Prostate
ProtecT (cribriform morphology secondary analysis)
ForPSA-screened clinically localized prostate cancer, cribriform status on diagnostic biopsy
TL;DRSecondary analysis: cribriform-negative disease (87% of reviewed cohort) got no significant 15-yr metastasis reduction from early radical treatment vs monitoring.
Reported via UroToday β
For the RT reader this is a selection question, not a technique one: it asks whether cribriform status identifies the ProtecT subgroup that actually earned the metastasis reduction from radical treatment. RT here was EBRT with 3-6mo neoadjuvant ADT, a dated backbone. No subgroup HRs, CIs or event counts appear in the source excerpt.
In PSA-screened clinically localized disease with cribriform-negative grade group 2 on biopsy, this analysis supports treating long-term metastasis risk as comparable to grade group 1; it says nothing about cribriform-positive pts, where guidelines already discourage surveillance.
The decision this moves is whether to offer definitive RT at all, not how to deliver it: cribriform-negative grade group 2 showed metastasis risk equivalent to grade group 1 at 15 years. The RT arm was EBRT with 3-6mo neoadjuvant ADT in a pre-MRI, systematic-biopsy cohort, so transferability to current practice is limited. No subgroup effect sizes in source.
Relevant to how neoadjuvant ADT exposure is weighed against a metastasis benefit that this analysis does not find in the 87% cribriform-negative majority. ProtecT's ADT was 3 to 6 months alongside EBRT. The result argues for a biomarker-gated rather than grade-group-gated treatment decision.
Bears on the counselling conversation before radical prostatectomy in grade group 2: cribriform-negative pts carried the same 15-year metastasis risk as grade group 1, supporting surveillance discussion in that stratum. Cribriform-positive disease is untouched by this read, and guidelines already discourage surveillance there.
9 details
Secondary pathological analysis of the ProtecT randomized trial (active monitoring vs radical prostatectomy vs EBRT with neoadjuvant ADT). Central review of biopsy slides retrieved for 712 of 1,643 randomized pts, with both intention-to-treat and per-protocol analyses, the latter accounting for crossover to radical treatment.
PSA-screened men with clinically localized prostate cancer, the original ProtecT eligibility. Slides were regraded under 2019 ISUP criteria rather than the trial-era 2005 criteria; the presenter reports regrading did not change the picture. Age, PSA and revised Gleason score did not differ significantly across arms in the reviewed subset.
The RT arm was external-beam radiotherapy with 3 to 6 months of neoadjuvant ADT. No dose, fractionation or target volume is given in the source. The presenter notes cribriform-positive disease was more prevalent in this arm, attributed to chance since cribriform status was not a randomization characteristic.
Primary: metastases at 15-year median follow-up, analysed by cribriform status. Multivariable Cox modelling was used to compare metastasis risk across grade groups within the cribriform-negative stratum.
Roughly 13% of the reviewed cohort was cribriform-positive. Among the 87% cribriform-negative, early radical treatment produced no statistically significant reduction in 15-year metastases vs active monitoring, in both ITT and per-protocol analyses. Cribriform-negative grade group 2 carried metastasis risk equivalent to grade group 1.
Slides were available for under half the randomized cohort, so the analysis rests on whichever centres have so far returned material. The source excerpt is a video interview that stops mid-presentation and reports no HRs, CIs or event counts, so the size of the null in the cribriform-negative group cannot be judged from it.
The interest here is the inverse of the usual cribriform argument. Rather than showing cribriform-positive pts do badly on surveillance, the useful signal is that cribriform-negative grade group 2 behaves like grade group 1 over 15 years, which is a de-escalation read. Whether the cribriform-positive stratum shows the reciprocal benefit is not in the source excerpt.
Post-hoc subgroup of a non-stratified variable in 712 of 1,643 pts, with a non-significant negative result and no effect sizes in the source.
- Metastasis outcomes in the cribriform-positive stratum on active monitoring
- Whether cribriform status holds as a marker in MRI-targeted biopsy cohorts
- Reproducibility of binary cribriform calls across pathologists
π Sources Β· π 1 paper
Abstract
ESTRO Prostate SBRT Consensus Recommendations
TL;DRDelphi: 36.25 Gy/5 fx standard, 100% vote against elective pelvic nodal RT with prostate SBRT outside trial.
PACE-BPACE-CHYPO-RT-PCNRG-GU005hypo-FLAMEMIRAGEPARTIQoL
Two operational lines move practice: elective pelvic nodal RT alongside prostate SBRT is rejected 100% (12 votes) outside a trial, and intra-fraction tracking is only carried by 71% (10 votes) once PTV margin drops below 5 mm, no consensus. Prior BPH surgery is permitted with a median 6-month wait (range 2-12).
In ISUP 2-3, cT1c-cT2c, PSA <20 ng/mL localised prostate cancer, this supports five-fraction SBRT as a standard option without elective pelvic nodal coverage or a rectal spacer; it does not extend to cT3b, ISUP 5, or pts needing nodal irradiation.
The actionable lines are operational: no elective pelvic nodal RT with prostate SBRT outside a trial (100%, 12 votes), no routine rectal spacer (85%, 11 votes), and intra-fraction tracking only at 71% (10 votes) once PTV margin falls under 5 mm. Standard is 36.25 Gy/5 fx to 95% PTV with 40 Gy to 95% CTV.
15 details 5 trials watching
ESTRO task force literature review, then two Delphi survey rounds with a purposively selected expert panel, refined at ESTRO 2025 in Vienna. Ten multiple-choice questions covered areas of controversy. Consensus was predefined at β₯75% agreement, strong consensus at β₯90%, thresholds borrowed from APCCC.
Panel: eleven radiation oncologists, three medical physicists, one RTT from nine European countries. Voting counts per question ran 12 to 14. Target patient population is localised prostate cancer, with ISUP 2-3, cT1c-cT2c, PSA <20 ng/mL carrying strong consensus for SBRT as standard treatment outside a trial.
Standard is 36.25 Gy in five fractions of 7.25 Gy to 95% of the PTV, with 40 Gy to 95% of the prostate CTV (PACE-B), or 42.7 Gy in seven fractions of 6.1 Gy (HYPO-RT-PC). Prostate is contoured on T2-weighted planning MRI registered to CT; seminal vesicles omitted in low risk, proximal 1 cm included for all in PACE, proximal 2 cm to 30 Gy/5 fx in Gleason 4+3 or NCCN high risk. Rectal, bladder, femoral head, bowel and optional urethra PRV / penile bulb / crura constraints are given for five-fraction schedules only.
ADT per existing international guidelines, independent of the radiation schedule (100%, 13 votes). Intermediate risk: short-term ADT with conventional fractionation improves overall and cancer-specific survival by 7%, with no added benefit beyond roughly four months. High risk: long-term ADT plus RT improves overall and disease-specific survival irrespective of dose escalation.
No efficacy endpoint. The output is a set of recommendations plus per-question panel agreement percentages, so every "result" here is opinion measured against opinion.
The dose recommendation tracks PACE-B rather than splitting the difference with HYPO-RT-PC, whose lower biologically effective dose was still non-inferior, which the authors read as evidence 40 Gy in five fractions may not be needed for everyone. The unresolved counterweight is NRG-GU005, presented in preliminary form at ASTRO 2025: 36.25 Gy in five fractions gave lower side effects but a slightly higher three-year biochemical relapse rate, cause not yet determined. On protons, PARTIQoL found no difference in outcomes or QoL versus IMRT, with pencil beam scanning in only 48% of cases.
High-risk practice is running ahead of its evidence: HYPO-RT-PC is the only phase III reporting oncologic outcomes in high-risk pts and they were 11% of participants, while PACE-C has published toxicity but not oncological outcomes. Urethral sparing is recommended on mechanistic and single-study grounds while a post hoc PACE-B analysis found no significant association between urinary substructure dose and late urinary toxicity, and the panel itself flags the PACE-B urethra V42 <50% constraint as possibly too permissive.
The document's real contribution is the negative recommendations: no elective pelvic nodal RT with prostate SBRT outside a trial (100%, 12 votes) and no routine rectal spacer (85%, 11 votes), both areas where practice has drifted ahead of randomised data. It does not settle prostate volume cut-off, prophylactic medication, or whether intra-fraction tracking is required below a 5 mm margin, all of which returned no consensus.
| Category | Recommend SBRT (% of votes) |
|---|---|
| ISUP 2 | 100% (13 votes) |
| ISUP 3 | 100% (13 votes) |
| ISUP 4 | 38% (5 votes) |
| ISUP 5 | 0% (0 votes) |
| cT1c-cT2a | 100% (13 votes) |
| cT2b-cT2c | 100% (13 votes) |
| cT3a | 38% (5 votes) |
| cT3b | 0% (0 votes) |
| cT4 | 0% (0 votes) |
| PSA <20 ng/mL | 100% (13 votes) |
| PSA 20-40 ng/mL | 8% (1 vote) |
| PSA >40 ng/mL | 0% (0 votes) |
| Question | Vote | Level |
|---|---|---|
| Elective pelvic nodal RT with prostate SBRT (Q6) | No 100% (12 votes) | Strong consensus against |
| Bladder/bowel prep protocol (Q8) | Yes 100% (14 votes) | Strong consensus |
| ADT per existing guidelines, fractionation-independent (Q7) | Yes 100% (13 votes) | Strong consensus |
| Rectal spacer (Q9) | No 85% (11 votes) | Consensus against |
| Max IPSS cut-off (Q3) | Yes 85% (11 votes) | Consensus; median 17, range 10-20 |
| Max prostate volume cut-off (Q2) | Yes 62% (8 votes) | No consensus; median 90 cc, range 70-150 |
| Prophylactic meds (Ξ±1-blockers etc, Q4) | No 46% (6 votes) | No consensus |
| SBRT after BPH surgery (Q5) | Selected pts with waiting period 100% (13 votes) | Strong consensus; median wait 6 mo, range 2-12 |
- Cause of higher 3y biochemical relapse with 36.25 Gy in NRG-GU005
- Whether focal GTV dose escalation improves outcome in high-risk SBRT recruiting Image-guided Focal Dose Escalation- Primary pc Treated With Primary External Beam Hypofract.Stereotactic rt Phase NAn=374 Β· primary completion 2025-08 Β· randomised focal dose escalation vs no boost, cN0n=54 Β· primary completion 2027-06 Β· SBRT + mpMRI focal boost, unfavourable/high-risk
- Whether online adaptive RT improves toxicity over non-adaptive SBRT recruiting Adaptive Radiation Therapy (ART) Stereotactic Ablative Body Radiotherapy (SABR) for Primary Localized Prostate Cancer Phase NAn=164 Β· primary completion 2026-08 Β· margin-less adaptive 2 fx vs standard 5 fx SABR QoLrecruiting Is Adaptive SBRT for Prostate vs Image-guided Radiotherapy a True Evolution (ASPIRE) Phase 3n=320 Β· primary completion 2030-02 Β· phase 3 adaptive vs image-guided SBRT, urinary EPrecruiting Image-Guidance and Online Adaptation With Stereotactic Body Radiation Therapy for the Treatment of Localized Prostate Cancer, MANTICORE Trial Phase NAn=186 Β· primary completion 2031-12 Β· online adaptation vs IGRT SBRT, toxicity endpoint