PRIME NCT03561961
ForHigh-risk, very high-risk or node-positive non-metastatic prostate; ECOG 0-2
TL;DRInterim: acute grade ≥2 GU ~5.4% vs ~4.0% (p=0.59) for 5-fx SBRT vs 25-fx, both with whole-pelvis RT; BFFS immature.
The transferable parameter is the nodal dose: 25 Gy in 5 fractions to elective pelvis in both arms, with SIB to involved nodes permitted only in the SBRT arm. Late grade ≥2 GU ran ~10-12% vs ~9-11% at 1-2 yr, so the 5-fraction schedule carried no toxicity penalty over 25 fractions in a node-covered field.
In high-risk or node-positive non-metastatic prostate cancer where whole-pelvis RT and ~2 years of ADT are already planned, this supports 5-fraction delivery on toxicity grounds; it does not yet inform biochemical control, and does not extend to pts treated to prostate alone.
The gate is the elective nodal dose: 25 Gy in 5 fractions to whole pelvis in both arms, SIB to involved nodes only in the SBRT arm. Grade 3+ GU/GI stayed <1% either way, so the decision this moves is whether pelvic coverage can be compressed to 5 fractions, not whether it controls nodes.
+1 more figure
| Feature | HYPO-RT-PC | PRIME |
|---|---|---|
| Fractionation | 42.7 Gy/7 fx vs 78 Gy/39 fx | 36.25 Gy/5 fx vs 68 Gy/25 fx |
| Pelvic RT | None (prostate + SV) | Whole pelvis, 25 Gy/5 fx, both arms |
| ADT | Not permitted | Long course (~2 years), both arms |
| Nodal status | Node-negative only | Includes node-positive |
| Primary result | 10-yr FFS 72% vs 65%, adj HR 0.84 (95% CI 0.69-1.03) | BFFS not yet mature |
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Phase III, open-label, randomized non-inferiority trial from Tata Memorial Centre and collaborating Indian centres. Accrual 2018 to 2023, completed at ~434 pts, 1:1, stratified by risk group and nodal status. Interim analysis with follow-up of 1 to 2 years.
High-risk, very high-risk and/or node-positive non-metastatic prostate cancer, ECOG 0-2, life expectancy 10 years. PSMA PET/CT staging was permitted, so nodal staging is not uniform across the cohort.
Arm A 36.25 Gy in 5 fractions (7.25 Gy/fx), every other day. Arm B ~68 Gy in 25 fractions (2.7 Gy/fx) over ~5 weeks. Both arms received whole-pelvis elective nodal RT at 25 Gy in 5 fractions or equivalent, with SIB to positive nodes allowed in the SBRT arm; delivery was modern IMRT/VMAT with daily IGRT.
Long-course ADT (~2 years) in both arms, so the randomised variable is fractionation alone, not systemic intensity.
Primary: biochemical failure-free survival (Phoenix, nadir + 2 ng/mL). Secondary: acute and late toxicity (RTOG/CTCAE v4.0/5.0), OS, MFS, cFFS, QoL (EORTC QLQ-C30, QLQ-PR25, IPSS) and cost-effectiveness.
No BFFS, MFS or OS estimate is reported in the source. The interim efficacy statement is only no signal of inferiority for the SBRT arm, with mature 4 to 5 year data awaited.
| Toxicity | SBRT 5 fx | Mod hypo 25 fx | p |
|---|---|---|---|
| Acute GU (≤90 days) | ~5.4% | ~4.0% | 0.59 |
| Acute GI (≤90 days) | ~2.2% | ~3.7% | 0.20 |
| Late GU (1-2 yr) | ~10-12% | ~9-11% | NS |
| Late GI (1-2 yr) | ~5-7% | ~4-6% | NS |
| Grade 3+ GU/GI | <1% | <1% | not reported |
QoL by EORTC QLQ-C30, QLQ-PR25 and IPSS showed urinary and bowel domains stable and comparable between arms, with transient declines during and soon after treatment then recovery. ADT-related sexual and hormonal effects were similar, as expected with a fixed 2-year backbone in both arms.
HYPO-RT-PC gave level-1 support for ultra-hypofractionation (10-yr FFS 72% vs 65%, adjusted HR 0.84, 95% CI 0.69-1.03), but in node-negative pts with no pelvic RT and no ADT, mostly on 3D-CRT. PRIME asks the fractionation question where the target includes the pelvis and the backbone is 2 years of ADT, so its toxicity read is not inherited from that trial.
Toxicity reaches the reader as approximate values on a third-party summary graphic rather than a published table, and late follow-up of 1 to 2 years is short for the GU and GI events that separate fractionation schedules. Open-label design also leaves the QoL and IPSS readouts unblinded.
If BFFS holds at 4 to 5 years, the practical claim is that elective pelvic coverage can be delivered in 5 fractions instead of 25, compressing a 5-week course to 1 to 2 weeks where linac time rations access. Toxicity is the necessary first gate and it clears; non-inferiority is an efficacy claim and nothing here tests it yet.
Interim toxicity and QoL readout at 1-2 yr; primary BFFS not reported and 4-5 yr efficacy pending. Safety comparability cannot establish non-inferiority of 5-fraction SBRT.
- Adequacy of 25 Gy/5 fx elective nodal dose for microscopic disease recruiting A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT Phase 3n=1128 · primary completion 2028-06 · phase 3, 5-fx prostate vs prostate+pelvic nodal SBRTrecruiting PRO-BOOST-N: Prostate-First Versus Combined Prostate and Nodal Dose Escalation in PSMA PET-Staged Node-Positive Prostate Cancer Phase 2/3n=600 · primary completion 2033-12 · randomises nodal dose escalation over UHF whole-pelvis
- Late GU/GI toxicity beyond 2 years with 5-fraction whole-pelvis RT
- Mature BFFS non-inferiority at 4-5 years recruiting Comparing Moderately Ultra Hypofractionated Radiation Treatments for Prostate Cancer Phase 2n=204 · primary completion 2030-11 · non-inferiority: 25 Gy/5 fx vs 44 Gy/20 fx pelvic nodes
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PRIME trial
— Rohit Malde (@roxboxfix) May 18, 2026
Can we safely deliver ultra-short SBRT including pelvic nodal irradiation in biologically aggressive disease treated with ADT?
With Pelvic RT
Moderate hypofractionation:
~68 Gy/25#/5w
Vs
Extreme hypofractionation/SBRT:
36.25 Gy / 5 # /1-2w
Compare HYPO RT PC pic.twitter.com/7NABknLsD5
The longer read
The question PRIME is asking is narrower than whether prostate SBRT is safe, which HYPO-RT-PC and PACE-B already addressed in node-negative disease treated to the prostate alone. What is untested is elective pelvic nodal irradiation delivered in five fractions, on top of two years of ADT, in men whose disease is high-risk, very high-risk or frankly node-positive. That is the variable, and it is why this interim readout should be read as a feasibility signal rather than a result.
Comparability of acute and late grade ≥2 GU and GI toxicity at one to two years is the expected finding, not a surprising one. Both arms received the same elective nodal dose, 25 Gy in five fractions or equivalent, so the pelvis is held constant and the contrast reduces to 36.25 Gy in five fractions against roughly 68 Gy in 25 to the prostate. HYPO-RT-PC reported a higher early urinary burden in its seven-fraction arm before the arms converged by ten years, so a null at one to two years does not close the late-toxicity question here; it opens it. The reported window is shorter than the interval over which the events that discriminate fractionation schedules accumulate.
The efficacy claim is weaker still, for a structural reason. With mandatory ADT of roughly two years in both arms, a Phoenix failure requires a nadir plus 2 ng/mL rise, and testosterone recovery has barely begun at this follow-up. At one to two years almost no interpretable BFFS events can exist to compare. No signal of inferiority at this timepoint says very little about the primary endpoint, and the trial's own framing, that mature four to five year data are awaited, is the honest read.
Where the result could go wrong is nodal control rather than the prostate. Five fractions to the elective pelvis is a low dose against microscopic nodal disease, and the SBRT arm permitted a simultaneous boost to involved nodes, which puts heterogeneity inside the arm that a pooled BFFS curve will not resolve. If SBRT underperforms at maturity, the likeliest site of failure is the elective volume, and the reader will want the pattern-of-failure analysis, in-field versus out-of-field and prostate versus node, more than the headline hazard ratio.
The technical floor matters for transfer. Delivery was modern IMRT/VMAT with daily IGRT; a centre without that setup cannot borrow this toxicity result. Against that, the practical stake is real. A five-week course compressed to one to two weeks, in a health system where machine time rations access, is a larger gain than the same change would be elsewhere, and the prespecified cost-effectiveness endpoint is not decoration. Nothing in the interim data licenses a change in practice, but it does justify carrying the approach to mature follow-up rather than abandoning it.