on survival, progression-free survival (PFS), failure-free survival (FFS), biochemical progression, and subgroup interactions were combined using fixed-effect meta-analysis. Results and limitations We identified one ongoing (PEACE-1) and two completed (HORRAD and STAMPEDE) eligible trials. Pooled results of the latter (2126 men; 90% of those eligible) showed no overall improvement in survival (HR = 0.92, 95% confidence interval [CI] 0.81–1.04, p = 0.195) or PFS (HR = 0.94, 95% CI 0.84–1.05, p = 0.238) with prostate radiotherapy. There was an overall improvement in biochemical progression (HR = 0.74, 95% CI 0.67–0.82, p = 0.94 × 10 −8 ) and FFS (HR = 0.76, 95% CI 0.69–0.84, p = 0.64 × 10 −7 ), equivalent to ∼10% benefit at 3 yr. The effect of prostate radiotherapy varied by metastatic burden—a pattern consistent across trials and outcome measures, including survival (<5, ≥5; interaction HR = 1.47, 95% CI 1.11–1.94, p = 0.007). There was 7% improvement in 3-yr survival in men with fewer than five bone metastases. Conclusions Prostate radiotherapy should be considered for men with mHSPC with a low metastatic burden. Patient summary Prostate cancer that has spread to other parts of the body (metastases) is usually treated with hormone therapy. In men with fewer than five bone metastases, addition of prostate radiotherapy helped them live longer and should be considered.

Comparison of aggregate and individual participant data approaches to meta-analysis of randomised trials: An observational study

“…Our results support the assertion that in order for a meta-analysis to be reliable, the information size should be at least as large as an adequately powered trial [46]. Although there is greater interest now in estimating the (absolute) information size of meta-analyses [47][48][49][50][51][52], surprisingly little attention has been paid to explicitly quantifying the relative information size of an AD meta-analysis [48][49][50][51]. A comprehensive systematic review of published comparisons of AD and IPD meta-analyses did not find that agreement was associated with the information they contained (the number of trials or participants) [53], but without access to the primary studies, the authors could not investigate this more thoroughly, and, as stated previously, multiple outcomes from the same meta-analyses were included.…”

“…Whereas, if an effect has been detected based on AD, there may be motivation to collect IPD in order to conduct subgroup or other detailed analyses and provide more nuanced results. The absolute and relative information size are also useful for anticipating when accumulating evidence from trials might be sufficient for reliable AD meta-analysis, using a prospective framework for adaptive meta-analysis (FAME) [48][49][50][51].…”

Novel treatment options in the management of metastatic castration-naïve prostate cancer; which treatment modality to choose?

“…Additionally, several meta-analyses have made some cautious, indirect comparisons on the best treatment of mCNPC patients in terms of OS and other end points [25][26][27][28][29][30][31][32]. A 23-27% reduction in the risk of death was observed when ADT was combined with docetaxel compared with ADT alone with pooled HRs of 0.73-0.77, and the addition of abiraterone to ADT resulted in a 37%-40% reduction in risk of death with pooled HRs of 0.60-0.63 (Table 4).…”

Lokale behandeling bij het primair gemetastaseerd prostaatcarcinoom

“…De resultaten van beide eerder genoemde RCT's zijn samengevoegd in een meta-analyse [14]. Hierbij werden analyses gedaan met de individuele patiëntendata van in totaal 2.126 patiënten.…”