Prostate
Conference presentation of an IPD meta-analysis reframing the dose-vs-ADT question for definitive RT: the bRFS gains from escalation don't translate to MFS or OS.
MARCAP Consortium
ForLocalized prostate cancer, NCCN intermediate to high risk, definitive RT
TL;DRIPD meta-analysis, 10,853 pts: ADT added to RT improved MFS HR 0.83 and OS HR 0.86; dose escalation improved bRFS only.
Reported via UroToday →
The dose-invariance result is the load-bearing one: ADT's benefit was identical at ≥74 Gy and <74 Gy (both HR 0.83), so escalating dose does not buy out the ADT decision. Adjuvant prolongation carries the benefit (MFS HR 0.84), neoadjuvant prolongation does not (HR 0.95), which moves sequencing, not just duration.
In NCCN intermediate- and high-risk localized prostate cancer receiving definitive RT, this supports adding and prolonging ADT on the adjuvant side rather than substituting dose escalation; it does not address node-positive or post-prostatectomy salvage settings.
ADT's benefit was identical at ≥74 Gy and <74 Gy (HR 0.83 both), so escalation does not buy out the hormone decision, and HEAT showed escalation to 79.2 Gy improved biochemical RFS but not MFS or OS. Adjuvant prolongation carries the survival benefit; neoadjuvant prolongation (HR 0.95) does not.
The duration and sequencing read: extending adjuvant ADT from 4-6 to 18-36 months gave MFS HR 0.84 and OS HR 0.85, while extending neoadjuvant ADT from 3-4 to 6-9 months gave HR 0.95 for both. Relative benefit held across NCCN groups, so risk stratification changes NNT, not effect size.
9 details 5 trials watching
Individual patient data meta-analysis from the MARCAP Consortium, 12 eligible trials, 10,853 patients, median follow-up 11.4 years (IQR 9.0-15.0). Three intensification questions analyzed separately: ADT use, neoadjuvant ADT prolongation, adjuvant ADT prolongation.
Localized prostate cancer treated with definitive radiotherapy, stratified by NCCN prognostic risk group. The RT ± ADT comparison ran 2,557 control vs 2,579 experimental (NCCN high 32.6% vs 32.8%, intermediate 47.6% vs 48.7%); the adjuvant-prolongation comparison was high-risk enriched at 71.5% vs 71.1% NCCN high across 1,900 vs 1,874 pts.
Dose was analyzed as a binary ≥74 Gy vs <74 Gy split, with the companion HEAT analysis using 64 to <74 Gy vs ≥74 Gy and escalation up to 79.2 Gy. Brachytherapy boost is discussed as an escalation route alongside external-beam dose.
ADT addition improved MFS HR 0.83 (0.77-0.89) and OS HR 0.86 (0.80-0.92). Adjuvant prolongation improved MFS HR 0.84 (0.78-0.91) and OS HR 0.85 (0.78-0.94); neoadjuvant prolongation did neither (MFS HR 0.95, OS HR 0.95). 10-yr MFS 61% (59-63) with ADT vs 52% (50-54) without; 10-yr OS 65% (63-67) vs 57% (55-59).
| Intervention | Intermediate risk | High risk |
|---|---|---|
| ADT addition | 18.0 | 8.4 |
| Adjuvant ADT prolongation | 16.1 | 10.4 |
The 2022 HEAT network meta-analysis (13 trials, 11,862 pts) found dose escalation improved biochemical RFS but not MFS or OS, and named high-dose RT plus long-term ADT the best strategy. PROG 05/09 and GETUG-18 are invoked to explain the gap: a 21% 5-year biochemical benefit in low risk where metastasis is rare, versus 3% in high risk where it is not.
The pooled trials span 30+ years of practice, so the RT technique behind the <74 Gy stratum is not the technique a reader delivers today. The stated optimal durations (closer to 12 months high risk, 24+ months very high risk) come from DHARMA, accepted but unpublished, so that specific number is not yet auditable.
The framing claim is that dose escalation and ADT are not interchangeable levers: escalation buys biochemical control, ADT buys metastasis-free and overall survival, and the two do not substitute. The dogma that dose escalation obviates ADT is named as widely repeated and never demonstrated.
IPD meta-analysis of randomised trials, large N, long f/u. Reinforces ADT intensification over dose escalation; no new randomisation, and duration guidance rests on unpublished DHARMA.
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